Protein Dossier — SERPINA1 (Alpha-1-antitrypsin)
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 |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0544 |
0.0173 |
0.00172 |
Wald ratio |
1 |
cis |
NA |
| Serum creatinine (eGFRcrea) |
0.00727 |
0.00234 |
0.00194 |
Wald ratio |
1 |
cis |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0874 |
0.0316 |
0.00573 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0149 |
0.00552 |
0.007 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0149 |
0.00582 |
0.0105 |
Wald ratio |
1 |
cis |
NA |
| Ischemic stroke |
0.107 |
0.0429 |
0.0129 |
Wald ratio |
1 |
cis |
NA |
| Parkinson’s disease |
0.274 |
0.113 |
0.0154 |
Wald ratio |
1 |
cis |
NA |
| Height |
-0.018 |
0.00797 |
0.0235 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0471 |
0.0209 |
0.0239 |
Wald ratio |
1 |
cis |
NA |
| LDL cholesterol |
-0.0321 |
0.0143 |
0.0247 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
0.0154 |
0.00689 |
0.0253 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: basal cell carcinoma |
-0.183 |
0.0851 |
0.0312 |
Wald ratio |
1 |
cis |
NA |
| …and 108 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3580_25_8 |
a1-Antitrypsin |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
1199 association rows across 796 traits (1162 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 |
| BSG/CKAP4 protein level ratio |
8e-1010 |
rs28929474 |
1 |
GCST90313531 |
no MR -> candidate analysis |
| CKAP4/PGF protein level ratio |
2e-983 |
rs28929474 |
1 |
GCST90314075 |
no MR -> candidate analysis |
| Circulating CKAP4 levels |
3e-742 |
rs112635299 |
1 |
GCST90860214 |
no MR -> candidate analysis |
| IFNGR1/LTBR protein level ratio |
4e-580 |
rs28929474 |
1 |
GCST90315128 |
no MR -> candidate analysis |
| Circulating LTBR levels |
2e-577 |
rs112635299 |
2 |
GCST90859931 |
no MR -> candidate analysis |
| CSF1/LTBR protein level ratio |
5e-550 |
rs28929474 |
1 |
GCST90314287 |
no MR -> candidate analysis |
| COLEC12/LTBR protein level ratio |
6e-512 |
rs28929474 |
1 |
GCST90314182 |
no MR -> candidate analysis |
| FSTL3/LTBR protein level ratio |
4e-490 |
rs28929474 |
1 |
GCST90314883 |
no MR -> candidate analysis |
| Neutrophil cytosol factor 2 levels |
7e-482 |
rs17580 |
3 |
GCST90248615 |
no MR -> candidate analysis |
| LTBR/TNFRSF14 protein level ratio |
1e-445 |
rs28929474 |
1 |
GCST90315340 |
no MR -> candidate analysis |
| Alpha-1-antitrypsin levels |
9e-444 |
rs28929474 |
6 |
GCST90246390 |
no MR -> candidate analysis |
| Syntaxin-2 levels |
1e-409 |
rs17580 |
1 |
GCST90249720 |
no MR -> candidate analysis |
| …and 784 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 1430 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 |
| Alpha-1-antitrypsin deficiency |
0.876 |
— |
established (curated) |
no MR -> candidate analysis |
| chronic obstructive pulmonary disease |
0.886 |
— |
established (curated) |
no MR -> candidate analysis |
| alpha 1-antitrypsin deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| cholelithiasis |
0.929 |
— |
common-variant locus |
no MR -> candidate analysis |
| pulmonary emphysema |
0.891 |
— |
common-variant locus |
no MR -> candidate analysis |
| cirrhosis of liver |
0.902 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery disorder |
0.907 |
— |
common-variant locus |
no MR -> candidate analysis |
| Abnormality of the skeletal system |
0.915 |
— |
common-variant locus |
no MR -> candidate analysis |
| liver disorder |
0.873 |
— |
common-variant locus |
no MR -> candidate analysis |
| gallstones |
0.877 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.875 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoarthritis, knee |
0.852 |
— |
common-variant locus |
MR: beta=0.0714, p=0.335 (cis) |
| chronic lung disease |
0.853 |
— |
common-variant locus |
no MR -> candidate analysis |
| carpal tunnel syndrome |
0.851 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoarthritis, hip |
0.851 |
— |
common-variant locus |
MR: beta=-0.0693, p=0.395 (cis) |
Of the 15 rows above, 13 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-antiproteinase) |
| gnomAD constraint |
pLI=8.8e-07, LOEUF=1.19 — LoF-tolerant |
| GWAS Catalog |
145 unique SNPs / 384 rows |
| ClinVar |
568 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1430 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 ‘SERPINA1’ and resolved to ‘Alpha-1-antiproteinase’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 568 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 796 traits by best p-value, aggregated from 1199 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/P01009 — 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/ENSG00000197249/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL1795142/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/SERPINA1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SERPINA1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SERPINA1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SERPINA1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:00:42 · 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