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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CACNG3
calcium voltage-gated channel auxiliary subunit gamma 3
Chromosome 16 · 16p12.1
NCBI Gene: 10368Ensembl: ENSG00000006116.5HGNC: HGNC:1407UniProt: O60359
21PubMed Papers
20Diseases
10Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedHub GeneIon ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
postsynaptic density membranepostsynaptic neurotransmitter receptor diffusion trappingprotein targetingregulation of AMPA receptor activityepilepsyfibromyalgianeuropathic painSeizure
✦AI Summary

CACNG3 (calcium voltage-gated channel auxiliary subunit gamma 3) is a regulatory protein that modulates AMPA receptor trafficking and calcium channel function in neurons. The protein promotes AMPA receptor targeting to synapses and modulates their gating properties by slowing activation, deactivation, and desensitization rates 1. CACNG3 is thought to stabilize calcium channels in an inactivated state and plays a role in synaptic transmission and neuronal excitability 1. Disease relevance studies demonstrate that CACNG3 expression is significantly decreased in multiple brain regions of Alzheimer's disease patients, where it appears to regulate synaptic plasticity through calcium signaling pathways 2. Additionally, CACNG3 shows associations with childhood absence epilepsy, with linkage analysis revealing significant associations in nuclear families and transmission disequilibrium in specific genomic regions 3. The gene also demonstrates prognostic significance in gliomas, where low expression correlates with shorter overall survival and higher tumor grades 4. Clinically, CACNG3 represents a potential biomarker for neurodegenerative diseases and epilepsy, with therapeutic implications for conditions involving synaptic dysfunction and altered neuronal excitability 23.

Sources cited
1
CACNG3 upregulation in glutamatergic synapses and ion channel activity, coupling with increased excitability in NRXN1α+/- cortical neurons
PMID: 34525970
2
CACNG3 expression significantly decreased in AD brain regions and involvement in synaptic plasticity through calcium signaling
PMID: 41483619
3
Significant linkage and association of CACNG3 with childhood absence epilepsy in nuclear families
PMID: 17264864
4
Low CACNG3 expression in gliomas correlates with shorter survival and higher tumor grades
PMID: 37697240
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
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
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
urinary system diseaseOpen Targets
0.37Weak
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
CACNA2D1Protein interaction98%CACNG1Protein interaction97%CACNB4Protein interaction96%CACNA1DProtein interaction96%CACNB3Protein interaction94%CACNA1FProtein interaction93%
Tissue Expression6 tissues
Brain
100%
Bone Marrow
0%
Liver
0%
Ovary
0%
Heart
0%
Lung
0%
Gene Interaction Network
Click a node to explore
CACNG3CACNA2D1CACNG1CACNB4CACNA1DCACNB3CACNA1F
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt O60359
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.30Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.11 [0.05–0.30]
RankingsWhere CACNG3 stands among ~20K protein-coding genes
  • #13,850of 20,598
    Most Researched21
  • #244of 1,025
    FDA-Approved Drug Targets7 · top quartile
  • #1,108of 17,882
    Most Constrained (LOEUF)0.30 · top 10%
Genes detectedCACNG3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Integrated profiling identifies CACNG3 as a prognostic biomarker for patients with glioma.
PMID: 37697240
BMC Cancer · 2023
1.00
2
Down regulation of Cathepsin W is associated with poor prognosis in pancreatic cancer.
PMID: 37794108
Sci Rep · 2023
0.90
3
NRXN1α
PMID: 34525970
BMC Neurosci · 2021
0.80
4
Linkage and association analysis of CACNG3 in childhood absence epilepsy.
PMID: 17264864
Eur J Hum Genet · 2007
0.70
5
Multi-omics integration identifies CACNG3 as a synaptic calcium channel regulator in Alzheimer's disease: Mechanistic insights and therapeutic implications.
PMID: 41483619
Int Immunopharmacol · 2026
0.60