CACNA1B

calcium voltage-gated channel subunit alpha1 B, the group of Calcium voltage-gated channel alpha1 subunits|EF-hand domain containing

Basic information

Region (hg38): 9:137877782-138124624

Previous symbols: [ "CACNL1A5" ]

Links

ENSG00000148408

∙ NCBI:774 ∙ OMIM:601012 ∙ HGNC:1389 ∙ Uniprot:Q00975 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (Strong), mode of inheritance: AR
neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (Limited), mode of inheritance: AR
undetermined early-onset epileptic encephalopathy (Supportive), mode of inheritance: AD
neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (Moderate), mode of inheritance: AR
neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movements (Strong), mode of inheritance: AR
complex neurodevelopmental disorder with motor features (Moderate), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Dystonia 23	AD	Cardiovascular	As the condition can include cardiac arrhythmias, awareness may allow surveillance and early management	Cardiovascular; Neurologic	21370267; 25296916; 30982612

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CACNA1B gene.

not_provided (1467 variants)
not_specified (275 variants)
Neurodevelopmental_disorder_with_seizures_and_nonepileptic_hyperkinetic_movements (71 variants)
CACNA1B-related_disorder (52 variants)
Dystonia_23 (6 variants)
See_cases (3 variants)
Complex_neurodevelopmental_disorder_with_motor_features (2 variants)
EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
CACNA1B-related_neurodevelopmental_disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CACNA1B gene is commonly pathogenic or not. These statistics are base on transcript: NM_000000718.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			6 clinvar	501 clinvar	20 clinvar	527
missense			576 clinvar	45 clinvar	4 clinvar	625
nonsense	12 clinvar	3 clinvar	1 clinvar			16
start loss						0
frameshift	18 clinvar	4 clinvar	7 clinvar			29
splice donor/acceptor (+/-2bp)	1 clinvar	13 clinvar	12 clinvar	4 clinvar		30
Total	31	20	602	550	24

Highest pathogenic variant AF is 0.000006956416

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CACNA1B	protein_coding	protein_coding	ENST00000371372	47	246836

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.0000189	117913	0	6765	124678	0.0275

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	4.52	841	1.30e+3	0.647	0.0000821	15050
Missense in Polyphen		198	375.01	0.52799		4039
Synonymous	-0.416	546	534	1.02	0.0000348	4663
Loss of Function	7.85	16	101	0.158	0.00000526	1179

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0505	0.0470
Ashkenazi Jewish	0.0557	0.0450
East Asian	0.0191	0.0167
Finnish	0.0273	0.0215
European (Non-Finnish)	0.0352	0.0296
Middle Eastern	0.0191	0.0167
South Asian	0.0441	0.0359
Other	0.0290	0.0246

dbNSFP

Source: dbNSFP

Function: FUNCTION: Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents. N-type calcium channels belong to the 'high-voltage activated' (HVA) group and are specifically blocked by omega-conotoxin-GVIA (AC P01522) (AC P01522) (By similarity). They are however insensitive to dihydropyridines (DHP). Calcium channels containing alpha-1B subunit may play a role in directed migration of immature neurons. {ECO:0000250|UniProtKB:Q02294}.;
Disease: DISEASE: Dystonia 23 (DYT23) [MIM:614860]: A form of dystonia, a disorder defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT23 is an autosomal dominant dystonia affecting the face, neck, limbs. Some DYT23 patients manifest generalized myoclonus in addition to progressive action-induced multifocal dystonia. {ECO:0000269|PubMed:25296916}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Synaptic vesicle cycle - Homo sapiens (human);Retrograde endocannabinoid signaling - Homo sapiens (human);GABAergic synapse - Homo sapiens (human);Serotonergic synapse - Homo sapiens (human);Dopaminergic synapse - Homo sapiens (human);Type II diabetes mellitus - Homo sapiens (human);Nicotine addiction - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Cholinergic synapse - Homo sapiens (human);Morphine addiction - Homo sapiens (human);Celecoxib Pathway, Pharmacodynamics;Beta-agonist/Beta-blocker Pathway, Pharmacodynamics;Sympathetic Nerve Pathway (Pre- and Post- Ganglionic Junction);Sympathetic Nerve Pathway (Neuroeffector Junction);Synaptic Vesicle Pathway;MAPK Signaling Pathway;Calcium Regulation in the Cardiac Cell;Neuronal System;Presynaptic depolarization and calcium channel opening;Transmission across Chemical Synapses (Consensus)

Recessive Scores

pRec: 0.215

Haploinsufficiency Scores

pHI: 0.364
hipred: Y
hipred_score: 0.706
ghis: 0.639

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap
gene_indispensability_pred: E
gene_indispensability_score: 0.892

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	High	High	High
Primary Immunodeficiency	High	High	High
Cancer	High	High	High

Mouse Genome Informatics

Gene name: Cacna1b
Phenotype: integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; homeostasis/metabolism phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms 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); 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); 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);

Gene ontology

Biological process: calcium ion transport;chemical synaptic transmission;neurotransmitter secretion;locomotory behavior;regulation of heart contraction;regulation of blood pressure;regulation of ion transmembrane transport;response to pain;modulation of chemical synaptic transmission;membrane depolarization;regulation of calcium ion transport;calcium ion import;calcium ion transmembrane transport;response to amyloid-beta
Cellular component: plasma membrane;voltage-gated calcium channel complex;dendrite;neuronal cell body;presynapse
Molecular function: amyloid-beta binding;voltage-gated calcium channel activity;calcium channel activity;calcium ion binding;protein binding;ATP binding;protein C-terminus binding;high voltage-gated calcium channel activity