CNNM2 Gene: Cyclin and CBS Domain Divalent Metal Cation Transport Mediator 2
A key regulator of magnesium homeostasis, implicated in hypomagnesemia, seizures, and neurodevelopmental disorders.
Gene Information Card
| Symbol | CNNM2 |
|---|---|
| Full Name | Cyclin and CBS domain divalent metal cation transport mediator 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 10q24.32 |
| NCBI Gene ID | 54805 ncbi.nlm.nih.gov/gene/54805 |
| Ensembl ID | ENSG00000148842 |
| UniProt ID | Q9H8M5 |
| OMIM ID | 607803 |
| HGNC ID | 24021 |
| Aliases | ACDP2, FLJ10305, MGC32951 |
Description
The CNNM2 gene encodes a protein that functions as a metal ion transporter, specifically involved in magnesium (Mg2+) homeostasis. It is expressed in various tissues, with high levels in the kidney and brain, where it plays a critical role in Mg2+ reabsorption and neuronal function. Mutations in CNNM2 are associated with dominant hypomagnesemia, seizures, and intellectual disability.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hypomagnesemia, seizures, and mental retardation | Loss-of-function mutations impair Mg2+ transport, leading to renal Mg2+ wasting and neurological symptoms. | ClinVar, OMIM |
| Renal hypomagnesemia | Mutations disrupt the basolateral Mg2+ transport in the distal convoluted tubule, causing hypomagnesemia. | OMIM, PubMed |
| Intellectual disability | CNNM2 is expressed in the brain; mutations affect neuronal Mg2+ homeostasis, contributing to cognitive impairment. | OMIM, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Kidney | 12.3 | High |
| Brain | 8.7 | Medium |
| Testis | 6.5 | Medium |
| Liver | 4.2 | Low |
| Heart | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression; used for functional studies |
| SH-SY5Y | 10.4 | Neuronal cell line; relevant for brain expression |
| HepG2 | 5.6 | Moderate expression |
| Caco-2 | 3.8 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.131C>T (p.Thr44Met) | Missense | Rare | Loss of function; associated with hypomagnesemia and seizures |
| c.512G>A (p.Arg171His) | Missense | Rare | Gain of function; linked to isolated hypomagnesemia |
| c.1124delC (p.Pro375LeufsTer23) | Frameshift | Not reported | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Most pathogenic mutations reduce Mg2+ transport activity, leading to renal Mg2+ wasting and neurological symptoms.
Gain of Function (GOF)
Some missense mutations increase Mg2+ transport, but may still cause hypomagnesemia due to altered regulation.
Dominant Negative (DN)
Not clearly established; however, some mutations may exert dominant-negative effects on the multimeric complex.
View complete mutation data：
Gene Ontology (GO)
| • magnesium ion transmembrane transporter activity (GO:0015095) | • cation transport (GO:0006812) |
| • integral component of membrane (GO:0016021) | • plasma membrane (GO:0005886) |
Pathways
• Magnesium transport
• Ion homeostasis
Protein Summary
The CNNM2 protein is a transmembrane protein that mediates Mg2+ transport across cell membranes. It contains a cyclin domain and CBS domains, which are involved in ATP binding and regulation. The protein is critical for Mg2+ reabsorption in the kidney and for neuronal function. Mutations can disrupt Mg2+ balance, leading to clinical phenotypes.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CNNM2 Knockout HEK293 Cell Line | EDC90274 | Human | 54805 | Details Get a Quote |
| CNNM2 Knockout A-549 Cell Line | EDJ-KQ40435 | Human | 54805 | Details Get a Quote |
| CNNM2 Knockout HCT 116 Cell Line | EDJ-KQ40436 | Human | 54805 | Details Get a Quote |
| CNNM2 Knockout HeLa Cell Line | EDJ-KQ40437 | Human | 54805 | Details Get a Quote |
