CausalSentinel

Protein Dossier — CLIC5 (Chloride intracellular channel protein 5)

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
Clear cell ovarian cancer -0.4 0.161 0.0131 Wald ratio 1 cis NA
Fracture resulting from simple fall 0.0488 0.0235 0.0382 Wald ratio 1 cis NA
Non-cancer illness code self-reported: gastro-oesophageal reflux (gord) or gastric reflux 0.0856 0.0419 0.0408 Wald ratio 1 cis NA
Sleep duration -0.015 0.00738 0.0415 Wald ratio 1 cis NA
Non-cancer illness code self-reported: polio or poliomyelitis 0.483 0.238 0.0429 Wald ratio 1 cis NA
Eye problems or disorders: Diabetes related eye disease 0.193 0.1 0.0545 Wald ratio 1 cis NA
Fractured bone site(s): Ankle -0.188 0.0985 0.0568 Wald ratio 1 cis NA
Diagnoses - main ICD10: N40 Hyperplasia of prostate 0.156 0.0849 0.0659 Wald ratio 1 cis NA
Hearing difficulty or problems: Yes -0.0297 0.0168 0.0775 Wald ratio 1 cis NA
Non-cancer illness code self-reported: bladder problem (not cancer) 0.177 0.105 0.0915 Wald ratio 1 cis NA
Diagnoses - main ICD10: K60 Fissure and fistula of anal and rectal regions 0.196 0.117 0.0935 Wald ratio 1 cis NA
Non-cancer illness code self-reported: arthritis (nos) -0.233 0.141 0.0974 Wald ratio 1 cis NA
…and 48 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

101 association rows across 63 traits (83 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
Ectonucleotide pyrophosphatase/phosphodiesterase family memb 1e-717 rs4714902 1 GCST90247463 no MR -> candidate analysis
Ectonucleotide pyrophosphatase/phosphodiesterase family memb 8e-278 rs144538541 1 GCST90241026 no MR -> candidate analysis
Chloride intracellular channel protein 5 levels 1e-189 rs35822882 2 GCST90247063 no MR -> candidate analysis
Blood protein levels 2e-182 rs62400860 2 GCST006585 no MR -> candidate analysis
ENPP5 protein levels 7e-105 rs116286373 21 GCST90469116 no MR -> candidate analysis
Serum levels of protein CLIC5 3e-95 rs35822882 1 GCST90087010 no MR -> candidate analysis
CLIC5 protein levels 3e-69 rs9381421 2 GCST90468780 no MR -> candidate analysis
Height 3e-67 rs1388244 9 GCST90245848 no MR -> candidate analysis
Chloride intracellular channel protein 5 levels (CLIC5.12475 7e-27 rs35822882 1 GCST90240686 no MR -> candidate analysis
TGF-beta receptor type-1 protein levels (SomaScan ID:6556-5) 1e-24 rs144538541 1 GCST90441524 no MR -> candidate analysis
GLIPR1 protein levels 4e-23 rs549005520 2 GCST90469357 no MR -> candidate analysis
HPSE protein levels 2e-22 rs7766019 1 GCST90469473 no MR -> candidate analysis
…and 51 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 1575 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
hearing loss, autosomal recessive 0.732 established (curated) no MR -> candidate analysis
deafness 0.764 established (curated) no MR -> candidate analysis
open-angle glaucoma 0.708 common-variant locus no MR -> candidate analysis
hair color 0.685 common-variant locus no MR -> candidate analysis
alcohol drinking 0.503 common-variant locus no MR -> candidate analysis
external ear disorder 0.5 common-variant locus no MR -> candidate analysis
Proteinuria 0.482 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.482 common-variant locus no MR -> candidate analysis
chronic venous hypertension 0.482 common-variant locus no MR -> candidate analysis
severe acute respiratory syndrome 0.465 common-variant locus no MR -> candidate analysis
COVID-19 0.465 common-variant locus no MR -> candidate analysis
hemorrhage 0.461 common-variant locus no MR -> candidate analysis
gastric ulcer 0.461 common-variant locus no MR -> candidate analysis
breast disorder 0.461 common-variant locus no MR -> candidate analysis
ovarian dysfunction 0.441 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 not available — no ChEMBL target (undrugged)
gnomAD constraint pLI=2.1e-06, LOEUF=1.18 — LoF-tolerant
GWAS Catalog 124 unique SNPs / 255 rows
ClinVar 225 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance