Version history

{
  "content_md": "# ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2\n\n\n\n## Pathway Diagram\n\nflowchart TD\n    ABCG2[\"ABCG2 Transporter\"]:::central --> BBB[\"Blood-Brain Barrier Function\"]:::protective\n    ABCG2 -->|\"efflux pump\"| Drug_Clearance[\"Drug Clearance\"]:::protective\n    BBB -->|\"compromised\"| Neurodegeneration[\"Neurodegeneration\"]:::pathological\n    \n    ABCG2 -->|\"activates\"| BCL2[\"BCL-2\"]:::protective\n    ABCG2 -->|\"activates\"| MFN2[\"MFN2\"]:::protective\n    BCL2 --> Apoptosis_Protection[\"Apoptosis Protection\"]:::protective\n    MFN2 --> Mitochondrial_Health[\"Mitochondrial Health\"]:::protective\n    \n    ABCG2 -->|\"activates\"| GSDMD[\"GSDMD\"]:::pathological\n    ABCG2 -->|\"activates\"| RIPK1[\"RIPK1\"]:::pathological\n    GSDMD --> Pyroptosis[\"Pyroptosis\"]:::pathological\n    RIPK1 --> Necroptosis[\"Necroptosis\"]:::pathological\n    \n    ABCG2 -->|\"associated\"| APOE[\"APOE\"]:::regulatory\n    APOE --> Alzheimer[\"Alzheimer Disease\"]:::pathological\n    \n    Drug_Clearance -->|\"reduced\"| CNS_Toxicity[\"CNS Toxicity\"]:::pathological\n    CNS_Toxicity --> Depression[\"Depression\"]:::pathological\n    CNS_Toxicity --> Anxiety[\"Anxiety\"]:::pathological\n\n    classDef central fill:#006494\n    classDef protective fill:#1b5e20\n    classDef pathological fill:#ef5350\n    classDef regulatory fill:#4a1a6b\n\n<div class=\"infobox infobox-gene\">\n<h3>ABCG2 (BCRP)</h3>\n<table>\n<tr><td><strong>Full Name</strong></td><td>ATP Binding Cassette Subfamily G Member 2</td></tr>\n<tr><td><strong>Gene Symbol</strong></td><td>ABCG2 (BCRP, MXR, ABCP)</td></tr> [@polli2009]\n<tr><td><strong>Chromosomal Location</strong></td><td>4q22.1</td></tr> [@de2003]\n<tr><td><strong>NCBI Gene ID</strong></td><td>[9429](https://www.ncbi.nlm.nih.gov/gene/9429)</td></tr> [@kim2002]\n<tr><td><strong>OMIM</strong></td><td>[603756](https://omim.org/entry/603756)</td></tr> [@imai2003]\n<tr><td><strong>Ensembl</strong></td><td>[ENSG00000118777](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118777)</td></tr> [@ascherio2009]\n<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9UNQ0 (BCRP)](https://www.uniprot.org/uniprot/Q9UNQ0)</td></tr> [@nicolazzo2022]\n<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Gout</td></tr>\n</table>\n</div>\n\n## Overview\n\n**ABCG2** (ATP Binding Cassette Subfamily G Member 2), also known as **BCRP** (Breast Cancer Resistance Protein) or **MXR** (Mitoxantrone Resistance Protein), encodes a 72 kDa half-transporter that functions as a homodimer at the [blood-brain barrier](/mechanisms/blood-brain-barrier). Together with [P-glycoprotein (ABCB1)](/genes/abcb1), BCRP forms the primary efflux transporter system protecting the brain from xenobiotics and potentially toxic metabolites. ABCG2 has emerged as an important player in neurodegenerative disease through its roles in urate transport, heme homeostasis, and neuroprotective compound efflux.\n\n## Gene Structure and Expression\n\nABCG2 spans approximately 66 kb on chromosome 4q22.1 and contains 16 exons. Unlike full transporters such as [ABCB1](/genes/abcb1), ABCG2 is a half-transporter containing a single NBD and single TMD, requiring homodimerization for function. The gene is regulated by hypoxia-inducible factors ([HIF-1α](/genes/hif1a), [HIF-2α](/genes/epas1)), estrogen receptor, and [NRF2](/genes/nfe2l2) antioxidant response elements.\n\nIn the brain, ABCG2 is highly expressed at the luminal membrane of brain capillary endothelial cells, co-localizing with [ABCB1](/genes/abcb1). Expression is also detected in [astrocytes](/entities/astrocytes), neural stem cells, and the choroid plexus. Notably, ABCG2 marks a side population of neural stem/progenitor cells with enhanced self-renewal capacity. Brain expression is maintained throughout aging, though functional activity may decline.\n\n## Protein Function and Mechanism\n\n### Transport Activity\n\nBCRP functions as an ATP-dependent efflux pump that transports substrates from the cytoplasm or inner membrane leaflet to the extracellular space. Key features include:\n\n- **Homodimeric architecture**: Two ABCG2 monomers assemble via extensive TMD interactions to form a functional transporter with a central drug-binding cavity\n- **Substrate specificity**: Preferentially transports sulfated and glucuronidated conjugates, porphyrins, dietary flavonoids, urate, and various chemotherapeutic agents\n- **Cooperative transport**: Some substrates show positive cooperativity, with binding at one site enhancing transport at the other\n\n### Key Substrates Relevant to Neurodegeneration\n\n1. **Urate/uric acid**: ABCG2 is the primary renal and intestinal urate transporter. The Q141K variant causes hyperuricemia and gout. Urate is a potent antioxidant that may be neuroprotective in [Parkinson's disease](/diseases/parkinsons-disease)\n2. **Heme and porphyrins**: BCRP exports protoporphyrin IX and heme, protecting cells from phototoxicity and oxidative damage. Disrupted heme homeostasis is implicated in neurodegeneration\n3. **Amyloid-beta**: Evidence suggests BCRP may contribute to Aβ efflux at the [BBB](/entities/blood-brain-barrier), though its role is secondary to [P-glycoprotein](/genes/abcb1)\n4. **Dietary flavonoids**: Transports neuroprotective polyphenols (quercetin, resveratrol) out of the brain, potentially limiting their therapeutic efficacy\n\n### BBB Gatekeeper Function\n\nAt the [blood-brain barrier](/mechanisms/blood-brain-barrier), BCRP and P-gp function cooperatively. Dual knockout of both transporters in mice dramatically increases brain penetration of shared substrates (up to 10-fold more than single knockouts), demonstrating synergistic BBB protection. This has major implications for CNS drug delivery strategies.\n\n## Disease Associations\n\n### Parkinson's Disease\n\nThe connection between ABCG2 and [Parkinson's disease](/diseases/parkinsons-disease) centers on the urate hypothesis:\n\n- **Urate as neuroprotectant**: Higher serum urate levels correlate with reduced PD risk and slower disease progression. ABCG2 variants that increase serum urate (by reducing renal excretion) may indirectly confer neuroprotection\n- **Q141K variant (rs2231142)**: This common variant (allele frequency ~10% in Europeans, ~30% in East Asians) reduces ABCG2 transport activity by ~50% and raises serum urate. Studies show modest association with reduced PD risk\n- **Toxin exposure**: BCRP effluxes several environmental neurotoxins; reduced function may increase vulnerability to pesticide-induced parkinsonism\n- **BBB integrity**: ABCG2 expression is reduced in PD midbrain capillaries, potentially compromising local BBB function\n\n### Alzheimer's Disease\n\n- **Aβ clearance**: BCRP contributes to Aβ40 and Aβ42 efflux at the BBB, complementing [ABCB1](/genes/abcb1)-mediated clearance. ABCG2 upregulation by [Aβ](/proteins/amyloid-beta) itself may represent a compensatory response\n- **Inflammatory regulation**: [NF-κB](/mechanisms/nf-kb-pathway)-mediated upregulation of ABCG2 during neuroinflammation alters the BBB transport profile\n- **Drug delivery barrier**: BCRP limits brain entry of several investigational AD therapeutics, complicating treatment strategies\n\n### Gout and Hyperuricemia\n\nThe Q141K variant is the strongest genetic risk factor for gout (OR ~1.7), causing reduced renal urate secretion. This is the most well-characterized clinical phenotype of ABCG2 dysfunction.