MR feasibility tier: C — No plasma pQTL found (accession + symbol match). Standard plasma pQTL MR is not currently feasible; gene-level genetic evidence below is the honest preview.
None in the EpiGraphDB pQTL resource. Absence of an estimate is not evidence of no effect.
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
23 association rows across 18 traits (22 genome-wide significant rows). Associations are loci, not causal claims; the mapped gene at a locus is not necessarily the effector gene.
| Trait | best p | lead SNP | n assoc | study | MR status |
|---|---|---|---|---|---|
| Height | 2e-108 | rs7156302 | 1 | GCST90245848 | no MR -> candidate analysis |
| Cathepsin H levels (CTSH.8465.52.3) | 4e-30 | rs140130028 | 2 | GCST90240624 | no MR -> candidate analysis |
| Refractive error | 7e-25 | rs73294488 | 3 | GCST010002 | no MR -> candidate analysis |
| NPC2 protein levels | 3e-23 | rs113587712 | 1 | GCST90470068 | no MR -> candidate analysis |
| ENTPD5 protein levels | 7e-18 | rs149199515 | 1 | GCST90469121 | no MR -> candidate analysis |
| Circulating LTBP2 levels | 5e-17 | rs117743573 | 1 | GCST90860485 | no MR -> candidate analysis |
| Lung function (FEV1) | 7e-14 | rs7144263 | 1 | GCST90244092 | no MR -> candidate analysis |
| Serum levels of protein CTSH | 2e-13 | rs10873267 | 1 | GCST90088501 | no MR -> candidate analysis |
| Primary open angle glaucoma (multi-trait analysis) | 2e-12 | rs73294447 | 1 | GCST90310211 | no MR -> candidate analysis |
| Primary open angle glaucoma (MTAG) | 1e-11 | rs73294447 | 1 | GCST90310210 | no MR -> candidate analysis |
| Type 2 diabetes | 8e-11 | rs8008540 | 2 | GCST010555 | no MR -> candidate analysis |
| Spherical equivalent | 3e-10 | rs73294470 | 1 | GCST010378 | no MR -> candidate analysis |
| …and 6 more traits (see JSON) |
Top diseases by Open Targets association (of 1507 total). Associations are loci, not causal claims. The causal-status column is a four-state triage per pair: established (curated) = a curated clinical assertion exists (ClinGen/G2P/GEL/Orphanet/ClinVar — any validity level, MR adds little); exploratory rare-variant signal = ExWAS burden evidence without curation — a candidate NEW gene-disease relationship; common-variant locus = GWAS signal, classic pQTL-MR territory; multi-layer = burden+GWAS together, an allelic-series candidate (the strongest causal setup). Burden estimand is carrier-vs-noncarrier, not per-SD MR.
| Disease | genetic assoc. | burden (ExWAS) | causal status | MR status |
|---|---|---|---|---|
| Niemann-Pick disease, type C2 | 0.938 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C | 0.85 | — | established (curated) | no MR -> candidate analysis |
| hereditary disease | 0.81 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease | 0.559 | — | established (curated) | no MR -> candidate analysis |
| open-angle glaucoma | 0.686 | — | common-variant locus | no MR -> candidate analysis |
| glaucoma | 0.678 | — | common-variant locus | no MR -> candidate analysis |
| Niemann-Pick disease, type C1 | 0.654 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C, severe early infantile neurologic onset | 0.608 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C, adult neurologic onset | 0.608 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C, severe perinatal form | 0.608 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C, juvenile neurologic onset | 0.608 | — | established (curated) | no MR -> candidate analysis |
| Niemann-Pick disease type C, late infantile neurologic onset | 0.608 | — | established (curated) | no MR -> candidate analysis |
| refractive error | 0.491 | — | common-variant locus | no MR -> candidate analysis |
| Abnormality of refraction | 0.483 | — | common-variant locus | no MR -> candidate analysis |
| alcohol drinking | 0.434 | — | common-variant locus | no MR -> candidate analysis |
Of the 15 rows above, 15 have no MR estimate in this resource. Across all retrieved diseases for this gene: 0 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
| Layer | Result |
|---|---|
| ChEMBL druggability | not available — no ChEMBL target (undrugged) |
| gnomAD constraint | pLI=7e-05, LOEUF=1.29 — LoF-tolerant |
| GWAS Catalog | 85 unique SNPs / 170 rows |
| ClinVar | 330 records; 4 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | no annotations |
phenome — Top 30 of 1507 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘NPC2’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 330 ClinVar records for this gene; it is a sample, not a rate.pharmgkb — No PharmGKB/ClinPGx clinical annotations (gene may not be a pharmacogene).gwas_traits — Top 18 of 18 traits by best p-value, aggregated from 23 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.uniprot: https://www.uniprot.org/uniprotkb/P61916 — UniProt release 2026_02 (10-June-2026)phenome: https://platform.opentargets.org/target/ENSG00000119655/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/NPC2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/NPC2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=NPC2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/NPC2 — GWAS Catalog search API (live; release not exposed)