TMC2
protein-codingtransmembrane channel like 2, the group of Transmembrane channel like family
Gene summary
This gene encodes a transmembrane protein that is necesssary for mechanotransduction in cochlear hair cells of the inner ear. Mutations in this gene may underlie hereditary disorders of balance and hearing. [provided by RefSeq, Aug 2015]
- C20orf145
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~107.0 kbGenCC 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 TMC2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_080751.3. 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 | 2 | 3 | |||
| missense | 139 | 7 | 146 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 140 | 10 | 0 | 150 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_542789.2 | 20 | MANE Select | |
| Ensembl | ENSP00000351732.1 | 20 | MANE Select | |
| Ensembl | ENSP00000495303.1 | 4 | Standard | |
| RefSeq | XP_005260717.1 | 18 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- detection of mechanical stimulus involved in sensory perception of sound
- vestibular reflex
- calcium ion transmembrane transport
- regulation of calcium ion transmembrane transport
Molecular Function
- molecular_function
- ion channel activity
- voltage-gated calcium channel activity
- mechanosensitive ion channel activity
Cellular Component
- cellular_component
- integral component of plasma membrane
- stereocilium tip
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000358864
- Coding exons
- 20
- Length
- 105178
- Individuals with no LoFs
- 124688
- Homozygous LoFs
- 5
- Heterozygous LoFs
- 1055
- Defined
- 125748
- p
- 0.00422
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.226 | 492 | 506 | 0.972 | 0.0000272 | 5915 |
| Missense (PolyPhen) | 213 | 197.31 | 1.0795 | 2284 | ||
| Synonymous | 0.742 | 184 | 197 | 0.933 | 0.0000109 | 1756 |
| Loss of Function | 0.679 | 44 | 49.1 | 0.895 | 0.00000277 | 534 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0030 | 0.0030 | notable |
| Latino/Admixed American | 0.0028 | 0.0028 | notable |
| Ashkenazi Jewish | 0.0022 | 0.0022 | notable |
| East Asian | 0.00038 | 0.00038 | rare |
| Finnish | 0.00097 | 0.00097 | rare |
| European (Non-Finnish) | 0.0072 | 0.0071 | notable |
| South Asian | 0.0010 | 0.00098 | notable |
| Other | 0.0041 | 0.0041 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable ion channel required for the normal function of cochlear hair cells (PubMed:11850618). Component of the hair cell's mechanotransduction (MET) machinery. Involved in mechanosensitive responses of the hair cells (By similarity). {ECO:0000250|UniProtKB:E7FFT2, ECO:0000269|PubMed:11850618}.;
Recessive Scores
- pRec
- 0.104
Intolerance Scores
- LoFtool
- 0.934
- RVIS EVS
- 0.3
- RVIS percentile EVS
- 71.68
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.150
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |