TMEM132E

protein-coding

transmembrane protein 132E

Gene summary

Involved in posterior lateral line neuromast hair cell development. Predicted to be located in cell body. Predicted to be active in membrane. Implicated in autosomal recessive nonsyndromic deafness 99. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001304438.2

Inheritance

ClinVar variants

U:202B:134

Top phenotype

Deafness, autosomal recessive 99

gnomAD constraint

pLI —, LoF o/e 0.4

Max pathogenic AF

—

Genomic locus

chr17:34,579,487-34,639,318

External References & Databases

Ensembl (ENSG00000181291)

Transcript & Mutation Effects

hg38 • Region Span ~59.8 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hearing loss, autosomal recessiveSUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: Orphanet

hearing loss, autosomal recessive 99MODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032776

Submitter: PanelApp Australia

hearing loss, autosomal recessive 99STRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032776

Submitter: Labcorp Genetics (formerly Invitae)

hearing loss, autosomal recessiveLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0019588

Submitter: ClinGen

TMEM132E was first reported in relation to autosomal recessive nonsyndromic hearing loss (ARNSHL) in 2003 (Cheng et al., 12673573). The proposed disease mechanism is loss of function. Evidence supporting this gene-disease relationship includes case-level data, segregation data, and experimental data. Three variants (all missense) have been reported in two probands in two publications (PMIDs: 25331638, 31656313) for a genetic evidence score of 1.75 points. Variants in this gene segregated with disease in 2 additional family members (PMID: 31656313). This gene-disease association is supported by animal models and an expression study (PMIDs: 25331638, 31656313) detailing expression of TMEM132E in the mouse cochlea, phenocopied ARNHL in Zebrafish, and wild type rescue of the phenotype seen in Zebrafish whereas the variant seen in the proband (PMID: 25331638) did not. This resulted in an experimental evidence score of 3.5 points. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged that contradicts the gene-disease relationship. This gene-disease pair was originally evaluated by the Hearing Loss Gene Curation Expert Panel on 11/21/2017 (SOP Version 5). It was reevaluated with the addition of one publication (PMID: 31656313) on 1/19/2022 (SOP v8). As a result of this reevaluation, the classification did not change.

hearing loss, autosomal recessive 99LIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0032776

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Deafness, autosomal recessive 99AR

Manifestation: Audiologic/Otolaryngologic

Intervention: Audiologic/Otolaryngologic

Rationale: Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development

Refs: 25331638; 31656313

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMEM132E variants in ClinVar

7 Conditions Cataloged

not providedTotal: 237

not specifiedTotal: 153

TMEM132E-related disorderTotal: 50

Hearing loss, autosomal recessive 99Total: 10

Breast-ovarian cancer, familial, susceptibility to, 2Total: 1

BRCA2-related cancer predispositionTotal: 1

Familial cancer of breastTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001304438.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	116 clinvar	7 clinvar	124
missense			198 clinvar	11 clinvar		209
nonsense			1 clinvar			1
start loss						0
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	202	127	7	336

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 4 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001304438.2	RefSeq	NP_001291367.1	9	MANE Select
ENST00000631683.2	Ensembl	ENSP00000487800.2	9	MANE Select
ENST00000321639.7	Ensembl	ENSP00000316532.5	10	Standard
ENST00001137661.1	Ensembl	ENSP00000814863.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
tmem132e	Danio rerio	Structure: auditory receptor cell Quality: decreased functionality abnormal

Gene / Model

Organism

Observed Phenotype

tmem132e

Danio rerio

Structure: auditory receptor cell

Quality: decreased functionality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Cellular Component

integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000321639
Coding exons: 10
Length: 58570
Individuals with no LoFs: 125719
Homozygous LoFs: 0
Heterozygous LoFs: 29
Defined: 125748
p: 0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.34	518	611	0.847	0.0000389	6196
Missense (PolyPhen)		162	227.73	0.71138		2363
Synonymous	0.594	273	286	0.955	0.0000191	2168
Loss of Function	3.12	13	32.1	0.405	0.00000165	343

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00029	0.00029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000055	0.000054	rare
Finnish	0.00010	0.000092	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.000033	0.000033	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Required for normal inner ear hair cell function and hearing. {ECO:0000269|PubMed:25331638}.;
Disease: DISEASE: Note=TMEM132E is located in a region involved in a heterozygous deletion of approximately 4.7 Mb; this deletion, involving the NF1 gene and contiguous genes lying in its flanking regions, is observed in a patient 17q11.2 microdeletion syndrome, a syndrome characterized by variable facial dysmorphism, mental retardation, developmental delay, and an excessive number of neurofibromas. {ECO:0000269|PubMed:14569139}.; DISEASE: Note=Several lines of evidence link the Gln-420 variant with autosomal recessive non-syndromic hearing loss. This variant has been reported in 2 siblings with prelingual, bilateral, severe to profound sensorineural hearing loss from a Chinese family of consanguineous marriage and was not found in 500 ethnically matched healthy controls. In mouse, TMEM132E is expressed in cochlea hair cells. In addition, knockdown in zebrafish affects the mechanotransduction of hair cells, a phenotype that can be rescued by wild-type human TMEM132E, but not by the Gln-420 variant. {ECO:0000269|PubMed:25331638}.;

Intolerance Scores

LoFtool: 0.618
RVIS EVS: 0.12
RVIS percentile EVS: 62.17

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.272

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium