Protein Dossier — CTSS (Cathepsin 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 |
| Forced vital capacity (FVC) |
0.0174 |
0.00411 |
2.29e-05 |
Wald ratio |
1 |
cis |
NA |
| Schizophrenia |
0.105 |
0.025 |
2.67e-05 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.0813 |
0.0205 |
7.29e-05 |
Wald ratio |
1 |
cis |
NA |
| Sleep duration |
0.0149 |
0.00391 |
1.41e-04 |
Wald ratio |
1 |
cis |
NA |
| Heel bone mineral density (BMD) T-score automated |
0.0241 |
0.00648 |
2.05e-04 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate |
-0.312 |
0.0846 |
2.24e-04 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
0.0142 |
0.00433 |
0.001 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level |
0.282 |
0.0955 |
0.00321 |
Wald ratio |
1 |
cis |
NA |
| Weight |
0.0125 |
0.00442 |
0.00458 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: prostate cancer |
-0.204 |
0.0723 |
0.0047 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: chronic obstructive airways disease or copd |
0.191 |
0.0712 |
0.00735 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: basal cell carcinoma |
-0.147 |
0.0607 |
0.0156 |
Wald ratio |
1 |
cis |
NA |
| …and 62 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3181_50_2 |
Cathepsin S |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
100 association rows across 82 traits (92 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 CTSS levels |
8e-582 |
rs41271951 |
1 |
GCST90859723 |
no MR -> candidate analysis |
| Cathepsin S levels |
4e-204 |
rs41271951 |
6 |
GCST90246854 |
no MR -> candidate analysis |
| ADAMTSL4 protein levels |
1e-179 |
rs758689051 |
1 |
GCST90468229 |
no MR -> candidate analysis |
| Serum levels of protein CTSS |
7e-120 |
rs41271951 |
1 |
GCST90088251 |
no MR -> candidate analysis |
| Cathepsin S levels (CTSS.3181.50.2) |
7e-94 |
rs41271951 |
1 |
GCST90240628 |
no MR -> candidate analysis |
| ACVRL1/SCARB2 protein level ratio |
3e-42 |
rs41271951 |
1 |
GCST90313157 |
no MR -> candidate analysis |
| Squamous cell carcinoma (MTAG) |
8e-36 |
rs7534124 |
1 |
GCST90137412 |
no MR -> candidate analysis |
| Height (baseline) |
4e-31 |
rs56404059 |
1 |
GCST90565843 |
no MR -> candidate analysis |
| Circulating TNFSF12 levels (id: OID00555_OID20624) |
1e-26 |
rs140691474 |
1 |
GCST90859905 |
no MR -> candidate analysis |
| MSR1 protein levels |
1e-26 |
rs41271951 |
1 |
GCST90469950 |
no MR -> candidate analysis |
| Phosphoglycerides levels |
5e-25 |
rs61386199 |
1 |
GCST90501228 |
no MR -> candidate analysis |
| Neutrophil-to-lymphocyte ratio |
2e-24 |
rs769400009 |
3 |
GCST90866310 |
no MR -> candidate analysis |
| …and 70 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 821 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 |
| basal cell carcinoma |
0.843 |
— |
common-variant locus |
MR: beta=-0.147, p=0.0156 (cis) |
| squamous cell carcinoma |
0.743 |
— |
common-variant locus |
no MR -> candidate analysis |
| skin cancer |
0.697 |
— |
common-variant locus |
no MR -> candidate analysis |
| cutaneous melanoma |
0.681 |
— |
common-variant locus |
no MR -> candidate analysis |
| skin neoplasm |
0.598 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrial fibrillation |
0.534 |
— |
common-variant locus |
no MR -> candidate analysis |
| nasal cavity polyp |
0.522 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery disorder |
0.476 |
— |
common-variant locus |
no MR -> candidate analysis |
| melanoma |
0.481 |
— |
common-variant locus |
no MR -> candidate analysis |
| actinic keratosis |
0.446 |
— |
common-variant locus |
no MR -> candidate analysis |
| atopic eczema |
0.384 |
— |
common-variant locus |
no MR -> candidate analysis |
| upper respiratory tract disorder |
0.331 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrial flutter |
0.328 |
— |
common-variant locus |
no MR -> candidate analysis |
| cancer |
0.272 |
— |
common-variant locus |
MR: beta=0.0813, p=7.29e-05 (cis) |
| non-melanoma skin carcinoma |
0.308 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 13 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 |
1 known modulators (Cathepsin S) |
| gnomAD constraint |
pLI=0.7, LOEUF=0.579 — LoF-tolerant |
| GWAS Catalog |
104 unique SNPs / 226 rows |
| ClinVar |
45 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 821 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 ‘CTSS’ and resolved to ‘Cathepsin S’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 45 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 82 traits by best p-value, aggregated from 100 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/P25774 — 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/ENSG00000163131/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2954/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CTSS — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CTSS — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CTSS%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CTSS — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:12:14 · 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