Protein Dossier — SERPIND1 (Heparin cofactor 2)
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 |
| LDL cholesterol |
-0.142 |
0.01 |
2.47e-45 |
Wald ratio |
1 |
trans |
NA |
| Total cholesterol |
-0.135 |
0.0096 |
1.13e-44 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: high cholesterol |
-0.169 |
0.0214 |
3.44e-15 |
Wald ratio |
1 |
trans |
NA |
| Weight |
-0.0263 |
0.00591 |
8.87e-06 |
Wald ratio |
1 |
trans |
NA |
| Triglycerides |
-0.0404 |
0.00916 |
1.06e-05 |
Wald ratio |
1 |
trans |
NA |
| Body mass index (BMI) |
-0.0272 |
0.00669 |
4.88e-05 |
Wald ratio |
1 |
trans |
NA |
| Myocardial infarction |
-0.0971 |
0.0265 |
2.50e-04 |
Wald ratio |
1 |
trans |
NA |
| Coronary heart disease |
-0.0809 |
0.0239 |
7.15e-04 |
Wald ratio |
1 |
trans |
NA |
| Childhood intelligence |
0.115 |
0.0356 |
0.00128 |
Wald ratio |
1 |
trans |
NA |
| Red blood cell count |
-0.0161 |
0.00589 |
0.00613 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate |
0.178 |
0.0692 |
0.0103 |
Wald ratio |
1 |
trans |
NA |
| Transferrin |
-0.0716 |
0.0281 |
0.011 |
Wald ratio |
1 |
trans |
NA |
| …and 104 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3316_58_1 |
Heparin cofactor II |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
12 association rows across 12 traits (11 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 |
| CRKL/DBNL protein level ratio |
2e-35 |
rs117858197 |
1 |
GCST90314263 |
no MR -> candidate analysis |
| CRKL/IRAK4 protein level ratio |
3e-33 |
rs117858197 |
1 |
GCST90314268 |
no MR -> candidate analysis |
| CASP3/CRKL protein level ratio |
2e-31 |
rs117858197 |
1 |
GCST90313631 |
no MR -> candidate analysis |
| CRKL/GRAP2 protein level ratio |
2e-23 |
rs117858197 |
1 |
GCST90314267 |
no MR -> candidate analysis |
| CRKL/PLA2G4A protein level ratio |
1e-21 |
rs117858197 |
1 |
GCST90314271 |
no MR -> candidate analysis |
| CRKL/MGLL protein level ratio |
3e-21 |
rs117858197 |
1 |
GCST90314270 |
no MR -> candidate analysis |
| CRKL/DOK2 protein level ratio |
2e-19 |
rs117858197 |
1 |
GCST90314264 |
no MR -> candidate analysis |
| CRKL/SERPINB1 protein level ratio |
3e-18 |
rs117858197 |
1 |
GCST90314272 |
no MR -> candidate analysis |
| CRKL/MANF protein level ratio |
2e-17 |
rs117858197 |
1 |
GCST90314269 |
no MR -> candidate analysis |
| CRKL/YES1 protein level ratio |
5e-17 |
rs117858197 |
1 |
GCST90314273 |
no MR -> candidate analysis |
| O-acetyl-ADP-ribose deacetylase MACROD2 level in Chronic kid |
1e-12 |
rs116401176 |
1 |
GCST90236940 |
no MR -> candidate analysis |
| Monocyte count |
5e-8 |
rs361993 |
1 |
GCST90018967 |
no MR -> candidate analysis |
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 265 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 |
| heparin cofactor 2 deficiency |
0.819 |
— |
established (curated) |
no MR -> candidate analysis |
| Venous thrombosis |
0.701 |
— |
established (curated) |
MR: beta=-0.0399, p=0.42 (trans) |
| hemorrhage |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| thrombotic disease |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| Varicose veins |
0.118 |
— |
common-variant locus |
MR: beta=-0.0667, p=0.183 (trans) |
| COVID-19 |
0.066 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 4 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 |
not available — no ChEMBL target (undrugged) |
| gnomAD constraint |
pLI=6.8e-12, LOEUF=1.29 — LoF-tolerant |
| GWAS Catalog |
44 unique SNPs / 88 rows |
| ClinVar |
548 records; 20 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 265 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 ‘SERPIND1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 548 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 12 of 12 traits by best p-value, aggregated from 12 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/P05546 — 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/ENSG00000099937/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/SERPIND1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/SERPIND1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=SERPIND1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/SERPIND1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T05:02:32 · 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