Protein Dossier — CTSB (Cathepsin B)
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 |
| Heel bone mineral density (BMD) T-score automated |
-0.0481 |
0.00833 |
7.87e-09 |
Wald ratio |
1 |
cis |
3.57e-25 |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
0.125 |
0.0252 |
7.89e-07 |
Wald ratio |
1 |
cis |
NA |
| Neuroticism |
0.04 |
0.00942 |
2.14e-05 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: K35 Acute appendicitis |
0.257 |
0.0718 |
3.46e-04 |
Wald ratio |
1 |
cis |
NA |
| Potassium in urine |
0.0225 |
0.00653 |
5.80e-04 |
Wald ratio |
1 |
cis |
NA |
| Triglycerides |
0.0457 |
0.0134 |
6.65e-04 |
Wald ratio |
1 |
cis |
NA |
| Systolic blood pressure automated reading |
-0.0218 |
0.00658 |
9.31e-04 |
Wald ratio |
1 |
cis |
NA |
| Body mass index (BMI) |
-0.0197 |
0.00643 |
0.00222 |
Wald ratio |
1 |
cis |
NA |
| Diastolic blood pressure automated reading |
-0.0193 |
0.00658 |
0.0033 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypertension |
-0.0314 |
0.0113 |
0.00545 |
Wald ratio |
1 |
cis |
NA |
| Pulse rate |
0.0302 |
0.0113 |
0.00771 |
Wald ratio |
1 |
cis |
NA |
| Knee and hip osteoarthritis |
-0.146 |
0.0579 |
0.0118 |
Wald ratio |
1 |
cis |
NA |
| …and 101 more outcomes (see JSON) |
|
|
|
|
|
|
|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3061_61_2 |
Cathepsin B |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
229 association rows across 135 traits (220 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 |
| Cathepsin B levels |
5e-423 |
rs1736084 |
8 |
GCST90246843 |
no MR -> candidate analysis |
| Serum levels of protein CTSB |
1e-211 |
rs1736081 |
3 |
GCST90089981 |
no MR -> candidate analysis |
| Serum levels of protein GNS |
1e-125 |
rs1293303 |
2 |
GCST90090122 |
no MR -> candidate analysis |
| Blood protein levels |
2e-121 |
rs1736089 |
7 |
GCST006585 |
no MR -> candidate analysis |
| Cerebrospinal fluid protein CTSB levels |
5e-116 |
rs1692812 |
1 |
GCST90944737 |
no MR -> candidate analysis |
| CTSB protein levels |
3e-105 |
rs148117767 |
7 |
GCST90468908 |
no MR -> candidate analysis |
| TMEM106A protein levels |
4e-58 |
rs1293303 |
1 |
GCST90470886 |
no MR -> candidate analysis |
| Cathepsin B levels (CTSB.3061.61.2) |
5e-54 |
rs1692819 |
1 |
GCST90240619 |
no MR -> candidate analysis |
| Macrosialin levels |
1e-50 |
rs1293303 |
1 |
GCST90248383 |
no MR -> candidate analysis |
| LAMP1 protein levels |
7e-47 |
rs1293303 |
1 |
GCST90469733 |
no MR -> candidate analysis |
| Transmembrane protein 106A levels |
1e-42 |
rs1293303 |
1 |
GCST90249752 |
no MR -> candidate analysis |
| PSAP protein levels |
2e-36 |
rs1736085 |
1 |
GCST90470351 |
no MR -> candidate analysis |
| …and 123 more traits (see JSON) |
|
|
|
|
|
4. Phenome map — where this gene is a genetic locus, vs. where MR exists
Top diseases by Open Targets association (of 1118 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 |
| Alzheimer disease |
0.757 |
— |
common-variant locus |
no MR -> candidate analysis |
| Parkinson disease |
0.695 |
— |
common-variant locus |
no MR -> candidate analysis |
| keratolytic winter erythema |
0.199 |
— |
established (curated) |
no MR -> candidate analysis |
| leprosy |
0.466 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 1 diabetes mellitus |
0.443 |
— |
common-variant locus |
no MR -> candidate analysis |
| alcohol drinking |
0.457 |
— |
common-variant locus |
no MR -> candidate analysis |
| hepatitis B virus infection |
0.439 |
— |
common-variant locus |
no MR -> candidate analysis |
| squalene synthase deficiency |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| diabetes mellitus |
0.41 |
— |
common-variant locus |
no MR -> candidate analysis |
| placental abruption |
0.432 |
— |
common-variant locus |
no MR -> candidate analysis |
| glomerulonephritis |
0.432 |
— |
common-variant locus |
no MR -> candidate analysis |
| urolithiasis |
0.426 |
— |
common-variant locus |
no MR -> candidate analysis |
| irritable bowel syndrome |
0.406 |
— |
common-variant locus |
no MR -> candidate analysis |
| type 2 diabetes mellitus |
0.308 |
— |
common-variant locus |
no MR -> candidate analysis |
| atrial fibrillation |
0.298 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 15 rows above, 15 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 (Cathepsin B) |
| gnomAD constraint |
pLI=3.5e-24, LOEUF=1.6 — LoF-tolerant |
| GWAS Catalog |
186 unique SNPs / 476 rows |
| ClinVar |
325 records; 3 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1118 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 ‘CTSB’ and resolved to ‘Cathepsin B’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 325 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 135 traits by best p-value, aggregated from 229 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/P07858 — 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/ENSG00000164733/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL4072/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CTSB — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CTSB — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CTSB%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CTSB — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:10:50 · 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