Protein Dossier — HGFAC (Hepatocyte growth factor activator serine protease)
MR feasibility tier: A — Published pQTL-MR estimates exist for this protein (retrieved below - not computed here).
1. Published MR estimates (retrieved, not computed)
| Outcome |
beta |
se |
p |
method |
nSNP |
cis/trans |
coloc |
| Forced vital capacity (FVC) |
0.0168 |
0.00403 |
3.17e-05 |
Wald ratio |
1 |
cis |
NA |
| Height |
0.0304 |
0.00792 |
1.20e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.016 |
0.00425 |
1.75e-04 |
Wald ratio |
1 |
cis |
NA |
| Endometrioid ovarian cancer |
-0.164 |
0.0594 |
0.00564 |
Wald ratio |
1 |
cis |
NA |
| Alzheimer’s disease |
0.084 |
0.0341 |
0.0137 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
-0.21 |
0.0976 |
0.0316 |
Wald ratio |
1 |
cis |
NA |
| Ovarian cancer |
-0.06 |
0.0281 |
0.0329 |
Wald ratio |
1 |
cis |
NA |
| Red blood cell count |
0.0136 |
0.00639 |
0.0334 |
Wald ratio |
1 |
cis |
NA |
| Weight |
0.00922 |
0.00434 |
0.0337 |
Wald ratio |
1 |
cis |
NA |
| High grade serous ovarian cancer |
-0.0702 |
0.0334 |
0.0354 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G47 Sleep disorders |
0.12 |
0.057 |
0.0356 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
-0.0285 |
0.0137 |
0.0372 |
Wald ratio |
1 |
cis |
NA |
| …and 87 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3617_80_4 |
HGFA |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
958 association rows across 540 traits (946 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 |
| Hepatocyte growth factor activator levels |
6e-1632 |
rs2498323 |
8 |
GCST90247876 |
no MR -> candidate analysis |
| Blood protein levels |
2e-476 |
rs2498323 |
2 |
GCST006585 |
no MR -> candidate analysis |
| Albumin levels |
4e-231 |
rs13108218 |
13 |
GCST90662901 |
no MR -> candidate analysis |
| Hepatocyte growth factor activator (analyte X3617.80) levels |
1e-226 |
rs2498323 |
1 |
GCST90425833 |
no MR -> candidate analysis |
| HGFAC protein levels |
4e-225 |
rs34491545 |
10 |
GCST90469448 |
no MR -> candidate analysis |
| Hepatocyte growth factor activator (analyte X8385.248) level |
2e-187 |
rs2498323 |
1 |
GCST90427369 |
no MR -> candidate analysis |
| Sex hormone-binding globulin levels adjusted for BMI |
3e-172 |
rs13108218 |
3 |
GCST90012110 |
no MR -> candidate analysis |
| Triglyceride levels |
1e-163 |
rs13108218 |
17 |
GCST90662893 |
no MR -> candidate analysis |
| Sex hormone-binding globulin levels |
9e-129 |
rs13108218 |
16 |
GCST90012111 |
no MR -> candidate analysis |
| Circulating HGF levels (id: OID00522_OID20656) |
2e-119 |
rs59950280 |
4 |
GCST90859878 |
no MR -> candidate analysis |
| C1QTNF1/COL4A1 protein level ratio |
6e-100 |
rs2498323 |
1 |
GCST90313552 |
no MR -> candidate analysis |
| Serum levels of protein HGFAC |
7e-97 |
rs3752440 |
2 |
GCST90088461 |
no MR -> candidate analysis |
| …and 528 more traits (see JSON) |
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4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 216 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 |
| Hypercholesterolemia |
0.825 |
— |
common-variant locus |
MR: beta=-0.0285, p=0.0372 (cis) |
| metabolic disease |
0.8 |
— |
common-variant locus |
no MR -> candidate analysis |
| hyperlipidemia |
0.717 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery disorder |
0.682 |
— |
common-variant locus |
no MR -> candidate analysis |
| inflammatory bowel disease |
0.594 |
— |
common-variant locus |
no MR -> candidate analysis |
| Crohn disease |
0.594 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.594 |
— |
common-variant locus |
no MR -> candidate analysis |
| cholelithiasis |
0.587 |
— |
common-variant locus |
MR: beta=-0.0541, p=0.135 (cis) |
| familial hypercholesterolemia |
0.584 |
— |
common-variant locus |
no MR -> candidate analysis |
| Disorder of lipid metabolism |
0.542 |
— |
common-variant locus |
no MR -> candidate analysis |
| familial hyperlipidemia |
0.512 |
— |
common-variant locus |
no MR -> candidate analysis |
| ischemic stroke |
0.506 |
— |
common-variant locus |
MR: beta=0.0666, p=0.12 (cis) |
| gallstones |
0.479 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.476 |
— |
common-variant locus |
no MR -> candidate analysis |
| venous thromboembolism |
0.476 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 12 have no MR estimate in this resource. Across all retrieved diseases for this gene: 1 exploratory rare-variant signal(s), 0 multi-layer (allelic-series candidate) pair(s). Final triage still belongs to a statistical geneticist.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
0 known modulators (Hepatocyte growth factor activator serine protease) |
| gnomAD constraint |
pLI=4.2e-28, LOEUF=1.3 — LoF-tolerant |
| GWAS Catalog |
129 unique SNPs / 324 rows |
| ClinVar |
324 records; 11 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 216 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 ‘HGFAC’ and resolved to ‘Hepatocyte growth factor activator serine protease’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 324 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 20 of 540 traits by best p-value, aggregated from 958 association rows. These are GWAS ASSOCIATIONS (loci), not causal claims; mapped genes at a locus are not necessarily the effector gene.
Sources
uniprot: https://www.uniprot.org/uniprotkb/Q04756 — 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/ENSG00000109758/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3351190/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/HGFAC — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/HGFAC — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=HGFAC%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/HGFAC — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T03:00:20 · Tier: A
- Fully mechanical: every cell above is rendered from tool return values. No language model wrote any part of this dossier.
- MR estimates, where present, are retrieved from published work (EpiGraphDB pQTL, Zheng et al. Nat Genet 2020); nothing is computed here.
- Tool errors this run: none