CACNA1B

Chr 9AR

calcium voltage-gated channel subunit alpha1 B

Also known as: BIII, CACNL1A5, CACNN, Cav2.2, DYT23, NEDNEH

NCBI Gene: 774 ENSG00000148408 UniProt: Q00975 OMIM: 601012

The CACNA1B protein forms the alpha-1B subunit of N-type voltage-gated calcium channels, which mediate calcium entry into excitable cells and control neurotransmitter release at synapses, pain signaling, and neuronal migration. Autosomal recessive mutations cause a neurodevelopmental disorder characterized by seizures and nonepileptic hyperkinetic movements. The protein is highly intolerant to loss-of-function mutations, suggesting pathogenicity occurs through severe disruption of calcium channel function.

OMIM ResearchSummary from OMIM, UniProt

The protein encoded by this gene is the pore-forming subunit of an N-type voltage-dependent calcium channel, which controls neurotransmitter release from neurons. The encoded protein forms a complex with alpha-2, beta, and delta subunits to form the high-voltage activated channel. This channel is sensitive to omega-conotoxin-GVIA and omega-agatoxin-IIIA but insensitive to dihydropyridines. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with seizures and nonepileptic hyperkinetic movementsMIM #618497

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder with motor features · ARModerateconsider for supplementary testing

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.24

LOEUF· LoF intol.

LOF

Mechanism· G2P