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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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TMC1
transmembrane channel like 1
Chromosome 9 · 9q21.13
NCBI Gene: 117531Ensembl: ENSG00000165091.18HGNC: HGNC:16513UniProt: Q8TDI8
62PubMed Papers
22Diseases
0Drugs
173Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
RESEARCH IMPACT
Variant-Rich
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
plasma membranecalcium channel activityvoltage-gated calcium channel activitystereociliumautosomal recessive nonsyndromic hearing loss 7autosomal dominant nonsyndromic hearing loss 36deafnessautosomal dominant nonsyndromic hearing loss
✦AI Summary

TMC1 (transmembrane channel-like 1) encodes a pore-forming subunit of the mechanotransducer (MET) ion channel complex essential for auditory and vestibular sensory transduction. Located at the tips of stereocilia in cochlear and vestibular hair cells, TMC1 directly senses mechanical stimuli and mediates calcium and cation influx 12. The protein functions as a mechanically gated ion channel activated by tension in tip-links connecting adjacent stereocilia; recent studies overcame previous technical barriers by demonstrating that membrane-localized TMC1 responds robustly to mechanical stimuli in heterologous cells and exhibits stretch-activated currents 13. TMC1 operates within a larger MET complex including auxiliary proteins LHFPL5, TMIE, CIB2/3, TOMT, and PCDH15, and functions redundantly with TMC2 in mechanotransduction 3. Pathogenic TMC1 variants cause nonsyndromic hearing loss, including both autosomal dominant (DFNA36) and recessive (DFNB7) forms, with TMC1 identified as a high-frequency deafness gene in multiple populations 4. Additionally, heterozygous TMC1 variants contribute to age-related hearing loss severity 5, and TMC1 was identified as a promising candidate for gene therapy interventions 6. Recent evidence indicates TMC1 also functions in vestibular mechanotransduction through interactions with mechanosensitive signaling proteins 7.

Sources cited
1
Human TMC1 and TMC2 are mechanically gated ion channels that respond to poking stimuli with stretch-activated currents and single-channel activity; deafness-related TMC1 mutations alter reversal potential
PMID: 39674179
2
TMC1 and TMC2 proteins are pore-forming subunits of mechanosensitive ion channels; purified proteins reconstituted in liposomes possess ion channel activity and respond to mechanical pressure
PMID: 31761710
3
TMC1/2 are mechanically gated ion channels in auditory mechanotransduction; expressed at stereocilia tips; recent in vitro studies confirmed TMC1/2 are mechanically activated ion channels
PMID: 40280017
4
TMC1 is among the most common deafness genes in a Chinese cohort of deaf children; detected in multiple cases with pathogenic variants
PMID: 36597107
5
Ultrarare heterozygous TMC1 pathogenic variants underlie severe presbycusis; TMC1:p.(Asn327Ile) variant was established as a mouse model for monogenic presbycusis
PMID: 33229591
6
TMC1 was identified as a promising candidate gene for hearing loss gene therapy based on favorable evaluation criteria including gene size, cochlear degradation timing, and efficacy in mouse models
PMID: 39951658
7
TMC1 is a representative molecular target shared between hearing loss and neurodegenerative processes, involved in auditory and neurodegenerative pathways
PMID: 40499729
8
TMC1 functions in vestibular mechanotransduction; LPHN2 converts force stimuli into increased open probability of TMC1 in utricular hair cells
PMID: 39966628
Disease Associationsⓘ22
autosomal recessive nonsyndromic hearing loss 7Open Targets
0.77Strong
autosomal dominant nonsyndromic hearing loss 36Open Targets
0.75Strong
deafnessOpen Targets
0.70Moderate
autosomal dominant nonsyndromic hearing lossOpen Targets
0.68Moderate
hearing loss, autosomal recessiveOpen Targets
0.64Moderate
nonsyndromic genetic hearing lossOpen Targets
0.63Moderate
Rare genetic deafnessOpen Targets
0.55Moderate
Hearing impairmentOpen Targets
0.47Moderate
Sensorineural hearing impairmentOpen Targets
0.40Moderate
Non-syndromic genetic deafnessOpen Targets
0.39Weak
hearing lossOpen Targets
0.39Weak
Abnormality of the earOpen Targets
0.34Weak
ear malformationOpen Targets
0.34Weak
Delayed speech and language developmentOpen Targets
0.33Weak
Moderate intellectual disabilityOpen Targets
0.33Weak
MutismOpen Targets
0.30Weak
liver diseaseOpen Targets
0.27Weak
tooth diseaseOpen Targets
0.27Weak
EpiphoraOpen Targets
0.27Weak
sensorineural hearing lossOpen Targets
0.27Weak
Deafness, autosomal dominant, 36UniProt
Deafness, autosomal recessive, 7UniProt
Pathogenic Variants173
NM_138691.3(TMC1):c.884+1G>APathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 7
★★☆☆2026
NM_138691.3(TMC1):c.1763+3A>GPathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 7|Autosomal dominant nonsyndromic hearing loss 36|Nonsyndromic genetic hearing loss|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36|Monogenic hearing loss
★★☆☆2026
NM_138691.3(TMC1):c.1166G>A (p.Arg389Gln)Pathogenic
not provided|Nonsyndromic genetic hearing loss|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025→ Residue 389
NM_138691.3(TMC1):c.332G>A (p.Trp111Ter)Pathogenic
not provided
★★☆☆2025→ Residue 111
NM_138691.3(TMC1):c.64+2T>APathogenic
Autosomal recessive nonsyndromic hearing loss 7|not provided
★★☆☆2025
NM_138691.3(TMC1):c.1714G>C (p.Asp572His)Pathogenic
Autosomal dominant nonsyndromic hearing loss 36|Monogenic hearing loss|not provided
★★☆☆2025→ Residue 572
NM_138691.3(TMC1):c.1165C>T (p.Arg389Ter)Pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 7|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025→ Residue 389
NM_138691.3(TMC1):c.674C>T (p.Pro225Leu)Likely pathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025→ Residue 225
NM_138691.3(TMC1):c.2050G>C (p.Asp684His)Pathogenic
not provided|TMC1-related disorder|Autosomal dominant nonsyndromic hearing loss 36;Autosomal recessive nonsyndromic hearing loss 7|Autosomal recessive nonsyndromic hearing loss 7
★★☆☆2025→ Residue 684
NM_138691.3(TMC1):c.589G>A (p.Gly197Arg)Pathogenic
not provided|Nonsyndromic genetic hearing loss
★★☆☆2025→ Residue 197
NM_138691.3(TMC1):c.1405-2A>TLikely pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025
NM_138691.3(TMC1):c.1534C>T (p.Arg512Ter)Pathogenic
not provided|Autosomal recessive nonsyndromic hearing loss 7|Autosomal dominant nonsyndromic hearing loss 36;Autosomal recessive nonsyndromic hearing loss 7
★★☆☆2025→ Residue 512
NM_138691.3(TMC1):c.100C>T (p.Arg34Ter)Pathogenic
Autosomal recessive nonsyndromic hearing loss 7|Rare genetic deafness|not provided|Hearing loss, autosomal recessive|Autosomal dominant nonsyndromic hearing loss 36|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025→ Residue 34
NM_138691.3(TMC1):c.2030T>C (p.Ile677Thr)Pathogenic
not provided|Autosomal dominant nonsyndromic hearing loss 36;Autosomal recessive nonsyndromic hearing loss 7|Autosomal recessive nonsyndromic hearing loss 7
★★☆☆2025→ Residue 677
NM_138691.3(TMC1):c.582G>A (p.Trp194Ter)Pathogenic
not provided
★★☆☆2025→ Residue 194
NM_138691.3(TMC1):c.2130-1delPathogenic
not provided
★★☆☆2025
NM_138691.3(TMC1):c.236+1G>TPathogenic
not provided
★★☆☆2025
NM_138691.3(TMC1):c.1810C>T (p.Arg604Ter)Pathogenic
Hearing loss, autosomal recessive|not provided|Autosomal recessive nonsyndromic hearing loss 7;Autosomal dominant nonsyndromic hearing loss 36
★★☆☆2025→ Residue 604
NM_138691.3(TMC1):c.741+1G>APathogenic
Rare genetic deafness|not provided|Autosomal recessive nonsyndromic hearing loss 7
★★☆☆2025
NM_138691.3(TMC1):c.1398CAA[1] (p.Asn467del)Likely pathogenic
not provided|Nonsyndromic genetic hearing loss
★★☆☆2024→ Residue 467
View on ClinVar ↗
Related Genes
USH1GProtein interaction100%CIB3Protein interaction98%TMIEProtein interaction95%SLC26A4Protein interaction84%OTOFProtein interaction84%TMPRSS3Protein interaction84%
Tissue Expression6 tissues
Brain
100%
Heart
53%
Ovary
40%
Liver
11%
Lung
8%
Bone Marrow
4%
Gene Interaction Network
Click a node to explore
TMC1USH1GCIB3TMIESLC26A4OTOFTMPRSS3
PROTEIN STRUCTURE
Preparing viewer…
PDB8XOQ · 2.41 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.91LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.62–0.91]
RankingsWhere TMC1 stands among ~20K protein-coding genes
  • #7,517of 20,598
    Most Researched62
  • #425of 5,498
    Most Pathogenic Variants173 · top 10%
  • #8,353of 17,882
    Most Constrained (LOEUF)0.91
Genes detectedTMC1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human TMC1 and TMC2 are mechanically gated ion channels.
PMID: 39674179
Neuron · 2025
1.00
2
Genetic screening of a Chinese cohort of children with hearing loss using a next-generation sequencing panel.
PMID: 36597107
Hum Genomics · 2023
0.90
3
Gene Therapy for Hearing Loss: Which Genes Next?
PMID: 39951658
Otol Neurotol · 2025
0.80
4
TMC1 and TMC2 Proteins Are Pore-Forming Subunits of Mechanosensitive Ion Channels.
PMID: 31761710
Neuron · 2020
0.70
5
TMC1 and TMC2 function as the mechano-electrical transduction ion channel in hearing.
PMID: 40280017
Curr Opin Neurobiol · 2025
0.60