CausalSentinel

Protein Dossier — TMEM132D (Transmembrane protein 132D)

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
Diagnoses - main ICD10: C50 Malignant neoplasm of breast 0.237 0.0697 6.63e-04 Wald ratio 1 cis NA
Hippocampus volume -66 22.5 0.00329 Wald ratio 1 cis NA
Alcohol intake frequency -0.0479 0.0166 0.00394 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.0772 0.0282 0.00613 Wald ratio 1 cis NA
Diagnoses - main ICD10: K57 Diverticular disease of intestine 0.176 0.0666 0.0081 Wald ratio 1 cis NA
Diagnoses - main ICD10: D12 Benign neoplasm of colon rectum anus and anal canal -0.295 0.13 0.0235 Wald ratio 1 cis NA
Cancer code self-reported: small intestine or small bowel cancer 0.667 0.303 0.0276 Wald ratio 1 cis NA
Non-cancer illness code self-reported: muscle or soft tissue injuries 0.207 0.109 0.0581 Wald ratio 1 cis NA
Diagnoses - main ICD10: R55 Syncope and collapse 0.189 0.0998 0.0585 Wald ratio 1 cis NA
Diagnoses - main ICD10: S66 Injury of muscle and tendon at wrist and hand level 0.377 0.203 0.0626 Wald ratio 1 cis NA
Eye problems or disorders: Glaucoma -0.2 0.117 0.0877 Wald ratio 1 cis NA
Pallidum volume -15.2 9.3 0.103 Wald ratio 1 cis NA
…and 56 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

94 association rows across 78 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
Bone mineral density mean 1e-300 rs117043263 1 GCST90321120 no MR -> candidate analysis
Transmembrane protein 132B levels 7e-60 rs73159540 2 GCST90249903 no MR -> candidate analysis
Transmembrane protein 132D levels 2e-52 rs61943557 1 GCST90249905 no MR -> candidate analysis
Serum levels of protein TMEM132D 9e-34 rs61943547 1 GCST90087429 no MR -> candidate analysis
Transmembrane protein 132D levels (TMEM132D.13416.8.3) 3e-27 rs139574809 1 GCST90243092 no MR -> candidate analysis
Cerebellar grey matter morphology (MOSTest) 1e-23 rs10773610 2 GCST90728589 no MR -> candidate analysis
Blood protein levels 1e-18 rs61943549 1 GCST006585 no MR -> candidate analysis
GLIPR1 protein levels 8e-13 rs529141134 1 GCST90469357 no MR -> candidate analysis
Serum levels of protein TMEM132B 2e-12 rs12369635 1 GCST90090363 no MR -> candidate analysis
Transmembrane protein 132B levels (TMEM132B.8890.9.3) 3e-12 rs73159540 1 GCST90243089 no MR -> candidate analysis
Free Cholesterol to Cholesteryl Esters in Small HDL ratio 4e-12 rs73151095 1 GCST90827928 no MR -> candidate analysis
Pulmonary embolism 1e-11 rs708362 1 GCST90278093 no MR -> candidate analysis
…and 66 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 103 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
cutaneous melanoma 0.6 common-variant locus no MR -> candidate analysis
cervical carcinoma 0.578 common-variant locus no MR -> candidate analysis
cardiovascular disorder 0.55 common-variant locus no MR -> candidate analysis
alcohol drinking 0.543 common-variant locus no MR -> candidate analysis
stroke disorder 0.535 common-variant locus no MR -> candidate analysis
upper respiratory tract disorder 0.517 common-variant locus no MR -> candidate analysis
herpes simplex infectious disease 0.5 common-variant locus no MR -> candidate analysis
pulmonary embolism 0.497 common-variant locus no MR -> candidate analysis
placenta praevia 0.49 common-variant locus no MR -> candidate analysis
bursitis 0.485 common-variant locus no MR -> candidate analysis
autoimmune disorder of musculoskeletal system 0.485 common-variant locus no MR -> candidate analysis
optic neuritis 0.485 common-variant locus no MR -> candidate analysis
neuropathy 0.485 common-variant locus no MR -> candidate analysis
type 1 diabetes nephropathy 0.482 common-variant locus no MR -> candidate analysis
polyp 0.472 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=0.99, LOEUF=0.485 — LoF-INTOLERANT
GWAS Catalog 108 unique SNPs / 213 rows
ClinVar 252 records; 4 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance