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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CACNB2
calcium voltage-gated channel auxiliary subunit beta 2
Chromosome 10 · 10p12.33-p12.31
NCBI Gene: 783Ensembl: ENSG00000165995.24HGNC: HGNC:1402UniProt: A0A494C0B2
90PubMed Papers
21Diseases
10Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Hub GeneIon ChannelTransporter
CLINICAL
FDA Approved TargetOMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
regulation of heart rate by cardiac conductionmembrane depolarization during atrial cardiac muscle cell action potentialvoltage-gated calcium channel complexvoltage-gated calcium channel activityepilepsyfibromyalgianeuropathic painSeizure
✦AI Summary

CACNB2 encodes the β2 auxiliary subunit of voltage-gated L-type calcium channels, which enhances peak calcium current and modulates voltage-dependent activation and inactivation 1. It facilitates membrane targeting of the channel α1-subunit CACNA1C and may regulate β-adrenergic augmentation of cardiac calcium influx, controlling heart rate and contractile force 23. CACNB2 functions in cardiac action potentials and calcium ion transport across multiple cardiac tissues including atrial and AV nodal cells. Genome-wide association studies identified CACNB2 variants as shared genetic risk factors across five major psychiatric disorders, with pathway analysis supporting pleiotropic effects of calcium-channel signaling genes on psychopathology 4. The CACNB2 rs11013860 polymorphism associates with structural and functional brain abnormalities in bipolar disorder, including altered grey matter volume in emotional processing circuits 56. Clinically, CACNB2 loss-of-function variants cause Brugada syndrome through reduced L-type calcium current and accelerated channel inactivation, responsive to beta-blockers and quinidine treatment 1. Additionally, CACNB2 polymorphisms associate with essential hypertension and elevated blood pressure in children and adolescents, potentially through RAS-MAPK pathway dysregulation independent of calcium channel activity 789.

Sources cited
1
CACNB2 loss-of-function variant reduces L-type calcium channel current and causes Brugada syndrome; CACNB2 protein expression is decreased in patient-derived cardiomyocytes
PMID: 35955449
2
CACNB2 may contribute to β-adrenergic augmentation of calcium influx in cardiomyocytes, regulating heart rate and contractile force
PMID: 36424916
3
CACNB2 is involved in membrane targeting of the alpha-1 subunit CACNA1C
PMID: 17525370
4
CACNB2 variants surpass genome-wide significance threshold for cross-disorder association in five psychiatric disorders; pathway analysis supports role of calcium channel signaling genes
PMID: 23453885
5
CACNB2 rs11013860 polymorphism associates with altered grey matter volume and abnormal brain function in emotional circuits of bipolar disorder patients
PMID: 40016690
6
CACNB2 rs11013860 A-allele carriers with bipolar disorder show thinner prefrontal cortex, particularly superior frontal cortex, compared to healthy controls
PMID: 32158010
7
CACNB2 rs7069292 polymorphism associates with essential hypertension; T>C mutation affects CACNB2 gene expression levels
PMID: 23744328
8
CACNB2 rs12258967 polymorphism associates with higher odds of high blood pressure in adolescents aged 12-15 years
PMID: 29982197
9
CACNB2 over-expression triggers cell proliferation via RAS-MAPK pathway upregulation; CACNB2 expression is upregulated in hypertensive salt-sensitive rat kidneys
PMID: 30992131
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
cardiovascular diseaseOpen Targets
0.57Moderate
anxiety disorderOpen Targets
0.57Moderate
postherpetic neuralgiaOpen Targets
0.57Moderate
Brugada syndromeOpen Targets
0.56Moderate
spinal cord injuryOpen Targets
0.54Moderate
hypertensionOpen Targets
0.54Moderate
Abnormality of the skeletal systemOpen Targets
0.51Moderate
essential hypertensionOpen Targets
0.50Moderate
diverticular diseaseOpen Targets
0.50Moderate
Focal-onset seizureOpen Targets
0.48Moderate
alcohol drinkingOpen Targets
0.46Moderate
Increased blood pressureOpen Targets
0.45Moderate
Urinary incontinenceOpen Targets
0.43Moderate
PainOpen Targets
0.42Moderate
Brugada syndrome 4UniProt
Pathogenic Variants2
NM_201596.3(CACNB2):c.804+162G>TLikely pathogenic
Brugada syndrome 4
★☆☆☆2025
NM_201590.3(CACNB2):c.32C>T (p.Thr11Ile)Pathogenic
Brugada syndrome 4
☆☆☆☆2009→ Residue 11
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%SCN5AProtein interaction95%CACNA2D3Protein interaction94%CACNG7Protein interaction94%CACNA2D4Protein interaction92%CACNG8Protein interaction91%
Tissue Expression6 tissues
Heart
100%
Ovary
79%
Brain
47%
Liver
34%
Bone Marrow
18%
Lung
16%
Gene Interaction Network
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CACNB2CACNA2D2SCN5ACACNA2D3CACNG7CACNA2D4CACNG8
PROTEIN STRUCTURE
Preparing viewer…
PDB8HMB · 3.30 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.77LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.57 [0.43–0.77]
RankingsWhere CACNB2 stands among ~20K protein-coding genes
  • #5,289of 20,598
    Most Researched90
  • #231of 1,025
    FDA-Approved Drug Targets7 · top quartile
  • #4,339of 5,498
    Most Pathogenic Variants2
  • #6,237of 17,882
    Most Constrained (LOEUF)0.77
Genes detectedCACNB2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Involvement of muscle satellite cell dysfunction in neuromuscular disorders: Expanding the portfolio of satellite cell-opathies.
PMID: 35302338
Eur J Transl Myol · 2022
1.00
2
Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis.
PMID: 23453885
Lancet · 2013
0.90
3
A Preclinical Study on Brugada Syndrome with a CACNB2 Variant Using Human Cardiomyocytes from Induced Pluripotent Stem Cells.
PMID: 35955449
Int J Mol Sci · 2022
0.80
4
[Association between CACNB2 gene polymorphisms and essential hypertension].
PMID: 23744328
Zhonghua Yi Xue Yi Chuan Xue Za Zhi · 2013
0.70
5
The impact of the CACNB2 Rs11013860 polymorphism on grey matter volume and brain function in bipolar disorder.
PMID: 40016690
BMC Psychiatry · 2025
0.60