\n\n## Common Variants\n\n| Variant | rsID | Consequence | Clinical Significance |\n|---------|------|-------------|----------------------|\n| Q141K | rs2231142 | Gln141Lys | Reduced transport (~50%); gout, hyperuricemia; possible PD protection |\n| V12M | rs2231137 | Val12Met | Modest functional effect; population-specific associations |\n| S441N | - | Ser441Asn | Severe loss of function; membrane trafficking defect |\n| R482G/T | - | Arg482Gly/Thr | Altered substrate specificity (gain of anthracycline transport) |\n\n## Therapeutic Implications\n\n### Neuroprotective Strategies\n- **Urate-elevating approaches**: ABCG2 inhibition to raise CNS urate levels as a PD neuroprotection strategy (inosine supplementation trials)\n- **BBB modulation**: Selective ABCG2 inhibition (fumitremorgin C analogs, Ko143) to enhance CNS drug delivery while maintaining [ABCB1](/genes/abcb1) function\n\n### Drug Development Considerations\n- ABCG2 substrate profiling is essential for CNS drug candidates\n- Dual ABCB1/ABCG2 inhibitor strategies may be needed for effective BBB penetration\n- Pharmacogenomic testing for Q141K to predict drug exposure variability\n\n### Neural Stem Cell Biology\nABCG2 expression marks neural stem cell populations; understanding its role in stem cell maintenance may inform regenerative medicine approaches for neurodegeneration.\n\n## Expression Profile\n\n- **Brain endothelium**: High expression at BBB luminal membrane (co-localizes with [ABCB1](/genes/abcb1))\n- **Choroid plexus**: Blood-CSF barrier expression\n- **Neural stem cells**: Side population marker; maintains stemness\n- **Astrocytes**: Low-moderate expression, inducible by hypoxia\n- **Peripheral**: Liver canalicular membrane, kidney proximal tubule, intestinal epithelium, placenta\n\n## See Also\n- [ABCB1](/genes/abcb1) — P-glycoprotein, primary BBB efflux transporter\n- [SLC2A1](/genes/slc2a1) — GLUT1 glucose transporter at BBB\n- [CLDN5](/genes/cldn5) — Claudin-5 tight junction protein\n- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) — BBB structure and function\n- [Amyloid-Beta](/proteins/amyloid-beta) — Aβ peptide clearance\n- [NRF2/NFE2L2](/genes/nfe2l2) — Transcriptional regulator of ABCG2\n- [Alpha-Synuclein](/proteins/alpha-synuclein) — PD-associated protein\n\n## External Links\n- [NCBI Gene: ABCG2](https://www.ncbi.nlm.nih.gov/gene/9429)\n- [UniProt: Q9UNQ0](https://www.uniprot.org/uniprot/Q9UNQ0)\n- [GeneCards: ABCG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCG2)\n- [OMIM: 603756](https://omim.org/entry/603756)\n- [PharmGKB: ABCG2](https://www.pharmgkb.org/gene/PA390)\n\n\n## Brain Atlas Resources\n\n- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data\n- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome\n- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression\n\n## References\n\n1. [Agarwal S et al., Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up (2011) (2011)](https://doi.org/10.2174/138920011795495769)\n2. [Matsuo H et al., Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population (2009) (2009)](https://doi.org/10.1126/scitranslmed.3000237)\n3. [Weisberg IS et al., ABCG2 and neuroprotection: urate hypothesis revisited (2020) (2020)](https://doi.org/10.1002/mds.28016)\n4. [Do TM et al., ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1-40 at the mouse blood-brain barrier (2012) (2012)](https://doi.org/10.3233/JAD-2012-112189)\n5. [Polli JW et al., An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (2009) (2009)](https://doi.org/10.1124/dmd.108.024646)\n6. [de Boer AG et al., The role of drug transporters at the blood-brain barrier (2003) (2003)](https://doi.org/10.1146/annurev.pharmtox.43.100901.140204)\n7. [Unknown, Kim RB, Drugs as P-glycoprotein substrates, inhibitors, and inducers (2002) (2002)](https://doi.org/10.1124/dmd.30.4.470)\n8. [Imai Y et al., Breast cancer resistance protein exports sulfated estrogens but not free estrogens (2003) (2003)](https://doi.org/10.1124/mol.63.3.544)\n9. [Ascherio A et al., Urate as a predictor of the rate of clinical decline in Parkinson disease (2009) (2009)](https://doi.org/10.1001/archneurol.2009.247)\n10. [Unknown, Nicolazzo JA & Bhatt DK, Role of breast cancer resistance protein (BCRP/ABCG2) in the efflux of amyloid-β from the brain (2022) (2022)](https://doi.org/10.1016/j.bcp.2022.115071)\n\n## Pathway Diagram\n\nThe following diagram shows the key molecular relationships involving ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2 discovered through SciDEX knowledge graph analysis:\n\n```mermaid\ngraph TD\n    AMPK[\"AMPK\"] -->|\"activates\"| ABCG2[\"ABCG2\"]\n    CHAT[\"CHAT\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC30A8[\"SLC30A8\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    APOE[\"APOE\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    HMGCR[\"HMGCR\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    OPRM1[\"OPRM1\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    CYP2D6[\"CYP2D6\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    COMT[\"COMT\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    NBEA[\"NBEA\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    HTR2C[\"HTR2C\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    ADRA2A[\"ADRA2A\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    BCHE[\"BCHE\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC6A2[\"SLC6A2\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC6A3[\"SLC6A3\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    GABRA1[\"GABRA1\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    style AMPK fill:#ce93d8,stroke:#333,color:#000\n    style ABCG2 fill:#ce93d8,stroke:#333,color:#000\n    style CHAT fill:#ce93d8,stroke:#333,color:#000\n    style SLC30A8 fill:#ce93d8,stroke:#333,color:#000\n    style APOE fill:#ce93d8,stroke:#333,color:#000\n    style HMGCR fill:#ce93d8,stroke:#333,color:#000\n    style OPRM1 fill:#ce93d8,stroke:#333,color:#000\n    style CYP2D6 fill:#ce93d8,stroke:#333,color:#000\n    style COMT fill:#ce93d8,stroke:#333,color:#000\n    style NBEA fill:#ce93d8,stroke:#333,color:#000\n    style HTR2C fill:#ce93d8,stroke:#333,color:#000\n    style ADRA2A fill:#ce93d8,stroke:#333,color:#000\n    style BCHE fill:#ce93d8,stroke:#333,color:#000\n    style SLC6A2 fill:#ce93d8,stroke:#333,color:#000\n    style SLC6A3 fill:#ce93d8,stroke:#333,color:#000\n    style GABRA1 fill:#ce93d8,stroke:#333,color:#000\n```\n\n",
  "entity_type": "gene"
}

{
  "content_md": "# ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2\n\n\n\n## Pathway Diagram\n\n```mermaid\nflowchart TD\n    ABCG2[\"ABCG2 Transporter\"]:::central --> BBB[\"Blood-Brain Barrier Function\"]:::protective\n    ABCG2 -->|\"efflux pump\"| Drug_Clearance[\"Drug Clearance\"]:::protective\n    BBB -->|\"compromised\"| Neurodegeneration[\"Neurodegeneration\"]:::pathological\n    \n    ABCG2 -->|\"activates\"| BCL2[\"BCL-2\"]:::protective\n    ABCG2 -->|\"activates\"| MFN2[\"MFN2\"]:::protective\n    BCL2 --> Apoptosis_Protection[\"Apoptosis Protection\"]:::protective\n    MFN2 --> Mitochondrial_Health[\"Mitochondrial Health\"]:::protective\n    \n    ABCG2 -->|\"activates\"| GSDMD[\"GSDMD\"]:::pathological\n    ABCG2 -->|\"activates\"| RIPK1[\"RIPK1\"]:::pathological\n    GSDMD --> Pyroptosis[\"Pyroptosis\"]:::pathological\n    RIPK1 --> Necroptosis[\"Necroptosis\"]:::pathological\n    \n    ABCG2 -->|\"associated\"| APOE[\"APOE\"]:::regulatory\n    APOE --> Alzheimer[\"Alzheimer Disease\"]:::pathological\n    \n    Drug_Clearance -->|\"reduced\"| CNS_Toxicity[\"CNS Toxicity\"]:::pathological\n    CNS_Toxicity --> Depression[\"Depression\"]:::pathological\n    CNS_Toxicity --> Anxiety[\"Anxiety\"]:::pathological\n\n    classDef central fill:#006494\n    classDef protective fill:#1b5e20\n    classDef pathological fill:#ef5350\n    classDef regulatory fill:#4a1a6b\n```\n\n<div class=\"infobox infobox-gene\">\n<h3>ABCG2 (BCRP)</h3>\n<table>\n<tr><td><strong>Full Name</strong></td><td>ATP Binding Cassette Subfamily G Member 2</td></tr>\n<tr><td><strong>Gene Symbol</strong></td><td>ABCG2 (BCRP, MXR, ABCP)</td></tr> [@polli2009]\n<tr><td><strong>Chromosomal Location</strong></td><td>4q22.1</td></tr> [@de2003]\n<tr><td><strong>NCBI Gene ID</strong></td><td>[9429](https://www.ncbi.nlm.nih.gov/gene/9429)</td></tr> [@kim2002]\n<tr><td><strong>OMIM</strong></td><td>[603756](https://omim.org/entry/603756)</td></tr> [@imai2003]\n<tr><td><strong>Ensembl</strong></td><td>[ENSG00000118777](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118777)</td></tr> [@ascherio2009]\n<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9UNQ0 (BCRP)](https://www.uniprot.org/uniprot/Q9UNQ0)</td></tr> [@nicolazzo2022]\n<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Gout</td></tr>\n</table>\n</div>\n\n## Overview\n\n**ABCG2** (ATP Binding Cassette Subfamily G Member 2), also known as **BCRP** (Breast Cancer Resistance Protein) or **MXR** (Mitoxantrone Resistance Protein), encodes a 72 kDa half-transporter that functions as a homodimer at the [blood-brain barrier](/mechanisms/blood-brain-barrier). Together with [P-glycoprotein (ABCB1)](/genes/abcb1), BCRP forms the primary efflux transporter system protecting the brain from xenobiotics and potentially toxic metabolites. ABCG2 has emerged as an important player in neurodegenerative disease through its roles in urate transport, heme homeostasis, and neuroprotective compound efflux.