Protein Dossier — CST5 (Cystatin-D)
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) |
0.0209 |
0.00348 |
1.97e-09 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: mania or bipolar disorder or manic depression |
0.192 |
0.0707 |
0.00664 |
Wald ratio |
1 |
cis |
NA |
| Paget’s disease |
-0.289 |
0.117 |
0.0132 |
Wald ratio |
1 |
cis |
NA |
| HDL cholesterol |
0.0213 |
0.00892 |
0.0168 |
Wald ratio |
1 |
cis |
NA |
| Mean cell volume |
-0.105 |
0.0463 |
0.0235 |
Wald ratio |
1 |
cis |
NA |
| Depressive symptoms |
-0.0125 |
0.00557 |
0.0244 |
Wald ratio |
1 |
cis |
NA |
| Neuroticism |
-0.0153 |
0.00697 |
0.0278 |
Wald ratio |
1 |
cis |
NA |
| Body fat |
0.0203 |
0.00975 |
0.037 |
Wald ratio |
1 |
cis |
NA |
| Transferrin |
-0.0379 |
0.0188 |
0.0439 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages |
0.108 |
0.0544 |
0.0464 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: uterine fibroids |
0.0611 |
0.0331 |
0.0649 |
Wald ratio |
1 |
cis |
NA |
| Anorexia nervosa |
-0.0903 |
0.0498 |
0.0699 |
Wald ratio |
1 |
cis |
NA |
| …and 84 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3803_10_2 |
CYTD |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
57 association rows across 19 traits (51 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 |
2e-3604 |
rs4239743 |
3 |
GCST90859850 |
no MR -> candidate analysis |
| Cystatin D levels |
2e-541 |
rs4815244 |
2 |
GCST90274777 |
no MR -> candidate analysis |
| Cystatin-D levels |
8e-500 |
rs4642010 |
9 |
GCST90247217 |
no MR -> candidate analysis |
| CST5 protein levels |
2e-251 |
rs150230325 |
23 |
GCST90468895 |
no MR -> candidate analysis |
| Blood protein levels |
7e-186 |
rs2071444 |
1 |
GCST006585 |
no MR -> candidate analysis |
| Cystatin C levels |
4e-115 |
rs8184710 |
3 |
GCST90019504 |
no MR -> candidate analysis |
| CST1 protein levels |
6e-68 |
rs73093347 |
4 |
GCST90468893 |
no MR -> candidate analysis |
| Protein quantitative trait loci |
3e-19 |
rs4387871 |
1 |
GCST010900 |
no MR -> candidate analysis |
| Serum levels of protein CST5 |
8e-14 |
rs4815243 |
1 |
GCST90088518 |
no MR -> candidate analysis |
| Cystatin-SN levels |
2e-13 |
rs6036565 |
1 |
GCST90162410 |
no MR -> candidate analysis |
| Cystatin-SA levels |
9e-13 |
rs4813509 |
1 |
GCST90162049 |
no MR -> candidate analysis |
| Carbonic anhydrase 12 protein levels (SomaScan ID:3803-10) |
9e-10 |
rs6049191 |
1 |
GCST90442950 |
no MR -> candidate analysis |
| …and 7 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 585 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 |
0.576 |
— |
common-variant locus |
no MR -> candidate analysis |
| urolithiasis |
0.429 |
— |
common-variant locus |
no MR -> candidate analysis |
| response to antihypertensive drug |
0.429 |
— |
common-variant locus |
no MR -> candidate analysis |
| stroke disorder |
0.355 |
— |
common-variant locus |
no MR -> candidate analysis |
| arthropathy |
0.285 |
— |
common-variant locus |
no MR -> candidate analysis |
| movement disorder |
0.244 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 6 rows above, 6 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=1.1e-05, LOEUF=1.79 — LoF-tolerant |
| GWAS Catalog |
88 unique SNPs / 175 rows |
| ClinVar |
54 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
1 clinical annotations across 1 drugs |
phenome — Top 30 of 585 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 ‘CST5’.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 54 ClinVar records for this gene; it is a sample, not a rate.gwas_traits — Top 19 of 19 traits by best p-value, aggregated from 57 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/P28325 — 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/ENSG00000170367/associations — Open Targets data release 26.06gnomad: https://gnomad.broadinstitute.org/gene/CST5 — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CST5 — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CST5%5Bgene%5D — ClinVar build Build260809-1055.1pharmgkb: https://www.pharmgkb.org/search?query=CST5 — ClinPGx clinicalAnnotation via https://api.clinpgx.org/v1/datagwas_traits: https://www.ebi.ac.uk/gwas/genes/CST5 — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:07:53 · 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