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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TMC2
transmembrane channel like 2
Chromosome 20 · 20p13
NCBI Gene: 117532Ensembl: ENSG00000149488.14HGNC: HGNC:16527UniProt: Q8TDI7
23PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
detection of mechanical stimulus involved in sensory perception of soundstereociliumcalcium channel activitycuticular plateneurodegenerative diseaseovarian neoplasmspontaneous abortionneuropathy
✦AI Summary

TMC2 (transmembrane channel-like 2) is a pore-forming subunit of the mechanotransducer (MET) ion channel complex located at stereocilia tips in cochlear and vestibular hair cells 1. TMC2 functions as a mechanically-gated, non-selective cation channel that converts mechanical vibrations into electrical signals essential for auditory mechanotransduction 23. The channel is highly permeable to calcium and transports monovalent cations, responding to tension in tip-links connecting stereocilia 4. TMC2 operates as a pore-forming subunit alone or as part of a dimeric complex 5, with activity modulated by auxiliary proteins including TMIE, CIB2, LHFPL5, and PCDH15 67. Mutations in TMC2 disrupt mechanotransduction and cause hearing loss, with deafness-related variants altering ion selectivity properties 2. TMC2 also participates in vestibular mechanotransduction, contributing to balance and spatial orientation 4. The channel's subcellular localization and functional assembly depend on interactions with regulatory proteins, though TMC2 shows greater developmental flexibility than TMC1 regarding these cofactors 8.

Sources cited
1
TMC2 is a pore-forming subunit of the MET channel complex at stereocilia tips mediating auditory sensory transduction
PMID: 11850618
2
Human TMC2 is a mechanically-gated ion channel; deafness mutations alter reversal potential indicating pore-forming function
PMID: 39674179
3
TMC2 proteins are pore-forming subunits of mechanosensitive ion channels that directly respond to mechanical stimuli
PMID: 31761710
4
TMC2 functions as the mechano-electrical transduction ion channel in hearing through mechanically-gated mechanisms
PMID: 40280017
5
Mouse TMC2 alone forms mechanosensitive channels; TMIE modulates TMC2 gating; TMC2 constitutes the sole pore-forming subunit
PMID: 39999170
6
CIB2 interacts with TMC2 and is essential for mechanotransduction in auditory hair cells
PMID: 28663585
7
TMC2 is located at stereocilia tips, required for hair cell mechanotransduction, and assembles as part of mechanotransduction complex
PMID: 30291150
8
TMC2-driven developmental channels do not require LOXHD1 for maintaining localization at the tip link, unlike TMC1
PMID: 39256406
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.41Moderate
ovarian neoplasmOpen Targets
0.34Weak
spontaneous abortionOpen Targets
0.26Weak
neuropathyOpen Targets
0.13Weak
optic neuritisOpen Targets
0.13Weak
macular degenerationOpen Targets
0.13Weak
bone remodeling diseaseOpen Targets
0.12Weak
deafnessOpen Targets
0.02Suggestive
esophageal adenocarcinomaOpen Targets
0.02Suggestive
posterior cortical atrophyOpen Targets
0.01Suggestive
Cornelia de Lange syndromeOpen Targets
0.01Suggestive
Hearing impairmentOpen Targets
0.01Suggestive
cancerOpen Targets
0.00Suggestive
neoplasmOpen Targets
0.00Suggestive
SepsisOpen Targets
0.00Suggestive
hearing lossOpen Targets
0.00Suggestive
cardiovascular diseaseOpen Targets
0.00Suggestive
colorectal cancerOpen Targets
0.00Suggestive
ovarian serous cystadenocarcinomaOpen Targets
0.00Suggestive
Testicular Germ Cell TumorOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CIB3Protein interaction85%MYO7AProtein interaction75%USH1CProtein interaction75%CIB2Protein interaction75%WHRNProtein interaction75%CDH23Protein interaction75%
Tissue Expression6 tissues
Lung
100%
Ovary
66%
Brain
50%
Liver
8%
Bone Marrow
3%
Heart
0%
Gene Interaction Network
Click a node to explore
TMC2CIB3MYO7AUSH1CCIB2WHRNCDH23
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q8TDI7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.15LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.96 [0.80–1.15]
RankingsWhere TMC2 stands among ~20K protein-coding genes
  • #13,543of 20,598
    Most Researched23
  • #12,000of 17,882
    Most Constrained (LOEUF)1.15
Genes detectedTMC2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human TMC1 and TMC2 are mechanically gated ion channels.
PMID: 39674179
Neuron · 2025
1.00
2
TMC1 and TMC2 Proteins Are Pore-Forming Subunits of Mechanosensitive Ion Channels.
PMID: 31761710
Neuron · 2020
0.90
3
TMC1 and TMC2 function as the mechano-electrical transduction ion channel in hearing.
PMID: 40280017
Curr Opin Neurobiol · 2025
0.80
4
Ectopic mouse TMC1 and TMC2 alone form mechanosensitive channels that are potently modulated by TMIE.
PMID: 39999170
Proc Natl Acad Sci U S A · 2025
0.70
5
CIB2 interacts with TMC1 and TMC2 and is essential for mechanotransduction in auditory hair cells.
PMID: 28663585
Nat Commun · 2017
0.60