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{
  "description": "While the study shows the variant creates intron-retained transcripts that correlate with reduced enzyme activity, the precise molecular mechanism linking aberrant RNA to protein reduction is not explained. This mechanistic gap limits therapeutic target identification.\n\nGap type: unexplained_observation\nSource paper: African ancestry neurodegeneration risk variant disrupts an intronic branchpoint in GBA1. (2024, Nature structural & molecular biology, PMID:39668204)",
  "domain": "neurodegeneration",
  "status": "investigating",
  "priority_score": 0.87,
  "importance_score": 0.85,
  "tractability_score": 0.9,
  "source": "pubmed:39668204",
  "resolution_criteria": "Resolution requires: (1) RNA-seq of GBA-associated Parkinson's disease vs idiopathic PD vs controls, identifying intron-retained isoform in GBA and its abundance; (2) functional study in neurons where modulating the retained intron changes GBA protein levels and alpha-synuclein aggregation; (3) CSF biomarker study showing correlation between isoform levels and disease severity. Descriptive transcriptomics without functional follow-up is insufficient.",
  "market_price": 0.5
}