MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
| Outcome | beta | se | p | method | nSNP | cis/trans | coloc |
|---|---|---|---|---|---|---|---|
| Weight | 0.0345 | 0.00957 | 3.08e-04 | Wald ratio | 1 | trans | NA |
| Body mass index (BMI) | 0.0348 | 0.0108 | 0.00133 | Wald ratio | 1 | trans | NA |
| Non-cancer illness code self-reported: mania or bipolar disorder or manic depression | 0.389 | 0.148 | 0.00854 | Wald ratio | 1 | trans | NA |
| Diagnoses - main ICD10: R55 Syncope and collapse | 0.197 | 0.0955 | 0.0392 | Wald ratio | 1 | trans | NA |
| Diagnoses - main ICD10: Z09 Follow-up examination after treatment for conditions other than malignant neoplasms | -0.233 | 0.113 | 0.0392 | Wald ratio | 1 | trans | NA |
| Potassium in urine | 0.0222 | 0.011 | 0.0432 | Wald ratio | 1 | trans | NA |
| Thalamus volume | -64.9 | 34.5 | 0.0599 | Wald ratio | 1 | trans | NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate | -0.34 | 0.196 | 0.0823 | Wald ratio | 1 | trans | NA |
| Non-cancer illness code self-reported: diverticular disease or diverticulitis | 0.15 | 0.089 | 0.0927 | Wald ratio | 1 | trans | NA |
| Cancer code self-reported: prostate cancer | -0.296 | 0.177 | 0.0948 | Wald ratio | 1 | trans | NA |
| Creatinine (enzymatic) in urine | 0.0166 | 0.0104 | 0.109 | Wald ratio | 1 | trans | NA |
| Non-cancer illness code self-reported: depression | 0.0667 | 0.0419 | 0.111 | Wald ratio | 1 | trans | NA |
| …and 61 more outcomes (see JSON) |
No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).
673 association rows across 372 traits (644 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 |
|---|---|---|---|---|---|
| High density lipoprotein cholesterol levels | 1e-268 | rs1800961 | 15 | GCST90239649 | no MR -> candidate analysis |
| high density lipoprotein cholesterol (HDLC, mean, inv-norm t | 3e-236 | rs1800961 | 4 | GCST90475352 | no MR -> candidate analysis |
| high density lipoprotein cholesterol (HDLC, minimm, inv-norm | 1e-211 | rs1800961 | 3 | GCST90475356 | no MR -> candidate analysis |
| high density lipoprotein cholesterol (HDLC, maximum, inv-nor | 1e-208 | rs1800961 | 3 | GCST90475348 | no MR -> candidate analysis |
| High-density lipoprotein levels | 9e-190 | rs1800961 | 1 | GCST90662894 | no MR -> candidate analysis |
| Apolipoprotein A1 levels | 2e-152 | rs1800961 | 6 | GCST010241 | no MR -> candidate analysis |
| Apolipoprotein A levels (UKB data field 30630) | 7e-142 | rs1800961 | 1 | GCST90468061 | no MR -> candidate analysis |
| HDL cholesterol levels | 1e-140 | rs1800961 | 10 | GCST010242 | no MR -> candidate analysis |
| Concentration of HDL particles | 2e-134 | rs1800961 | 3 | GCST90501116 | no MR -> candidate analysis |
| Haematocrit percentage (UKB data field 30030) | 2e-134 | rs1800961 | 1 | GCST90468073 | no MR -> candidate analysis |
| Total concentration of lipoprotein particles | 2e-123 | rs1800961 | 3 | GCST90501280 | no MR -> candidate analysis |
| Cholesterol in Medium HDL | 4e-117 | rs1800961 | 2 | GCST90501182 | no MR -> candidate analysis |
| …and 360 more traits (see JSON) |
Top diseases by Open Targets association (of 1631 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 |
|---|---|---|---|---|
| MODY | 0.894 | — | established (curated) | no MR -> candidate analysis |
| type 2 diabetes mellitus | 0.831 | 0.57 | established (curated) | no MR -> candidate analysis |
| renal cysts and diabetes syndrome | 0.846 | — | established (curated) | no MR -> candidate analysis |
| maturity-onset diabetes of the young | 0.928 | — | established (curated) | no MR -> candidate analysis |
| monogenic diabetes | 0.964 | — | established (curated) | no MR -> candidate analysis |
| diabetes mellitus | 0.826 | 0.644 | multi-layer: burden+GWAS (allelic-series candidate) | no MR -> candidate analysis |
| cholelithiasis | 0.853 | — | common-variant locus | no MR -> candidate analysis |
| gallstones | 0.78 | — | common-variant locus | no MR -> candidate analysis |
| Intrahepatic cholestasis of pregnancy | 0.745 | — | common-variant locus | no MR -> candidate analysis |
| Cholecystitis | 0.745 | — | common-variant locus | no MR -> candidate analysis |
| hyperinsulinism due to HNF4A deficiency | 0.596 | — | established (curated) | no MR -> candidate analysis |
| metabolic syndrome | 0.685 | — | common-variant locus | no MR -> candidate analysis |
| alcohol drinking | 0.685 | — | common-variant locus | no MR -> candidate analysis |
| Hyperinsulinemia | 0.657 | — | established (curated) | no MR -> candidate analysis |
| metabolic dysfunction-associated steatotic liver disease | 0.548 | — | 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: 1 exploratory rare-variant signal(s), 1 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
| Layer | Result |
|---|---|
| ChEMBL druggability | 1 known modulators (Hepatocyte nuclear factor 4-alpha) |
| gnomAD constraint | pLI=1, LOEUF=0.441 — LoF-INTOLERANT |
| GWAS Catalog | 69 unique SNPs / 138 rows |
| ClinVar | 788 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx | 7 clinical annotations across 5 drugs |
phenome — Top 30 of 1631 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — ChEMBL target matched by text search on ‘HNF4A’ and resolved to ‘Hepatocyte nuclear factor 4-alpha’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 788 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 372 traits by best p-value, aggregated from 673 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/P41235 — 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/ENSG00000101076/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5398/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/HNF4A — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/HNF4A — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=HNF4A%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=HNF4A — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/HNF4A — GWAS Catalog search API (live; release not exposed)