TMIE

Chr 3AR

transmembrane inner ear

Also known as: DFNB6

NCBI Gene: 259236ENSG00000181585UniProt: Q8NEW7

This gene encodes a transmembrane inner ear protein. Studies in mouse suggest that this gene is required for normal postnatal maturation of sensory hair cells in the cochlea, including correct development of stereocilia bundles. This gene is one of multiple genes responsible for recessive non-syndromic deafness (DFNB), also known as autosomal recessive nonsyndromic hearing loss (ARNSHL), the most common form of congenitally acquired inherited hearing impairment. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Deafness, autosomal recessive 6MIM #600971
AR
152
ClinVar variants
24
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— TMIE
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
24 Pathogenic / Likely Pathogenic· 66 VUS of 152 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.81LOEUF
pLI 0.000
Z-score -0.11
OE 1.05 (0.57–1.81)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.05Z-score
OE missense 0.98 (0.81–1.19)
74 obs / 75.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.1.05 (0.57–1.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.81–1.19)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.80
0≤1.21.6
LoF obs/exp: 6 / 5.7Missense obs/exp: 74 / 75.3Syn Z: 0.87

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic14
Likely Pathogenic10
VUS66
Likely Benign25
Benign20
Conflicting16
14
Pathogenic
10
Likely Pathogenic
66
VUS
25
Likely Benign
20
Benign
16
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
5
1
8
0
14
Likely Pathogenic
4
3
3
0
10
VUS
1
39
24
2
66
Likely Benign
0
1
16
8
25
Benign
0
0
20
0
20
Conflicting
—16
Total10447110151

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.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Deafness, autosomal recessive 6

MIM #600971

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Analysis of TMIE gene mutations including the first large deletion of exon 1 with autosomal recessive non-syndromic deafness.
Rayat S et al.·BMC Med Genomics
2022
Global Distribution of Founder Variants Associated with Non-Syndromic Hearing Impairment.
Aboagye ET et al.·Genes (Basel)
2023Review
Short-term outcome of totally minimally invasive versus hybrid minimally invasive Ivor-Lewis esophagectomy.
Yu WQ et al.·Asian J Surg
2023
Recurrent and Novel Pathogenic Variants in Genes Involved with Hearing Loss in the Pakistani Population.
Shadab M et al.·Mol Diagn Ther
2025
Robotic minimally invasive esophagectomy provides superior surgical resection.
Ali AM et al.·Surg Endosc
2021
Evaluating the role of rare genetic variation in sleep duration.
Meng P et al.·Sleep Health
2022
Propensity Score-Matched Analysis Comparing Minimally Invasive Ivor Lewis Versus Minimally Invasive Mckeown Esophagectomy.
van Workum F et al.·Ann Surg
2020
Identification of novel variants in the TMIE gene of patients with nonsyndromic hearing loss.
Yang JJ et al.·Int J Pediatr Otorhinolaryngol
2010Cohort
Homozygous mutations in Pakistani consanguineous families with prelingual nonsyndromic hearing loss.
Park HR et al.·Mol Biol Rep
2020
Novel sequence variants in the TMIE gene in families with autosomal recessive nonsyndromic hearing impairment.
Santos RL et al.·J Mol Med (Berl)
2006
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools