Protein Dossier — CST3 (Cystatin-C)
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) |
-0.178 |
0.00585 |
1.90e-203 |
Wald ratio |
1 |
cis |
NA |
| Eye problems or disorders: Diabetes related eye disease |
0.292 |
0.0709 |
3.91e-05 |
Wald ratio |
1 |
cis |
NA |
| Birth weight |
0.03 |
0.0109 |
0.00607 |
Wald ratio |
1 |
cis |
NA |
| Alcohol intake frequency |
-0.0299 |
0.0109 |
0.00607 |
Wald ratio |
1 |
cis |
NA |
| Autism |
-0.245 |
0.0903 |
0.00668 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
0.0249 |
0.00956 |
0.00929 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: osteoporosis |
-0.182 |
0.0714 |
0.011 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: polio or poliomyelitis |
0.466 |
0.184 |
0.0115 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: kidney stone or ureter stone or bladder stone |
0.174 |
0.0704 |
0.0133 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R11 Nausea and vomiting |
0.227 |
0.0946 |
0.0165 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: deep venous thrombosis (dvt) |
0.112 |
0.0469 |
0.0171 |
Wald ratio |
1 |
cis |
NA |
| PGC cross-disorder traits |
-0.0849 |
0.0382 |
0.0262 |
Wald ratio |
1 |
cis |
NA |
| …and 98 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-2609_59_2 |
Cystatin C |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
69 association rows across 43 traits (63 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 in bottom 99% of individuals by creatinine |
2e-4504 |
rs13041070 |
1 |
GCST90566734 |
no MR -> candidate analysis |
| Cystatin C levels |
8e-3580 |
rs13039144 |
12 |
GCST90019504 |
no MR -> candidate analysis |
| Estimated glomerular filtration rate based on creatinine and |
1e-1876 |
rs911119 |
1 |
GCST90566737 |
no MR -> candidate analysis |
| CST3/IGFBP6 protein level ratio |
1e-662 |
rs59059917 |
1 |
GCST90314293 |
no MR -> candidate analysis |
| CST3/RELT protein level ratio |
7e-618 |
rs59059917 |
1 |
GCST90314296 |
no MR -> candidate analysis |
| COL6A3/CST3 protein level ratio |
7e-494 |
rs59059917 |
1 |
GCST90314174 |
no MR -> candidate analysis |
| Transmembrane emp24 domain-containing protein 10 levels |
4e-483 |
rs8115423 |
2 |
GCST90249921 |
no MR -> candidate analysis |
| Circulating CST3 levels |
9e-462 |
rs35488434 |
3 |
GCST90860429 |
no MR -> candidate analysis |
| CST3/TIMP1 protein level ratio |
1e-403 |
rs59059917 |
1 |
GCST90314300 |
no MR -> candidate analysis |
| CST3/EFEMP1 protein level ratio |
7e-403 |
rs59059917 |
1 |
GCST90314292 |
no MR -> candidate analysis |
| CST3/IL18BP protein level ratio |
1e-396 |
rs59059917 |
1 |
GCST90314294 |
no MR -> candidate analysis |
| Estimated glomerular filtration rate (creatinine, cystatin c |
5e-324 |
rs6048936 |
1 |
GCST90428446 |
no MR -> candidate analysis |
| …and 31 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 1466 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 |
| ACys amyloidosis |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| Hereditary cerebral hemorrhage with amyloidosis |
0.706 |
— |
established (curated) |
no MR -> candidate analysis |
| Hereditary cerebral hemorrhage with amyloidosis, Icelandic type |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| age-related macular degeneration |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| age related macular degeneration 11 |
0.489 |
— |
established (curated) |
no MR -> candidate analysis |
| leukodystrophy, adult-onset, autosomal dominant, without amyloid angiopathy |
0.745 |
— |
established (curated) |
no MR -> candidate analysis |
| aging |
0.705 |
— |
common-variant locus |
no MR -> candidate analysis |
| chronic kidney disease |
0.58 |
— |
common-variant locus |
MR: beta=0.0458, p=0.317 (cis) |
| acute coronary syndrome |
0.418 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.427 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 10 rows above, 9 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 (Protein cereblon/Cystatin-C) |
| gnomAD constraint |
not available |
| GWAS Catalog |
90 unique SNPs / 179 rows |
| ClinVar |
99 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1466 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 ‘CST3’ and resolved to ‘Protein cereblon/Cystatin-C’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 99 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 43 traits by best p-value, aggregated from 69 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/P01034 — 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/ENSG00000101439/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4742267/ — ChEMBL_37 (released 2026-05-01)gwas: https://www.ebi.ac.uk/gwas/genes/CST3 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST3%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CST3 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:07:23 · 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: gnomad