CACNB4

calcium voltage-gated channel auxiliary subunit beta 4, the group of Calcium voltage-gated channel auxiliary beta subunits|Membrane associated guanylate kinases

Basic information

Region (hg38): 2:151832770-152099167

Links

ENSG00000182389 ∙ NCBI:785 ∙ OMIM:601949 ∙ HGNC:1404 ∙ Uniprot:O00305 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• epilepsy, idiopathic generalized, susceptibility to, 13 (Limited), mode of inheritance: AD
• juvenile myoclonic epilepsy (Supportive), mode of inheritance: AD
• episodic ataxia type 5 (Supportive), mode of inheritance: AD
• epilepsy, idiopathic generalized, susceptibility to, 9 (Limited), mode of inheritance: AD
• epilepsy (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Episodic ataxia, type 5	AD	Neurologic	Individuals may manifest with recurrent attacks of vertigo and ataxia, and treatment with acetazolamide has been reported as being effective	Neurologic	10762541; 16100538; 18755274; 20301317
Variants may modify seizure-related conditions due to variants in other genes (eg, SCN1A)

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNB4 gene.

• Episodic ataxia type 5 (130 variants)
• Juvenile myoclonic epilepsy (101 variants)
• Idiopathic generalized epilepsy (96 variants)
• not provided (71 variants)
• not specified (40 variants)
• Hereditary episodic ataxia (16 variants)
• Inborn genetic diseases (11 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 9 (7 variants)
• Episodic ataxia type 5;Epilepsy, idiopathic generalized, susceptibility to, 9 (3 variants)
• Epilepsy, idiopathic generalized, susceptibility to, 9;Episodic ataxia type 5 (2 variants)
• Spastic ataxia (1 variants)
• CACNB4-related condition (1 variants)
• CACNB4-Related Disorders (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNB4 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			9	29	5	43
missense		1	76		2	79
nonsense			3			3
start loss						0
frameshift						0
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			8	4		12
non coding			68	43	20	131
Total	0	1	159	72	27

Variants in CACNB4

This is a list of pathogenic ClinVar variants found in the CACNB4 region.

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

Position	Type	Phenotype	Significance	ClinVar
2-151832936-T-C		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-151832979-C-A		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Benign/Likely benign (Jan 13, 2018)
2-151833048-A-C		Episodic ataxia type 5	Uncertain significance (Jan 12, 2018)
2-151833123-A-AT		Juvenile myoclonic epilepsy • Hereditary episodic ataxia	Uncertain significance (Jun 14, 2016)
2-151833142-C-A		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
2-151833256-A-C		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Uncertain significance (Jan 13, 2018)
2-151833264-T-G		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Benign/Likely benign (Jan 13, 2018)
2-151833265-T-C		Episodic ataxia type 5	Uncertain significance (Jan 13, 2018)
2-151833440-C-T		Episodic ataxia type 5	Uncertain significance (Jan 12, 2018)
2-151833497-G-A		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Benign/Likely benign (Jan 12, 2018)
2-151833557-T-C		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Benign/Likely benign (Jan 13, 2018)
2-151833632-A-G		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Uncertain significance (Jan 13, 2018)
2-151833686-T-C		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Conflicting classifications of pathogenicity (Jan 13, 2018)
2-151833701-A-G		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Uncertain significance (Jan 13, 2018)
2-151833734-G-A		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Benign (Jan 13, 2018)
2-151833747-A-G		Juvenile myoclonic epilepsy • Episodic ataxia type 5	Benign/Likely benign (Jan 13, 2018)
2-151833863-C-T		Episodic ataxia type 5	Uncertain significance (Jan 12, 2018)
2-151833884-A-G		Episodic ataxia type 5	Uncertain significance (Jan 12, 2018)
2-151833977-G-A		Episodic ataxia type 5	Uncertain significance (Jan 13, 2018)
2-151833997-G-A		Juvenile myoclonic epilepsy • Hereditary episodic ataxia	Uncertain significance (Jun 14, 2016)
2-151834085-C-T		Episodic ataxia type 5	Uncertain significance (Feb 02, 2018)
2-151834090-A-G		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Benign (Jan 12, 2018)
2-151834097-T-C		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Conflicting classifications of pathogenicity (Oct 01, 2022)
2-151834113-T-C		Episodic ataxia type 5	Uncertain significance (Jan 12, 2018)
2-151834143-A-G		Episodic ataxia type 5 • Juvenile myoclonic epilepsy	Benign/Likely benign (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNB4	protein_coding	protein_coding	ENST00000539935	14	266304

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0307	0.969	124641	0	14	124655	0.0000562

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.69	161	290	0.555	0.0000163	3367
Missense in Polyphen		62	141.13	0.43932		1620
Synonymous	0.863	95	106	0.894	0.00000604	1008
Loss of Function	3.77	9	32.0	0.281	0.00000187	347

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000575	0.0000556
Finnish	0.0000464	0.0000464
European (Non-Finnish)	0.0000904	0.0000885
Middle Eastern	0.0000575	0.0000556
South Asian	0.0000673	0.0000654
Other	0.00	0.00

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. {ECO:0000269|PubMed:11880487}.
• Disease: DISEASE: Juvenile myoclonic epilepsy 6 (EJM6) [MIM:607682]: A subtype of idiopathic generalized epilepsy. Patients have afebrile seizures only, with onset in adolescence (rather than in childhood) and myoclonic jerks which usually occur after awakening and are triggered by sleep deprivation and fatigue. {ECO:0000269|PubMed:10762541}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Episodic ataxia 5 (EA5) [MIM:613855]: A disorder characterized by episodes of vertigo and ataxia that last for several hours. Interictal examination show spontaneous downbeat and gaze-evoked nystagmus, mild dysarthria and truncal ataxia. {ECO:0000269|PubMed:10762541}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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;Arrhythmogenic Right Ventricular Cardiomyopathy;MAPK Signaling Pathway;Developmental Biology;GPCR Dopamine D1like receptor;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 (Consensus)

Recessive Scores

• pRec: 0.139

Intolerance Scores

• loftool: 0.290
• rvis_EVS: 0.08
• rvis_percentile_EVS: 60.09

Haploinsufficiency Scores

• pHI: 0.199
• hipred: Y
• hipred_score: 0.639
• ghis: 0.499

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.764

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Cacnb4
• Phenotype: 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); reproductive system phenotype; hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; vision/eye 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); digestive/alimentary phenotype; muscle phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype

Zebrafish Information Network

• Gene name: cacnb4a
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: dead

Gene ontology

• Biological process: chemical synaptic transmission;neuromuscular junction development;membrane depolarization;calcium ion transmembrane transport;regulation of voltage-gated calcium channel activity
• Cellular component: cytosol;plasma membrane;voltage-gated calcium channel complex;cytoplasmic side of plasma membrane
• Molecular function: voltage-gated calcium channel activity;calcium channel activity;protein binding;high voltage-gated calcium channel activity