TMEM132E

Chr 17AR

transmembrane protein 132E

Also known as: DFNB99

NCBI Gene: 124842 ENSG00000181291 UniProt: Q6IEE7 OMIM: 616178

TMEM132E encodes a protein required for normal inner ear hair cell function and hearing. Mutations cause autosomal recessive nonsyndromic deafness 99, affecting hearing without other organ systems involved. The gene shows low constraint to loss-of-function variants (pLI 0.00004), consistent with its recessive inheritance pattern.

OMIM ResearchSummary from RefSeq, UniProt

Involved in posterior lateral line neuromast hair cell development. Predicted to be located in cell body. Implicated in autosomal recessive nonsyndromic deafness 99. [provided by Alliance of Genome Resources, Jul 2025]

OMIM ResearchGenerating clinical summary…

ARLOEUF 0.641 OMIM phenotype

Clinical Summary— TMEM132E

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Gene-Disease Validity (ClinGen)

hearing loss, autosomal recessive · ARLimited

Limited evidence — not for standalone diagnostic reporting

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

4 unique Pathogenic / Likely Pathogenic· 223 VUS of 411 total submissions

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.64LOEUF

pLI 0.000

Z-score 3.12

OE 0.40 (0.26–0.64)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

1.34Z-score

OE missense 0.85 (0.79–0.91)

518 obs / 611.4 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.40 (0.26–0.64)

0≤0.351.4

Missense OE?0.85 (0.79–0.91)

0≤0.61.4

Synonymous OE?0.96

0≤1.21.6

LoF obs/exp: 13 / 32.1Missense obs/exp: 518 / 611.4Syn Z: 0.59

ClinVar Variant Classifications

411 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic3

Likely Pathogenic1

VUS223

Likely Benign141

Benign38

Conflicting4

Pathogenic

Likely Pathogenic

223

VUS

141

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	0	3	0	3
Likely Pathogenic	0	0	1	0	1
VUS	1	174	48	0	223
Likely Benign	0	8	26	107	141
Benign	0	5	21	12	38
Conflicting	—				4
Total	1	187	99	119	410

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

5 pathogenic / likely-pathogenic (of 15) ClinVar copy-number / structural variants overlap TMEM132E — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →