Gene Liability Evaluation

Gene Liability Evaluation

Assess whether reducing a human gene's function is likely to be unsafe. Resolve the gene, gather independent human and model-system evidence, calculate a transparent 0–100 liability score, and recommend an appropriate modulation strategy.

Higher scores mean greater predicted liability from the stated intervention. This is a safety score, not a target-efficacy or druggability score.

Required Input

Accept a gene symbol, name, Ensembl ID, or UniProt accession. Also capture:

• intervention modality: knockout, knockdown, degrader, irreversible inhibitor, reversible inhibitor, antibody, or unknown;
• intended tissue and indication, when supplied;
• desired inhibition depth and duration, when supplied.

If modality is absent, assess complete systemic loss of function and label that assumption prominently. Do not silently generalize a knockout result to partial or tissue-restricted pharmacology.

Evidence Rules

• Look up the gene before reasoning. Do not score an ambiguous identifier.
• Use human causal evidence before animal models, screens, expression, or prediction.
• Treat absent data as unknown, never as evidence of safety.
• Cite every score-changing observation with the source and identifier.
• Separate germline loss of function, somatic loss, acute pharmacology, and chronic pharmacology.
• Treat DepMap as cancer-cell essentiality, not normal-tissue essentiality.
• Report contradictory evidence instead of averaging it away.

Grade evidence as:

• T1: human clinical outcome or replicated causal human genetics;
• T2: curated human evidence, mammalian knockout phenotype, or established drug class safety;
• T3: functional screen, tissue expression, or single experimental study;
• T4: computational prediction or catalog annotation.