Protein Dossier — COL18A1 (Collagen alpha-1(XVIII) chain)
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: M72 Fibroblastic disorders |
0.424 |
0.14 |
0.00246 |
Wald ratio |
1 |
cis |
NA |
| Eczema |
0.271 |
0.109 |
0.0131 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
0.0374 |
0.0157 |
0.0175 |
Wald ratio |
1 |
cis |
NA |
| Depressive symptoms |
-0.0663 |
0.0301 |
0.0278 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N40 Hyperplasia of prostate |
0.265 |
0.125 |
0.0344 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I83 Varicose veins of lower extremities |
0.18 |
0.0906 |
0.0472 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Diabetes related eye disease |
0.297 |
0.151 |
0.0487 |
Wald ratio |
1 |
cis |
NA |
| Sleep duration |
0.0232 |
0.012 |
0.0536 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gout |
0.201 |
0.107 |
0.0597 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
-0.28 |
0.151 |
0.063 |
Wald ratio |
1 |
cis |
NA |
| Happiness |
0.0354 |
0.019 |
0.0634 |
Wald ratio |
1 |
cis |
NA |
| Fractured bone site(s): Other bones |
-0.144 |
0.0778 |
0.0645 |
Wald ratio |
1 |
cis |
NA |
| …and 44 more outcomes (see JSON) |
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|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2201_17_6 |
Endostatin |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
131 association rows across 70 traits (120 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 |
| Epididymal secretory protein E1 levels (NPC2.6259.60.3) |
2e-364 |
rs12483377 |
1 |
GCST90241092 |
no MR -> candidate analysis |
| COL4A1 protein levels |
8e-303 |
rs12483377 |
5 |
GCST90468818 |
no MR -> candidate analysis |
| Circulating COL4A1 levels |
3e-299 |
rs12483377 |
7 |
GCST90860524 |
no MR -> candidate analysis |
| Endostatin levels |
2e-187 |
rs144147445 |
8 |
GCST90247456 |
no MR -> candidate analysis |
| Circulating COL18A1 levels |
9e-142 |
rs79633299 |
9 |
GCST90860468 |
no MR -> candidate analysis |
| COL18A1 protein levels |
2e-129 |
rs201662370 |
10 |
GCST90468812 |
no MR -> candidate analysis |
| triglyceride (mean, inv-norm transformed) |
6e-55 |
rs114139997 |
2 |
GCST90476434 |
no MR -> candidate analysis |
| Circulating C1QTNF1 levels |
2e-50 |
rs2838952 |
1 |
GCST90860498 |
no MR -> candidate analysis |
| Triglyceride levels |
5e-49 |
rs114139997 |
5 |
GCST90239662 |
no MR -> candidate analysis |
| triglyceride (maximum, inv-norm transformed) |
7e-48 |
rs186170773 |
2 |
GCST90476430 |
no MR -> candidate analysis |
| C1QTNF1 protein levels |
1e-47 |
rs2838952 |
1 |
GCST90468488 |
no MR -> candidate analysis |
| triglyceride (minimum, inv-norm transformed) |
1e-46 |
rs114139997 |
2 |
GCST90476438 |
no MR -> candidate analysis |
| …and 58 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 2913 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 |
| Knobloch syndrome 1 |
0.856 |
— |
established (curated) |
no MR -> candidate analysis |
| Knobloch syndrome |
0.863 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary glaucoma, primary closed-angle |
0.749 |
— |
established (curated) |
no MR -> candidate analysis |
| severe early-childhood-onset retinal dystrophy |
0.801 |
— |
established (curated) |
no MR -> candidate analysis |
| Retinal dystrophy |
0.793 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.684 |
— |
established (curated) |
no MR -> candidate analysis |
| cataract |
0.504 |
— |
established (curated) |
no MR -> candidate analysis |
| retinitis pigmentosa |
0.532 |
— |
established (curated) |
no MR -> candidate analysis |
| Cowden syndrome 1 |
0.559 |
— |
established (curated) |
no MR -> candidate analysis |
| myopia |
0.532 |
— |
established (curated) |
no MR -> candidate analysis |
| Nystagmus |
0.532 |
— |
established (curated) |
no MR -> candidate analysis |
| pathological myopia |
0.532 |
— |
established (curated) |
no MR -> candidate analysis |
| familial lipoprotein lipase deficiency |
0.48 |
— |
common-variant locus |
no MR -> candidate analysis |
| neurodegenerative disease |
0.426 |
— |
established (curated) |
no MR -> candidate analysis |
| Macular dystrophy |
0.426 |
— |
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 |
2 known modulators (Collagen) |
| gnomAD constraint |
pLI=1.8e-35, LOEUF=0.914 — LoF-tolerant |
| GWAS Catalog |
100 unique SNPs / 200 rows |
| ClinVar |
3414 records; 6 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 2913 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 ‘COL18A1’ and resolved to ‘Collagen’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 3414 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 70 traits by best p-value, aggregated from 131 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/P39060 — 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/ENSG00000182871/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2364188/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/COL18A1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/COL18A1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=COL18A1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/COL18A1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T01:57:21 · 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