NBEA

Chr 13AD

neurobeachin

Also known as: BCL8B, LYST2, NEDEGE

NCBI Gene: 26960 ENSG00000172915 UniProt: Q8NFP9 OMIM: 604889

This protein anchors protein kinase A to specific membrane locations and is involved in neuronal membrane trafficking. Mutations cause neurodevelopmental disorder with or without early-onset generalized epilepsy with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants (pLI = 1, LOEUF = 0.074), indicating intolerance to protein disruption.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of a large, diverse group of A-kinase anchor proteins that target the activity of protein kinase A to specific subcellular sites by binding to its type II regulatory subunits. Brain-specific expression and coat protein-like membrane recruitment of a highly similar protein in mouse suggest an involvement in neuronal post-Golgi membrane traffic. Mutations in this gene may be associated with a form of autism. This gene and its expression are frequently disrupted in patients with multiple myeloma. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Additional transcript variants may exist, but their full-length nature has not been determined.[provided by RefSeq, Feb 2011]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with or without early-onset generalized epilepsyMIM #619157

Clinical highlights

Gene-disease validity (ClinGen)

complex neurodevelopmental disorder · ADDefinitivesufficient evidence for diagnostic panels

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)

—

P/LP submissions

—

P/LP missense

0.07

LOEUF· LoF intol.

LOF

Mechanism· G2P