Submission Details

The NBEA gene is located on chromosome 13 at 13q13.3 and encodes the neurobeachin protein. Neurobeachin is an A-kinase anchor protein and thus functions in the anchoring or targeting of protein kinase A. It is highly expressed in the brain, and studies have suggested it may play a role in membrane trafficking in neurons. NBEA was first reported in relation to autosomal dominant NBEA-related intellectual disability in 2018 (30269351: Mulhern et al. 2018). At least eight unique variants, primarily null variants, have been reported in humans. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in eight probands from a single publication (30269351: Mulhern et al. 2018). In the majority of cases, the variant occurred de novo. While the maximum score for genetic evidence (12 pts.) has been reached, additional independent reports are needed to replicate the association. The mechanism of disease appears to involve haploinsufficiency. This gene-disease association is supported by expression data and the observation of reduced synaptic current amplitudes in cultured neurons from knock-out mice (11102458: Wang et al. 2000; 23277425: Nair et al. 2013). In summary, there is strong evidence to support this gene-disease relationship.

PubMed IDs:

30269351 11102458 23277425

Assertion Criteria:

Click here to view assertion criteria

https://clinicalgenome.org/site/assets/files/2169/gene_curation_sop_2016_version_5_11_6_17.pdf

Submitter Submitted Date:

10/15/2020

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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