Protein Dossier — CTSH (Pro-cathepsin H)
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 |
| Hearing difficulty or problems: Yes |
0.017 |
0.00584 |
0.00351 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: enlarged prostate |
0.0738 |
0.0273 |
0.00693 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K29 Gastritis and duodenitis |
0.0534 |
0.0211 |
0.0114 |
Wald ratio |
1 |
cis |
NA |
| Forced expiratory volume in 1-second (FEV1) |
-0.0074 |
0.00298 |
0.0129 |
Wald ratio |
1 |
cis |
NA |
| Forced vital capacity (FVC) |
-0.00678 |
0.00282 |
0.0162 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: asthma |
-0.0214 |
0.00985 |
0.0301 |
Wald ratio |
1 |
cis |
NA |
| Cancer code self-reported: malignant melanoma |
-0.0903 |
0.0428 |
0.0349 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K20 Oesophagitis |
-0.0787 |
0.0376 |
0.0365 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M72 Fibroblastic disorders |
0.088 |
0.0429 |
0.0403 |
Wald ratio |
1 |
cis |
NA |
| Clear cell ovarian cancer |
0.118 |
0.0597 |
0.0474 |
Wald ratio |
1 |
cis |
NA |
| Alzheimer’s disease |
0.0535 |
0.0272 |
0.0491 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: C61 Malignant neoplasm of prostate |
-0.0905 |
0.0463 |
0.0508 |
Wald ratio |
1 |
cis |
NA |
| …and 72 more outcomes (see JSON) |
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2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3737_6_3 |
Cathepsin H |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
99 association rows across 68 traits (86 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 CTSH levels |
1e-3816 |
rs7177831 |
3 |
GCST90860379 |
no MR -> candidate analysis |
| Cathepsin H levels |
3e-1084 |
rs2289702 |
8 |
GCST90246850 |
no MR -> candidate analysis |
| Cathepsin H (analyte X8465.52) levels |
1e-353 |
rs2289702 |
1 |
GCST90427402 |
no MR -> candidate analysis |
| Cathepsin H (analyte X8644.46) levels |
2e-264 |
rs2289702 |
1 |
GCST90427433 |
no MR -> candidate analysis |
| Cathepsin H levels (CTSH.8465.52.3) |
3e-241 |
rs34593439 |
3 |
GCST90240624 |
no MR -> candidate analysis |
| Blood protein levels |
4e-212 |
rs7177831 |
2 |
GCST006585 |
no MR -> candidate analysis |
| Pro-cathepsin H levels |
4e-208 |
rs62013200 |
2 |
GCST90179275 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein CTSH levels |
7e-184 |
rs2289702 |
1 |
GCST90943245 |
no MR -> candidate analysis |
| Serum levels of protein CTSH |
4e-81 |
rs75508148 |
3 |
GCST90090247 |
no MR -> candidate analysis |
| A0A087X0D5 protein level (protein group normalized intensity |
2e-73 |
rs2289702 |
1 |
GCST90570733 |
no MR -> candidate analysis |
| CTSH protein levels |
5e-65 |
rs543745721 |
4 |
GCST90468913 |
no MR -> candidate analysis |
| PSAP protein levels |
2e-32 |
rs2289702 |
1 |
GCST90470351 |
no MR -> candidate analysis |
| …and 56 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 842 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 |
| type 1 diabetes mellitus |
0.868 |
— |
common-variant locus |
no MR -> candidate analysis |
| skin cancer |
0.798 |
— |
common-variant locus |
no MR -> candidate analysis |
| basal cell carcinoma |
0.79 |
— |
common-variant locus |
MR: beta=-0.0599, p=0.117 (cis) |
| narcolepsy-cataplexy syndrome |
0.722 |
— |
common-variant locus |
no MR -> candidate analysis |
| multiple sclerosis |
0.473 |
— |
common-variant locus |
MR: beta=-0.03, p=0.2 (cis) |
| type 2 diabetes mellitus |
0.58 |
— |
common-variant locus |
no MR -> candidate analysis |
| autoimmune disease |
0.581 |
— |
common-variant locus |
no MR -> candidate analysis |
| Sensorineural hearing impairment |
0.58 |
— |
common-variant locus |
no MR -> candidate analysis |
| hearing loss disorder |
0.578 |
— |
common-variant locus |
no MR -> candidate analysis |
| cardiovascular disorder |
0.452 |
— |
common-variant locus |
no MR -> candidate analysis |
| angina pectoris |
0.447 |
— |
common-variant locus |
no MR -> candidate analysis |
| myocardial ischemia |
0.442 |
— |
common-variant locus |
no MR -> candidate analysis |
| myocardial infarction |
0.416 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary artery bypass |
0.413 |
— |
common-variant locus |
no MR -> candidate analysis |
| coronary atherosclerosis |
0.412 |
— |
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 |
0 known modulators (Pro-cathepsin H) |
| gnomAD constraint |
pLI=7.2e-17, LOEUF=1.16 — LoF-tolerant |
| GWAS Catalog |
120 unique SNPs / 307 rows |
| ClinVar |
99 records; 2 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 842 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 ‘CTSH’ and resolved to ‘Pro-cathepsin H’ — 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 68 traits by best p-value, aggregated from 99 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/P09668 — 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/ENSG00000103811/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2225/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CTSH — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CTSH — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CTSH%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CTSH — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:11:55 · 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