CACNA1B encodes the (α1B) pore-forming subunit of the N-type voltage-gated calcium channel. CACNA1B was first reported in relation to autosomal recessive complex neurodevelopmental disorder with motor features in 2019 (Gorman KM et al., PMID: 30982612). Four variants have been reported in 6 children from 3 unrelated families, in one publication; all probands presented with early onset epileptic encephalopathy, severe neurodevelopmental delay with regression, and hyperkinetic movement disorder (PMID: 30982612). A different publication reported on a proband with a compound deep intronic splicing variant and missense variant. However, due to the high variant frequencies in gnomAD, the pathogenicity of these variants is unclear and these were not scored (PMID: 37095367).
To date, no experimental evidence supports the relationship between CACNA1B and AR complex neurodevelopmental disorder with motor features.
In summary, there is MODERATE evidence to support this gene-disease relationship. The ClinGen Cerebral Palsy Working Group approved this classification on August 21, 2023 (SOP Version 9).
The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).
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