\n\n## Gene Structure and Expression\n\nABCG2 spans approximately 66 kb on chromosome 4q22.1 and contains 16 exons. Unlike full transporters such as [ABCB1](/genes/abcb1), ABCG2 is a half-transporter containing a single NBD and single TMD, requiring homodimerization for function. The gene is regulated by hypoxia-inducible factors ([HIF-1α](/genes/hif1a), [HIF-2α](/genes/epas1)), estrogen receptor, and [NRF2](/genes/nfe2l2) antioxidant response elements.\n\nIn the brain, ABCG2 is highly expressed at the luminal membrane of brain capillary endothelial cells, co-localizing with [ABCB1](/genes/abcb1). Expression is also detected in [astrocytes](/entities/astrocytes), neural stem cells, and the choroid plexus. Notably, ABCG2 marks a side population of neural stem/progenitor cells with enhanced self-renewal capacity. Brain expression is maintained throughout aging, though functional activity may decline.\n\n## Protein Function and Mechanism\n\n### Transport Activity\n\nBCRP functions as an ATP-dependent efflux pump that transports substrates from the cytoplasm or inner membrane leaflet to the extracellular space. Key features include:\n\n- **Homodimeric architecture**: Two ABCG2 monomers assemble via extensive TMD interactions to form a functional transporter with a central drug-binding cavity\n- **Substrate specificity**: Preferentially transports sulfated and glucuronidated conjugates, porphyrins, dietary flavonoids, urate, and various chemotherapeutic agents\n- **Cooperative transport**: Some substrates show positive cooperativity, with binding at one site enhancing transport at the other\n\n### Key Substrates Relevant to Neurodegeneration\n\n1. **Urate/uric acid**: ABCG2 is the primary renal and intestinal urate transporter. The Q141K variant causes hyperuricemia and gout. Urate is a potent antioxidant that may be neuroprotective in [Parkinson's disease](/diseases/parkinsons-disease)\n2. **Heme and porphyrins**: BCRP exports protoporphyrin IX and heme, protecting cells from phototoxicity and oxidative damage. Disrupted heme homeostasis is implicated in neurodegeneration\n3. **Amyloid-beta**: Evidence suggests BCRP may contribute to Aβ efflux at the [BBB](/entities/blood-brain-barrier), though its role is secondary to [P-glycoprotein](/genes/abcb1)\n4. **Dietary flavonoids**: Transports neuroprotective polyphenols (quercetin, resveratrol) out of the brain, potentially limiting their therapeutic efficacy\n\n### BBB Gatekeeper Function\n\nAt the [blood-brain barrier](/mechanisms/blood-brain-barrier), BCRP and P-gp function cooperatively. Dual knockout of both transporters in mice dramatically increases brain penetration of shared substrates (up to 10-fold more than single knockouts), demonstrating synergistic BBB protection. This has major implications for CNS drug delivery strategies.\n\n## Disease Associations\n\n### Parkinson's Disease\n\nThe connection between ABCG2 and [Parkinson's disease](/diseases/parkinsons-disease) centers on the urate hypothesis:\n\n- **Urate as neuroprotectant**: Higher serum urate levels correlate with reduced PD risk and slower disease progression. ABCG2 variants that increase serum urate (by reducing renal excretion) may indirectly confer neuroprotection\n- **Q141K variant (rs2231142)**: This common variant (allele frequency ~10% in Europeans, ~30% in East Asians) reduces ABCG2 transport activity by ~50% and raises serum urate. Studies show modest association with reduced PD risk\n- **Toxin exposure**: BCRP effluxes several environmental neurotoxins; reduced function may increase vulnerability to pesticide-induced parkinsonism\n- **BBB integrity**: ABCG2 expression is reduced in PD midbrain capillaries, potentially compromising local BBB function\n\n### Alzheimer's Disease\n\n- **Aβ clearance**: BCRP contributes to Aβ40 and Aβ42 efflux at the BBB, complementing [ABCB1](/genes/abcb1)-mediated clearance. ABCG2 upregulation by [Aβ](/proteins/amyloid-beta) itself may represent a compensatory response\n- **Inflammatory regulation**: [NF-κB](/mechanisms/nf-kb-pathway)-mediated upregulation of ABCG2 during neuroinflammation alters the BBB transport profile\n- **Drug delivery barrier**: BCRP limits brain entry of several investigational AD therapeutics, complicating treatment strategies\n\n### Gout and Hyperuricemia\n\nThe Q141K variant is the strongest genetic risk factor for gout (OR ~1.7), causing reduced renal urate secretion. This is the most well-characterized clinical phenotype of ABCG2 dysfunction.\n\n## Common Variants\n\n| Variant | rsID | Consequence | Clinical Significance |\n|---------|------|-------------|----------------------|\n| Q141K | rs2231142 | Gln141Lys | Reduced transport (~50%); gout, hyperuricemia; possible PD protection |\n| V12M | rs2231137 | Val12Met | Modest functional effect; population-specific associations |\n| S441N | - | Ser441Asn | Severe loss of function; membrane trafficking defect |\n| R482G/T | - | Arg482Gly/Thr | Altered substrate specificity (gain of anthracycline transport) |\n\n## Therapeutic Implications\n\n### Neuroprotective Strategies\n- **Urate-elevating approaches**: ABCG2 inhibition to raise CNS urate levels as a PD neuroprotection strategy (inosine supplementation trials)\n- **BBB modulation**: Selective ABCG2 inhibition (fumitremorgin C analogs, Ko143) to enhance CNS drug delivery while maintaining [ABCB1](/genes/abcb1) function\n\n### Drug Development Considerations\n- ABCG2 substrate profiling is essential for CNS drug candidates\n- Dual ABCB1/ABCG2 inhibitor strategies may be needed for effective BBB penetration\n- Pharmacogenomic testing for Q141K to predict drug exposure variability\n\n### Neural Stem Cell Biology\nABCG2 expression marks neural stem cell populations; understanding its role in stem cell maintenance may inform regenerative medicine approaches for neurodegeneration.\n\n## Expression Profile\n\n- **Brain endothelium**: High expression at BBB luminal membrane (co-localizes with [ABCB1](/genes/abcb1))\n- **Choroid plexus**: Blood-CSF barrier expression\n- **Neural stem cells**: Side population marker; maintains stemness\n- **Astrocytes**: Low-moderate expression, inducible by hypoxia\n- **Peripheral**: Liver canalicular membrane, kidney proximal tubule, intestinal epithelium, placenta\n\n## See Also\n- [ABCB1](/genes/abcb1) — P-glycoprotein, primary BBB efflux transporter\n- [SLC2A1](/genes/slc2a1) — GLUT1 glucose transporter at BBB\n- [CLDN5](/genes/cldn5) — Claudin-5 tight junction protein\n- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) — BBB structure and function\n- [Amyloid-Beta](/proteins/amyloid-beta) — Aβ peptide clearance\n- [NRF2/NFE2L2](/genes/nfe2l2) — Transcriptional regulator of ABCG2\n- [Alpha-Synuclein](/proteins/alpha-synuclein) — PD-associated protein\n\n## External Links\n- [NCBI Gene: ABCG2](https://www.ncbi.nlm.nih.gov/gene/9429)\n- [UniProt: Q9UNQ0](https://www.uniprot.org/uniprot/Q9UNQ0)\n- [GeneCards: ABCG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCG2)\n- [OMIM: 603756](https://omim.org/entry/603756)\n- [PharmGKB: ABCG2](https://www.pharmgkb.org/gene/PA390)\n\n\n## Brain Atlas Resources\n\n- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data\n- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome\n- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression\n\n## References\n\n1. [Agarwal S et al., Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up (2011) (2011)](https://doi.org/10.2174/138920011795495769)\n2. [Matsuo H et al., Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population (2009) (2009)](https://doi.org/10.1126/scitranslmed.3000237)\n3. [Weisberg IS et al., ABCG2 and neuroprotection: urate hypothesis revisited (2020) (2020)](https://doi.org/10.1002/mds.28016)\n4. [Do TM et al., ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1-40 at the mouse blood-brain barrier (2012) (2012)](https://doi.org/10.3233/JAD-2012-112189)\n5. [Polli JW et al., An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (2009) (2009)](https://doi.org/10.1124/dmd.108.024646)\n6. [de Boer AG et al., The role of drug transporters at the blood-brain barrier (2003) (2003)](https://doi.org/10.1146/annurev.pharmtox.43.100901.140204)\n7. [Unknown, Kim RB, Drugs as P-glycoprotein substrates, inhibitors, and inducers (2002) (2002)](https://doi.org/10.1124/dmd.30.4.470)\n8. [Imai Y et al., Breast cancer resistance protein exports sulfated estrogens but not free estrogens (2003) (2003)](https://doi.org/10.1124/mol.63.3.544)\n9. [Ascherio A et al., Urate as a predictor of the rate of clinical decline in Parkinson disease (2009) (2009)](https://doi.org/10.1001/archneurol.2009.247)\n10. [Unknown, Nicolazzo JA & Bhatt DK, Role of breast cancer resistance protein (BCRP/ABCG2) in the efflux of amyloid-β from the brain (2022) (2022)](https://doi.org/10.1016/j.bcp.2022.115071)\n\n## Pathway Diagram\n\nThe following diagram shows the key molecular relationships involving ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2 discovered through SciDEX knowledge graph analysis:\n\n```mermaid\ngraph TD\n    AMPK[\"AMPK\"] -->|\"activates\"| ABCG2[\"ABCG2\"]\n    CHAT[\"CHAT\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC30A8[\"SLC30A8\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    APOE[\"APOE\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    HMGCR[\"HMGCR\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    OPRM1[\"OPRM1\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    CYP2D6[\"CYP2D6\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    COMT[\"COMT\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    NBEA[\"NBEA\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    HTR2C[\"HTR2C\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    ADRA2A[\"ADRA2A\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    BCHE[\"BCHE\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC6A2[\"SLC6A2\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    SLC6A3[\"SLC6A3\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    GABRA1[\"GABRA1\"] -->|\"associated with\"| ABCG2[\"ABCG2\"]\n    style AMPK fill:#ce93d8,stroke:#333,color:#000\n    style ABCG2 fill:#ce93d8,stroke:#333,color:#000\n    style CHAT fill:#ce93d8,stroke:#333,color:#000\n    style SLC30A8 fill:#ce93d8,stroke:#333,color:#000\n    style APOE fill:#ce93d8,stroke:#333,color:#000\n    style HMGCR fill:#ce93d8,stroke:#333,color:#000\n    style OPRM1 fill:#ce93d8,stroke:#333,color:#000\n    style CYP2D6 fill:#ce93d8,stroke:#333,color:#000\n    style COMT fill:#ce93d8,stroke:#333,color:#000\n    style NBEA fill:#ce93d8,stroke:#333,color:#000\n    style HTR2C fill:#ce93d8,stroke:#333,color:#000\n    style ADRA2A fill:#ce93d8,stroke:#333,color:#000\n    style BCHE fill:#ce93d8,stroke:#333,color:#000\n    style SLC6A2 fill:#ce93d8,stroke:#333,color:#000\n    style SLC6A3 fill:#ce93d8,stroke:#333,color:#000\n    style GABRA1 fill:#ce93d8,stroke:#333,color:#000\n```\n\n",
  "entity_type": "gene"
}

{
  "content_md": "# ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2\n\n\n\n## Pathway Diagram\n\nflowchart TD\n    ABCG2[\"ABCG2 Transporter\"]:::central --> BBB[\"Blood-Brain Barrier Function\"]:::protective\n    ABCG2 -->|\"efflux pump\"| Drug_Clearance[\"Drug Clearance\"]:::protective\n    BBB -->|\"compromised\"| Neurodegeneration[\"Neurodegeneration\"]:::pathological\n    \n    ABCG2 -->|\"activates\"| BCL2[\"BCL-2\"]:::protective\n    ABCG2 -->|\"activates\"| MFN2[\"MFN2\"]:::protective\n    BCL2 --> Apoptosis_Protection[\"Apoptosis Protection\"]:::protective\n    MFN2 --> Mitochondrial_Health[\"Mitochondrial Health\"]:::protective\n    \n    ABCG2 -->|\"activates\"| GSDMD[\"GSDMD\"]:::pathological\n    ABCG2 -->|\"activates\"| RIPK1[\"RIPK1\"]:::pathological\n    GSDMD --> Pyroptosis[\"Pyroptosis\"]:::pathological\n    RIPK1 --> Necroptosis[\"Necroptosis\"]:::pathological\n    \n    ABCG2 -->|\"associated\"| APOE[\"APOE\"]:::regulatory\n    APOE --> Alzheimer[\"Alzheimer Disease\"]:::pathological\n    \n    Drug_Clearance -->|\"reduced\"| CNS_Toxicity[\"CNS Toxicity\"]:::pathological\n    CNS_Toxicity --> Depression[\"Depression\"]:::pathological\n    CNS_Toxicity --> Anxiety[\"Anxiety\"]:::pathological\n\n    classDef central fill:#006494\n    classDef protective fill:#1b5e20\n    classDef pathological fill:#ef5350\n    classDef regulatory fill:#4a1a6b\n\n<div class=\"infobox infobox-gene\">\n<h3>ABCG2 (BCRP)</h3>\n<table>\n<tr><td><strong>Full Name</strong></td><td>ATP Binding Cassette Subfamily G Member 2</td></tr>\n<tr><td><strong>Gene Symbol</strong></td><td>ABCG2 (BCRP, MXR, ABCP)</td></tr> [@polli2009]\n<tr><td><strong>Chromosomal Location</strong></td><td>4q22.1</td></tr> [@de2003]\n<tr><td><strong>NCBI Gene ID</strong></td><td>[9429](https://www.ncbi.nlm.nih.gov/gene/9429)</td></tr> [@kim2002]\n<tr><td><strong>OMIM</strong></td><td>[603756](https://omim.org/entry/603756)</td></tr> [@imai2003]\n<tr><td><strong>Ensembl</strong></td><td>[ENSG00000118777](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118777)</td></tr> [@ascherio2009]\n<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9UNQ0 (BCRP)](https://www.uniprot.org/uniprot/Q9UNQ0)</td></tr> [@nicolazzo2022]\n<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Gout</td></tr>\n</table>\n</div>\n\n## Overview\n\n**ABCG2** (ATP Binding Cassette Subfamily G Member 2), also known as **BCRP** (Breast Cancer Resistance Protein) or **MXR** (Mitoxantrone Resistance Protein), encodes a 72 kDa half-transporter that functions as a homodimer at the [blood-brain barrier](/mechanisms/blood-brain-barrier). Together with [P-glycoprotein (ABCB1)](/genes/abcb1), BCRP forms the primary efflux transporter system protecting the brain from xenobiotics and potentially toxic metabolites. ABCG2 has emerged as an important player in neurodegenerative disease through its roles in urate transport, heme homeostasis, and neuroprotective compound efflux.\n\n## Gene Structure and Expression\n\nABCG2 spans approximately 66 kb on chromosome 4q22.1 and contains 16 exons. Unlike full transporters such as [ABCB1](/genes/abcb1), ABCG2 is a half-transporter containing a single NBD and single TMD, requiring homodimerization for function. The gene is regulated by hypoxia-inducible factors ([HIF-1α](/genes/hif1a), [HIF-2α](/genes/epas1)), estrogen receptor, and [NRF2](/genes/nfe2l2) antioxidant response elements.\n\nIn the brain, ABCG2 is highly expressed at the luminal membrane of brain capillary endothelial cells, co-localizing with [ABCB1](/genes/abcb1). Expression is also detected in [astrocytes](/entities/astrocytes), neural stem cells, and the choroid plexus. Notably, ABCG2 marks a side population of neural stem/progenitor cells with enhanced self-renewal capacity. Brain expression is maintained throughout aging, though functional activity may decline.\n\n## Protein Function and Mechanism\n\n### Transport Activity\n\nBCRP functions as an ATP-dependent efflux pump that transports substrates from the cytoplasm or inner membrane leaflet to the extracellular space. Key features include:\n\n- **Homodimeric architecture**: Two ABCG2 monomers assemble via extensive TMD interactions to form a functional transporter with a central drug-binding cavity\n- **Substrate specificity**: Preferentially transports sulfated and glucuronidated conjugates, porphyrins, dietary flavonoids, urate, and various chemotherapeutic agents\n- **Cooperative transport**: Some substrates show positive cooperativity, with binding at one site enhancing transport at the other\n\n### Key Substrates Relevant to Neurodegeneration\n\n1. **Urate/uric acid**: ABCG2 is the primary renal and intestinal urate transporter. The Q141K variant causes hyperuricemia and gout. Urate is a potent antioxidant that may be neuroprotective in [Parkinson's disease](/diseases/parkinsons-disease)\n2. **Heme and porphyrins**: BCRP exports protoporphyrin IX and heme, protecting cells from phototoxicity and oxidative damage. Disrupted heme homeostasis is implicated in neurodegeneration\n3. **Amyloid-beta**: Evidence suggests BCRP may contribute to Aβ efflux at the [BBB](/entities/blood-brain-barrier), though its role is secondary to [P-glycoprotein](/genes/abcb1)\n4. **Dietary flavonoids**: Transports neuroprotective polyphenols (quercetin, resveratrol) out of the brain, potentially limiting their therapeutic efficacy\n\n### BBB Gatekeeper Function\n\nAt the [blood-brain barrier](/mechanisms/blood-brain-barrier), BCRP and P-gp function cooperatively. Dual knockout of both transporters in mice dramatically increases brain penetration of shared substrates (up to 10-fold more than single knockouts), demonstrating synergistic BBB protection. This has major implications for CNS drug delivery strategies.\n\n## Disease Associations\n\n### Parkinson's Disease\n\nThe connection between ABCG2 and [Parkinson's disease](/diseases/parkinsons-disease) centers on the urate hypothesis:\n\n- **Urate as neuroprotectant**: Higher serum urate levels correlate with reduced PD risk and slower disease progression. ABCG2 variants that increase serum urate (by reducing renal excretion) may indirectly confer neuroprotection\n- **Q141K variant (rs2231142)**: This common variant (allele frequency ~10% in Europeans, ~30% in East Asians) reduces ABCG2 transport activity by ~50% and raises serum urate. Studies show modest association with reduced PD risk\n- **Toxin exposure**: BCRP effluxes several environmental neurotoxins; reduced function may increase vulnerability to pesticide-induced parkinsonism\n- **BBB integrity**: ABCG2 expression is reduced in PD midbrain capillaries, potentially compromising local BBB function\n\n### Alzheimer's Disease\n\n- **Aβ clearance**: BCRP contributes to Aβ40 and Aβ42 efflux at the BBB, complementing [ABCB1](/genes/abcb1)-mediated clearance. ABCG2 upregulation by [Aβ](/proteins/amyloid-beta) itself may represent a compensatory response\n- **Inflammatory regulation**: [NF-κB](/mechanisms/nf-kb-pathway)-mediated upregulation of ABCG2 during neuroinflammation alters the BBB transport profile\n- **Drug delivery barrier**: BCRP limits brain entry of several investigational AD therapeutics, complicating treatment strategies\n\n### Gout and Hyperuricemia\n\nThe Q141K variant is the strongest genetic risk factor for gout (OR ~1.7), causing reduced renal urate secretion. This is the most well-characterized clinical phenotype of ABCG2 dysfunction.\n\n## Common Variants\n\n| Variant | rsID | Consequence | Clinical Significance |\n|---------|------|-------------|----------------------|\n| Q141K | rs2231142 | Gln141Lys | Reduced transport (~50%); gout, hyperuricemia; possible PD protection |\n| V12M | rs2231137 | Val12Met | Modest functional effect; population-specific associations |\n| S441N | - | Ser441Asn | Severe loss of function; membrane trafficking defect |\n| R482G/T | - | Arg482Gly/Thr | Altered substrate specificity (gain of anthracycline transport) |\n\n## Therapeutic Implications\n\n### Neuroprotective Strategies\n- **Urate-elevating approaches**: ABCG2 inhibition to raise CNS urate levels as a PD neuroprotection strategy (inosine supplementation trials)\n- **BBB modulation**: Selective ABCG2 inhibition (fumitremorgin C analogs, Ko143) to enhance CNS drug delivery while maintaining [ABCB1](/genes/abcb1) function\n\n### Drug Development Considerations\n- ABCG2 substrate profiling is essential for CNS drug candidates\n- Dual ABCB1/ABCG2 inhibitor strategies may be needed for effective BBB penetration\n- Pharmacogenomic testing for Q141K to predict drug exposure variability\n\n### Neural Stem Cell Biology\nABCG2 expression marks neural stem cell populations; understanding its role in stem cell maintenance may inform regenerative medicine approaches for neurodegeneration.\n\n## Expression Profile\n\n- **Brain endothelium**: High expression at BBB luminal membrane (co-localizes with [ABCB1](/genes/abcb1))\n- **Choroid plexus**: Blood-CSF barrier expression\n- **Neural stem cells**: Side population marker; maintains stemness\n- **Astrocytes**: Low-moderate expression, inducible by hypoxia\n- **Peripheral**: Liver canalicular membrane, kidney proximal tubule, intestinal epithelium, placenta\n\n## See Also\n- [ABCB1](/genes/abcb1) — P-glycoprotein, primary BBB efflux transporter\n- [SLC2A1](/genes/slc2a1) — GLUT1 glucose transporter at BBB\n- [CLDN5](/genes/cldn5) — Claudin-5 tight junction protein\n- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) — BBB structure and function\n- [Amyloid-Beta](/proteins/amyloid-beta) — Aβ peptide clearance\n- [NRF2/NFE2L2](/genes/nfe2l2) — Transcriptional regulator of ABCG2\n- [Alpha-Synuclein](/proteins/alpha-synuclein) — PD-associated protein\n\n## External Links\n- [NCBI Gene: ABCG2](https://www.ncbi.nlm.nih.gov/gene/9429)\n- [UniProt: Q9UNQ0](https://www.uniprot.org/uniprot/Q9UNQ0)\n- [GeneCards: ABCG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCG2)\n- [OMIM: 603756](https://omim.org/entry/603756)\n- [PharmGKB: ABCG2](https://www.pharmgkb.org/gene/PA390)\n\n\n## Brain Atlas Resources\n\n- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data\n- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome\n- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression\n\n## References\n\n1. [Agarwal S et al., Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up (2011) (2011)](https://doi.org/10.2174/138920011795495769)\n2. [Matsuo H et al., Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population (2009) (2009)](https://doi.org/10.1126/scitranslmed.3000237)\n3. [Weisberg IS et al., ABCG2 and neuroprotection: urate hypothesis revisited (2020) (2020)](https://doi.org/10.1002/mds.28016)\n4. [Do TM et al., ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1-40 at the mouse blood-brain barrier (2012) (2012)](https://doi.org/10.3233/JAD-2012-112189)\n5. [Polli JW et al., An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (2009) (2009)](https://doi.org/10.1124/dmd.108.024646)\n6. [de Boer AG et al., The role of drug transporters at the blood-brain barrier (2003) (2003)](https://doi.org/10.1146/annurev.pharmtox.43.100901.140204)\n7. [Unknown, Kim RB, Drugs as P-glycoprotein substrates, inhibitors, and inducers (2002) (2002)](https://doi.org/10.1124/dmd.30.4.470)\n8. [Imai Y et al., Breast cancer resistance protein exports sulfated estrogens but not free estrogens (2003) (2003)](https://doi.org/10.1124/mol.63.3.544)\n9. [Ascherio A et al., Urate as a predictor of the rate of clinical decline in Parkinson disease (2009) (2009)](https://doi.org/10.1001/archneurol.2009.247)\n10. [Unknown, Nicolazzo JA & Bhatt DK, Role of breast cancer resistance protein (BCRP/ABCG2) in the efflux of amyloid-β from the brain (2022) (2022)](https://doi.org/10.1016/j.bcp.2022.115071)",
  "entity_type": "gene"
}

{
