Protein Dossier — CTSD (Cathepsin 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 |
| Non-cancer illness code self-reported: bladder problem (not cancer) |
0.213 |
0.0799 |
0.00752 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: M17 Gonarthrosis [arthrosis of knee] |
-0.153 |
0.0631 |
0.015 |
Wald ratio |
1 |
cis |
NA |
| Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) |
0.0451 |
0.0191 |
0.0184 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: gout |
-0.176 |
0.0753 |
0.0195 |
Wald ratio |
1 |
cis |
NA |
| Lumbar spine bone mineral density |
-0.0592 |
0.0281 |
0.0355 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: N20 Calculus of kidney and ureter |
0.159 |
0.0765 |
0.0373 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: uterine fibroids |
0.112 |
0.0542 |
0.0386 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hypothyroidism or myxoedema |
-0.07 |
0.0357 |
0.0499 |
Wald ratio |
1 |
cis |
NA |
| Non-cancer illness code self-reported: hayfever or allergic rhinitis |
0.0561 |
0.0291 |
0.0542 |
Wald ratio |
1 |
cis |
NA |
| Hearing difficulty or problems: Yes |
0.0241 |
0.0126 |
0.0562 |
Wald ratio |
1 |
cis |
NA |
| Diagnoses - main ICD10: R35 Polyuria |
0.19 |
0.1 |
0.0576 |
Wald ratio |
1 |
cis |
NA |
| Pulse rate |
0.0246 |
0.0132 |
0.0635 |
Wald ratio |
1 |
cis |
NA |
| …and 56 more outcomes (see JSON) |
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|
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|
2. pQTL instrument availability (Tier-B probe)
| Dataset |
Trait |
Author |
Year |
prot-c-3180_46_2 |
Cathepsin D |
Suhre K |
2019 |
3. GWAS Catalog results — traits with signal at this locus
40 association rows across 26 traits (37 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 CTSD levels |
1e-812 |
rs55861089 |
4 |
GCST90859967 |
no MR -> candidate analysis |
| CTSD/PRCP protein level ratio |
5e-604 |
rs55861089 |
1 |
GCST90314312 |
no MR -> candidate analysis |
| Bone mineral density mean |
1e-300 |
rs141856334 |
1 |
GCST90321120 |
no MR -> candidate analysis |
| Cathepsin D levels |
7e-224 |
rs55861089 |
5 |
GCST90012053 |
no MR -> candidate analysis |
| CTSD protein levels |
1e-109 |
rs72850953 |
5 |
GCST90468910 |
no MR -> candidate analysis |
| Circulating THPO levels |
4e-91 |
rs72850956 |
1 |
GCST90859812 |
no MR -> candidate analysis |
| ESAM/THPO protein level ratio |
6e-87 |
rs79194907 |
1 |
GCST90314719 |
no MR -> candidate analysis |
| THPO protein levels |
6e-80 |
rs11555039 |
1 |
GCST90470857 |
no MR -> candidate analysis |
| CD36 protein levels |
1e-70 |
rs11555039 |
1 |
GCST90468627 |
no MR -> candidate analysis |
| CD226 protein levels |
3e-68 |
rs55797351 |
1 |
GCST90468609 |
no MR -> candidate analysis |
| Serum levels of protein CTSD |
3e-46 |
rs55861089 |
1 |
GCST90089067 |
no MR -> candidate analysis |
| Beta-1,3-galactosyltransferase 2 levels |
2e-35 |
rs138335441 |
1 |
GCST90246636 |
no MR -> candidate analysis |
| …and 14 more traits (see JSON) |
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|
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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 1566 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 |
| neuronal ceroid lipofuscinosis 10 |
0.894 |
— |
established (curated) |
no MR -> candidate analysis |
| CLN10 disease |
0.76 |
— |
established (curated) |
no MR -> candidate analysis |
| neuronal ceroid lipofuscinosis |
0.928 |
— |
established (curated) |
no MR -> candidate analysis |
| late infantile neuronal ceroid lipofuscinosis 10 |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| juvenile neuronal ceroid lipofuscinosis 10 |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| congenital neuronal ceroid lipofuscinosis 10 |
0.608 |
— |
established (curated) |
no MR -> candidate analysis |
| hereditary disease |
0.56 |
— |
established (curated) |
no MR -> candidate analysis |
| multiple epiphyseal dysplasia, Al-Gazali type |
0.438 |
— |
established (curated) |
no MR -> candidate analysis |
| microlissencephaly |
0.426 |
— |
established (curated) |
no MR -> candidate analysis |
| Exaggerated startle response |
0.426 |
— |
established (curated) |
no MR -> candidate analysis |
| idiopathic pulmonary fibrosis |
0.154 |
— |
common-variant locus |
no MR -> candidate analysis |
| postinflammatory pulmonary fibrosis |
0.154 |
— |
common-variant locus |
no MR -> candidate analysis |
Of the 12 rows above, 12 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 D) |
| gnomAD constraint |
pLI=1.7e-06, LOEUF=0.881 — LoF-tolerant |
| GWAS Catalog |
87 unique SNPs / 174 rows |
| ClinVar |
859 records; 7 pathogenic in sample of 30 |
| PharmGKB/ClinPGx |
no annotations |
phenome — Top 30 of 1566 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 ‘CTSD’ and resolved to ‘Cathepsin D’ — confirm this is the intended target.clinvar — Pathogenic count is over the 30 record(s) retrieved, NOT over all 859 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 26 traits by best p-value, aggregated from 40 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/P07339 — 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/ENSG00000117984/associations — Open Targets data release 26.06chembl: https://www.ebi.ac.uk/chembl/target_report_card/CHEMBL2581/ — ChEMBL_37 (released 2026-05-01)gnomad: https://gnomad.broadinstitute.org/gene/CTSD — gnomAD constraint via GraphQL API (reference genome GRCh38)gwas: https://www.ebi.ac.uk/gwas/genes/CTSD — GWAS Catalog REST (live; release not exposed by this endpoint)clinvar: https://www.ncbi.nlm.nih.gov/clinvar/?term=CTSD%5Bgene%5D — ClinVar build Build260809-1055.1gwas_traits: https://www.ebi.ac.uk/gwas/genes/CTSD — GWAS Catalog search API (live; release not exposed)
Provenance
- Generated: 2026-08-14T02:11:21 · 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