CausalSentinel

Protein Dossier — CTSF (Cathepsin F)

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
Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.132 0.0294 7.53e-06 Wald ratio 1 cis NA
ER-positive Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) 0.147 0.0349 2.58e-05 Wald ratio 1 cis NA
Bipolar disorder -0.433 0.108 6.28e-05 Wald ratio 1 cis NA
Years of schooling -0.0511 0.017 0.0027 Wald ratio 1 cis NA
Knee osteoarthritis -0.309 0.128 0.0157 Wald ratio 1 cis NA
Diagnoses - main ICD10: R04 Haemorrhage from respiratory passages 0.279 0.12 0.0202 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.151 0.0682 0.0272 Wald ratio 1 cis NA
Diagnoses - main ICD10: C61 Malignant neoplasm of prostate 0.238 0.11 0.0306 Wald ratio 1 cis NA
Fractured bone site(s): Wrist -0.211 0.1 0.0348 Wald ratio 1 cis NA
PGC cross-disorder traits -0.115 0.0545 0.0352 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0414 0.0202 0.0401 Wald ratio 1 cis NA
Neo-openness to experience -0.635 0.318 0.0459 Wald ratio 1 cis NA
…and 105 more outcomes (see JSON)              

2. pQTL instrument availability (Tier-B probe)

No prot-* pQTL GWAS dataset found for this protein (matched by UniProt accession and symbol).

3. GWAS Catalog results — traits with signal at this locus

16 association rows across 14 traits (13 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
CTSF protein levels 2e-229 rs1044522 2 GCST90468912 no MR -> candidate analysis
Circulating CTSF levels 1e-223 rs1044522 2 GCST90860585 no MR -> candidate analysis
Cathepsin F levels 1e-65 rs4930383 1 GCST90246848 no MR -> candidate analysis
Copper chaperone for superoxide dismutase levels 2e-36 rs636128 1 GCST90246926 no MR -> candidate analysis
Islet amyloid polypeptide levels 6e-36 rs4930384 1 GCST90247967 no MR -> candidate analysis
B4GAT1 protein levels 4e-30 rs544975859 1 GCST90468413 no MR -> candidate analysis
Circulating B4GAT1 levels 4e-28 rs544975859 1 GCST90860648 no MR -> candidate analysis
Cathepsin F levels (CTSF.9212.22.3) 3e-18 rs1791679 1 GCST90240621 no MR -> candidate analysis
Chronotype 5e-13 rs662094 1 GCST007576 no MR -> candidate analysis
Posterior thigh muscle fat infiltration percentage 2e-10 rs662094 1 GCST90267355 no MR -> candidate analysis
CCS protein levels 3e-8 rs692892 1 GCST90453013 no MR -> candidate analysis
Airway imaging phenotypes 9e-7 rs113835537 1 GCST002941 no MR -> candidate analysis
…and 2 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 1455 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 13 0.892 established (curated) no MR -> candidate analysis
CLN13 disease 0.608 established (curated) no MR -> candidate analysis
neuronal ceroid lipofuscinosis 0.826 established (curated) no MR -> candidate analysis
Abnormality of the skeletal system 0.815 common-variant locus no MR -> candidate analysis
hereditary disease 0.77 established (curated) no MR -> candidate analysis
bipolar disorder 0.664 common-variant locus MR: beta=-0.433, p=6.28e-05 (cis)
asthma 0.572 common-variant locus no MR -> candidate analysis
ulcerative colitis 0.55 common-variant locus no MR -> candidate analysis
neurodevelopmental disorder 0.547 established (curated) no MR -> candidate analysis
mental disorder 0.357 common-variant locus no MR -> candidate analysis
total hip arthroplasty 0.342 common-variant locus no MR -> candidate analysis
osteoarthritis, hip 0.342 common-variant locus MR: beta=0.126, p=0.321 (cis)
developmental disability 0.195 established (curated) no MR -> candidate analysis

Of the 13 rows above, 11 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 F)
gnomAD constraint pLI=4.7e-23, LOEUF=1.26 — LoF-tolerant
GWAS Catalog 75 unique SNPs / 150 rows
ClinVar 339 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance