Version history

{
  "content_md": "# ALYREF\n> Auto-generated from SciDEX local knowledge graph, hypothesis, and literature context.\n\n> This page is auto-generated from SciDEX local KG, hypothesis, and paper context.\n\n## Description\n\nALYREF (also known as ALY or Aly/REF export factor) is a nuclear export factor protein involved in the export of messenger RNA (mRNA) from the nucleus to the cytoplasm. As a member of the REF (RNA and export factor-binding protein) family, ALYREF plays a role in coupling transcription with mRNA export machinery.\n\n## Biological Function\n\nALYREF functions as an adapter protein that facilitates the nuclear export of mRNA by bridging between mRNA binding proteins and the nuclear export receptor CRM1 (exportin 1). The protein is thought to contribute to the integrity of nuclear export complexes and may participate in quality control mechanisms that ensure proper mRNA processing before export.\n\n## Key Relationshipships\n\nALYREF exhibits several documented molecular interactions:\n\n- **Binds** to Yap mRNA (biomarker) with high confidence (strength: 0.88)\n- **Interacts with** YBX1 (gene) and YAP (gene)\n- **Activates** multiple downstream targets including:\n  - CTGF (gene)\n  - MMP2 (gene)\n  - MMP9 (gene)\n  - YBX1 (gene)\n  - YAP (gene)\n  - NSUN2 (gene)\n- **Activated by** AGO2 (gene), as indicated by incoming edge\n\nThese relationships suggest ALYREF operates within the YAP signaling network and may influence matrix remodeling processes through MMP activation.\n\n## Relevant Hypotheses\n\nALYREF is linked to the hypothesis **\"Nuclear Export Deficits Increase Cytosolic TDP-43 Burden\"** (score: 0.58, disease: neurodegeneration). This hypothesis proposes that dysfunction in nuclear export machinery may contribute to the accumulation of TDP-43 in the cytoplasm, a hallmark of neurodegenerative diseases including ALS and frontotemporal dementia. The connection positions ALYREF as a potential modifier of nuclear export fidelity in neuronal cells.\n\n## Literature References References\n\n- NSUN2 promoted tumor growth and metastatic via m... [PMID 41794778](https://pubmed.ncbi.nlm.nih.gov/41794778/) — Cell Death & Disease (2026)\n\n## Neurodegeneration Research Context\n\nALYREF has emerged as a critical factor in ALS (amyotrophic lateral sclerosis) and frontotemporal dementia (FTD) research. Genetic studies in *Drosophila* models have demonstrated that the fly ortholog Ref1/ALYREF modulates toxicity associated with disease-linked mutations in TDP-43 and C9ORF72, both major ALS/FTD genetic drivers. Loss of aly/ALYREF suppresses toxicity in both tau and TDP-43 neurodegeneration models, positioning it as a potential genetic modifier of disease severity [@PMID:35122183].\n\nThe mechanistic connection runs through nuclear RNA export. TDP-43 (TARDBP), the pathological protein in most ALS and FTLD cases, normally shuttles between nucleus and cytoplasm to regulate RNA metabolism. When nuclear export machinery is disrupted — through sequestration of export factors like ALYREF by toxic repeat-expansion RNA from C9ORF72 or other mechanisms — TDP-43 undergoes abnormal cytoplasmic mislocalization and aggregation, a hallmark of ALS/FTD pathology. *Drosophila* Ref1/ALYREF specifically regulates RNA Pol II-dependent transcription and modulates toxicity in ALS/FTD disease models [@PMID:31036086].\n\nThese findings suggest that ALYREF acts as a modifier of TDP-43 proteinopathy by influencing the balance of nuclear-cytoplasmic RNA trafficking. In neurons, which have particularly high demands on RNA export due to their complex transcriptional programs and long axons, disruption of ALYREF function may amplify the accumulation of toxic cytoplasmic TDP-43 aggregates. This positions ALYREF within a broader network of nuclear RNA quality control factors whose dysfunction contributes to neurodegeneration.