CACNA1G

Chr 17AD

calcium voltage-gated channel subunit alpha1 G

Also known as: Ca(V)T.1, Cav3.1, NBR13, SCA42, SCA42ND

NCBI Gene: 8913 ENSG00000006283 UniProt: O43497 OMIM: 604065

This gene encodes the alpha-1G subunit of T-type voltage-gated calcium channels, which generate low-threshold calcium currents essential for neuronal pacemaking, oscillations, and burst firing patterns. Mutations cause spinocerebellar ataxia 42 through an autosomal dominant inheritance pattern, with early-onset variants associated with severe neurodevelopmental deficits. The gene is highly constrained against loss-of-function variants, and mutations can cause disease predominantly through gain-of-function mechanisms that likely disrupt normal neuronal calcium signaling.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt, Mechanism

Voltage-sensitive calcium channels 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. This gene encodes a T-type, low-voltage activated calcium channel. The T-type channels generate currents that are both transient, owing to fast inactivation, and tiny, owing to small conductance. T-type channels are thought to be involved in pacemaker activity, low-threshold calcium spikes, neuronal oscillations and resonance, and rebound burst firing. Many alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Sep 2011]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Spinocerebellar ataxia 42MIM #616795

Spinocerebellar ataxia 42, early-onset, severe, with neurodevelopmental deficitsMIM #618087

Clinical highlights

Gene-disease validity (ClinGen)

spinocerebellar ataxia type 42 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Gain of function is the established mechanism, so a variant that simply removes the protein may not be the pathogenic class here — missense variants in functional domains often carry more weight.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.21

LOEUF· LoF intol.

GOF

Mechanism· annotated

📖

GeneReview available — CACNA1G