TMC3

protein-coding

transmembrane channel like 3, the group of Transmembrane channel like family

Gene summary

Predicted to enable mechanosensitive monoatomic ion channel activity. Predicted to be involved in monoatomic ion transmembrane transport. Located in cytosol. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001080532.3

Inheritance

—

ClinVar variants

U:185B:10

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.79

Max pathogenic AF

—

Genomic locus

chr15:81,331,088-81,374,213

External References & Databases

Ensembl (ENSG00000188869)

Transcript & Mutation Effects

hg38 • Region Span ~43.1 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 TMC3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 181

not providedTotal: 3

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001080532.3. 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	2 clinvar		3
missense			181 clinvar	7 clinvar		188
nonsense			1 clinvar		1 clinvar	2
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	185	9	1	195

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 5 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001080532.3	RefSeq	NP_001074001.1	22	MANE Select
ENST00000359440.6	Ensembl	ENSP00000352413.5	22	MANE Select
ENST00000558726.5	Ensembl	ENSP00000452681.1	22	Standard
ENST00000558726.6	Ensembl	ENSP00000452681.1	22	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

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000359440
Coding exons: 22
Length: 42997
Individuals with no LoFs: 124497
Homozygous LoFs: 1
Heterozygous LoFs: 161
Defined: 124659
p: 0.000650

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.514	582	618	0.942	0.0000347	7196
Missense (PolyPhen)		137	158.04	0.86686		1958
Synonymous	0.335	237	244	0.973	0.0000148	2100
Loss of Function	1.35	39	49.2	0.792	0.00000259	543

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00093	0.00090	rare
Latino/Admixed American	0.00032	0.00032	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00050	0.00050	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00091	0.00089	rare
South Asian	0.00078	0.00072	rare
Other	0.00085	0.00083	rare

dbNSFP Gene Annotations

Source: dbNSFP

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

Recessive Scores

pRec: 0.124

Intolerance Scores

LoFtool: 0.878
RVIS EVS: 1.48
RVIS percentile EVS: 95.29

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.111

Gene Damage Prediction

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