\n\nIn the context of the SciDEX hypothesis **\"Nuclear Export Deficits Increase Cytosolic TDP-43 Burden\"** (score: 0.58), ALYREF dysfunction represents a plausible upstream mechanism that could amplify TDP-43 mislocalization and aggregation in motor and cortical neurons.\n\n## Cross-Links\n\n- [[TDP-43]] — Key pathological protein whose mislocalization defines ALS/FTD\n- [[C9ORF72]] — Most common genetic cause of ALS and FTD; repeat expansions trap export factors\n- [[ALS Pathogenesis]] — Disease mechanisms linking nuclear export to motor neuron death\n- [[Frontotemporal Dementia]] — Related neurodegenerative disease with TDP-43 pathology\n- [[Nuclear Pore Complex]] — Transport machinery through which ALYREF facilitates mRNA export\n\n## Disease Associations\n\n*Source: Open Targets Platform (opentargets.org)*\n\n| Disease | Association Score | Disease ID |\n|--------|-------------------|------------|\n| neurodegenerative disease | 0.5385 | EFO_0005772 |\n| dengue disease | 0.3696 | EFO_0005547 |\n| non-small cell lung carcinoma | 0.1001 | EFO_0003060 |\n| neoplasm | 0.0978 | EFO_0000616 |\n| cancer | 0.0902 | MONDO_0004992 |\n",
  "entity_type": "gene"
}

{
  "content_md": "# ALYREF\n> Auto-generated from SciDEX local knowledge graph, hypothesis, and literature context.\n\n> This page is auto-generated from SciDEX local KG, hypothesis, and paper context.\n\n## Description\n\nALYREF (also known as ALY or Aly/REF export factor) is a nuclear export factor protein involved in the export of messenger RNA (mRNA) from the nucleus to the cytoplasm. As a member of the REF (RNA and export factor-binding protein) family, ALYREF plays a role in coupling transcription with mRNA export machinery.\n\n## Biological Function\n\nALYREF functions as an adapter protein that facilitates the nuclear export of mRNA by bridging between mRNA binding proteins and the nuclear export receptor CRM1 (exportin 1). The protein is thought to contribute to the integrity of nuclear export complexes and may participate in quality control mechanisms that ensure proper mRNA processing before export.\n\n## Key Relationshipships\n\nALYREF exhibits several documented molecular interactions:\n\n- **Binds** to Yap mRNA (biomarker) with high confidence (strength: 0.88)\n- **Interacts with** YBX1 (gene) and YAP (gene)\n- **Activates** multiple downstream targets including:\n  - CTGF (gene)\n  - MMP2 (gene)\n  - MMP9 (gene)\n  - YBX1 (gene)\n  - YAP (gene)\n  - NSUN2 (gene)\n- **Activated by** AGO2 (gene), as indicated by incoming edge\n\nThese relationships suggest ALYREF operates within the YAP signaling network and may influence matrix remodeling processes through MMP activation.\n\n## Relevant Hypotheses\n\nALYREF is linked to the hypothesis **\"Nuclear Export Deficits Increase Cytosolic TDP-43 Burden\"** (score: 0.58, disease: neurodegeneration). This hypothesis proposes that dysfunction in nuclear export machinery may contribute to the accumulation of TDP-43 in the cytoplasm, a hallmark of neurodegenerative diseases including ALS and frontotemporal dementia. The connection positions ALYREF as a potential modifier of nuclear export fidelity in neuronal cells.\n\n## Literature References References\n\n- NSUN2 promoted tumor growth and metastatic via m... [PMID 41794778](https://pubmed.ncbi.nlm.nih.gov/41794778/) — Cell Death & Disease (2026)\n\n## Neurodegeneration Research Context\n\nALYREF has emerged as a critical factor in ALS (amyotrophic lateral sclerosis) and frontotemporal dementia (FTD) research. Genetic studies in *Drosophila* models have demonstrated that the fly ortholog Ref1/ALYREF modulates toxicity associated with disease-linked mutations in TDP-43 and C9ORF72, both major ALS/FTD genetic drivers. Loss of aly/ALYREF suppresses toxicity in both tau and TDP-43 neurodegeneration models, positioning it as a potential genetic modifier of disease severity [@PMID:35122183].