CALHM3: Calcium Homeostasis Modulator Family Member 3
A pore-forming subunit of the CALHM1/CALHM3 ion channel complex involved in neuronal excitability and taste transduction.
Gene Information Card
| Symbol | CALHM3 |
|---|---|
| Full Name | Calcium Homeostasis Modulator Family Member 3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 10q24.33 |
| NCBI Gene ID | 119395 ncbi.nlm.nih.gov/gene/119395 |
| Ensembl ID | ENSG00000198722 |
| UniProt ID | Q86XH1 |
| OMIM ID | 612896 |
| HGNC ID | 23497 |
| Aliases | FAM26C, MGC129935 |
Description
CALHM3 encodes a member of the calcium homeostasis modulator (CALHM) family. The protein forms a heterohexameric ion channel with CALHM1 that is permeable to monovalent cations and calcium. This channel is activated by membrane depolarization and plays a critical role in neuronal excitability and ATP release. CALHM3 is essential for the function of the CALHM1/CALHM3 channel in taste bud cells, mediating sweet, bitter, and umami taste transduction. Mutations in CALHM3 have been linked to neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Epilepsy, familial, with variable foci (FEPVF) | Loss-of-function mutations in CALHM3 impair the CALHM1/CALHM3 channel, reducing neuronal excitability and predisposing to seizures. | ClinVar, OMIM #612896 |
| Taste dysfunction | Disruption of CALHM3 expression or function alters taste bud cell signaling, affecting sweet, bitter, and umami perception. | UniProt, literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 0.8 | Low |
| Salivary gland | 0.5 | Low |
| Testis | 0.3 | Low |
| Tongue (taste buds) | Not available | Detected by RNA-seq |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 0.2 | Low; used for heterologous expression studies |
| SH-SY5Y | 0.1 | Low; neuronal model |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.247C>T (p.Arg83Cys) | Missense | Rare | Loss of channel function; associated with epilepsy |
| c.389G>A (p.Arg130His) | Missense | Rare | Reduced channel activity; potential pathogenic |
Mutation functional classification
Loss of Function (LOF)
p.Arg83Cys and p.Arg130His reduce or abolish CALHM1/CALHM3 channel conductance, impairing neuronal and taste cell signaling.
Gain of Function (GOF)
No gain-of-function mutations reported in CALHM3.
Dominant Negative (DN)
Not established; CALHM3 likely acts as a recessive or haploinsufficient allele.
View complete mutation data：
Gene Ontology (GO)
| • calcium channel activity (GO:0005262) | • protein binding (GO:0005515) |
| • plasma membrane (GO:0005886) | • integral component of membrane (GO:0016021) |
| • ion transmembrane transport (GO:0034220) | • transmembrane transport (GO:0055085) |
Pathways
• CALHM1/CALHM3 channel-mediated ATP release
• Taste transduction (sweet
• bitter
• umami)
Protein Summary
CALHM3 is a 4-transmembrane domain protein that, together with CALHM1, forms a voltage-gated ion channel permeable to Na+, K+, and Ca2+. The channel is activated by depolarization and mediates ATP release in neurons and taste cells. CALHM3 is required for the proper assembly and function of the channel complex. Loss-of-function mutations are associated with familial epilepsy with variable foci.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CALHM3 Knockout HEK293 Cell Line | EDJ-KQ7638 | Human | 119395 | Details Get a Quote |
| CALHM3 Knockout HeLa Cell Line | EDJ-KQ58039 | Human | 119395 | Details Get a Quote |
| CALHM3 Knockout A-549 Cell Line | EDJ-KQ66527 | Human | 119395 | Details Get a Quote |
| CALHM3 Knockout HCT 116 Cell Line | EDJ-KQ74942 | Human | 119395 | Details Get a Quote |
