CausalSentinel

Protein Dossier — INPP5B (Type II inositol 1,4,5-trisphosphate 5-phosphatase)

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
Bulimia nervosa -0.0786 0.0274 0.00415 Wald ratio 1 cis NA
Forearm bone mineral density 0.116 0.0412 0.00479 Wald ratio 1 cis NA
Femoral neck bone mineral density 0.0544 0.0197 0.00565 Wald ratio 1 cis NA
Fasting glucose 0.075 0.0293 0.0104 Wald ratio 1 cis NA
Forced expiratory volume in 1-second (FEV1) -0.014 0.00555 0.0118 Wald ratio 1 cis NA
Diagnoses - main ICD10: B37 Candidiasis 0.49 0.196 0.0127 Wald ratio 1 cis NA
Years of schooling -0.0219 0.00914 0.0164 Wald ratio 1 cis NA
ER-negative Breast cancer (Combined Oncoarray; iCOGS; GWAS meta analysis) -0.0751 0.0322 0.0195 Wald ratio 1 cis NA
Diastolic blood pressure automated reading 0.0152 0.00657 0.0205 Wald ratio 1 cis NA
Large vessel disease 0.212 0.0947 0.025 Wald ratio 1 cis NA
Serum creatinine (eGFRcrea) 0.00512 0.00238 0.0313 Wald ratio 1 cis NA
Pancreatic cancer 0.286 0.133 0.0322 Wald ratio 1 cis NA
…and 113 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

63 association rows across 38 traits (58 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
Bone mineral density mean 1e-257 rs112495211 1 GCST90321120 no MR -> candidate analysis
Type II inositol 1,4,5-trisphosphate 5-phosphatase levels 1e-115 rs61776676 2 GCST90249876 no MR -> candidate analysis
Hypothyroidism 3e-25 rs35978921 4 GCST90572791 no MR -> candidate analysis
Alzheimer’s disease or family history of Alzheimer’s disease 2e-23 rs1488544082 2 GCST90624094 no MR -> candidate analysis
Pulse pressure 5e-22 rs28570969 3 GCST90132905 no MR -> candidate analysis
Physical function (baseline) 6e-22 rs28391281 1 GCST90565837 no MR -> candidate analysis
Height 2e-21 rs2170169 7 GCST90245845 no MR -> candidate analysis
Autoimmune hypothyroidism 4e-21 rs12752271 1 GCST90837324 no MR -> candidate analysis
height (mean, inv-normal transformed) 9e-21 rs28611172 1 GCST90479635 no MR -> candidate analysis
Height (maximum, inv-normal transformed) 3e-20 rs28611172 1 GCST90479634 no MR -> candidate analysis
Body size (confirmatory factor analysis Factor 21) 4e-18 rs146988606 1 GCST90309355 no MR -> candidate analysis
height (minimum, inv-normal transformed) 1e-17 rs28611172 1 GCST90479636 no MR -> candidate analysis
…and 26 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 201 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
hypothyroidism 0.704 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.562 common-variant locus no MR -> candidate analysis
colorectal cancer 0.562 common-variant locus no MR -> candidate analysis
thyroid gland disorder 0.517 common-variant locus no MR -> candidate analysis
heart failure 0.503 common-variant locus no MR -> candidate analysis
myocardial infarction 0.484 common-variant locus no MR -> candidate analysis
coronary atherosclerosis 0.484 common-variant locus no MR -> candidate analysis
myxedema 0.476 common-variant locus no MR -> candidate analysis
autoimmune thyroid disease 0.466 common-variant locus no MR -> candidate analysis
migraine disorder 0.432 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.434 common-variant locus no MR -> candidate analysis
Dent disease type 2 0.426 established (curated) no MR -> candidate analysis
coronary artery bypass 0.394 common-variant locus no MR -> candidate analysis
hypertensive disorder 0.384 common-variant locus no MR -> candidate analysis
myocardial ischemia 0.378 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 (Type II inositol 1,4,5-trisphosphate 5-phosphatase)
gnomAD constraint pLI=2.8e-23, LOEUF=0.905 — LoF-tolerant
GWAS Catalog 84 unique SNPs / 168 rows
ClinVar 236 records; 0 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance