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TMEM132E

gene
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Also known as DFNB99

Summary

TMEM132E (transmembrane protein 132E, HGNC:26991) is a protein-coding gene on chromosome 17q12, encoding Transmembrane protein 132E (Q6IEE7). Required for normal inner ear hair cell function and hearing.

Involved in posterior lateral line neuromast hair cell development. Predicted to be located in cell body. Implicated in autosomal recessive nonsyndromic deafness 99.

Source: NCBI Gene 124842 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): hearing loss, autosomal recessive 99 (Strong, GenCC) — +1 more curated relationship
  • GWAS associations: 5
  • Clinical variants (ClinVar): 413 total — 3 pathogenic, 1 likely-pathogenic
  • Phenotypes (HPO): 4
  • MANE Select transcript: NM_001304438

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:26991
Approved symbolTMEM132E
Nametransmembrane protein 132E
Location17q12
Locus typegene with protein product
StatusApproved
AliasesDFNB99
Ensembl geneENSG00000181291
Ensembl biotypeprotein_coding
OMIM616178
Entrez124842

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 retained_intron

ENST00000321639, ENST00000577271, ENST00000631683

RefSeq mRNA: 1 — MANE Select: NM_001304438 NM_001304438

CCDS: CCDS11283

Canonical transcript exons

ENST00000631683 — 9 exons

ExonStartEnd
ENSE000009468793463000834630151
ENSE000009468803463270434632909
ENSE000009468813463479934635087
ENSE000009468823463600734636198
ENSE000011059583462901234629204
ENSE000011613263462856334628709
ENSE000037812183457958234581143
ENSE000037813983462612734627057
ENSE000039015643463717734639318

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 86.38.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.3167 / max 22.8677, expressed in 132 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter IDTPM avgSamples expressed
1603220.214998
1603210.101847

Top tissues by expression

240 total, by Bgee expression score (0-100, higher = more expressed):

TissueAnatomy IDExpression scoreQuality
kidney epitheliumUBERON:000481986.38gold quality
right hemisphere of cerebellumUBERON:001489085.65gold quality
cerebellar hemisphereUBERON:000224584.84gold quality
cerebellar cortexUBERON:000212984.74gold quality
cerebellumUBERON:000203783.78gold quality
nasal cavity epitheliumUBERON:000538481.77gold quality
pancreatic ductal cellCL:000207981.11silver quality
left ventricle myocardiumUBERON:000656676.78gold quality
cardiac muscle of right atriumUBERON:000337976.48gold quality
primary visual cortexUBERON:000243675.17gold quality
middle temporal gyrusUBERON:000277173.81gold quality
right frontal lobeUBERON:000281073.27gold quality
Brodmann (1909) area 23UBERON:001355473.15silver quality
parotid glandUBERON:000183173.06gold quality
myocardiumUBERON:000234972.66gold quality
entorhinal cortexUBERON:000272871.42gold quality
cerebellar vermisUBERON:000472071.29silver quality
superior frontal gyrusUBERON:000266170.77gold quality
postcentral gyrusUBERON:000258170.70gold quality
frontal cortexUBERON:000187070.61gold quality
prefrontal cortexUBERON:000045170.36gold quality
Brodmann (1909) area 9UBERON:001354070.27gold quality
dorsal root ganglionUBERON:000004470.21gold quality
occipital lobeUBERON:000202170.00gold quality
neocortexUBERON:000195069.65gold quality
dorsolateral prefrontal cortexUBERON:000983469.64gold quality
medial globus pallidusUBERON:000247769.41silver quality
upper arm skinUBERON:000426369.34gold quality
hypothalamusUBERON:000189868.82gold quality
temporal lobeUBERON:000187168.74gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

ExperimentMarker?Max mean expression
E-ANND-3no1.62

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 3)

  • Whole-exome sequencing revealed a homozygous missense mutation (c.1259G>A, p.Arg420Gln) in the gene-encoding transmembrane protein 132E (TMEM132E) as the causative variant of autosomal-recessive nonsyndromic hearing loss. (PMID:25331638)
  • The authors present a second Autosomal-recessive (AR) nonsyndromic hearing impairment (NSHI) family with TMEM132E variants which strengthens the evidence of the involvement of this gene in the etiology of ARNSHI. (PMID:31656313)
  • Hair cell alpha9alpha10 nicotinic acetylcholine receptor functional expression regulated by ligand binding and deafness gene products. (PMID:32929005)

Cross-species orthologs

5 orthologs

OrganismSymbolGene ID
danio_reriotmem132eENSDARG00000090830
mus_musculusTmem132eENSMUSG00000020701
rattus_norvegicusTmem132eENSRNOG00000007455
drosophila_melanogasterdtnFBGN0262730
caenorhabditis_elegansWBGENE00022175

Paralogs (4): TMEM132A (ENSG00000006118), TMEM132B (ENSG00000139364), TMEM132D (ENSG00000151952), TMEM132C (ENSG00000181234)

Protein

Protein identifiers

Transmembrane protein 132E — Q6IEE7 (reviewed: Q6IEE7)

All UniProt accessions (2): Q6IEE7, A0A494BWY4

UniProt curated annotations — full annotation on UniProt →

Function. Required for normal inner ear hair cell function and hearing.

