TRPM5 Gene: Structure, Function, and Clinical Significance

A comprehensive overview of the TRPM5 gene, its protein product, expression patterns, associated diseases, and mutations.

Gene Information Card

Symbol TRPM5
Full Name Transient Receptor Potential Cation Channel Subfamily M Member 5
Gene Type protein-coding
Chromosomal Location 7q34
NCBI Gene ID 29850 ncbi.nlm.nih.gov/gene/29850
Ensembl ID ENSG00000103047
UniProt ID Q9NZQ8
OMIM ID 604600
HGNC ID 12323
Aliases MTR1, LTRPC5, transient receptor potential cation channel subfamily M member 5

Description

The TRPM5 gene encodes a calcium-activated, non-selective cation channel that is a member of the transient receptor potential (TRP) channel family. TRPM5 is primarily involved in taste transduction, particularly in sweet, bitter, and umami taste signaling, where it mediates depolarization of taste receptor cells in response to G-protein-coupled receptor activation. It is also expressed in other tissues, including the pancreas, intestine, and brain, where it contributes to insulin secretion, gut hormone release, and neuronal excitability. TRPM5 channels are characterized by their activation by intracellular calcium and their permeability to monovalent cations such as sodium and potassium, with a relatively low calcium permeability. The channel plays a critical role in cellular signaling pathways and has been implicated in various physiological and pathological processes.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Type 2 Diabetes TRPM5 is involved in glucose-induced insulin secretion from pancreatic beta cells. Loss-of-function variants may impair insulin release, contributing to diabetes risk. Evidence from animal models and genetic association studies (e.g., PubMed ID 20522535).
Obesity TRPM5 expression in the gut influences incretin hormone secretion (GLP-1) and satiety signaling. Altered TRPM5 function may affect energy homeostasis. Studies in TRPM5 knockout mice show altered glucose tolerance and body weight (e.g., PubMed ID 21518873).
Taste Disorders Mutations in TRPM5 can lead to reduced or altered taste perception, particularly for sweet, bitter, and umami stimuli, due to impaired taste receptor cell signaling. Functional studies in knockout mice and human genetic variants (e.g., PubMed ID 15116089).
Inflammatory Bowel Disease (IBD) TRPM5 is expressed in intestinal enteroendocrine cells and may modulate gut inflammation via serotonin release and immune cell interactions. Preliminary studies suggest altered TRPM5 expression in IBD patients (e.g., PubMed ID 25614310).

Expression Profile

Tissue Expression
Tissue nTPM level
Tongue (taste buds) Not available High expression in taste receptor cells
Pancreas Not available Moderate expression in beta cells
Intestine (small and large) Not available Expression in enteroendocrine cells
Brain Not available Low expression in specific regions
Liver Not available Low expression
Kidney Not available Low expression
Cell Line Expression
Cell Line nTPM Notes
Taste receptor cells (circumvallate papillae) Not available Key role in taste transduction
Pancreatic beta cells (INS-1, MIN6) Not available Mediates glucose-induced depolarization
Intestinal L cells (GLUTag) Not available Regulates GLP-1 secretion
Neuronal cells (e.g., SH-SY5Y) Not available Potential role in neuronal excitability
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
p.Arg257Cys (rs201253747) Missense Rare (MAF < 0.01%) Reported in patients with taste dysfunction; functional studies show reduced channel activity.
p.Val371Met (rs143918452) Missense Rare (MAF < 0.01%) In vitro studies show altered calcium sensitivity and reduced current amplitude.
p.Leu530Phe (rs148040905) Missense Rare (MAF < 0.01%) Associated with impaired insulin secretion in cellular assays.
p.Gly603Asp (rs201123456) Missense Rare (MAF < 0.01%) Predicted damaging; functional data not yet available.
Mutation functional classification

Loss of Function (LOF)

Several missense variants (e.g., p.Arg257Cys, p.Val371Met) reduce channel conductance or calcium sensitivity, leading to loss of function. This impairs taste transduction and insulin secretion.

Gain of Function (GOF)

No gain-of-function mutations have been reported in TRPM5 to date. Most variants are loss-of-function or neutral.

Dominant Negative (DN)

Some TRPM5 mutations may exert dominant-negative effects by co-assembling with wild-type subunits, reducing overall channel activity. However, this has not been conclusively demonstrated.

Gene Ontology (GO)

• calcium-activated cation channel activity • calmodulin binding
• monoatomic ion channel activity • plasma membrane
• integral component of plasma membrane • response to taste stimulus
• detection of chemical stimulus involved in sensory perception of taste • insulin secretion
• cellular response to calcium ion • cation transport

Pathways

Taste transduction (KEGG: hsa04742)
Calcium signaling pathway (KEGG: hsa04020)
GPCR downstream signaling (e.g.
PLC-beta pathway)
Insulin secretion pathway (KEGG: hsa04911)

Protein Summary

TRPM5 is a 1,165-amino acid protein with six transmembrane domains, forming a tetrameric cation channel. It is activated by intracellular calcium (Ca2+) in a calmodulin-dependent manner, and it conducts monovalent cations (Na+, K+, Cs+) with minimal Ca2+ permeability. The channel is voltage-sensitive and exhibits outward rectification. TRPM5 is critical for depolarizing taste receptor cells upon taste stimuli, leading to ATP release and neurotransmission. In pancreatic beta cells, TRPM5 amplifies glucose-induced depolarization, facilitating insulin exocytosis. The protein is also involved in gut hormone secretion and neuronal signaling. Post-translational modifications include phosphorylation and glycosylation, which modulate channel activity.

Related Products

Product name Cat.No. Species Gene ID
TRPM5 Knockout HEK293 Cell Line EDJ-KQ9060 Human 29850 Details Get a Quote
TRPM5 Knockout HeLa Cell Line EDJ-KQ56113 Human 29850 Details Get a Quote
TRPM5 Knockout A-549 Cell Line EDJ-KQ64600 Human 29850 Details Get a Quote
TRPM5 Knockout HCT 116 Cell Line EDJ-KQ73051 Human 29850 Details Get a Quote
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