Protein Dossier — CST2 (Cystatin-SA)
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 |
| Iron |
-0.0855 |
0.0208 |
3.92e-05 |
Wald ratio |
1 |
cis |
NA |
| Transferrin Saturation |
-0.0726 |
0.021 |
5.34e-04 |
Wald ratio |
1 |
cis |
NA |
| Pallidum volume |
11.6 |
3.92 |
0.00295 |
Wald ratio |
1 |
cis |
NA |
| Serum cystatin C (eGFRcys) |
-0.0113 |
0.00389 |
0.00373 |
Wald ratio |
1 |
cis |
NA |
| Pulse rate |
-0.025 |
0.00901 |
0.00552 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
-0.0134 |
0.00523 |
0.0101 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
-0.204 |
0.0827 |
0.0138 |
Wald ratio |
1 |
cis |
NA |
| Ischemic stroke |
0.0808 |
0.034 |
0.0174 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
0.0156 |
0.00661 |
0.0183 |
Wald ratio |
1 |
cis |
NA |
| Subjective well being |
0.0136 |
0.00583 |
0.0196 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0365 |
0.0159 |
0.0219 |
Wald ratio |
1 |
cis |
NA |
| Cigarettes smoked per day |
0.367 |
0.173 |
0.0344 |
Wald ratio |
1 |
cis |
NA |
| …and 109 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-4324_33_2 |
CYTT |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
56 association rows across 17 traits (50 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 |
| Circulating CST5 levels |
9e-3177 |
rs35275385 |
2 |
GCST90859850 |
no MR -> candidate analysis |
| Cystatin-D levels |
8e-500 |
rs4642010 |
7 |
GCST90247217 |
no MR -> candidate analysis |
| Cystatin C levels |
1e-349 |
rs6106728 |
4 |
GCST90019504 |
no MR -> candidate analysis |
| Cystatin C plasma levels |
9e-306 |
rs6106728 |
1 |
GCST90100559 |
no MR -> candidate analysis |
| CST5 protein levels |
2e-251 |
rs150230325 |
21 |
GCST90468895 |
no MR -> candidate analysis |
| CST1 protein levels |
6e-68 |
rs73093347 |
9 |
GCST90468893 |
no MR -> candidate analysis |
| Cystatin D levels |
5e-34 |
rs57922873 |
1 |
GCST90000456 |
no MR -> candidate analysis |
| Protein quantitative trait loci |
3e-19 |
rs4387871 |
1 |
GCST010900 |
no MR -> candidate analysis |
| Cystatin-SN levels |
2e-15 |
rs7270053 |
2 |
GCST90162410 |
no MR -> candidate analysis |
| Carbonic anhydrase 12 protein levels (SomaScan ID:3803-10) |
9e-10 |
rs6049191 |
1 |
GCST90442950 |
no MR -> candidate analysis |
| Bone mineral density mean |
2e-8 |
rs150080077 |
1 |
GCST90321120 |
no MR -> candidate analysis |
| Gut microbiome abundance (class Bacteroides sp. 8 (at 1 year |
5e-7 |
rs72490828 |
1 |
GCST90568892 |
no MR -> candidate analysis |
| …and 5 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 97 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 |
0.067 |
— |
common-variant locus |
no MR -> candidate analysis |
| liver disorder |
0.055 |
— |
common-variant locus |
no MR -> candidate analysis |
| ovarian dysfunction |
0.055 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 3 rows above, 3 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=1.2e-13, LOEUF=2.7 — LoF-tolerant |
| GWAS Catalog |
101 unique SNPs / 218 rows |
| ClinVar |
77 records; 0 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 97 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 ‘CST2’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 77 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 17 of 17 traits by best p-value, aggregated from 56 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/P09228 — 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/ENSG00000170369/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CST2 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CST2 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST2%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CST2 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:06:35 · 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