\n\nThe mechanistic connection runs through nuclear RNA export. TDP-43 (TARDBP), the pathological protein in most ALS and FTLD cases, normally shuttles between nucleus and cytoplasm to regulate RNA metabolism. When nuclear export machinery is disrupted — through sequestration of export factors like ALYREF by toxic repeat-expansion RNA from C9ORF72 or other mechanisms — TDP-43 undergoes abnormal cytoplasmic mislocalization and aggregation, a hallmark of ALS/FTD pathology. *Drosophila* Ref1/ALYREF specifically regulates RNA Pol II-dependent transcription and modulates toxicity in ALS/FTD disease models [@PMID:31036086].\n\nThese findings suggest that ALYREF acts as a modifier of TDP-43 proteinopathy by influencing the balance of nuclear-cytoplasmic RNA trafficking. In neurons, which have particularly high demands on RNA export due to their complex transcriptional programs and long axons, disruption of ALYREF function may amplify the accumulation of toxic cytoplasmic TDP-43 aggregates. This positions ALYREF within a broader network of nuclear RNA quality control factors whose dysfunction contributes to neurodegeneration.\n\nIn the context of the SciDEX hypothesis **\"Nuclear Export Deficits Increase Cytosolic TDP-43 Burden\"** (score: 0.58), ALYREF dysfunction represents a plausible upstream mechanism that could amplify TDP-43 mislocalization and aggregation in motor and cortical neurons.\n\n## Cross-Links\n\n- [[TDP-43]] — Key pathological protein whose mislocalization defines ALS/FTD\n- [[C9ORF72]] — Most common genetic cause of ALS and FTD; repeat expansions trap export factors\n- [[ALS Pathogenesis]] — Disease mechanisms linking nuclear export to motor neuron death\n- [[Frontotemporal Dementia]] — Related neurodegenerative disease with TDP-43 pathology\n- [[Nuclear Pore Complex]] — Transport machinery through which ALYREF facilitates mRNA export\n",
  "entity_type": "gene"
}

{
  "content_md": "# ALYREF\n> Auto-generated from SciDEX local knowledge graph, hypothesis, and literature context.\n\n> This page is auto-generated from SciDEX local KG, hypothesis, and paper context.\n\n## Description\n\nALYREF (also known as ALY or Aly/REF export factor) is a nuclear export factor protein involved in the export of messenger RNA (mRNA) from the nucleus to the cytoplasm. As a member of the REF (RNA and export factor-binding protein) family, ALYREF plays a role in coupling transcription with mRNA export machinery.\n\n## Biological Function\n\nALYREF functions as an adapter protein that facilitates the nuclear export of mRNA by bridging between mRNA binding proteins and the nuclear export receptor CRM1 (exportin 1). The protein is thought to contribute to the integrity of nuclear export complexes and may participate in quality control mechanisms that ensure proper mRNA processing before export.\n\n## Key Relationshipships\n\nALYREF exhibits several documented molecular interactions:\n\n- **Binds** to Yap mRNA (biomarker) with high confidence (strength: 0.88)\n- **Interacts with** YBX1 (gene) and YAP (gene)\n- **Activates** multiple downstream targets including:\n  - CTGF (gene)\n  - MMP2 (gene)\n  - MMP9 (gene)\n  - YBX1 (gene)\n  - YAP (gene)\n  - NSUN2 (gene)\n- **Activated by** AGO2 (gene), as indicated by incoming edge\n\nThese relationships suggest ALYREF operates within the YAP signaling network and may influence matrix remodeling processes through MMP activation.\n\n## Relevant Hypotheses\n\nALYREF is linked to the hypothesis **\"Nuclear Export Deficits Increase Cytosolic TDP-43 Burden\"** (score: 0.58, disease: neurodegeneration). This hypothesis proposes that dysfunction in nuclear export machinery may contribute to the accumulation of TDP-43 in the cytoplasm, a hallmark of neurodegenerative diseases including ALS and frontotemporal dementia. The connection positions ALYREF as a potential modifier of nuclear export fidelity in neuronal cells.\n\n## Literature References References\n\n- NSUN2 promoted tumor growth and metastatic via m... [PMID 41794778](https://pubmed.ncbi.nlm.nih.gov/41794778/) — Cell Death & Disease (2026)",
  "entity_type": "gene"
}