Protein Dossier — PROC (Vitamin K-dependent protein C)
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 |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.191 |
0.0297 |
1.27e-10 |
Wald ratio |
1 |
trans |
NA |
| Height |
0.0334 |
0.00585 |
1.10e-08 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: I80 Phlebitis and thrombophlebitis |
0.249 |
0.0581 |
1.84e-05 |
Wald ratio |
1 |
trans |
NA |
| Coronary heart disease |
-0.0725 |
0.0173 |
2.92e-05 |
Wald ratio |
1 |
trans |
NA |
| Myocardial infarction |
-0.0739 |
0.0192 |
1.13e-04 |
Wald ratio |
1 |
trans |
NA |
| Creatinine (enzymatic) in urine |
-0.0186 |
0.00485 |
1.27e-04 |
Wald ratio |
1 |
trans |
NA |
| Body mass index (BMI) |
-0.0193 |
0.00507 |
1.37e-04 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: pulmonary embolism (with or without) dvt |
0.171 |
0.0474 |
3.03e-04 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: M72 Fibroblastic disorders |
0.194 |
0.057 |
6.86e-04 |
Wald ratio |
1 |
trans |
NA |
| Heel bone mineral density (BMD) T-score automated |
-0.0222 |
0.00657 |
7.19e-04 |
Wald ratio |
1 |
trans |
NA |
| Sodium in urine |
-0.0135 |
0.00499 |
0.00669 |
Wald ratio |
1 |
trans |
NA |
| Potassium in urine |
-0.0138 |
0.00515 |
0.00737 |
Wald ratio |
1 |
trans |
NA |
| …and 114 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2961_1_2 |
Protein C |
Suhre K |
2019 |
prot-c-3758_68_3 |
Activated Protein C |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
27 association rows across 13 traits (26 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 |
| Circulating PROC levels |
1e-254 |
rs1799809 |
4 |
GCST90860431 |
no MR -> candidate analysis |
| PROC protein levels |
1e-245 |
rs1799810 |
5 |
GCST90470335 |
no MR -> candidate analysis |
| F9/PROC protein level ratio |
2e-231 |
rs1799810 |
1 |
GCST90314748 |
no MR -> candidate analysis |
| Protein C levels |
2e-42 |
rs1799810 |
2 |
GCST006119 |
no MR -> candidate analysis |
| Height |
4e-41 |
rs7599210 |
1 |
GCST90245848 |
MR: beta=0.0334, p=1.10e-08 (trans) |
| Vitamin K-dependent protein C levels |
8e-32 |
rs1799810 |
3 |
GCST90250174 |
no MR -> candidate analysis |
| Venous thromboembolism |
7e-29 |
rs1158867 |
2 |
GCST90244158 |
no MR -> candidate analysis |
| Serum levels of protein PROC |
2e-22 |
rs1799809 |
2 |
GCST90088150 |
no MR -> candidate analysis |
| Encounter for long-term (current) use of anticoagulants (Phe |
4e-19 |
rs200045749 |
2 |
GCST90479975 |
no MR -> candidate analysis |
| Blood protein levels |
5e-13 |
rs2069901 |
2 |
GCST006585 |
no MR -> candidate analysis |
| Coagulation defects (PheCode 286) |
2e-11 |
rs200045749 |
1 |
GCST90479980 |
no MR -> candidate analysis |
| Takes medication for blood clot/ pulmonary embolism/ deep ve |
3e-11 |
rs200045749 |
1 |
GCST90479548 |
no MR -> candidate analysis |
| …and 1 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 423 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 |
| hereditary thrombophilia due to congenital protein C deficiency |
0.929 |
— |
established (curated) |
no MR -> candidate analysis |
| venous thromboembolism |
0.921 |
0.938 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| deep vein thrombosis |
0.937 |
0.97 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| thrombophilia due to protein C deficiency, autosomal dominant |
0.943 |
— |
established (curated) |
no MR -> candidate analysis |
| protein c deficiency |
0.813 |
— |
established (curated) |
no MR -> candidate analysis |
| thrombophilia due to protein C deficiency, autosomal recessive |
0.919 |
— |
established (curated) |
no MR -> candidate analysis |
| phlebitis |
0.855 |
0.978 |
multi-layer: burden+GWAS (allelic-series candidate) |
MR: beta=0.249, p=1.84e-05 (trans) |
| Thrombophlebitis |
0.85 |
0.971 |
multi-layer: burden+GWAS (allelic-series candidate) |
MR: beta=0.249, p=1.84e-05 (trans) |
| Abnormal thrombosis |
0.829 |
0.896 |
established (curated) |
no MR -> candidate analysis |
| thrombophilia |
0.829 |
0.829 |
exploratory rare-variant signal |
no MR -> candidate analysis |
| blood coagulation disease |
0.667 |
0.628 |
multi-layer: burden+GWAS (allelic-series candidate) |
no MR -> candidate analysis |
| Portal vein thrombosis |
0.883 |
0.883 |
exploratory rare-variant signal |
no MR -> candidate analysis |
| Thromboembolism |
0.675 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.759 |
— |
established (curated) |
no MR -> candidate analysis |
| heart disorder |
0.709 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 13 have no MR estimate in this resource. Across all retrieved diseases for this gene: 6 exploratory rare-variant signal(s), 6 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 |
2 known modulators (Vitamin K-dependent protein C) |
| gnomAD constraint |
pLI=7.3e-05, LOEUF=0.865 — LoF-tolerant |
| GWAS Catalog |
31 unique SNPs / 62 rows |
| ClinVar |
510 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 423 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 ‘PROC’ and resolved to ‘Vitamin K-dependent protein C’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 510 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 13 of 13 traits by best p-value, aggregated from 27 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/P04070 — 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/ENSG00000115718/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4444/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PROC — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PROC — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PROC%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=PROC — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/PROC — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:36:55 · 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