Protein Dossier — CST6 (Cystatin-M)
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 |
| Alcohol intake frequency |
0.0572 |
0.019 |
0.00255 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
0.0609 |
0.0206 |
0.0031 |
Wald ratio |
1 |
cis |
NA |
| Forearm bone mineral density |
-0.226 |
0.0809 |
0.00513 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0915 |
0.0355 |
0.01 |
Wald ratio |
1 |
cis |
NA |
| Pallidum volume |
-23.7 |
10.5 |
0.0238 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: H25 Senile cataract |
0.256 |
0.115 |
0.0264 |
Wald ratio |
1 |
cis |
NA |
| Hip osteoarthritis |
0.32 |
0.144 |
0.027 |
Wald ratio |
1 |
cis |
NA |
| Knee and hip osteoarthritis |
0.249 |
0.113 |
0.0284 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K40 Inguinal hernia |
-0.215 |
0.0984 |
0.0288 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0894 |
0.0427 |
0.0366 |
Wald ratio |
1 |
cis |
NA |
| Primary sclerosing cholangitis |
-0.343 |
0.168 |
0.0408 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
0.238 |
0.123 |
0.0522 |
Wald ratio |
1 |
cis |
NA |
| …and 70 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3303_23_2 |
Cystatin M |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
17 association rows across 15 traits (16 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 |
| Cystatin-M (analyte X3303.23) levels |
4e-281 |
rs1131544 |
1 |
GCST90425683 |
no MR -> candidate analysis |
| Cystatin-M (analyte X14711.27) levels |
1e-275 |
rs1131544 |
1 |
GCST90422581 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein CST6 levels |
1e-250 |
rs1131544 |
1 |
GCST90944731 |
no MR -> candidate analysis |
| CST6 protein levels |
4e-206 |
rs12576095 |
1 |
GCST90468896 |
no MR -> candidate analysis |
| Serum levels of protein CST6 |
1e-17 |
rs72930985 |
1 |
GCST90087915 |
no MR -> candidate analysis |
| Waist circumference adjusted for body mass index |
3e-15 |
rs12785292 |
1 |
GCST90020029 |
no MR -> candidate analysis |
| Height |
2e-14 |
rs684546 |
3 |
GCST008839 |
no MR -> candidate analysis |
| Serum uric acid levels |
2e-11 |
rs76541013 |
1 |
GCST010512 |
no MR -> candidate analysis |
| Multi-trait sex score |
1e-10 |
rs12785292 |
1 |
GCST90270116 |
no MR -> candidate analysis |
| Waist-hip index |
4e-10 |
rs12785292 |
1 |
GCST90020027 |
no MR -> candidate analysis |
| A body shape index |
1e-9 |
rs12785292 |
1 |
GCST90020024 |
no MR -> candidate analysis |
| Alzheimer’s disease |
1e-9 |
rs12785292 |
1 |
GCST90134416 |
MR: beta=0.116, p=0.156 (cis) |
| …and 3 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 1581 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 |
| autosomal recessive hypohidrotic ectodermal dysplasia |
0.555 |
— |
established (curated) |
no MR -> candidate analysis |
| total hip arthroplasty |
0.313 |
— |
common-variant locus |
no MR -> candidate analysis |
| osteoarthritis, hip |
0.313 |
— |
common-variant locus |
MR: beta=0.32, p=0.027 (cis) |
Of the 3 rows above, 2 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 |
0 known modulators (Cystatin-B) |
| gnomAD constraint |
pLI=0.0051, LOEUF=1.34 — LoF-tolerant |
| GWAS Catalog |
79 unique SNPs / 158 rows |
| ClinVar |
44 records; 4 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1581 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 ‘CST6’ and resolved to ‘Cystatin-B’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 44 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 15 of 15 traits by best p-value, aggregated from 17 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/Q15828 — 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/ENSG00000175315/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL6066979/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CST6 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CST6 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST6%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CST6 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:08:17 · 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