TMC1

transmembrane channel like 1, the group of Transmembrane channel like family

Basic information

Region (hg38): 9:72521608-72838297

Previous symbols: [ "DFNA36", "DFNB7", "DFNB11" ]

Links

ENSG00000165091

∙ NCBI:117531 ∙ OMIM:606706 ∙ HGNC:16513 ∙ Uniprot:Q8TDI8 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

autosomal dominant nonsyndromic hearing loss 36 (Strong), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 7 (Strong), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss (Supportive), mode of inheritance: AD
hearing loss, autosomal recessive (Supportive), mode of inheritance: AR
nonsyndromic genetic hearing loss (Strong), mode of inheritance: Semidominant
autosomal dominant nonsyndromic hearing loss 36 (Strong), mode of inheritance: AD
autosomal recessive nonsyndromic hearing loss 7 (Strong), mode of inheritance: AR
autosomal recessive nonsyndromic hearing loss 7 (Definitive), mode of inheritance: AR
nonsyndromic genetic hearing loss (Definitive), mode of inheritance: AD
autosomal dominant nonsyndromic hearing loss 36 (Moderate), mode of inheritance: AD
autosomal recessive nonsyndromic hearing loss 7 (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Deafness, autosomal recessive 7	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic	11850618; 17250663; 18616530; 23226338; 24827932; 34523024

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the TMC1 gene.

not provided (43 variants)
Autosomal recessive nonsyndromic hearing loss 7 (33 variants)
Rare genetic deafness (7 variants)
Autosomal dominant nonsyndromic hearing loss 36;Autosomal recessive nonsyndromic hearing loss 7 (5 variants)
Hearing loss, autosomal recessive (5 variants)
Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36 (4 variants)
Autosomal dominant nonsyndromic hearing loss 36 (2 variants)
Deafness (2 variants)
Nonsyndromic genetic hearing loss (1 variants)
Ear malformation (1 variants)
Hearing impairment (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the TMC1 gene is commonly pathogenic or not. These statistics are base on trasncript: . Only rare variants are included in the table.

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			4 clinvar	148 clinvar	1 clinvar	153
missense	5 clinvar	20 clinvar	169 clinvar	3 clinvar	1 clinvar	198
nonsense	28 clinvar	8 clinvar	1 clinvar			37
start loss						0
frameshift	27 clinvar	8 clinvar	2 clinvar			37
splice donor/acceptor (+/-2bp)	17 clinvar	15 clinvar	1 clinvar			33
Total	77	51	177	151	2

Highest pathogenic variant AF is 0.000289071

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
TMC1	protein_coding	protein_coding	ENST00000297784	20	314551

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
9.18e-19	0.359	125549	0	199	125748	0.000792

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.858	350	398	0.879	0.0000208	5063
Missense in Polyphen		106	129.51	0.81846		1717
Synonymous	-0.256	146	142	1.03	0.00000813	1353
Loss of Function	1.69	35	47.6	0.736	0.00000265	552

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000975	0.000975
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000548	0.000544
Finnish	0.00333	0.00333
European (Non-Finnish)	0.000637	0.000633
Middle Eastern	0.000548	0.000544
South Asian	0.000524	0.000523
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Probable ion channel required for the normal function of cochlear hair cells. {ECO:0000250}.;
Disease: DISEASE: Deafness, autosomal recessive, 7 (DFNB7) [MIM:600974]: A form of non-syndromic 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. {ECO:0000269|PubMed:11850618}. Note=The disease is caused by mutations affecting the gene represented in this entry.;

Recessive Scores

pRec: 0.171

Intolerance Scores

loftool: 0.819
rvis_EVS: -0.64
rvis_percentile_EVS: 16.68

Haploinsufficiency Scores

pHI: 0.117
hipred: Y
hipred_score: 0.540
ghis: 0.432

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: N
gene_indispensability_score: 0.209

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Tmc1
Phenotype: behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype;

Gene ontology

Biological process: detection of mechanical stimulus involved in sensory perception of sound;vestibular reflex;auditory receptor cell development;calcium ion transmembrane transport;regulation of calcium ion transmembrane transport
Cellular component: integral component of plasma membrane;external side of plasma membrane;stereocilium tip
Molecular function: ion channel activity;voltage-gated calcium channel activity;mechanosensitive ion channel activity