TMC5
protein-codingtransmembrane channel like 5, 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 extracellular exosome. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~88.6 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 TMC5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001261841.2. 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 | 3 | 3 | ||||
| missense | 89 | 8 | 97 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 98 | 8 | 0 | 106 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001248770.1 | 20 | MANE Select | |
| Ensembl | ENSP00000446274.2 | 20 | MANE Select | |
| RefSeq | NP_001098718.1 | 20 | Standard | |
| RefSeq | NP_001098719.1 | 19 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| tmc5 | Danio rerio | Structure: otolith Quality: morphology abnormal |
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
- extracellular exosome
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000396229
- Coding exons
- 20
- Length
- 88618
- Individuals with no LoFs
- 125666
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 80
- Defined
- 125746
- p
- 0.000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.653 | 503 | 546 | 0.921 | 0.0000288 | 6640 |
| Missense (PolyPhen) | 100 | 133.58 | 0.7486 | 1727 | ||
| Synonymous | -0.754 | 219 | 205 | 1.07 | 0.0000112 | 1926 |
| Loss of Function | 3.81 | 21 | 50.1 | 0.419 | 0.00000247 | 591 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00031 | 0.00031 | rare |
| Latino/Admixed American | 0.00023 | 0.00017 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00033 | 0.00033 | rare |
| Finnish | 0.00074 | 0.00074 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00046 | 0.00046 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable ion channel. {ECO:0000250}.;
Recessive Scores
- pRec
- 0.0860
Intolerance Scores
- LoFtool
- 0.932
- RVIS EVS
- 0.79
- RVIS percentile EVS
- 87.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.0913
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |