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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CACNG2
calcium voltage-gated channel auxiliary subunit gamma 2
Chromosome 22 · 22q12.3
NCBI Gene: 10369Ensembl: ENSG00000166862.7HGNC: HGNC:1406UniProt: Q9Y698
51PubMed Papers
21Diseases
10Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneIon ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingchannel regulator activityvoltage-gated calcium channel activitytransmission of nerve impulseepilepsyfibromyalgianeuropathic painSeizure
✦AI Summary

CACNG2 encodes stargazin (CaVγ2), an auxiliary calcium channel subunit with dual regulatory functions in neuronal excitability. Primarily, CACNG2 promotes trafficking and membrane targeting of AMPA-selective glutamate receptors (AMPARs) to synapses while modulating their gating kinetics by slowing activation, deactivation, and desensitization rates 1. The gene's transcriptional regulation involves a bidirectional promoter containing functional cAMP response elements that control expression of a long non-coding RNA (CACNG2-DT), which itself may enhance CaVγ2 protein levels 1. CACNG2 dysfunction contributes to multiple neurological and psychiatric disorders. Rare variants associate with bipolar disorder risk, with promoter and UTR variants showing stronger effects than coding variants 2. Common polymorphisms (rs2284015, rs4820242, rs2284017) confer susceptibility to chr22 peripheral neuropathic pain in the Mexican population 3, while genome-wide association identified CACNG2 among 12 risk loci for suicide attempt across multi-ancestry populations 4. Additionally, CACNG2 mutations cause intellectual developmental disorder, autosomal dominant 10, and dysregulation of its circular RNA form (circ-CACNG2) promotes cardiomyocyte apoptosis in multiple myeloma 5. These findings establish CACNG2 as a critical regulator of synaptic transmission and neuronal excitability with broad clinical relevance.

Sources cited
1
CACNG2/CaVγ2 promotes AMPAR trafficking to cell membrane and synapses, modulates gating kinetics, and its transcriptional regulation involves bidirectional promoter with cAMP response elements and lncRNA CACNG2-DT
PMID: 38033343
2
Rare variants in CACNG2 contribute to bipolar disorder risk, with promoter and UTR variants showing stronger associations than coding variants
PMID: 25730879
3
CACNG2 polymorphisms (rs2284015, rs4820242, rs2284017) associate with chronic peripheral neuropathic pain risk and severity in Mexican population
PMID: 35776036
4
CACNG2 identified as one of 12 genome-wide significant loci for suicide attempt across multi-ancestry populations in largest GWAS meta-analysis
PMID: 37777856
5
Circular CACNG2 (circ-CACNG2) in multiple myeloma exosomes promotes cardiomyocyte apoptosis via miR-197-3p/caspase3 axis
PMID: 35649477
6
CACNG2 identified as neuropathic pain susceptibility gene affecting pain phenotypes in both mice and humans
PMID: 22775325
Disease Associationsⓘ21
epilepsyOpen Targets
0.61Moderate
fibromyalgiaOpen Targets
0.60Moderate
neuropathic painOpen Targets
0.60Moderate
SeizureOpen Targets
0.60Moderate
restless legs syndromeOpen Targets
0.58Moderate
neuralgiaOpen Targets
0.58Moderate
anxiety disorderOpen Targets
0.57Moderate
postherpetic neuralgiaOpen Targets
0.57Moderate
spinal cord injuryOpen Targets
0.54Moderate
intellectual disability, autosomal dominant 10Open Targets
0.49Moderate
Focal-onset seizureOpen Targets
0.48Moderate
cardiovascular diseaseOpen Targets
0.46Moderate
Urinary incontinenceOpen Targets
0.43Moderate
PainOpen Targets
0.42Moderate
diabetic neuropathyOpen Targets
0.41Moderate
generalized anxiety disorderOpen Targets
0.40Weak
insomniaOpen Targets
0.40Weak
partial epilepsyOpen Targets
0.39Weak
Chronic painOpen Targets
0.39Weak
Hot flashesOpen Targets
0.37Weak
Intellectual developmental disorder, autosomal dominant 10UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Drug Targets10
ATAGABALINPhase II
Voltage-gated calcium channel modulator
insomnia
BEPRIDILApproved
Voltage-gated calcium channel blocker
cardiovascular disease
GABAPENTINApproved
Voltage-gated calcium channel modulator
epilepsy
GABAPENTIN ENACARBILApproved
Voltage-gated calcium channel modulator
restless legs syndrome
IMAGABALINPhase III
Voltage-gated calcium channel modulator
generalized anxiety disorder
PHLOROGLUCINOLApproved
Voltage-gated calcium channel blocker
gastrointestinal disease
PREGABALINApproved
Voltage-gated calcium channel modulator
neuropathic pain
SULOCTIDILApproved
Voltage-gated calcium channel blocker
cardiovascular disease
TERODILINEApproved
Muscarinic acetylcholine receptor antagonist
Urinary incontinence
TERODILINE HYDROCHLORIDEUNKNOWN
Muscarinic acetylcholine receptor antagonist
Related Genes
DLGAP1Protein interaction100%DLG1Protein interaction98%CACNA1BProtein interaction96%CACNA2D2Protein interaction96%DLG2Protein interaction94%CACNA1SProtein interaction92%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
2%
Ovary
0%
Heart
0%
Liver
0%
Lung
0%
Gene Interaction Network
Click a node to explore
CACNG2DLGAP1DLG1CACNA1BCACNA2D2DLG2CACNA1S
PROTEIN STRUCTURE
Preparing viewer…
PDB6TNO · 1.90 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.27Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.09 [0.03–0.27]
RankingsWhere CACNG2 stands among ~20K protein-coding genes
  • #8,653of 20,598
    Most Researched51
  • #238of 1,025
    FDA-Approved Drug Targets7 · top quartile
  • #918of 17,882
    Most Constrained (LOEUF)0.27 · top 10%
Genes detectedCACNG2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.
PMID: 37777856
Am J Psychiatry · 2023
1.00
2
Molecular cloning of the gene promoter encoding the human Ca
PMID: 38033343
Front Physiol · 2023
0.90
3
Rare variants in neuronal excitability genes influence risk for bipolar disorder.
PMID: 25730879
Proc Natl Acad Sci U S A · 2015
0.80
4
Association between CACNG2 polymorphisms (rs4820242, rs2284015 and rs2284017) and chronic peripheral neuropathic pain risk in a Mexican population.
PMID: 35776036
Eur Rev Med Pharmacol Sci · 2022
0.70
5
BDNF and Cerebellar Ataxia.
PMID: 37609676
Curr Drug Res Rev · 2024
0.60