Protein Dossier — C1S (Complement C1s subcomponent)
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 |
| Systolic blood pressure automated reading |
-0.0161 |
0.00478 |
7.33e-04 |
Wald ratio |
1 |
trans |
NA |
| Forearm bone mineral density |
-0.102 |
0.0306 |
8.48e-04 |
Wald ratio |
1 |
trans |
NA |
| Forced vital capacity (FVC) |
0.0114 |
0.00383 |
0.00298 |
Wald ratio |
1 |
trans |
NA |
| Mean cell haemoglobin concentration |
-0.0157 |
0.00661 |
0.0177 |
Wald ratio |
1 |
trans |
NA |
| Diastolic blood pressure automated reading |
-0.0105 |
0.00478 |
0.0283 |
Wald ratio |
1 |
trans |
NA |
| Clear cell ovarian cancer |
-0.17 |
0.0777 |
0.0286 |
Wald ratio |
1 |
trans |
NA |
| Eye problems or disorders: Glaucoma |
0.0773 |
0.0361 |
0.032 |
Wald ratio |
1 |
trans |
NA |
| Bulimia nervosa |
-0.0283 |
0.0132 |
0.0321 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
0.104 |
0.0502 |
0.0385 |
Wald ratio |
1 |
trans |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
-0.0403 |
0.02 |
0.0438 |
Wald ratio |
1 |
trans |
NA |
| Diagnoses - main ICD10: C50 Malignant neoplasm of breast |
-0.0755 |
0.0394 |
0.0553 |
Wald ratio |
1 |
trans |
NA |
| Sodium in urine |
-0.00874 |
0.00459 |
0.0568 |
Wald ratio |
1 |
trans |
NA |
| …and 94 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3590_8_3 |
C1s |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
145 association rows across 100 traits (141 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 C1s subcomponent levels |
3e-901 |
rs12146727 |
2 |
GCST90246772 |
no MR -> candidate analysis |
| Tyrosine-protein phosphatase non-receptor type 4 levels |
5e-282 |
rs12146727 |
2 |
GCST90250026 |
no MR -> candidate analysis |
| Serum levels of protein CASQ1 |
4e-250 |
rs12146727 |
1 |
GCST90086646 |
no MR -> candidate analysis |
| Segment polarity protein dishevelled homolog DVL-2 levels |
5e-221 |
rs12146727 |
1 |
GCST90247375 |
no MR -> candidate analysis |
| Serum levels of protein PTPN4 |
3e-146 |
rs12371227 |
1 |
GCST90087848 |
no MR -> candidate analysis |
| Blood protein levels |
2e-144 |
rs16933084 |
8 |
GCST006585 |
no MR -> candidate analysis |
| Serum levels of protein PKN1 |
1e-132 |
rs12146727 |
1 |
GCST90087070 |
no MR -> candidate analysis |
| Calsequestrin-1 levels |
1e-106 |
rs12146727 |
2 |
GCST90246821 |
no MR -> candidate analysis |
| Complement C1r subcomponent levels |
6e-106 |
rs12146727 |
4 |
GCST90246770 |
no MR -> candidate analysis |
| Amyloid beta A4 precursor protein-binding family B member 2 |
7e-101 |
rs12146727 |
1 |
GCST90246533 |
no MR -> candidate analysis |
| Complement C1q subcomponent levels |
3e-100 |
rs12368783 |
4 |
GCST90246760 |
no MR -> candidate analysis |
| SERPING1 protein levels |
2e-93 |
rs12371227 |
1 |
GCST90470600 |
no MR -> candidate analysis |
| …and 88 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 412 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 |
| Ehlers-Danlos syndrome, periodontal type 2 |
0.815 |
— |
established (curated) |
no MR -> candidate analysis |
| complement component C1s deficiency |
0.824 |
— |
established (curated) |
no MR -> candidate analysis |
| Ehlers-Danlos syndrome, periodontitis type |
0.681 |
— |
established (curated) |
no MR -> candidate analysis |
| coronary artery disorder |
0.809 |
— |
common-variant locus |
no MR -> candidate analysis |
| immunodeficiency due to a classical component pathway complement deficiency |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.317 |
— |
established (curated) |
no MR -> candidate analysis |
| placental retention |
0.123 |
— |
common-variant locus |
no MR -> candidate analysis |
| placenta praevia |
0.07 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 8 rows above, 8 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 |
2 known modulators (Complement C1s subcomponent) |
| gnomAD constraint |
pLI=7.9e-06, LOEUF=0.775 — LoF-tolerant |
| GWAS Catalog |
120 unique SNPs / 247 rows |
| ClinVar |
772 records; 5 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 412 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 ‘C1S’ and resolved to ‘Complement C1s subcomponent’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 772 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 100 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/P09871 — 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/ENSG00000182326/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL3913/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/C1S — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/C1S — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=C1S%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/C1S — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:21:56 · 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