Интеграция генетических факторов риска и лекарственно-ассоциированных генов при терапии биполярного расстройства: биоинформатический и системно-фармакологический анализ сигнальных путей
Ranked candidate evidence assessment
the total score ranges from 0 to 11. Bands reflect relation type (A, exact overlap; B, predefined bridge; C, thematic or one-sided evidence); tied scores share the same rank using competition ranking; the score is intended for hypothesis prioritization and is not a validated probability, clinical score, or treatment-response biomarker
No. | Gene | Band / score | Candidate role | Evidence summary | Principal limitation |
1 | HTR6 | A / 10 | Exact gene overlap | BD: strict; drug: Olanzapine (Tier 1; Ki = 7.943 nM). | Only direct overlap; overlap enrichment is not significant and target-specific human CNS engagement was not identified. |
2 | GSK3B | B / 6 | Predefined AKAP11-lithium mechanistic bridge | BD: none; drug: Lithium carbonate (Tier 1; Ki = 2.0 × 10⁶ nM). | Not a BD-prioritized gene in the mapping sets; predefined bridge; lithium Ki exceeds usual serum exposure. |
3 | HRH1 | C / 5 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Olanzapine (Tier 1; Ki = 3.5 nM); Quetiapine (Tier 1; Ki = 11.0 nM). | Human H1 occupancy exists, but there is no BD genetic prioritization; pathway relation is receptor-mediated and thematic. |
4 | CACNA1B | C / 4 | BD-side voltage-gated calcium signal | BD: strict; drug: none. | Strong disease-side evidence but no qualifying Tier 1 drug interaction in the curated set. |
4 | ADRA1A | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Quetiapine (Tier 1; Ki = 100.0 nM). | No BD genetic prioritization; calcium relation is based on a broad receptor-mediated pathway annotation. |
4 | ADRA1B | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Risperidone (Tier 1; Ki = 10.0 nM). | No BD genetic prioritization; calcium relation is based on a broad receptor-mediated pathway annotation. |
4 | CHRM1 | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Olanzapine (Tier 1; Ki = 10.0 nM). | No BD genetic prioritization; calcium relation is based on a broad receptor-mediated pathway annotation. |
4 | HTR2A | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Aripiprazole (Tier 1; Ki = 12.1 nM); Lurasidone (Tier 1; Ki = 2.0 nM); Olanzapine (Tier 1; Ki = 2.5 nM); Quetiapine (Tier 1; Ki = 120.0 nM); Risperidone (Tier 1; Ki = 0.29 nM). | Tier 1 and PGx annotations are present, but no BD genetic prioritization or target-specific CNS engagement was identified. |
4 | HTR2C | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Fluoxetine (Tier 1; Ki = 72.0 nM); Olanzapine (Tier 1; Ki = 10.0 nM). | No BD genetic prioritization; calcium relation is based on a broad receptor-mediated pathway annotation. |
4 | HTR7 | C / 4 | Tier 1 receptor-mediated calcium pathway contributor | BD: none; drug: Aripiprazole (Tier 1; Ki = 44.0 nM); Lurasidone (Tier 1; Ki = 0.5 nM); Risperidone (Tier 1; Ki = 4.3 nM). | No BD genetic prioritization; calcium relation is based on a broad receptor-mediated pathway annotation. |
11 | CACNA1C | C / 3 | BD-side voltage-gated calcium signal | BD: functionally expanded; drug: none. | Functionally expanded MAGMA evidence only; no qualifying Tier 1 drug interaction. |
11 | CACNB2 | C / 3 | BD-side voltage-gated calcium signal | BD: functionally expanded; drug: none. | Functionally expanded MAGMA evidence only; no qualifying Tier 1 drug interaction. |
11 | CACNA1E | C / 3 | Tier 2 calcium-channel mechanism | BD: none; drug: Lamotrigine (Tier 2; inhibitor). | Tier 2 mechanism without qualifying quantitative gene-level affinity; no strict BD mapping evidence. |