TRPM5
protein-codingtransient receptor potential cation channel subfamily M member 5, the group of Transient receptor potential cation channels
Gene summary
This gene encodes a member of the transient receptor potential (TRP) protein family, which is a diverse group of proteins with structural features typical of ion channels. This protein plays an important role in taste transduction, and has characteristics of a calcium-activated, non-selective cation channel that carries Na+, K+, and Cs+ ions equally well, but not Ca(2+) ions. It is activated by lower concentrations of intracellular Ca(2+), and inhibited by higher concentrations. It is also a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. This gene is located within the Beckwith-Wiedemann syndrome critical region-1 on chromosome 11p15.5, and has been shown to be imprinted, with exclusive expression from the paternal allele. [provided by RefSeq, Oct 2010]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~40.0 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 TRPM5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_014555.4. 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 | 2 | 7 | 5 | 14 | ||
| missense | 239 | 21 | 2 | 262 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 242 | 28 | 7 | 277 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_055370.1 | 24 | MANE Select | |
| Ensembl | ENSP00000512529.1 | 24 | MANE Select | |
| Ensembl | ENSP00000436809.1 | 24 | Standard | |
| Ensembl | ENSP00000434121.1 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Taste transduction - Homo sapiens (human)
- Stimuli-sensing channels
- Ion channel transport
- Transport of small molecules
- TRP channels
Biological Process
- regulation of ion transmembrane transport
- sodium ion transmembrane transport
- sensory perception of taste
- calcium ion transmembrane transport
- potassium ion transmembrane transport
Molecular Function
- ion channel activity
- calcium activated cation channel activity
- voltage-gated ion channel activity
- potassium channel activity
- sodium channel activity
Cellular Component
- plasma membrane
- integral component of membrane
- dendrite
- neuronal cell body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000155858
- Coding exons
- 24
- Length
- 18531
- Individuals with no LoFs
- 125498
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 222
- Defined
- 125720
- p
- 0.000883
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.0836 | 721 | 727 | 0.991 | 0.0000495 | 7416 |
| Missense (PolyPhen) | 221 | 254.01 | 0.87004 | 2768 | ||
| Synonymous | -1.16 | 362 | 335 | 1.08 | 0.0000248 | 2404 |
| Loss of Function | 1.56 | 40 | 52.1 | 0.767 | 0.00000256 | 583 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0010 | 0.00092 | notable |
| Latino/Admixed American | 0.00077 | 0.00075 | rare |
| Ashkenazi Jewish | 0.00042 | 0.00040 | rare |
| East Asian | 0.00066 | 0.00065 | rare |
| Finnish | 0.00040 | 0.00037 | rare |
| European (Non-Finnish) | 0.0012 | 0.0011 | notable |
| South Asian | 0.00084 | 0.00082 | rare |
| Other | 0.0014 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Voltage-modulated Ca(2+)-activated, monovalent cation channel (VCAM) that mediates a transient membrane depolarization and plays a central role in taste transduction. Monovalent- specific, non-selective cation channel that mediates the transport of Na(+), K(+) and Cs(+) ions equally well. Activated directly by increases in intracellular Ca(2+), but is impermeable to it. Gating is voltage-dependent and displays rapid activation and deactivation kinetics upon channel stimulation even during sustained elevations in Ca(2+). Also activated by a fast intracellular Ca(2+) increase in response to inositol 1,4,5- triphosphate-producing receptor agonists. The channel is blocked by extracellular acidification. External acidification has 2 effects, a fast reversible block of the current and a slower irreversible enhancement of current inactivation. Is a highly temperature-sensitive, heat activated channel showing a steep increase of inward currents at temperatures between 15 and 35 degrees Celsius. Heat activation is due to a shift of the voltage- dependent activation curve to negative potentials. Activated by arachidonic acid in vitro. May be involved in perception of bitter, sweet and umami tastes. May also be involved in sensing semiochemicals. {ECO:0000269|PubMed:14634208}.;
Intolerance Scores
- LoFtool
- 0.422
- RVIS EVS
- -0.84
- RVIS percentile EVS
- 11.29
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.477
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |