CausalSentinel

Protein Dossier — TMEM132B (Transmembrane protein 132B)

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
Potassium in urine 0.0504 0.0141 3.65e-04 Wald ratio 1 trans NA
Sodium in urine 0.0381 0.0137 0.00548 Wald ratio 1 trans NA
Non-cancer illness code self-reported: diverticular disease or diverticulitis 0.271 0.102 0.00773 Wald ratio 1 trans NA
Fractured bone site(s): Wrist 0.208 0.0813 0.0105 Wald ratio 1 trans NA
Non-cancer illness code self-reported: mania or bipolar disorder or manic depression 0.447 0.182 0.014 Wald ratio 1 trans NA
Cancer code self-reported: malignant melanoma 0.277 0.122 0.0229 Wald ratio 1 trans NA
Squamous cell lung cancer 0.335 0.148 0.0235 Wald ratio 1 trans NA
Autism -0.371 0.171 0.0302 Wald ratio 1 trans NA
Happiness -0.0369 0.0172 0.0316 Wald ratio 1 trans NA
Diagnoses - main ICD10: R10 Abdominal and pelvic pain -0.166 0.08 0.0381 Wald ratio 1 trans NA
Creatinine (enzymatic) in urine 0.0271 0.0133 0.042 Wald ratio 1 trans NA
Urate -0.062 0.0317 0.0507 Wald ratio 1 trans NA
…and 72 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

68 association rows across 52 traits (26 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
Transmembrane protein 132B levels 2e-23 rs148179158 2 GCST90249903 no MR -> candidate analysis
Type 2 diabetes 6e-23 rs11058150 1 GCST90134620 MR: beta=0.0722, p=0.323 (trans)
Smoking initiation 5e-21 rs1666839 3 GCST90243985 no MR -> candidate analysis
Serum levels of protein ASH2L 8e-13 rs146549691 1 GCST90087257 no MR -> candidate analysis
Bone mineral density mean 4e-11 rs188062158 1 GCST90321120 no MR -> candidate analysis
Protein quantitative trait loci (liver) 5e-11 rs74824119 1 GCST011427 no MR -> candidate analysis
Gut microbial network clusters (Turquoise (at 3 months) x An 6e-11 rs12578940 1 GCST90569243 no MR -> candidate analysis
Non-alcoholic fatty liver disease or type 2 diabetes 7e-11 rs73233361 1 GCST90272881 no MR -> candidate analysis
Triglyceride levels x short total sleep time interaction (2d 9e-11 rs10744213 1 GCST009363 no MR -> candidate analysis
Smoking initiation (ever regular vs never regular) (MTAG) 4e-10 rs1666839 1 GCST007468 no MR -> candidate analysis
Risk-taking behavior (multivariate analysis) 1e-9 rs326391 1 GCST90239693 no MR -> candidate analysis
Lifetime major depressive disorder (AutoComplete Impute and 3e-9 rs434211 1 GCST90449002 no MR -> candidate analysis
…and 40 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 123 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
smoking initiation 0.601 common-variant locus no MR -> candidate analysis
type 2 diabetes mellitus 0.571 common-variant locus no MR -> candidate analysis
major depressive disorder 0.512 common-variant locus no MR -> candidate analysis
stomach disorder 0.512 common-variant locus no MR -> candidate analysis
risk-taking behaviour 0.509 common-variant locus no MR -> candidate analysis
alcohol drinking 0.504 common-variant locus no MR -> candidate analysis
stroke disorder 0.489 common-variant locus no MR -> candidate analysis
preeclampsia 0.479 common-variant locus no MR -> candidate analysis
deficiency anemia 0.479 common-variant locus no MR -> candidate analysis
metabolic dysfunction-associated steatotic liver disease 0.477 common-variant locus no MR -> candidate analysis
peripheral vascular disease 0.472 common-variant locus no MR -> candidate analysis
Thromboembolism 0.472 common-variant locus no MR -> candidate analysis
corneal degeneration 0.47 common-variant locus no MR -> candidate analysis
nephrotic syndrome 0.41 common-variant locus no MR -> candidate analysis
ovarian neoplasm 0.41 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=1, LOEUF=0.294 — LoF-INTOLERANT
GWAS Catalog 71 unique SNPs / 129 rows
ClinVar 165 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance