CausalSentinel

Protein Dossier — TMEM106B (Transmembrane protein 106B)

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
Non-cancer illness code self-reported: depression 0.172 0.031 2.81e-08 Wald ratio 1 cis NA
Body mass index (BMI) -0.0355 0.00894 6.98e-05 Wald ratio 1 cis NA
Sleep duration -0.027 0.00698 1.08e-04 Wald ratio 1 cis NA
Height 0.0404 0.011 2.46e-04 Wald ratio 1 cis NA
Autism 0.312 0.106 0.00324 Wald ratio 1 cis NA
Vascular or heart problems diagnosed by doctor: Angina 0.129 0.0441 0.0035 Wald ratio 1 cis NA
Melanoma 0.592 0.208 0.00439 Wald ratio 1 cis NA
Coronary heart disease -0.1 0.0354 0.00474 Wald ratio 1 cis NA
Childhood intelligence -0.132 0.0478 0.00589 Wald ratio 1 cis NA
Non-cancer illness code self-reported: high cholesterol 0.06 0.0228 0.00841 Wald ratio 1 cis NA
Myocardial infarction -0.102 0.0393 0.00913 Wald ratio 1 cis NA
Depressive symptoms -0.0368 0.0147 0.0124 Wald ratio 1 cis NA
…and 119 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

195 association rows across 134 traits (148 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
Height 1e-79 rs6460895 5 GCST90245848 MR: beta=0.0404, p=2.46e-04 (cis)
Transmembrane protein 106B levels 6e-59 rs5011434 2 GCST90249753 no MR -> candidate analysis
Serum levels of protein TMEM106B 1e-42 rs1548884 1 GCST90090262 no MR -> candidate analysis
DPP4 protein levels 4e-31 rs10644564 1 GCST90469033 no MR -> candidate analysis
GFAP protein levels 1e-28 rs6460901 1 GCST90469325 no MR -> candidate analysis
Blood protein levels 6e-27 rs10950398 1 GCST006585 no MR -> candidate analysis
Circulating DPP4 levels 7e-27 rs4721061 1 GCST90860464 no MR -> candidate analysis
Educational attainment 8e-26 rs7810903 3 GCST90105038 no MR -> candidate analysis
Depression 8e-24 rs2043539 7 GCST007342 MR: beta=0.172, p=2.81e-08 (cis)
Differential aging in older adults (frontal cortex) 3e-23 rs1990622 1 GCST008795 no MR -> candidate analysis
Core binding factor acute myeloid leukemia 7e-20 rs10237821; rs12537849; rs7794113; rs10269431 2 GCST008413 no MR -> candidate analysis
GLIPR1 protein levels 1e-19 rs76752104 2 GCST90469357 no MR -> candidate analysis
…and 122 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 885 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
leukodystrophy, hypomyelinating, 16 0.774 established (curated) no MR -> candidate analysis
major depressive disorder 0.852 common-variant locus MR: beta=-0.123, p=0.12 (cis)
type 2 diabetes mellitus 0.81 common-variant locus no MR -> candidate analysis
coronary artery disorder 0.737 common-variant locus no MR -> candidate analysis
Alzheimer disease 0.701 common-variant locus no MR -> candidate analysis
diabetes mellitus 0.725 common-variant locus no MR -> candidate analysis
frontotemporal dementia 0.659 common-variant locus no MR -> candidate analysis
dementia 0.659 common-variant locus no MR -> candidate analysis
mental disorder 0.684 common-variant locus no MR -> candidate analysis
insomnia 0.656 common-variant locus no MR -> candidate analysis
aging 0.638 common-variant locus no MR -> candidate analysis
smoking initiation 0.636 common-variant locus no MR -> candidate analysis
sleep disorder 0.634 common-variant locus MR: beta=0.217, p=0.022 (cis)
neurodegenerative disease 0.539 common-variant locus no MR -> candidate analysis
depressive disorder 0.539 common-variant locus MR: beta=-0.123, p=0.12 (cis)

Of the 15 rows above, 12 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=0.028, LOEUF=0.743 — LoF-tolerant
GWAS Catalog 112 unique SNPs / 244 rows
ClinVar 183 records; 3 pathogenic in sample of 30
PharmGKB/ClinPGx no annotations

Caveats declared by the tools

Sources

Provenance