CACNB2

calcium voltage-gated channel auxiliary subunit beta 2, the group of Calcium voltage-gated channel auxiliary beta subunits|Membrane associated guanylate kinases

Basic information

Region (hg38): 10:18140424-18543557

Previous symbols: [ "MYSB", "CACNLB2" ]

Links

ENSG00000165995 ∙ NCBI:783 ∙ OMIM:600003 ∙ HGNC:1402 ∙ Uniprot:Q08289 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Brugada syndrome 4 (Limited), mode of inheritance: Unknown
• Brugada syndrome 4 (Disputed Evidence), mode of inheritance: AD
• Brugada syndrome 4 (Limited), mode of inheritance: AD
• Brugada syndrome 4 (Limited), mode of inheritance: AD
• Brugada syndrome 1 (Disputed Evidence), mode of inheritance: AD
• hypertrophic cardiomyopathy (Disputed Evidence), mode of inheritance: AD
• short QT syndrome (Disputed Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Brugada syndrome 4	AD	Cardiovascular; Pharmacogenomic	Surveillance with approximately yearly EKG and medical interventions, including daily quinidine for prevention (though treatment of asymptomatic individuals is controversial), ICD placement in individuals with previous cardiac arrest/syncope, and isoproterenol for electrical storms, may be beneficial; Certain agents should be avoided, including medications such as certain anesthetics, antidepressants, and antipsychotics, and care should be taken in the instance of high fever	Cardiovascular	17224476; 20301690; 22090166

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNB2 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNB2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	181	4	187
missense			342	15	2	359
nonsense			7			7
start loss			3			3
frameshift			6			6
inframe indel			13			13
splice donor/acceptor (+/-2bp)			6	6	1	13
splice region			16	28	5	49
non coding			22	121	84	227
Total	0	0	401	323	91

Variants in CACNB2

This is a list of pathogenic ClinVar variants found in the CACNB2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
10-18140454-C-T			Benign (Jun 26, 2018)
10-18140478-C-A			Benign (Jun 14, 2018)
10-18140679-G-A			Benign (Mar 03, 2015)
10-18140695-C-A		not specified	Benign (Jun 25, 2013)
10-18140701-G-A			Benign (Mar 03, 2015)
10-18140706-G-A		not specified	Benign (Jul 15, 2014)
10-18140707-G-A		not specified	Likely benign (Jul 27, 2016)
10-18140720-G-T		not specified	Benign (May 25, 2017)
10-18140733-G-A		not specified	Likely benign (Nov 21, 2016)
10-18140737-A-G		not specified	Uncertain significance (Oct 20, 2016)
10-18140739-G-A		Brugada syndrome 4	Uncertain significance (-)
10-18140740-G-A		Cardiovascular phenotype	Uncertain significance (Feb 13, 2024)
10-18140752-AT-A		not specified • CACNB2-related disorder	Uncertain significance (Jul 06, 2023)
10-18140767-C-A		Cardiovascular phenotype	Uncertain significance (Apr 15, 2024)
10-18140789-C-T			Uncertain significance (Mar 15, 2023)
10-18140790-G-C			Likely benign (Jun 06, 2018)
10-18140796-G-C		Cardiovascular phenotype	Uncertain significance (Jan 05, 2022)
10-18140820-C-T		not specified	Likely benign (May 27, 2016)
10-18140823-G-T		not specified	Likely benign (Jan 27, 2016)
10-18140832-G-A			Likely benign (Sep 11, 2018)
10-18140833-G-A		Cardiovascular phenotype	Uncertain significance (Mar 25, 2024)
10-18140836-G-T			Uncertain significance (Mar 21, 2024)
10-18140838-G-T		Brugada syndrome 4	Conflicting classifications of pathogenicity (Oct 14, 2024)
10-18140840-T-C		Brugada syndrome 4	Uncertain significance (Oct 01, 2021)
10-18140861-C-A			Benign (May 05, 2015)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNB2	protein_coding	protein_coding	ENST00000324631	14	401193

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000267	0.999	125646	0	102	125748	0.000406

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.0654	390	394	0.991	0.0000246	4316
Missense in Polyphen		154	183.64	0.83859		2009
Synonymous	-2.22	179	145	1.24	0.00000904	1267
Loss of Function	2.95	15	33.4	0.449	0.00000182	394

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000452	0.000452
Ashkenazi Jewish	0.00387	0.00388
East Asian	0.000223	0.000217
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.000301	0.000299
Middle Eastern	0.000223	0.000217
South Asian	0.000299	0.000294
Other	0.000490	0.000489

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting.
• Disease: DISEASE: Brugada syndrome 4 (BRGDA4) [MIM:611876]: A heart disease characterized by the association of Brugada syndrome with shortened QT intervals. Brugada syndrome is a tachyarrhythmia characterized by right bundle branch block and ST segment elevation on an electrocardiogram (ECG). It can cause the ventricles to beat so fast that the blood is prevented from circulating efficiently in the body. When this situation occurs, the individual will faint and may die in a few minutes if the heart is not reset. {ECO:0000269|PubMed:17224476}. Note=The gene represented in this entry may be involved in disease pathogenesis.
• Pathway: Oxytocin signaling pathway - Homo sapiens (human);Cardiac muscle contraction - Homo sapiens (human);Dilated cardiomyopathy (DCM) - Homo sapiens (human);Arrhythmogenic right ventricular cardiomyopathy (ARVC) - Homo sapiens (human);Hypertrophic cardiomyopathy (HCM) - Homo sapiens (human);Adrenergic signaling in cardiomyocytes - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Antiarrhythmic Pathway, Pharmacodynamics;Arrhythmogenic Right Ventricular Cardiomyopathy;MAPK Signaling Pathway;Developmental Biology;GPCR Dopamine D1like receptor;Metabolism;Regulation of insulin secretion;Neuronal System;Phase 0 - rapid depolarisation;Phase 2 - plateau phase;Cardiac conduction;Muscle contraction;Presynaptic depolarization and calcium channel opening;NCAM signaling for neurite out-growth;NCAM1 interactions;Transmission across Chemical Synapses;Axon guidance;Integration of energy metabolism (Consensus)

Recessive Scores

• pRec: 0.156

Intolerance Scores

• loftool: 0.0128
• rvis_EVS: -0.71
• rvis_percentile_EVS: 14.78

Haploinsufficiency Scores

• pHI: 0.182
• hipred: Y
• hipred_score: 0.602
• ghis: 0.547

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.225

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Cacnb2
• Phenotype: hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); craniofacial phenotype; vision/eye phenotype; growth/size/body region phenotype; homeostasis/metabolism phenotype

Zebrafish Information Network

• Gene name: cacnb2a
• Affected structure: heart tube
• Phenotype tag: abnormal
• Phenotype quality: increased fragility

Gene ontology

• Biological process: chemical synaptic transmission;neuromuscular junction development;visual perception;positive regulation of calcium ion transport;calcium ion import;calcium ion transmembrane transport;protein localization to plasma membrane;membrane depolarization during AV node cell action potential;regulation of heart rate by cardiac conduction;membrane depolarization during atrial cardiac muscle cell action potential;induction of synaptic vesicle exocytosis by positive regulation of presynaptic cytosolic calcium ion concentration;regulation of voltage-gated calcium channel activity;positive regulation of high voltage-gated calcium channel activity;positive regulation of calcium ion transmembrane transport via high voltage-gated calcium channel
• Cellular component: plasma membrane;integral component of plasma membrane;voltage-gated calcium channel complex;photoreceptor ribbon synapse;presynapse;L-type voltage-gated calcium channel complex
• Molecular function: voltage-gated calcium channel activity;calcium channel activity;protein binding;high voltage-gated calcium channel activity;actin filament binding;voltage-gated calcium channel activity involved in cardiac muscle cell action potential;voltage-gated calcium channel activity involved in AV node cell action potential;voltage-gated calcium channel activity involved in positive regulation of presynaptic cytosolic calcium levels