Protein Dossier — C9 (Complement component C9)
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: muscle or soft tissue injuries |
0.419 |
0.146 |
0.0042 |
Wald ratio |
1 |
cis |
NA |
| HOMA-IR |
-0.0827 |
0.0293 |
0.00483 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypopituitarism |
1.1 |
0.393 |
0.00491 |
Wald ratio |
1 |
cis |
NA |
| HOMA-B |
-0.0747 |
0.0267 |
0.00511 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Injury or trauma resulting in loss of vision |
0.428 |
0.162 |
0.00818 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
0.0674 |
0.0272 |
0.013 |
Wald ratio |
1 |
cis |
NA |
| Lung adenocarcinoma |
0.604 |
0.245 |
0.0137 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: G56 Mononeuropathies of upper limb |
0.25 |
0.11 |
0.0238 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal |
0.268 |
0.121 |
0.0264 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: iron deficiency anaemia |
0.378 |
0.179 |
0.035 |
Wald ratio |
1 |
cis |
NA |
| Neo-extraversion |
0.977 |
0.471 |
0.038 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
-0.202 |
0.0989 |
0.0415 |
Wald ratio |
1 |
cis |
NA |
| …and 87 more outcomes (see JSON) |
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|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3060_43_2 |
C9 |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
56 association rows across 35 traits (49 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 |
| C9 protein levels |
5e-52 |
rs34000044 |
7 |
GCST90468505 |
no MR -> candidate analysis |
| OSMR protein levels |
2e-51 |
rs72738461 |
4 |
GCST90470132 |
no MR -> candidate analysis |
| CREB-binding protein levels (CREBBP.13614.6.3) |
3e-38 |
rs62358361 |
1 |
GCST90240801 |
no MR -> candidate analysis |
| CREB-binding protein levels |
2e-31 |
rs835219 |
1 |
GCST90247152 |
no MR -> candidate analysis |
| ADP-ribosylation factor-like protein 5B levels |
2e-31 |
rs835219 |
1 |
GCST90246577 |
no MR -> candidate analysis |
| 39S ribosomal protein L34, mitochondrial level in Chronic ki |
4e-29 |
rs80127731 |
1 |
GCST90238409 |
no MR -> candidate analysis |
| Complement component C9 levels (C9.3060.43.2) |
9e-27 |
rs62358364 |
1 |
GCST90240776 |
no MR -> candidate analysis |
| Complement component C9 (analyte X13722.105) levels |
4e-26 |
rs62358364 |
1 |
GCST90422323 |
no MR -> candidate analysis |
| Core binding factor acute myeloid leukemia |
4e-26 |
rs155377; rs3776534; rs11953280; rs187875; rs2542705; rs13354342; rs10064820; rs696758; rs13165067 |
2 |
GCST008413 |
no MR -> candidate analysis |
| Complement component C9 levels |
1e-25 |
rs696766 |
3 |
GCST90246795 |
no MR -> candidate analysis |
| Macular degeneration, dry (PheCode 362.21) |
2e-25 |
rs34882957 |
2 |
GCST90475851 |
no MR -> candidate analysis |
| Creatinine levels |
5e-24 |
rs4957473 |
1 |
GCST90019502 |
no MR -> candidate analysis |
| …and 23 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 450 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 |
0.826 |
— |
established (curated) |
no MR -> candidate analysis |
| age-related macular degeneration |
0.703 |
— |
established (curated) |
no MR -> candidate analysis |
| macular degeneration |
0.875 |
— |
common-variant locus |
no MR -> candidate analysis |
| immunodeficiency due to a late component of complement deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| wet macular degeneration |
0.582 |
— |
common-variant locus |
no MR -> candidate analysis |
| degeneration of macula and posterior pole |
0.582 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrophic macular degeneration |
0.582 |
— |
common-variant locus |
no MR -> candidate analysis |
| placental abruption |
0.49 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic kidney disease |
0.464 |
— |
common-variant locus |
no MR -> candidate analysis |
| circadian rhythm sleep disorder |
0.407 |
— |
common-variant locus |
no MR -> candidate analysis |
| gout |
0.392 |
— |
common-variant locus |
MR: beta=-0.161, p=0.395 (cis) |
| hereditary disease |
0.317 |
— |
established (curated) |
no MR -> candidate analysis |
| liver disorder |
0.097 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.098 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.095 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 14 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=4.2e-21, LOEUF=1.19 — LoF-tolerant |
| GWAS Catalog |
104 unique SNPs / 226 rows |
| ClinVar |
459 records; 4 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 450 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 459 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 35 traits by best p-value, aggregated from 56 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/P02748 — 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/ENSG00000113600/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/C9 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/C9 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=C9%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/C9 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:23:54 · 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