TMC1 Gene: Transmembrane Channel-Like 1
Essential for Auditory Hair Cell Mechanotransduction
Gene Information Card
| Symbol | TMC1 |
|---|---|
| Full Name | Transmembrane Channel-Like 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 9q21.13 |
| NCBI Gene ID | 117531 ncbi.nlm.nih.gov/gene/117531 |
| Ensembl ID | ENSG00000165091 |
| UniProt ID | Q8TDI8 |
| OMIM ID | 606706 |
| HGNC ID | 19166 |
| Aliases | DFNA36, DFNB7/11, MGC138236 |
Description
TMC1 (Transmembrane Channel-Like 1) is a protein-coding gene located on chromosome 9q21.13. It encodes a multi-pass transmembrane protein that is a core component of the mechanotransduction channel in auditory hair cells. TMC1 is essential for converting sound-induced mechanical stimuli into electrical signals. Mutations in TMC1 are associated with both autosomal dominant (DFNA36) and autosomal recessive (DFNB7/11) nonsyndromic hearing loss.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Nonsyndromic hearing loss DFNA36 | Dominant missense mutations (e.g., p.Met418Lys) alter channel gating or conductance, leading to progressive hearing loss. | ClinVar, OMIM |
| Nonsyndromic hearing loss DFNB7/11 | Recessive loss-of-function mutations (e.g., nonsense, frameshift) abolish TMC1 protein function, causing congenital severe-to-profound hearing loss. | ClinVar, OMIM |
| Age-related hearing loss | Common variants in TMC1 may contribute to susceptibility to presbycusis. | NCBI Gene, GWAS catalog |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Cochlea | Not available (nTPM) | High (RNA-seq in mouse) |
| Testis | 0.2 | Low |
| Brain | 0.1 | Low |
| Lung | 0.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.1 | Low endogenous expression |
| Hair cell (inner ear) | Not available | High, specific expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1253T>A (p.Met418Lys) | Missense | Dominant, rare | Gain-of-function? Alters channel properties |
| c.100C>T (p.Arg34*) | Nonsense | Recessive, rare | Loss-of-function |
| c.776delG (p.Gly259Valfs*18) | Frameshift | Recessive, rare | Loss-of-function |
Mutation functional classification
Loss of Function (LOF)
Recessive mutations (nonsense, frameshift, splice-site) that truncate or destabilize TMC1 protein, leading to absence of mechanotransduction current in hair cells.
Gain of Function (GOF)
Dominant missense mutations (e.g., p.Met418Lys) that alter channel conductance or gating kinetics, possibly increasing resting current or altering calcium permeability.
Dominant Negative (DN)
Some dominant mutations may exert a dominant-negative effect by forming nonfunctional heteromeric channels with wild-type TMC1 or TMC2.
View complete mutation data：
Gene Ontology (GO)
| • intracellularly ATP-gated chloride channel activity (GO:0005254) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • sensory perception of sound (GO:0007605) |
| • integral component of membrane (GO:0016021) | • ion transmembrane transport (GO:0034220) |
Pathways
• Mechanotransduction in auditory hair cells
• Sensory perception of sound
Protein Summary
TMC1 is a multi-pass transmembrane protein (approximately 760 amino acids) localized to the plasma membrane of inner ear hair cell stereocilia. It forms a complex with TMC2 and other proteins (e.g., LHFPL5, TMIE) to constitute the mechanoelectrical transduction (MET) channel. The channel is gated by tip-link tension and conducts cations (primarily K+ and Ca2+) into the hair cell, depolarizing it and triggering auditory nerve signals. TMC1 is essential for normal hearing; loss of function leads to deafness.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| TMC1 Knockout HEK293 Cell Line | EDJ-KQ7609 | Human | 117531 | Details Get a Quote |
| TMC1 Knockout HeLa Cell Line | EDJ-KQ58018 | Human | 117531 | Details Get a Quote |
| TMC1 Knockout A-549 Cell Line | EDJ-KQ66505 | Human | 117531 | Details Get a Quote |
| TMC1 Knockout HCT 116 Cell Line | EDJ-KQ74924 | Human | 117531 | Details Get a Quote |