  "content_md": "# ABCG2 (BCRP) - ATP Binding Cassette Subfamily G Member 2\n\n\n\n## Pathway Diagram\n\n```mermaid\nflowchart TD\n    ABCG2[\"ABCG2 Transporter\"]:::central --> BBB[\"Blood-Brain Barrier Function\"]:::protective\n    ABCG2 -->|\"efflux pump\"| Drug_Clearance[\"Drug Clearance\"]:::protective\n    BBB -->|\"compromised\"| Neurodegeneration[\"Neurodegeneration\"]:::pathological\n    \n    ABCG2 -->|\"activates\"| BCL2[\"BCL-2\"]:::protective\n    ABCG2 -->|\"activates\"| MFN2[\"MFN2\"]:::protective\n    BCL2 --> Apoptosis_Protection[\"Apoptosis Protection\"]:::protective\n    MFN2 --> Mitochondrial_Health[\"Mitochondrial Health\"]:::protective\n    \n    ABCG2 -->|\"activates\"| GSDMD[\"GSDMD\"]:::pathological\n    ABCG2 -->|\"activates\"| RIPK1[\"RIPK1\"]:::pathological\n    GSDMD --> Pyroptosis[\"Pyroptosis\"]:::pathological\n    RIPK1 --> Necroptosis[\"Necroptosis\"]:::pathological\n    \n    ABCG2 -->|\"associated\"| APOE[\"APOE\"]:::regulatory\n    APOE --> Alzheimer[\"Alzheimer Disease\"]:::pathological\n    \n    Drug_Clearance -->|\"reduced\"| CNS_Toxicity[\"CNS Toxicity\"]:::pathological\n    CNS_Toxicity --> Depression[\"Depression\"]:::pathological\n    CNS_Toxicity --> Anxiety[\"Anxiety\"]:::pathological\n\n    classDef central fill:#006494\n    classDef protective fill:#1b5e20\n    classDef pathological fill:#ef5350\n    classDef regulatory fill:#4a1a6b\n```\n\n<div class=\"infobox infobox-gene\">\n<h3>ABCG2 (BCRP)</h3>\n<table>\n<tr><td><strong>Full Name</strong></td><td>ATP Binding Cassette Subfamily G Member 2</td></tr>\n<tr><td><strong>Gene Symbol</strong></td><td>ABCG2 (BCRP, MXR, ABCP)</td></tr> [@polli2009]\n<tr><td><strong>Chromosomal Location</strong></td><td>4q22.1</td></tr> [@de2003]\n<tr><td><strong>NCBI Gene ID</strong></td><td>[9429](https://www.ncbi.nlm.nih.gov/gene/9429)</td></tr> [@kim2002]\n<tr><td><strong>OMIM</strong></td><td>[603756](https://omim.org/entry/603756)</td></tr> [@imai2003]\n<tr><td><strong>Ensembl</strong></td><td>[ENSG00000118777](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118777)</td></tr> [@ascherio2009]\n<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9UNQ0 (BCRP)](https://www.uniprot.org/uniprot/Q9UNQ0)</td></tr> [@nicolazzo2022]\n<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Gout</td></tr>\n</table>\n</div>\n\n## Overview\n\n**ABCG2** (ATP Binding Cassette Subfamily G Member 2), also known as **BCRP** (Breast Cancer Resistance Protein) or **MXR** (Mitoxantrone Resistance Protein), encodes a 72 kDa half-transporter that functions as a homodimer at the [blood-brain barrier](/mechanisms/blood-brain-barrier). Together with [P-glycoprotein (ABCB1)](/genes/abcb1), BCRP forms the primary efflux transporter system protecting the brain from xenobiotics and potentially toxic metabolites. ABCG2 has emerged as an important player in neurodegenerative disease through its roles in urate transport, heme homeostasis, and neuroprotective compound efflux.\n\n## Gene Structure and Expression\n\nABCG2 spans approximately 66 kb on chromosome 4q22.1 and contains 16 exons. Unlike full transporters such as [ABCB1](/genes/abcb1), ABCG2 is a half-transporter containing a single NBD and single TMD, requiring homodimerization for function. The gene is regulated by hypoxia-inducible factors ([HIF-1α](/genes/hif1a), [HIF-2α](/genes/epas1)), estrogen receptor, and [NRF2](/genes/nfe2l2) antioxidant response elements.\n\nIn the brain, ABCG2 is highly expressed at the luminal membrane of brain capillary endothelial cells, co-localizing with [ABCB1](/genes/abcb1). Expression is also detected in [astrocytes](/entities/astrocytes), neural stem cells, and the choroid plexus. Notably, ABCG2 marks a side population of neural stem/progenitor cells with enhanced self-renewal capacity. Brain expression is maintained throughout aging, though functional activity may decline.\n\n## Protein Function and Mechanism\n\n### Transport Activity\n\nBCRP functions as an ATP-dependent efflux pump that transports substrates from the cytoplasm or inner membrane leaflet to the extracellular space. Key features include:\n\n- **Homodimeric architecture**: Two ABCG2 monomers assemble via extensive TMD interactions to form a functional transporter with a central drug-binding cavity\n- **Substrate specificity**: Preferentially transports sulfated and glucuronidated conjugates, porphyrins, dietary flavonoids, urate, and various chemotherapeutic agents\n- **Cooperative transport**: Some substrates show positive cooperativity, with binding at one site enhancing transport at the other\n\n### Key Substrates Relevant to Neurodegeneration\n\n1. **Urate/uric acid**: ABCG2 is the primary renal and intestinal urate transporter. The Q141K variant causes hyperuricemia and gout. Urate is a potent antioxidant that may be neuroprotective in [Parkinson's disease](/diseases/parkinsons-disease)\n2. **Heme and porphyrins**: BCRP exports protoporphyrin IX and heme, protecting cells from phototoxicity and oxidative damage. Disrupted heme homeostasis is implicated in neurodegeneration\n3. **Amyloid-beta**: Evidence suggests BCRP may contribute to Aβ efflux at the [BBB](/entities/blood-brain-barrier), though its role is secondary to [P-glycoprotein](/genes/abcb1)\n4. **Dietary flavonoids**: Transports neuroprotective polyphenols (quercetin, resveratrol) out of the brain, potentially limiting their therapeutic efficacy\n\n### BBB Gatekeeper Function\n\nAt the [blood-brain barrier](/mechanisms/blood-brain-barrier), BCRP and P-gp function cooperatively. Dual knockout of both transporters in mice dramatically increases brain penetration of shared substrates (up to 10-fold more than single knockouts), demonstrating synergistic BBB protection. This has major implications for CNS drug delivery strategies.\n\n## Disease Associations\n\n### Parkinson's Disease\n\nThe connection between ABCG2 and [Parkinson's disease](/diseases/parkinsons-disease) centers on the urate hypothesis:\n\n- **Urate as neuroprotectant**: Higher serum urate levels correlate with reduced PD risk and slower disease progression. ABCG2 variants that increase serum urate (by reducing renal excretion) may indirectly confer neuroprotection\n- **Q141K variant (rs2231142)**: This common variant (allele frequency ~10% in Europeans, ~30% in East Asians) reduces ABCG2 transport activity by ~50% and raises serum urate. Studies show modest association with reduced PD risk\n- **Toxin exposure**: BCRP effluxes several environmental neurotoxins; reduced function may increase vulnerability to pesticide-induced parkinsonism\n- **BBB integrity**: ABCG2 expression is reduced in PD midbrain capillaries, potentially compromising local BBB function\n\n### Alzheimer's Disease\n\n- **Aβ clearance**: BCRP contributes to Aβ40 and Aβ42 efflux at the BBB, complementing [ABCB1](/genes/abcb1)-mediated clearance. ABCG2 upregulation by [Aβ](/proteins/amyloid-beta) itself may represent a compensatory response\n- **Inflammatory regulation**: [NF-κB](/mechanisms/nf-kb-pathway)-mediated upregulation of ABCG2 during neuroinflammation alters the BBB transport profile\n- **Drug delivery barrier**: BCRP limits brain entry of several investigational AD therapeutics, complicating treatment strategies\n\n### Gout and Hyperuricemia\n\nThe Q141K variant is the strongest genetic risk factor for gout (OR ~1.7), causing reduced renal urate secretion. This is the most well-characterized clinical phenotype of ABCG2 dysfunction.\n\n## Common Variants\n\n| Variant | rsID | Consequence | Clinical Significance |\n|---------|------|-------------|----------------------|\n| Q141K | rs2231142 | Gln141Lys | Reduced transport (~50%); gout, hyperuricemia; possible PD protection |\n| V12M | rs2231137 | Val12Met | Modest functional effect; population-specific associations |\n| S441N | - | Ser441Asn | Severe loss of function; membrane trafficking defect |\n| R482G/T | - | Arg482Gly/Thr | Altered substrate specificity (gain of anthracycline transport) |\n\n## Therapeutic Implications\n\n### Neuroprotective Strategies\n- **Urate-elevating approaches**: ABCG2 inhibition to raise CNS urate levels as a PD neuroprotection strategy (inosine supplementation trials)\n- **BBB modulation**: Selective ABCG2 inhibition (fumitremorgin C analogs, Ko143) to enhance CNS drug delivery while maintaining [ABCB1](/genes/abcb1) function\n\n### Drug Development Considerations\n- ABCG2 substrate profiling is essential for CNS drug candidates\n- Dual ABCB1/ABCG2 inhibitor strategies may be needed for effective BBB penetration\n- Pharmacogenomic testing for Q141K to predict drug exposure variability\n\n### Neural Stem Cell Biology\nABCG2 expression marks neural stem cell populations; understanding its role in stem cell maintenance may inform regenerative medicine approaches for neurodegeneration.\n\n## Expression Profile\n\n- **Brain endothelium**: High expression at BBB luminal membrane (co-localizes with [ABCB1](/genes/abcb1))\n- **Choroid plexus**: Blood-CSF barrier expression\n- **Neural stem cells**: Side population marker; maintains stemness\n- **Astrocytes**: Low-moderate expression, inducible by hypoxia\n- **Peripheral**: Liver canalicular membrane, kidney proximal tubule, intestinal epithelium, placenta\n\n## See Also\n- [ABCB1](/genes/abcb1) — P-glycoprotein, primary BBB efflux transporter\n- [SLC2A1](/genes/slc2a1) — GLUT1 glucose transporter at BBB\n- [CLDN5](/genes/cldn5) — Claudin-5 tight junction protein\n- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) — BBB structure and function\n- [Amyloid-Beta](/proteins/amyloid-beta) — Aβ peptide clearance\n- [NRF2/NFE2L2](/genes/nfe2l2) — Transcriptional regulator of ABCG2\n- [Alpha-Synuclein](/proteins/alpha-synuclein) — PD-associated protein\n\n## External Links\n- [NCBI Gene: ABCG2](https://www.ncbi.nlm.nih.gov/gene/9429)\n- [UniProt: Q9UNQ0](https://www.uniprot.org/uniprot/Q9UNQ0)\n- [GeneCards: ABCG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCG2)\n- [OMIM: 603756](https://omim.org/entry/603756)\n- [PharmGKB: ABCG2](https://www.pharmgkb.org/gene/PA390)\n\n\n## Brain Atlas Resources\n\n- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data\n- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome\n- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression\n\n## References\n\n1. [Agarwal S et al., Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up (2011) (2011)](https://doi.org/10.2174/138920011795495769)\n2. [Matsuo H et al., Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population (2009) (2009)](https://doi.org/10.1126/scitranslmed.3000237)\n3. [Weisberg IS et al., ABCG2 and neuroprotection: urate hypothesis revisited (2020) (2020)](https://doi.org/10.1002/mds.28016)\n4. [Do TM et al., ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1-40 at the mouse blood-brain barrier (2012) (2012)](https://doi.org/10.3233/JAD-2012-112189)\n5. [Polli JW et al., An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (2009) (2009)](https://doi.org/10.1124/dmd.108.024646)\n6. [de Boer AG et al., The role of drug transporters at the blood-brain barrier (2003) (2003)](https://doi.org/10.1146/annurev.pharmtox.43.100901.140204)\n7. [Unknown, Kim RB, Drugs as P-glycoprotein substrates, inhibitors, and inducers (2002) (2002)](https://doi.org/10.1124/dmd.30.4.470)\n8. [Imai Y et al., Breast cancer resistance protein exports sulfated estrogens but not free estrogens (2003) (2003)](https://doi.org/10.1124/mol.63.3.544)\n9. [Ascherio A et al., Urate as a predictor of the rate of clinical decline in Parkinson disease (2009) (2009)](https://doi.org/10.1001/archneurol.2009.247)\n10. [Unknown, Nicolazzo JA & Bhatt DK, Role of breast cancer resistance protein (BCRP/ABCG2) in the efflux of amyloid-β from the brain (2022) (2022)](https://doi.org/10.1016/j.bcp.2022.115071)",
  "entity_type": "gene"
}

{
  "content_md": "\n\n## Pathway Diagram\n\n```mermaid\nflowchart TD\n    ABCG2[\"ABCG2 Transporter\"]:::central --> BBB[\"Blood-Brain Barrier Function\"]:::protective\n    ABCG2 -->|\"efflux pump\"| Drug_Clearance[\"Drug Clearance\"]:::protective\n    BBB -->|\"compromised\"| Neurodegeneration[\"Neurodegeneration\"]:::pathological\n    \n    ABCG2 -->|\"activates\"| BCL2[\"BCL-2\"]:::protective\n    ABCG2 -->|\"activates\"| MFN2[\"MFN2\"]:::protective\n    BCL2 --> Apoptosis_Protection[\"Apoptosis Protection\"]:::protective\n    MFN2 --> Mitochondrial_Health[\"Mitochondrial Health\"]:::protective\n    \n    ABCG2 -->|\"activates\"| GSDMD[\"GSDMD\"]:::pathological\n    ABCG2 -->|\"activates\"| RIPK1[\"RIPK1\"]:::pathological\n    GSDMD --> Pyroptosis[\"Pyroptosis\"]:::pathological\n    RIPK1 --> Necroptosis[\"Necroptosis\"]:::pathological\n    \n    ABCG2 -->|\"associated\"| APOE[\"APOE\"]:::regulatory\n    APOE --> Alzheimer[\"Alzheimer Disease\"]:::pathological\n    \n    Drug_Clearance -->|\"reduced\"| CNS_Toxicity[\"CNS Toxicity\"]:::pathological\n    CNS_Toxicity --> Depression[\"Depression\"]:::pathological\n    CNS_Toxicity --> Anxiety[\"Anxiety\"]:::pathological\n\n    classDef central fill:#006494\n    classDef protective fill:#1b5e20\n    classDef pathological fill:#ef5350\n    classDef regulatory fill:#4a1a6b\n```\n\n<div class=\"infobox infobox-gene\">\n<h3>ABCG2 (BCRP)</h3>\n<table>\n<tr><td><strong>Full Name</strong></td><td>ATP Binding Cassette Subfamily G Member 2</td></tr>\n<tr><td><strong>Gene Symbol</strong></td><td>ABCG2 (BCRP, MXR, ABCP)</td></tr> [@polli2009]\n<tr><td><strong>Chromosomal Location</strong></td><td>4q22.1</td></tr> [@de2003]\n<tr><td><strong>NCBI Gene ID</strong></td><td>[9429](https://www.ncbi.nlm.nih.gov/gene/9429)</td></tr> [@kim2002]\n<tr><td><strong>OMIM</strong></td><td>[603756](https://omim.org/entry/603756)</td></tr> [@imai2003]\n<tr><td><strong>Ensembl</strong></td><td>[ENSG00000118777](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000118777)</td></tr> [@ascherio2009]\n<tr><td><strong>UniProt (Protein)</strong></td><td>[Q9UNQ0 (BCRP)](https://www.uniprot.org/uniprot/Q9UNQ0)</td></tr> [@nicolazzo2022]\n<tr><td><strong>Associated Diseases</strong></td><td>[Alzheimer's Disease](/diseases/alzheimers-disease), [Parkinson's Disease](/diseases/parkinsons-disease), Gout</td></tr>\n</table>\n</div>\n\n## Overview\n\n**ABCG2** (ATP Binding Cassette Subfamily G Member 2), also known as **BCRP** (Breast Cancer Resistance Protein) or **MXR** (Mitoxantrone Resistance Protein), encodes a 72 kDa half-transporter that functions as a homodimer at the [blood-brain barrier](/mechanisms/blood-brain-barrier). Together with [P-glycoprotein (ABCB1)](/genes/abcb1), BCRP forms the primary efflux transporter system protecting the brain from xenobiotics and potentially toxic metabolites. ABCG2 has emerged as an important player in neurodegenerative disease through its roles in urate transport, heme homeostasis, and neuroprotective compound efflux.\n\n## Gene Structure and Expression\n\nABCG2 spans approximately 66 kb on chromosome 4q22.1 and contains 16 exons. Unlike full transporters such as [ABCB1](/genes/abcb1), ABCG2 is a half-transporter containing a single NBD and single TMD, requiring homodimerization for function. The gene is regulated by hypoxia-inducible factors ([HIF-1α](/genes/hif1a), [HIF-2α](/genes/epas1)), estrogen receptor, and [NRF2](/genes/nfe2l2) antioxidant response elements.\n\nIn the brain, ABCG2 is highly expressed at the luminal membrane of brain capillary endothelial cells, co-localizing with [ABCB1](/genes/abcb1). Expression is also detected in [astrocytes](/entities/astrocytes), neural stem cells, and the choroid plexus. Notably, ABCG2 marks a side population of neural stem/progenitor cells with enhanced self-renewal capacity. Brain expression is maintained throughout aging, though functional activity may decline.