TMC4

protein-coding

transmembrane channel like 4, the group of Transmembrane channel like family

Gene summary

Enables voltage-gated chloride channel activity. Predicted to be involved in sensory perception of salty taste. Located in extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_144686.4

Inheritance

—

ClinVar variants

U:112B:11

Top phenotype

TMC4-related disorder

gnomAD constraint

pLI —, LoF o/e 0.72

Max pathogenic AF

—

Genomic locus

chr19:54,160,108-54,173,250

External References & Databases

Ensembl (ENSG00000167608)

Transcript & Mutation Effects

hg38 • Region Span ~13.1 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to TMC4 variants in ClinVar

4 Conditions Cataloged

not specifiedTotal: 103

TMC4-related disorderTotal: 5

not providedTotal: 3

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_144686.4. 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	3 clinvar		4
missense			103 clinvar	8 clinvar		111
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			8 clinvar			8
Total	0	0	112	11	0	123

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 44 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_144686.4	RefSeq	NP_653287.2	15	MANE Select
ENST00000619895.5	Ensembl	ENSP00000479458.1	15	MANE Select
NM_001145303.3	RefSeq	NP_001138775.2	15	Standard
ENST00000446291.1	Ensembl	ENSP00000416444.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

ion transmembrane transport

Molecular Function

ion channel activity
mechanosensitive ion channel activity

Cellular Component

integral component of plasma membrane
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000376591
Coding exons: 15
Length: 13099
Individuals with no LoFs: 125592
Homozygous LoFs: 0
Heterozygous LoFs: 156
Defined: 125748
p: 0.000620

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.07	346	407	0.851	0.0000238	4437
Missense (PolyPhen)		96	122.03	0.78669		1381
Synonymous	0.483	175	183	0.955	0.0000108	1569
Loss of Function	1.53	25	34.8	0.719	0.00000174	370

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00050	0.00049	rare
Latino/Admixed American	0.00033	0.00032	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00060	0.00054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00078	0.00076	rare
South Asian	0.0013	0.0013	notable
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable ion channel. {ECO:0000250}.;

Recessive Scores

pRec: 0.0868

Intolerance Scores

RVIS EVS: 0.67
RVIS percentile EVS: 84.68

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.308

Gene Damage Prediction

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