Protein Dossier — C5 (Complement C5)
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: C50 Malignant neoplasm of breast |
0.303 |
0.079 |
1.27e-04 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
-0.0419 |
0.0139 |
0.00254 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: B37 Candidiasis |
0.882 |
0.297 |
0.00298 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
0.138 |
0.0516 |
0.00745 |
Wald ratio |
1 |
cis |
NA |
| Sodium in urine |
0.0352 |
0.0134 |
0.00832 |
Wald ratio |
1 |
cis |
NA |
| Underlying (primary) cause of death: ICD10: E85.4 Organ-limited amyloidosis |
1.89 |
0.722 |
0.0087 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.135 |
0.0529 |
0.0108 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.0896 |
0.0352 |
0.0109 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: pernicious anaemia |
0.424 |
0.169 |
0.0123 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.102 |
0.0418 |
0.0144 |
Wald ratio |
1 |
cis |
NA |
| Fracture resulting from simple fall |
-0.0916 |
0.0394 |
0.0199 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
0.0473 |
0.0203 |
0.0201 |
Wald ratio |
1 |
cis |
NA |
| …and 94 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2381_52_4 |
C5 |
Suhre K |
2019 |
prot-c-2851_63_3 |
C5a |
Suhre K |
2019 |
prot-c-4482_66_2 |
C5b, 6 Complex |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
40 association rows across 27 traits (32 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 |
| Complement C5 levels |
1e-74 |
rs41309886 |
5 |
GCST90246786 |
no MR -> candidate analysis |
| Complement C5b-C6 complex levels |
9e-71 |
rs41309886 |
4 |
GCST90246789 |
no MR -> candidate analysis |
| C5a anaphylatoxin levels |
8e-32 |
rs17220750 |
2 |
GCST90246788 |
no MR -> candidate analysis |
| GSN protein levels |
3e-18 |
rs117952610 |
1 |
GCST90469409 |
no MR -> candidate analysis |
| Height (baseline) |
3e-17 |
rs76481162 |
1 |
GCST90565843 |
no MR -> candidate analysis |
| Height |
2e-15 |
rs12685289 |
2 |
GCST90435412 |
MR: beta=0.0203, p=0.217 (cis) |
| Serum levels of protein C5 |
2e-15 |
rs1035029 |
2 |
GCST90087935 |
no MR -> candidate analysis |
| Elevated prostate specific antigen [PSA] (PheCode 796) |
5e-15 |
rs7045519 |
1 |
GCST90480590 |
no MR -> candidate analysis |
| Blood protein levels |
2e-13 |
rs1035029 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Estimated glomerular filtration rate (cystatin c) |
5e-13 |
rs141350020 |
1 |
GCST90428448 |
no MR -> candidate analysis |
| Rheumatoid arthritis (rheumatoid factor and/or anti-cyclic c |
6e-13 |
rs35942002 |
1 |
GCST90131438 |
no MR -> candidate analysis |
| Hypothyroidism |
6e-13 |
rs10739580 |
1 |
GCST90627750 |
MR: beta=0.135, p=0.0108 (cis) |
| …and 15 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 814 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 |
| Immunodeficiency due to a late component of complements deficiency |
0.841 |
— |
established (curated) |
no MR -> candidate analysis |
| immunodeficiency due to a late component of complement deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| lathosterolosis |
0.559 |
— |
established (curated) |
no MR -> candidate analysis |
| alcohol drinking |
0.514 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery disorder |
0.48 |
— |
common-variant locus |
no MR -> candidate analysis |
| peripheral vascular disease |
0.403 |
— |
common-variant locus |
no MR -> candidate analysis |
| urolithiasis |
0.403 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 7 rows above, 7 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=3.4e-28, LOEUF=0.736 — LoF-tolerant |
| GWAS Catalog |
89 unique SNPs / 175 rows |
| ClinVar |
951 records; 8 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 814 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 951 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 27 traits by best p-value, aggregated from 40 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/P01031 — 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/ENSG00000106804/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/C5 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/C5 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=C5%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=C5 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/C5 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:22:40 · 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: chembl