\n\n## Protein Function and Mechanism\n\n### Transport Activity\n\nBCRP functions as an ATP-dependent efflux pump that transports substrates from the cytoplasm or inner membrane leaflet to the extracellular space. Key features include:\n\n- **Homodimeric architecture**: Two ABCG2 monomers assemble via extensive TMD interactions to form a functional transporter with a central drug-binding cavity\n- **Substrate specificity**: Preferentially transports sulfated and glucuronidated conjugates, porphyrins, dietary flavonoids, urate, and various chemotherapeutic agents\n- **Cooperative transport**: Some substrates show positive cooperativity, with binding at one site enhancing transport at the other\n\n### Key Substrates Relevant to Neurodegeneration\n\n1. **Urate/uric acid**: ABCG2 is the primary renal and intestinal urate transporter. The Q141K variant causes hyperuricemia and gout. Urate is a potent antioxidant that may be neuroprotective in [Parkinson's disease](/diseases/parkinsons-disease)\n2. **Heme and porphyrins**: BCRP exports protoporphyrin IX and heme, protecting cells from phototoxicity and oxidative damage. Disrupted heme homeostasis is implicated in neurodegeneration\n3. **Amyloid-beta**: Evidence suggests BCRP may contribute to Aβ efflux at the [BBB](/entities/blood-brain-barrier), though its role is secondary to [P-glycoprotein](/genes/abcb1)\n4. **Dietary flavonoids**: Transports neuroprotective polyphenols (quercetin, resveratrol) out of the brain, potentially limiting their therapeutic efficacy\n\n### BBB Gatekeeper Function\n\nAt the [blood-brain barrier](/mechanisms/blood-brain-barrier), BCRP and P-gp function cooperatively. Dual knockout of both transporters in mice dramatically increases brain penetration of shared substrates (up to 10-fold more than single knockouts), demonstrating synergistic BBB protection. This has major implications for CNS drug delivery strategies.\n\n## Disease Associations\n\n### Parkinson's Disease\n\nThe connection between ABCG2 and [Parkinson's disease](/diseases/parkinsons-disease) centers on the urate hypothesis:\n\n- **Urate as neuroprotectant**: Higher serum urate levels correlate with reduced PD risk and slower disease progression. ABCG2 variants that increase serum urate (by reducing renal excretion) may indirectly confer neuroprotection\n- **Q141K variant (rs2231142)**: This common variant (allele frequency ~10% in Europeans, ~30% in East Asians) reduces ABCG2 transport activity by ~50% and raises serum urate. Studies show modest association with reduced PD risk\n- **Toxin exposure**: BCRP effluxes several environmental neurotoxins; reduced function may increase vulnerability to pesticide-induced parkinsonism\n- **BBB integrity**: ABCG2 expression is reduced in PD midbrain capillaries, potentially compromising local BBB function\n\n### Alzheimer's Disease\n\n- **Aβ clearance**: BCRP contributes to Aβ40 and Aβ42 efflux at the BBB, complementing [ABCB1](/genes/abcb1)-mediated clearance. ABCG2 upregulation by [Aβ](/proteins/amyloid-beta) itself may represent a compensatory response\n- **Inflammatory regulation**: [NF-κB](/mechanisms/nf-kb-pathway)-mediated upregulation of ABCG2 during neuroinflammation alters the BBB transport profile\n- **Drug delivery barrier**: BCRP limits brain entry of several investigational AD therapeutics, complicating treatment strategies\n\n### Gout and Hyperuricemia\n\nThe Q141K variant is the strongest genetic risk factor for gout (OR ~1.7), causing reduced renal urate secretion. This is the most well-characterized clinical phenotype of ABCG2 dysfunction.\n\n## Common Variants\n\n| Variant | rsID | Consequence | Clinical Significance |\n|---------|------|-------------|----------------------|\n| Q141K | rs2231142 | Gln141Lys | Reduced transport (~50%); gout, hyperuricemia; possible PD protection |\n| V12M | rs2231137 | Val12Met | Modest functional effect; population-specific associations |\n| S441N | - | Ser441Asn | Severe loss of function; membrane trafficking defect |\n| R482G/T | - | Arg482Gly/Thr | Altered substrate specificity (gain of anthracycline transport) |\n\n## Therapeutic Implications\n\n### Neuroprotective Strategies\n- **Urate-elevating approaches**: ABCG2 inhibition to raise CNS urate levels as a PD neuroprotection strategy (inosine supplementation trials)\n- **BBB modulation**: Selective ABCG2 inhibition (fumitremorgin C analogs, Ko143) to enhance CNS drug delivery while maintaining [ABCB1](/genes/abcb1) function\n\n### Drug Development Considerations\n- ABCG2 substrate profiling is essential for CNS drug candidates\n- Dual ABCB1/ABCG2 inhibitor strategies may be needed for effective BBB penetration\n- Pharmacogenomic testing for Q141K to predict drug exposure variability\n\n### Neural Stem Cell Biology\nABCG2 expression marks neural stem cell populations; understanding its role in stem cell maintenance may inform regenerative medicine approaches for neurodegeneration.\n\n## Expression Profile\n\n- **Brain endothelium**: High expression at BBB luminal membrane (co-localizes with [ABCB1](/genes/abcb1))\n- **Choroid plexus**: Blood-CSF barrier expression\n- **Neural stem cells**: Side population marker; maintains stemness\n- **Astrocytes**: Low-moderate expression, inducible by hypoxia\n- **Peripheral**: Liver canalicular membrane, kidney proximal tubule, intestinal epithelium, placenta\n\n## See Also\n- [ABCB1](/genes/abcb1) — P-glycoprotein, primary BBB efflux transporter\n- [SLC2A1](/genes/slc2a1) — GLUT1 glucose transporter at BBB\n- [CLDN5](/genes/cldn5) — Claudin-5 tight junction protein\n- [Blood-Brain Barrier](/mechanisms/blood-brain-barrier) — BBB structure and function\n- [Amyloid-Beta](/proteins/amyloid-beta) — Aβ peptide clearance\n- [NRF2/NFE2L2](/genes/nfe2l2) — Transcriptional regulator of ABCG2\n- [Alpha-Synuclein](/proteins/alpha-synuclein) — PD-associated protein\n\n## External Links\n- [NCBI Gene: ABCG2](https://www.ncbi.nlm.nih.gov/gene/9429)\n- [UniProt: Q9UNQ0](https://www.uniprot.org/uniprot/Q9UNQ0)\n- [GeneCards: ABCG2](https://www.genecards.org/cgi-bin/carddisp.pl?gene=ABCG2)\n- [OMIM: 603756](https://omim.org/entry/603756)\n- [PharmGKB: ABCG2](https://www.pharmgkb.org/gene/PA390)\n\n\n## Brain Atlas Resources\n\n- [Allen Human Brain Atlas](https://human.brain-map.org/) — gene expression data\n- [BrainSpan Atlas](https://brainspan.org/) — developmental transcriptome\n- [Allen Mouse Brain Atlas](https://mouse.brain-map.org/) — mouse brain gene expression\n\n## References\n\n1. [Agarwal S et al., Breast cancer resistance protein and P-glycoprotein in brain cancer: two gatekeepers team up (2011) (2011)](https://doi.org/10.2174/138920011795495769)\n2. [Matsuo H et al., Common defects of ABCG2, a high-capacity urate exporter, cause gout: a function-based genetic analysis in a Japanese population (2009) (2009)](https://doi.org/10.1126/scitranslmed.3000237)\n3. [Weisberg IS et al., ABCG2 and neuroprotection: urate hypothesis revisited (2020) (2020)](https://doi.org/10.1002/mds.28016)\n4. [Do TM et al., ABCG2- and ABCG4-mediated efflux of amyloid-β peptide 1-40 at the mouse blood-brain barrier (2012) (2012)](https://doi.org/10.3233/JAD-2012-112189)\n5. [Polli JW et al., An unexpected synergist role of P-glycoprotein and breast cancer resistance protein on the central nervous system penetration of the tyrosine kinase inhibitor lapatinib (2009) (2009)](https://doi.org/10.1124/dmd.108.024646)\n6. [de Boer AG et al., The role of drug transporters at the blood-brain barrier (2003) (2003)](https://doi.org/10.1146/annurev.pharmtox.43.100901.140204)\n7. [Unknown, Kim RB, Drugs as P-glycoprotein substrates, inhibitors, and inducers (2002) (2002)](https://doi.org/10.1124/dmd.30.4.470)\n8. [Imai Y et al., Breast cancer resistance protein exports sulfated estrogens but not free estrogens (2003) (2003)](https://doi.org/10.1124/mol.63.3.544)\n9. [Ascherio A et al., Urate as a predictor of the rate of clinical decline in Parkinson disease (2009) (2009)](https://doi.org/10.1001/archneurol.2009.247)\n10. [Unknown, Nicolazzo JA & Bhatt DK, Role of breast cancer resistance protein (BCRP/ABCG2) in the efflux of amyloid-β from the brain (2022) (2022)](https://doi.org/10.1016/j.bcp.2022.115071)",
  "entity_type": "gene"
}