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GeneE
10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CACNB3
calcium voltage-gated channel auxiliary subunit beta 3
Chromosome 12 · 12q13.12
NCBI Gene: 784Ensembl: ENSG00000167535.9HGNC: HGNC:1403UniProt: P54284
35PubMed Papers
20Diseases
10Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Ion ChannelTransporter
CLINICAL
FDA Approved Target
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingcalcium ion transmembrane transportvoltage-gated calcium channel activityvoltage-gated calcium channel complexepilepsyfibromyalgianeuropathic painSeizure
✦AI Summary

CACNB3 encodes the beta-3 auxiliary subunit of voltage-gated calcium channels, which plays a crucial role in modulating calcium channel function and cellular excitability. As a regulatory component, CACNB3 increases peak calcium current and shifts voltage dependencies of channel activation and inactivation for both L-type (CACNA1C) and N-type (CACNA1B) calcium channels 1. The protein facilitates proper channel assembly through interactions with the endoplasmic reticulum membrane protein complex (EMC), functioning as a holdase during channel biogenesis 1. CACNB3 demonstrates tissue-specific expression patterns and functional roles beyond traditional calcium channel regulation. In immune cells, it exclusively controls ATP-dependent migration of dendritic cells by regulating inositol 1,4,5-trisphosphate receptor-mediated calcium release from the endoplasmic reticulum 2. Clinically, CACNB3 dysregulation is associated with multiple pathological conditions. Altered expression has been identified in drug-resistant mesial temporal lobe epilepsy, representing a potential therapeutic target 3. The gene also contributes to circadian rhythm regulation, with genetic variations affecting lithium's therapeutic efficacy in bipolar disorder 4. Additionally, CACNB3 serves as a diagnostic biomarker in polycystic ovary syndrome 5 and shows prognostic relevance in cervical cancer 6, highlighting its broad clinical significance across neurological, psychiatric, and reproductive disorders.

Sources cited
1
CACNB3 functions as calcium channel auxiliary subunit facilitating channel assembly through EMC interactions
PMID: 37196677
2
CACNB3 exclusively regulates ATP-dependent dendritic cell migration via IP3 receptor-mediated calcium release
PMID: 37729408
3
CACNB3 expression is significantly altered in drug-resistant mesial temporal lobe epilepsy
PMID: 37341859
4
CACNB3 genetic variations affect lithium's amplification of circadian rhythms in bipolar disorder
PMID: 26476274
5
CACNB3 serves as a diagnostic biomarker for polycystic ovary syndrome
PMID: 39754246
6
CACNB3 shows prognostic relevance in cervical cancer survival prediction
PMID: 35924232
Disease Associationsⓘ20
epilepsyOpen Targets
0.62Moderate
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
gastrointestinal 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
CACNA2D2Protein interaction98%CACNG7Protein interaction94%CACNA1AProtein interaction94%CACNA1CProtein interaction94%CACNA1DProtein interaction94%CACNA1FProtein interaction94%
Tissue Expression6 tissues
Ovary
100%
Brain
55%
Lung
17%
Bone Marrow
10%
Heart
9%
Liver
3%
Gene Interaction Network
Click a node to explore
CACNB3CACNA2D2CACNG7CACNA1ACACNA1CCACNA1DCACNA1F
PROTEIN STRUCTURE
Preparing viewer…
PDB8WE6 · 2.90 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.72LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.55 [0.42–0.72]
RankingsWhere CACNB3 stands among ~20K protein-coding genes
  • #10,926of 20,598
    Most Researched35
  • #242of 1,025
    FDA-Approved Drug Targets7 · top quartile
  • #5,583of 17,882
    Most Constrained (LOEUF)0.72
Genes detectedCACNB3
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
EMC chaperone-Ca
PMID: 37196677
Nature · 2023
1.00
2
Differential Expression of the β3 Subunit of Voltage-Gated Ca
PMID: 37341859
Mol Neurobiol · 2023
0.90
3
Calcium channel β3 subunit regulates ATP-dependent migration of dendritic cells.
PMID: 37729408
Sci Adv · 2023
0.80
4
Small Nucleolar RNAs in Pseudoexfoliation Glaucoma.
PMID: 36078146
Cells · 2022
0.70
5
Unraveling the significance of PPP1R1A gene in pancreatic β-cell function: A study in INS-1 cells and human pancreatic islets.
PMID: 38574885
Life Sci · 2024
0.60