Subcellular location. Membrane.

Disease relevance. 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 with 17q11.2 microdeletion syndrome, a syndrome characterized by variable facial dysmorphism, intellectual disability, developmental delay, and an excessive number of neurofibromas. Deafness, autosomal recessive, 99 (DFNB99) [MIM:618481] A form of non-syndromic deafness characterized by prelingual, bilateral, severe-to-profound sensorineural hearing loss. Sensorineural deafness results from damage to the neural receptors of the inner ear, the nerve pathways to the brain, or the area of the brain that receives sound information. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TMEM132 family.

RefSeq proteins (1): NP_001291367* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR026307TMEM132Family
IPR031435TMEM132_NDomain
IPR031436TMEM132_CDomain
IPR031437Ig_TMEM132_4thDomain
IPR055421TMEM132_3rdDomain
IPR055422Ig_TMEM132_2ndDomain
IPR055423Ig_TMEM132_5thDomain
IPR055424Ig_TMEM132_6thDomain

Pfam: PF15705, PF15706, PF16070, PF23039, PF23481, PF23486, PF23487

UniProt features (20 total): region of interest 5, compositionally biased region 4, glycosylation site 4, topological domain 2, signal peptide 1, chain 1, sequence variant 1, sequence conflict 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q6IEE7-F172.440.39

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Glycosylation sites (4): 70, 91, 318, 399

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 102 (showing top): GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, LFA1_Q6, GOBP_NEUROGENESIS, AP2_Q3, USF_C, GOBP_EPIDERMAL_CELL_DIFFERENTIATION, CEBP_Q2, USF_01, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_DN, HIF1_Q3, GOBP_EPIDERMIS_DEVELOPMENT, GOBP_MECHANORECEPTOR_DIFFERENTIATION, AACTTT_UNKNOWN, MYB_Q3

GO Biological Process (1): posterior lateral line neuromast hair cell development (GO:0035677)

GO Molecular Function (0):

GO Cellular Component (2): membrane (GO:0016020), cell body (GO:0044297)

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
cellular anatomical structure2
neuromast hair cell development1
posterior lateral line neuromast hair cell differentiation1

Protein interactions and networks

STRING

642 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
TMEM132ETMEM221A6NGB7590
TMEM132ECYLC1P35663516
TMEM132EMFSD12Q6NUT3498
TMEM132EWDR27A2RRH5469
TMEM132ELHFPL7Q6ICI0463
TMEM132EGPR137CQ8N3F9460
TMEM132EZC4H2Q9NQZ6443
TMEM132EOVOL3O00110441
TMEM132EOPHN1O60890432
TMEM132EGTF2IRD1Q9UHL9431
TMEM132ECAPN7Q9Y6W3400
TMEM132ETMEM171Q8WVE6398
TMEM132ECCDC198Q9NVL8395
TMEM132EFRMPD3Q5JV73394
TMEM132ENXPE2Q96DL1387
TMEM132ETMEM150CB9EJG8387

IntAct

3 interactions, top by confidence:

ABTypeScore
C1orf54AGRNpsi-mi:“MI:0914”(association)0.350
SLC30A7ESYT2psi-mi:“MI:0914”(association)0.350

BioGRID (8): TMEM132E (Affinity Capture-MS), TMEM132E (Affinity Capture-MS), TMEM132E (Co-fractionation), TMEM132E (Co-fractionation), TMEM132E (Co-fractionation), TMEM132E (Co-fractionation), TMEM132E (Co-fractionation), TMEM132E (Affinity Capture-MS)

ESM2 similar proteins: A0JPH4, A2AWP8, A2RRU4, A2SXS5, A4D2P6, A6QM06, D4A6L0, E1BBQ2, E9Q6C8, F1LQY6, O00255, O88559, O94827, P29590, P56726, P97260, P97698, Q0GA42, Q0P5I0, Q0VF94, Q12770, Q17RQ9, Q29RM4, Q49LS8, Q5GH57, Q5GH73, Q5MNU5, Q5SNT2, Q5T848, Q69Z89, Q6DVA0, Q6GQT6, Q6IEE7, Q70EL4, Q8BUM9, Q8C190, Q8C419, Q8NC56, Q8TCT7, Q91ZP9

