TMEM132E

transmembrane protein 132E

Basic information

Region (hg38): 17:34579486-34639318

Links

ENSG00000181291 ∙ NCBI:124842 ∙ OMIM:616178 ∙ HGNC:26991 ∙ Uniprot:Q6IEE7 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hearing loss, autosomal recessive 99 (Moderate), mode of inheritance: AR
• hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
• hearing loss, autosomal recessive 99 (Limited), mode of inheritance: AR
• hearing loss, autosomal recessive 99 (Strong), mode of inheritance: AR
• hearing loss, autosomal recessive (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 99	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	25331638; 31656313

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMEM132E gene.

• not provided (164 variants)
• Inborn genetic diseases (48 variants)
• Hearing loss, autosomal recessive 99 (7 variants)
• not specified (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMEM132E gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	47	11	61
missense			93	5	5	103
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)			1			1
splice region			1			1
non coding				12	21	33
Total	0	0	98	64	37

Variants in TMEM132E

This is a list of pathogenic ClinVar variants found in the TMEM132E region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
17-34580843-G-A			Benign (May 15, 2021)
17-34581017-C-T			Benign (Nov 12, 2018)
17-34581045-T-C		Hearing loss, autosomal recessive 99	Benign (Sep 10, 2021)
17-34581103-C-T			Likely benign (Sep 26, 2022)
17-34581127-A-T			Likely benign (Oct 21, 2022)
17-34581134-C-T		not specified	Uncertain significance (Jul 29, 2023)
17-34581156-G-A			Likely benign (Jan 22, 2024)
17-34581191-T-C		Hearing loss, autosomal recessive 99	Benign (Sep 10, 2021)
17-34581198-G-A			Benign (May 15, 2021)
17-34625985-G-A			Benign (May 16, 2021)
17-34626120-T-C			Likely benign (Jul 31, 2023)
17-34626130-C-T		not specified	Uncertain significance (Dec 09, 2023)
17-34626143-C-G		not specified	Uncertain significance (Feb 26, 2024)
17-34626163-C-T			Uncertain significance (Jun 07, 2021)
17-34626169-C-T		not specified	Uncertain significance (Apr 07, 2022)
17-34626170-G-T		TMEM132E-related disorder	Likely benign (Jan 22, 2024)
17-34626181-C-T		not specified	Uncertain significance (Nov 13, 2023)
17-34626182-G-A			Likely benign (Mar 31, 2022)
17-34626188-G-A			Likely benign (Aug 04, 2023)
17-34626213-A-G		not specified	Uncertain significance (Dec 28, 2022)
17-34626234-C-G		not specified	Uncertain significance (Dec 20, 2023)
17-34626238-A-T		not specified	Uncertain significance (Feb 06, 2023)
17-34626239-G-A			Benign (Jan 31, 2024)
17-34626246-C-A		not specified	Uncertain significance (Jun 21, 2023)
17-34626250-C-T		not specified	Uncertain significance (Oct 12, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMEM132E	protein_coding	protein_coding	ENST00000321639	10	58570

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000449	1.00	125719	0	29	125748	0.000115

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.34	518	611	0.847	0.0000389	6196
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000292	0.000292
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000545	0.0000544
Finnish	0.000103	0.0000924
European (Non-Finnish)	0.000119	0.000114
Middle Eastern	0.0000545	0.0000544
South Asian	0.0000328	0.0000327
Other	0.000326	0.000326

dbNSFP

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

Haploinsufficiency Scores

• pHI: 0.366
• hipred: Y
• hipred_score: 0.589
• ghis: 0.569

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.272

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Tmem132e

Zebrafish Information Network

• Gene name: tmem132e
• Affected structure: auditory receptor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased functionality

Gene ontology

• Cellular component: integral component of membrane