Protein Dossier — CST4 (Cystatin-S)
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 |
| Serum cystatin C (eGFRcys) |
0.071 |
0.00645 |
3.82e-28 |
Wald ratio |
1 |
cis |
NA |
| Myocardial infarction |
-0.106 |
0.0376 |
0.00462 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: psoriasis |
0.169 |
0.0648 |
0.00927 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Glaucoma |
0.15 |
0.0587 |
0.0105 |
Wald ratio |
1 |
cis |
NA |
| Coronary heart disease |
-0.087 |
0.034 |
0.0105 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: vitiligo |
0.686 |
0.269 |
0.0108 |
Wald ratio |
1 |
cis |
NA |
| Age at menopause |
0.215 |
0.086 |
0.0124 |
Wald ratio |
1 |
cis |
NA |
| Urate |
-0.0452 |
0.0187 |
0.0158 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
-0.0292 |
0.0125 |
0.019 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: depression |
0.0612 |
0.0315 |
0.0519 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: I30 Acute pericarditis |
0.558 |
0.293 |
0.0563 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux |
0.0693 |
0.0365 |
0.0576 |
Wald ratio |
1 |
cis |
NA |
| …and 81 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3802_50_1 |
Cystatin-S |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
42 association rows across 22 traits (36 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 C levels |
8e-3580 |
rs13039144 |
4 |
GCST90019504 |
no MR -> candidate analysis |
| Circulating CST3 levels |
9e-462 |
rs35488434 |
3 |
GCST90860429 |
no MR -> candidate analysis |
| Cystatin C plasma levels |
1e-308 |
rs66590796 |
1 |
GCST90100559 |
no MR -> candidate analysis |
| Cystatin-S levels |
4e-130 |
rs7263473 |
3 |
GCST90247221 |
no MR -> candidate analysis |
| Cystatin-SA levels |
6e-113 |
rs6036489 |
4 |
GCST90247222 |
no MR -> candidate analysis |
| Cystatin-SN levels |
7e-76 |
rs6049008 |
4 |
GCST90247223 |
no MR -> candidate analysis |
| Serum levels of protein CST4 |
9e-62 |
rs7263473 |
1 |
GCST90087762 |
no MR -> candidate analysis |
| CST3 protein levels |
7e-54 |
rs28463225 |
2 |
GCST90468894 |
no MR -> candidate analysis |
| Serum levels of protein CST3 |
1e-51 |
rs2254635 |
1 |
GCST90087977 |
no MR -> candidate analysis |
| CST1 protein levels |
5e-44 |
rs3004155 |
4 |
GCST90468893 |
no MR -> candidate analysis |
| Cystatin-C levels |
3e-42 |
rs16985615 |
4 |
GCST90247216 |
no MR -> candidate analysis |
| Blood protein levels |
2e-31 |
rs7270028 |
1 |
GCST006585 |
no MR -> candidate analysis |
| …and 10 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 371 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 |
| alcohol drinking |
0.423 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic laryngitis |
0.244 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 2 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 |
not available — no ChEMBL target (undrugged) |
| gnomAD constraint |
pLI=2.6e-08, LOEUF=2.27 — LoF-tolerant |
| GWAS Catalog |
101 unique SNPs / 222 rows |
| ClinVar |
62 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 371 associated diseases by overall score. genetic_association aggregates GWAS common-variant AND rare-variant evidence. These are ASSOCIATIONS (loci), not causal claims.chembl — No ChEMBL target for ‘CST4’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 62 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 22 traits by best p-value, aggregated from 42 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/P01036 — 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/ENSG00000101441/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CST4 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CST4 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST4%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CST4 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:07:41 · 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