Protein Dossier — C3 (Complement C3)
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: I80 Phlebitis and thrombophlebitis |
0.401 |
0.109 |
2.27e-04 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.133 |
0.0427 |
0.00187 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0293 |
0.00947 |
0.00197 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.0255 |
0.00898 |
0.00448 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: sleep apnoea |
0.377 |
0.138 |
0.00647 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: osteoarthritis |
0.0803 |
0.0338 |
0.0176 |
Wald ratio |
1 |
cis |
NA |
| Invasive mucinous ovarian cancer |
-0.416 |
0.203 |
0.0405 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
-0.0222 |
0.0112 |
0.0476 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: iron deficiency anaemia |
0.237 |
0.12 |
0.0491 |
Wald ratio |
1 |
cis |
NA |
| ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
-0.119 |
0.0625 |
0.057 |
Wald ratio |
1 |
cis |
NA |
| HOMA-B |
-0.0417 |
0.022 |
0.0579 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I84 Haemorrhoids |
0.118 |
0.0628 |
0.06 |
Wald ratio |
1 |
cis |
NA |
| …and 86 more outcomes (see JSON) |
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|
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|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2683_1_2 |
iC3b |
Suhre K |
2019 |
prot-c-2754_50_2 |
C3 |
Suhre K |
2019 |
prot-c-2755_8_2 |
C3adesArg |
Suhre K |
2019 |
prot-c-4480_59_2 |
C3b |
Suhre K |
2019 |
prot-c-4875_73_1 |
C3d |
Suhre K |
2019 |
prot-c-4900_8_1 |
C3a |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
145 association rows across 81 traits (128 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 |
| ER membrane protein complex subunit 4 levels |
5e-947 |
rs594974 |
2 |
GCST90247444 |
no MR -> candidate analysis |
| TNFSF14 protein levels |
6e-208 |
rs413141 |
1 |
GCST90470922 |
no MR -> candidate analysis |
| ER membrane protein complex subunit 4 levels (EMC4.13516.46. |
1e-135 |
rs8112351 |
1 |
GCST90241100 |
no MR -> candidate analysis |
| Neonatal circulating Complement Component 3 (C3) protein con |
6e-123 |
rs11672613 |
2 |
GCST90281041 |
no MR -> candidate analysis |
| Macular degeneration, dry (PheCode 362.21) |
2e-94 |
rs2230199 |
2 |
GCST90475851 |
no MR -> candidate analysis |
| Tumor necrosis factor ligand superfamily member 14 levels |
1e-84 |
rs413141 |
3 |
GCST90249822 |
no MR -> candidate analysis |
| CFP protein levels |
3e-78 |
rs2230199 |
2 |
GCST90468731 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 hospitalization |
2e-71 |
rs11569415 |
1 |
GCST90250833 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 infection (MTAG |
2e-71 |
rs11569415 |
1 |
GCST90250834 |
no MR -> candidate analysis |
| Age-related macular degeneration or COVID-19 critical illnes |
2e-71 |
rs11569415 |
1 |
GCST90250832 |
no MR -> candidate analysis |
| Advanced age-related macular degeneration |
4e-69 |
rs2230199 |
2 |
GCST003219 |
no MR -> candidate analysis |
| CD70 protein levels |
3e-66 |
rs2250656 |
7 |
GCST90468645 |
no MR -> candidate analysis |
| …and 69 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 2519 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 |
| atypical hemolytic-uremic syndrome with C3 anomaly |
0.921 |
— |
established (curated) |
no MR -> candidate analysis |
| complement component 3 deficiency |
0.828 |
— |
established (curated) |
no MR -> candidate analysis |
| age-related macular degeneration |
0.866 |
— |
established (curated) |
no MR -> candidate analysis |
| atypical hemolytic-uremic syndrome |
0.812 |
— |
established (curated) |
no MR -> candidate analysis |
| macular degeneration |
0.91 |
— |
common-variant locus |
no MR -> candidate analysis |
| age related macular degeneration 9 |
0.683 |
— |
established (curated) |
no MR -> candidate analysis |
| retinal disorder |
0.887 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrophic macular degeneration |
0.724 |
— |
common-variant locus |
no MR -> candidate analysis |
| degeneration of macula and posterior pole |
0.863 |
— |
common-variant locus |
no MR -> candidate analysis |
| COVID-19 |
0.785 |
— |
common-variant locus |
no MR -> candidate analysis |
| dry age related macular degeneration |
0.793 |
— |
common-variant locus |
no MR -> candidate analysis |
| wet macular degeneration |
0.788 |
— |
common-variant locus |
no MR -> candidate analysis |
| C3 glomerulonephritis |
0.674 |
— |
established (curated) |
no MR -> candidate analysis |
| eye disorder |
0.579 |
— |
common-variant locus |
no MR -> candidate analysis |
| atypical hemolytic uremic syndrome with complement gene abnormality |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
Of the 15 rows above, 15 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=1.2e-07, LOEUF=0.552 — LoF-tolerant |
| GWAS Catalog |
102 unique SNPs / 212 rows |
| ClinVar |
1890 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 2519 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 1890 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 20 of 81 traits by best p-value, aggregated from 145 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/P01024 — 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/ENSG00000125730/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/C3 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/C3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=C3%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=C3 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/C3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:22:12 · 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