TMIE
Chr 3transmembrane inner ear
Also known as: DFNB6
TMIE encodes a transmembrane protein that functions as an auxiliary subunit of the mechanotransducer channel complex at cochlear hair cell stereocilia tips, which is essential for auditory sensory transduction. Mutations cause autosomal recessive nonsyndromic hearing loss (DFNB6), typically presenting as congenital deafness. The gene shows low constraint against loss-of-function variants (pLI < 0.1), consistent with its recessive inheritance pattern.
Definitive — sufficient evidence for diagnostic panels
Some data sources returned errors (1)
omim: Error: OMIM fetch failed: 429
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
This gene has evidence for multiple mechanisms of pathogenicity (gain-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to gain-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
154 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 7 | 1 | 7 | 0 | 15 |
Likely Pathogenic | 5 | 3 | 2 | 0 | 10 |
VUS | 1 | 41 | 23 | 2 | 67 |
Likely Benign | 0 | 3 | 14 | 8 | 25 |
Benign | 0 | 2 | 18 | 0 | 20 |
Conflicting | — | 16 | |||
| Total | 13 | 50 | 64 | 10 | 153 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
TMIE · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools