Protein Dossier — PCSK7 (Proprotein convertase subtilisin/kexin type 7)
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 |
| Triglycerides |
-0.0302 |
0.00544 |
2.77e-08 |
Wald ratio |
1 |
cis |
NA |
| Total cholesterol |
-0.0235 |
0.00604 |
1.03e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
0.00876 |
0.00239 |
2.56e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M16 Coxarthrosis [arthrosis of hip] |
0.0781 |
0.0225 |
5.14e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I84 Haemorrhoids |
-0.065 |
0.02 |
0.00116 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
-0.0122 |
0.00378 |
0.00122 |
Wald ratio |
1 |
cis |
NA |
| Systemic lupus erythematosus |
0.187 |
0.0584 |
0.00135 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
-0.0152 |
0.00505 |
0.0027 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
-0.0339 |
0.0124 |
0.00631 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: high cholesterol |
-0.0216 |
0.00807 |
0.00732 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
-0.0584 |
0.0223 |
0.00884 |
Wald ratio |
1 |
cis |
NA |
| Rheumatoid arthritis |
0.0411 |
0.0161 |
0.0105 |
Wald ratio |
1 |
cis |
NA |
| …and 124 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4459_68_2 |
PCSK7 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
415 association rows across 208 traits (408 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 |
| Proprotein convertase subtilisin/kexin type 7 levels |
5e-1552 |
rs35186251 |
5 |
GCST90248897 |
no MR -> candidate analysis |
| Soluble transferrin receptor concentration |
2e-137 |
rs11216316 |
2 |
GCST90451684 |
no MR -> candidate analysis |
| Circulating TFRC levels |
1e-103 |
rs508487 |
2 |
GCST90859941 |
no MR -> candidate analysis |
| Triglycerides |
5e-91 |
rs508487 |
8 |
GCST007142 |
MR: beta=-0.0302, p=2.77e-08 (cis) |
| Monounsaturated fatty acids to total fatty acids percentage |
4e-59 |
rs508487 |
26 |
GCST90502373 |
no MR -> candidate analysis |
| Apolipoprotein A1 levels |
2e-57 |
rs74988348 |
4 |
GCST90019495 |
no MR -> candidate analysis |
| Cholesterol to total lipids ratio in medium HDL |
4e-50 |
rs555766713 |
1 |
GCST90092893 |
no MR -> candidate analysis |
| Phospholipids to total lipids ratio in large VLDL |
2e-49 |
rs555766713 |
1 |
GCST90092877 |
no MR -> candidate analysis |
| Ratio of triglycerides to phosphoglycerides |
3e-49 |
rs555766713 |
1 |
GCST90092983 |
no MR -> candidate analysis |
| Cholesterol levels in chylomicrons and extremely large VLDL |
3e-49 |
rs555766713 |
1 |
GCST90093040 |
no MR -> candidate analysis |
| Cholesteryl ester levels in large HDL |
3e-48 |
rs555766713 |
1 |
GCST90092846 |
no MR -> candidate analysis |
| Free cholesterol levels in chylomicrons and extremely large |
3e-48 |
rs555766713 |
1 |
GCST90093044 |
no MR -> candidate analysis |
| …and 196 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 148 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 |
| hypothyroidism |
0.416 |
— |
common-variant locus |
MR: beta=0.0223, p=0.0787 (cis) |
| familial lipoprotein lipase deficiency |
0.385 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.385 |
— |
common-variant locus |
no MR -> candidate analysis |
| hyperlipidemia |
0.384 |
— |
common-variant locus |
no MR -> candidate analysis |
| Pericallosal lipoma |
0.243 |
— |
established (curated) |
no MR -> candidate analysis |
| Skin tags |
0.243 |
— |
established (curated) |
no MR -> candidate analysis |
| Hereditary breast and ovarian cancer syndrome |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| Preauricular skin tag |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| Midline facial cleft |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary breast ovarian cancer syndrome |
0.195 |
— |
established (curated) |
no MR -> candidate analysis |
| myxedema |
0.053 |
— |
common-variant locus |
no MR -> candidate analysis |
| Hashimoto thyroiditis |
0.05 |
— |
common-variant locus |
no MR -> candidate analysis |
| asthma |
0.048 |
— |
common-variant locus |
MR: beta=-0.0141, p=0.0891 (cis) |
| diverticular disease |
0.046 |
— |
common-variant locus |
MR: beta=0.024, p=0.232 (cis) |
| autoimmune disease |
0.045 |
— |
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: 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 (Proprotein convertase subtilisin/kexin type 7) |
| gnomAD constraint |
pLI=2.3e-05, LOEUF=0.679 — LoF-tolerant |
| GWAS Catalog |
157 unique SNPs / 384 rows |
| ClinVar |
165 records; 1 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 148 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 ‘PCSK7’ and resolved to ‘Proprotein convertase subtilisin/kexin type 7’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 165 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 208 traits by best p-value, aggregated from 415 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/Q16549 — 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/ENSG00000160613/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2232/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/PCSK7 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/PCSK7 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=PCSK7%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/PCSK7 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T04:13:39 · 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