Diamond homologs: L7VG99, Q14C87, Q14DG7, Q24JP5, Q6IEE6, Q6IEE7, Q76HP2, Q76HP3, Q80WF4, Q8CEF9, Q8N3T6, Q922P8

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

413 variants total. Per-class counts are floors (≥ shown; pagination cap):

ClassificationCount (floor)
Pathogenic3
Likely pathogenic1
Uncertain significance223
Likely benign137
Benign38

Top pathogenic / likely-pathogenic (4)

Variant IDHGVSClassification
3778948NC_000017.10:g.(?32944559)(32945161_?)dupPathogenic
3778953NM_001304438.2(TMEM132E):c.67+22403_68-22210delPathogenic
3779448NM_001304438.2(TMEM132E):c.67+6798_67+6799dupPathogenic
3779450NC_000017.10:g.32936661_32969071dupLikely pathogenic

SpliceAI

1669 predictions. Top by Δscore:

VariantEffectΔscore
17:34581141:ACGG:Adonor_loss1.0000
17:34581144:G:Cdonor_loss1.0000
17:34581144:G:GGdonor_gain1.0000
17:34581145:T:Gdonor_loss1.0000
17:34626978:G:Tdonor_gain1.0000
17:34627055:CAGG:Cdonor_loss1.0000
17:34627057:GG:Gdonor_loss1.0000
17:34629002:A:AGacceptor_gain1.0000
17:34629002:ACCCT:Aacceptor_gain1.0000
17:34629003:C:Gacceptor_gain1.0000
17:34629006:T:Aacceptor_gain1.0000
17:34629010:AG:Aacceptor_gain1.0000
17:34629011:G:GTacceptor_gain1.0000
17:34629011:GG:Gacceptor_gain1.0000
17:34629175:G:GTdonor_gain1.0000
17:34630003:T:TAacceptor_gain1.0000
17:34630004:GCA:Gacceptor_loss1.0000
17:34630005:CA:Cacceptor_loss1.0000
17:34630006:A:ACacceptor_loss1.0000
17:34630006:A:AGacceptor_gain1.0000
17:34630006:AG:Aacceptor_gain1.0000
17:34630007:G:GCacceptor_gain1.0000
17:34630007:GG:Gacceptor_gain1.0000
17:34630007:GGA:Gacceptor_gain1.0000
17:34630007:GGAC:Gacceptor_gain1.0000
17:34630007:GGACA:Gacceptor_gain1.0000
17:34630150:AG:Adonor_loss1.0000
17:34630151:GG:Gdonor_loss1.0000
17:34630152:GTGG:Gdonor_loss1.0000
17:34630153:T:Gdonor_loss1.0000

AlphaMissense

6884 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
17:34626518:G:CW153C1.000
17:34626518:G:TW153C1.000
17:34629097:T:AW411R1.000
17:34629097:T:CW411R1.000
17:34629099:G:CW411C1.000
17:34629099:G:TW411C1.000
17:34630025:C:AN452K1.000
17:34630025:C:GN452K1.000
17:34632816:T:AV532D1.000
17:34632818:T:AW533R1.000
17:34632818:T:CW533R1.000
17:34632820:G:CW533C1.000
17:34632820:G:TW533C1.000
17:34632825:C:AP535H1.000
17:34632881:T:AW554R1.000
17:34632881:T:CW554R1.000
17:34632883:G:CW554C1.000
17:34632883:G:TW554C1.000
17:34634912:T:CF601S1.000
17:34634912:T:GF601C1.000
17:34637688:T:AL894Q1.000
17:34637688:T:CL894P1.000
17:34637693:G:CG896R1.000
17:34637699:T:CF898L1.000
17:34637701:C:AF898L1.000
17:34637701:C:GF898L1.000
17:34637702:T:CC899R1.000
17:34637720:T:CF905L1.000
17:34637722:C:AF905L1.000
17:34637722:C:GF905L1.000

dbSNP variants (sampled 300 via entrez): RS1000020337 (17:34577875 G>A,T), RS1000055974 (17:34616120 C>G), RS1000079695 (17:34611612 G>T), RS1000129478 (17:34620973 A>G), RS1000161989 (17:34620771 C>T), RS1000167758 (17:34578267 G>A,C), RS1000191876 (17:34615805 C>G), RS1000270934 (17:34615335 C>T), RS1000329418 (17:34588316 A>C,G), RS1000446061 (17:34582803 A>C), RS1000466158 (17:34619743 C>T), RS1000476105 (17:34615560 A>G), RS1000524286 (17:34614605 G>T), RS1000561222 (17:34581821 G>A,C,T), RS1000599161 (17:34582590 G>C)

Disease associations

OMIM: gene MIM:616178 | disease phenotypes: MIM:618481, MIM:612555, MIM:114480

GenCC curated gene-disease

DiseaseClassificationInheritance
hearing loss, autosomal recessive 99StrongAutosomal recessive
hearing loss, autosomal recessiveSupportiveAutosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

DiseaseClassificationInheritance
hearing loss, autosomal recessiveLimitedAR

Mondo (5): hearing loss, autosomal recessive 99 (MONDO:0032776), BRCA2-related cancer predisposition (MONDO:0700269), breast-ovarian cancer, familial, susceptibility to, 2 (MONDO:0012933), hereditary breast carcinoma (MONDO:0016419), hearing loss, autosomal recessive (MONDO:0019588)

Orphanet (2): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), Hereditary breast cancer (Orphanet:227535)

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPOTerm
HP:0000007Autosomal recessive inheritance
HP:0000407Sensorineural hearing impairment
HP:0001751Abnormal vestibular function
HP:0003577Congenital onset

GWAS associations

5 associations (top):

StudyTraitp-value
GCST002111_5Personality dimensions2.000000e-06
GCST002266_2Lobular breast cancer (menopausal hormone therapy interaction)3.000000e-06
GCST002337_43Amyotrophic lateral sclerosis (sporadic)1.000000e-07
GCST003981_4Insomnia2.000000e-08
GCST008154_58Trunk fat mass5.000000e-06

EFO canonical traits (3, from GWAS)

EFO IDTrait name
EFO:0004365personality trait
EFO:0003961hormone replacement therapy
EFO:0007876insomnia measurement

MeSH disease descriptors (2)

DescriptorNameTree numbers
C562840Breast Cancer, Familial (supp.)
C564609Deafness, Autosomal Recessive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

16 total (human), top 16 by PubMed support.

ChemicalActions (top 5)PubMed papers
mercuric bromidedecreases expression, affects cotreatment2
Phenylmercuric Acetateaffects cotreatment, decreases expression2
methylmercuric chloridedecreases expression1
bisphenol Aaffects cotreatment, decreases methylation1
butyraldehydeincreases expression1
CGP 52608affects binding, increases reaction1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamideaffects cotreatment, decreases expression1
abrineincreases expression1
dorsomorphinaffects cotreatment, decreases expression1
theaflavin-3,3’-digallateaffects expression1
Fulvestrantaffects cotreatment, decreases methylation1
Atrazineincreases expression1
Benzo(a)pyreneincreases methylation1
Valproic Acidincreases expression1
1-Methyl-4-phenylpyridiniumincreases expression1
Aflatoxin B1decreases methylation1

Clinical trials (associated diseases)

10 trials via MONDO — disease-level, not drug-specific.

TrialPhaseStatusTitle
NCT00040222Not specifiedCOMPLETEDClinical, Genetic, Behavioral, Laboratory and Epidemiologic Characterization of Individuals and Families at High Risk of Breast/Ovarian Cancer
NCT02557776Not specifiedCOMPLETEDWritten Genetic Counseling and Mutation Analysis of BRCA1 and BRCA2 to Patients With Breast Cancer
NCT03495544Not specifiedUNKNOWNStudy Estimating Association Between Germline Mutations and PD-L1 Expression in Breast Cancer
NCT03959267Not specifiedCOMPLETEDTesting a Culturally Adapted Telephone Genetic Counseling Intervention
NCT04058418Not specifiedCOMPLETEDSpecialist Recommendation on FBC (Familial Breast Cancer) Chemoprevention Prescribing
NCT04125914Not specifiedACTIVE_NOT_RECRUITINGWeight Management and Health Behavior Intervention in Lowering Cancer Risk for BRCA Positive and Lynch Syndrome Families
NCT04169542Not specifiedRECRUITINGImpact of COVID-19 Pandemic on Out-of-Pocket Costs, Lost Wages, and Unemployment in Patients With Breast Cancer Undergoing Breast Surgery
NCT04197856Not specifiedACTIVE_NOT_RECRUITINGDirect Information to At-risk Relatives
NCT07292246Not specifiedRECRUITINGA Prospective CohorT Study of HandX - Assisted ENdoscopic MAstectomy: Feasibility and Safety (ATHENA I Study)
NCT07307664Not specifiedRECRUITINGIncreasing Germline Genetic Testing for Patients With Cancer

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 74

This page pulls from 74 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomerefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot