Protein Dossier — SERPINA3 (Alpha-1-antichymotrypsin)
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 |
| Diagnoses - main ICD10: M54 Dorsalgia |
0.181 |
0.0473 |
1.28e-04 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: basal cell carcinoma |
-0.302 |
0.104 |
0.00379 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0167 |
0.0063 |
0.00808 |
Wald ratio |
1 |
cis |
NA |
| Urinary albumin-to-creatinine ratio |
-0.0463 |
0.0178 |
0.00939 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.0213 |
0.00902 |
0.0183 |
Wald ratio |
1 |
cis |
NA |
| Caudate volume |
-32.9 |
14.5 |
0.0234 |
Wald ratio |
1 |
cis |
NA |
| Anorexia nervosa |
-0.215 |
0.0951 |
0.0236 |
Wald ratio |
1 |
cis |
NA |
| Microalbuminuria |
-0.139 |
0.0625 |
0.0263 |
Wald ratio |
1 |
cis |
NA |
| Red blood cell count |
-0.0148 |
0.00671 |
0.0273 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.203 |
0.0957 |
0.0343 |
Wald ratio |
1 |
cis |
NA |
| Myocardial infarction |
0.0702 |
0.0336 |
0.0366 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
-0.0222 |
0.0108 |
0.0392 |
Wald ratio |
1 |
cis |
NA |
| …and 99 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2879_9_2 |
a1-Antichymotrypsin |
Suhre K |
2019 |
prot-c-4153_11_2 |
alpha-1-antichymotrypsin complex |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
55 association rows across 24 traits (52 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 |
| alpha-1-antichymotrypsin complex levels |
7e-200 |
rs8023057 |
6 |
GCST90246389 |
no MR -> candidate analysis |
| SERPINA5 protein levels |
2e-187 |
rs1130267 |
7 |
GCST90470585 |
no MR -> candidate analysis |
| Circulating CTSL levels |
3e-106 |
rs6575449 |
2 |
GCST90859820 |
no MR -> candidate analysis |
| SERPINA3 protein levels |
1e-94 |
rs10129374 |
2 |
GCST90470583 |
no MR -> candidate analysis |
| SERPINA4 protein levels |
3e-78 |
rs61976079 |
3 |
GCST90470584 |
no MR -> candidate analysis |
| Cathepsin L1 levels |
2e-64 |
rs6575449 |
1 |
GCST90012073 |
no MR -> candidate analysis |
| SERPINA12 protein levels |
1e-62 |
rs61976121 |
10 |
GCST90470581 |
no MR -> candidate analysis |
| SERPINA11 protein levels |
2e-58 |
rs11622033 |
1 |
GCST90470580 |
no MR -> candidate analysis |
| CELA3A protein levels |
8e-47 |
rs6575449 |
1 |
GCST90468702 |
no MR -> candidate analysis |
| Plasma serine protease inhibitor levels |
7e-35 |
rs4062 |
1 |
GCST90248892 |
no MR -> candidate analysis |
| Alpha-1-antichymotrypsin levels |
2e-21 |
rs8023057 |
3 |
GCST90246388 |
no MR -> candidate analysis |
| Prostate-specific antigen levels |
1e-20 |
rs58643524 |
2 |
GCST90461907 |
no MR -> candidate analysis |
| …and 12 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 640 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 |
| prostate carcinoma |
0.543 |
— |
common-variant locus |
no MR -> candidate analysis |
| peripheral arterial occlusive disease 1 |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 2 rows above, 2 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.
5. Downstream annotation (druggability & safety preview)
| Layer |
Result |
| ChEMBL druggability |
0 known modulators (Alpha-1-antichymotrypsin) |
| gnomAD constraint |
pLI=3.6e-13, LOEUF=1.61 — LoF-tolerant |
| GWAS Catalog |
134 unique SNPs / 340 rows |
| ClinVar |
148 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 640 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 ‘SERPINA3’ and resolved to ‘Alpha-1-antichymotrypsin’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 148 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 24 traits by best p-value, aggregated from 55 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/P01011 — 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/ENSG00000196136/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL5960/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SERPINA3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SERPINA3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SERPINA3%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=SERPINA3 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/SERPINA3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:01:41 · 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