Protein Dossier — CST1 (Cystatin-SN)
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 |
-0.078 |
0.019 |
3.92e-05 |
Wald ratio |
1 |
cis |
NA |
| Transferrin Saturation |
-0.0663 |
0.0191 |
5.34e-04 |
Wald ratio |
1 |
cis |
NA |
| Pallidum volume |
10.6 |
3.57 |
0.00295 |
Wald ratio |
1 |
cis |
NA |
| Serum cystatin C (eGFRcys) |
-0.0103 |
0.00355 |
0.00373 |
Wald ratio |
1 |
cis |
NA |
| Pulse rate |
-0.0228 |
0.00822 |
0.00552 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
-0.0123 |
0.00477 |
0.0101 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
-0.184 |
0.0739 |
0.0127 |
Wald ratio |
1 |
cis |
NA |
| Ischemic stroke |
0.0738 |
0.031 |
0.0174 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
0.0142 |
0.00603 |
0.0183 |
Wald ratio |
1 |
cis |
NA |
| Subjective well being |
0.0124 |
0.00532 |
0.0196 |
Wald ratio |
1 |
cis |
NA |
| ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0333 |
0.0145 |
0.0219 |
Wald ratio |
1 |
cis |
NA |
| Cigarettes smoked per day |
0.335 |
0.158 |
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-5459_33_3 |
CYTN |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
44 association rows across 15 traits (43 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-SN levels |
2e-346 |
rs4260306 |
7 |
GCST90247223 |
no MR -> candidate analysis |
| Cystatin C levels |
2e-307 |
rs13043045 |
5 |
GCST90019504 |
no MR -> candidate analysis |
| Cystatin-SA levels |
4e-265 |
rs4260306 |
5 |
GCST90247222 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein CST1 levels |
7e-244 |
rs4383402 |
1 |
GCST90944226 |
no MR -> candidate analysis |
| Serum levels of protein CST1 |
4e-221 |
rs4260306 |
3 |
GCST90089041 |
no MR -> candidate analysis |
| Serum levels of protein CST2 |
1e-145 |
rs4260306 |
2 |
GCST90088663 |
no MR -> candidate analysis |
| Blood protein levels |
1e-115 |
rs4260306 |
2 |
GCST006585 |
no MR -> candidate analysis |
| CST3/TFF3 protein level ratio |
9e-111 |
rs6114264 |
1 |
GCST90314299 |
no MR -> candidate analysis |
| CST1 protein levels |
2e-82 |
rs117730889 |
8 |
GCST90468893 |
no MR -> candidate analysis |
| Cystatin-D levels |
1e-22 |
rs8115901 |
2 |
GCST90161908 |
no MR -> candidate analysis |
| CST5 protein levels |
7e-22 |
rs147068635 |
3 |
GCST90468895 |
no MR -> candidate analysis |
| Cerebrospinal fluid biomarker levels |
1e-20 |
rs4328700 |
1 |
GCST004000 |
no MR -> candidate analysis |
| …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 150 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 |
0.216 |
— |
common-variant locus |
no MR -> candidate analysis |
| liver disorder |
0.166 |
— |
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=8.4e-10, LOEUF=2.61 — LoF-tolerant |
| GWAS Catalog |
96 unique SNPs / 192 rows |
| ClinVar |
69 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 150 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 ‘CST1’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 69 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 44 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/P01037 — 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/ENSG00000170373/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CST1 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CST1 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST1%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CST1 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:06:21 · 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