CALHM1: Calcium Homeostasis Modulator 1
A key regulator of calcium homeostasis and neuronal excitability, implicated in Alzheimer's disease and cancer.
Gene Information Card
| Symbol | CALHM1 |
|---|---|
| Full Name | Calcium Homeostasis Modulator 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.33 |
| NCBI Gene ID | 255022 ncbi.nlm.nih.gov/gene/255022 |
| Ensembl ID | ENSG00000185973 |
| UniProt ID | Q8IU99 |
| OMIM ID | 612234 |
| HGNC ID | 23494 |
| Aliases | FAM26A, MGC33887 |
Description
CALHM1 (Calcium Homeostasis Modulator 1) encodes a voltage-gated ion channel that mediates calcium and sodium permeability in neurons. It is primarily expressed in the brain and plays a critical role in maintaining calcium homeostasis, neuronal excitability, and neurotransmitter release. Dysregulation of CALHM1 has been linked to Alzheimer's disease and certain cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Alzheimer's disease | Altered calcium homeostasis and amyloid-beta accumulation; the P86L variant increases amyloid-beta levels. | PMID: 18628398, ClinVar |
| Colorectal cancer | Overexpression of CALHM1 promotes tumor growth and metastasis via calcium signaling. | PMID: 25964276, COSMIC |
| Breast cancer | CALHM1 expression correlates with poor prognosis and invasive phenotype. | PMID: 27806324, COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Spinal cord | 8.3 | Low |
| Testis | 6.1 | Low |
| Colon | 4.2 | Low |
| Breast | 3.8 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 2.1 | Low expression |
| HCT116 (colorectal carcinoma) | 9.8 | Moderate expression |
| MCF7 (breast cancer) | 7.5 | Moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| P86L | Missense | 0.5% in Alzheimer's cohorts | Increases amyloid-beta production; loss of calcium channel function |
| R154H | Missense | Rare | Reduced calcium permeability |
| L112P | Missense | Rare | Altered channel gating |
Mutation functional classification
Loss of Function (LOF)
P86L reduces calcium influx, impairing neuronal calcium homeostasis.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
P86L may exert dominant-negative effects on wild-type CALHM1 channels.
View complete mutation data：
Gene Ontology (GO)
| • calcium channel activity (GO:0005262) | • calcium ion transport (GO:0006816) |
| • integral component of membrane (GO:0016021) | • synapse (GO:0045202) |
| • transmembrane transport (GO:0055085) |
Pathways
• Calcium signaling pathway (KEGG: hsa04020)
• Alzheimer's disease (KEGG: hsa05010)
Protein Summary
CALHM1 is a 346-amino acid protein with four transmembrane domains, forming a hexameric ion channel. It is permeable to Ca2+ and Na+ and is activated by voltage and extracellular calcium. The protein is predominantly expressed in the brain, where it modulates neuronal excitability and synaptic transmission. The P86L variant is associated with late-onset Alzheimer's disease.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CALHM1 Knockout HEK293 Cell Line | EDJ-KQ11783 | Human | 255022 | Details Get a Quote |
| CALHM1 Knockout HeLa Cell Line | EDJ-KQ59268 | Human | 255022 | Details Get a Quote |
| CALHM1 Knockout A-549 Cell Line | EDJ-KQ67735 | Human | 255022 | Details Get a Quote |
| CALHM1 Knockout HCT 116 Cell Line | EDJ-KQ76119 | Human | 255022 | Details Get a Quote |
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