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).
1236 association rows across 660 traits (1195 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 |
|---|---|---|---|---|---|
| Alanine aminotransferase levels | 2e-495 | rs738409 | 19 | GCST90428729 | no MR -> candidate analysis |
| Aspartate aminotransferase levels | 3e-361 | rs738409 | 17 | GCST90018944 | no MR -> candidate analysis |
| Chronic liver disease and cirrhosis (PheCode 571) | 1e-323 | rs738409 | 6 | GCST90476081 | no MR -> candidate analysis |
| Other chronic nonalcoholic liver disease (PheCode 571.5) | 1e-323 | rs738409 | 6 | GCST90476084 | no MR -> candidate analysis |
| Abnormal results of function study of liver (PheCode 573.7) | 1e-323 | rs738409 | 6 | GCST90476097 | no MR -> candidate analysis |
| Alanine transaminase (ALT, maximum, inv-norm transformed) | 1e-323 | rs738409 | 4 | GCST90475109 | no MR -> candidate analysis |
| Alanine transaminase (ALT, minimum, inv-norm transformed) | 1e-323 | rs738409 | 4 | GCST90475115 | no MR -> candidate analysis |
| Alanine transaminase (ALT, mean, inv-norm transformed) | 1e-323 | rs738409 | 4 | GCST90475112 | no MR -> candidate analysis |
| Aspartate aminotransferase (AST, maximum, inv-norm transform | 1e-323 | rs738409 | 4 | GCST90475118 | no MR -> candidate analysis |
| Aspartate aminotransferase (AST, mean, inv-norm transformed) | 1e-323 | rs738409 | 4 | GCST90475121 | no MR -> candidate analysis |
| Aspartate aminotransferase (AST, minimum, inv-norm transform | 1e-323 | rs738409 | 4 | GCST90475124 | no MR -> candidate analysis |
| Liver enzyme levels (alanine transaminase) | 1e-300 | rs738409 | 2 | GCST90013405 | no MR -> candidate analysis |
| …and 648 more traits (see JSON) |
Top diseases by Open Targets association (of 308 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 |
|---|---|---|---|---|
| metabolic dysfunction-associated steatotic liver disease | 0.869 | — | established (curated) | no MR -> candidate analysis |
| liver disorder | 0.901 | — | common-variant locus | no MR -> candidate analysis |
| gout | 0.883 | — | common-variant locus | no MR -> candidate analysis |
| cirrhosis of liver | 0.874 | — | common-variant locus | no MR -> candidate analysis |
| type 2 diabetes mellitus | 0.845 | — | common-variant locus | no MR -> candidate analysis |
| hepatocellular carcinoma | 0.65 | — | established (curated) | no MR -> candidate analysis |
| diabetes mellitus | 0.826 | — | common-variant locus | no MR -> candidate analysis |
| alcoholic liver diseases | 0.832 | — | common-variant locus | no MR -> candidate analysis |
| esophageal varices | 0.837 | — | common-variant locus | no MR -> candidate analysis |
| liver cancer | 0.786 | — | common-variant locus | no MR -> candidate analysis |
| coronary artery disorder | 0.758 | — | common-variant locus | no MR -> candidate analysis |
| Abnormality of the liver | 0.79 | — | common-variant locus | no MR -> candidate analysis |
| portal hypertension | 0.773 | — | common-variant locus | no MR -> candidate analysis |
| Hypercholesterolemia | 0.774 | — | common-variant locus | no MR -> candidate analysis |
| intrahepatic bile duct cancer | 0.751 | — | 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=1.6e-14, LOEUF=1.26 — LoF-tolerant |
| GWAS Catalog | 109 unique SNPs / 256 rows |
| ClinVar | 216 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | 2 clinical annotations across 6 drugs |
mr_outcomes — No pQTL MR estimates for PNPLA3 in this resource. ABSENCE OF AN ESTIMATE IS NOT EVIDENCE OF NO EFFECT.phenome — Top 30 of 308 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 ‘PNPLA3’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 216 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 660 traits by best p-value, aggregated from 1236 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/Q9NST1 — UniProt release 2026_02 (10-June-2026)mr_outcomes: https://epigraphdb.org/pqtl/ — EpiGraphDB pQTL MR (Zheng et al., Nat Genet 2020) — pre-computed two-sample MR; retrieved, not computed by this agent; EpiGraphDB build 1.0, pQTL dataset v3.0phenome: https://platform.opentargets.org/target/ENSG00000100344/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/PNPLA3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PNPLA3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PNPLA3%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=PNPLA3 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/PNPLA3 — GWAS Catalog search API (live; release not exposed)