This report describes a newly characterized neurodevelopmental disorder associated with the human gene UNC79; a spectrum of neurologic pathologies is observed, including seizures. All cases characterized to date carry a de novo heterozygous truncating variant in UNC79. UNC79 encodes an accessory subunit of the NALCN channel, which plays a key role in neuron resting membrane potential and neuronal excitability. There is a single orthologous gene in Drosophila, Dmel\unc79, for which RNAi-targeting constructs, an overexpression construct, and alleles caused by insertional mutagenesis have been generated.
The human UNC79 gene has not been introduced into Drosophila.
Knockdown of Dmel\unc79, effected by RNAi and assayed in adults, results in increased levels of bang sensitivity, a seizure-like behavior. Neuron-specific knockdown produces results similar to that of global knockdown.
[updated Dec. 2023 by FlyBase; FBrf0222196]
Phenotypic presentation is variable, usually characterized by mild developmental delay including delay in speech, mild to moderate intellectual disability, and/or seizures, autistic features, or behavioral issues (Bayat et al., 2023; pubmed:37183800; FBrf0257524).
Of the 6 patients initially characterized, all carried a de novo heterozygous truncating variant in UNC79 (Bayat et al., 2023; pubmed:37183800; FBrf0257524).
UNC79 is given a score 2 (strong candidate) in the SFARI gene autism susceptibility database (https://gene.sfari.org/database/human-gene/UNC79).
The NALCN channel is a voltage-gated ion channel responsible for the resting Na(+) permeability that controls neuronal excitability. The protein encoded by UNC79, along with UNC80, is an accessory subunit of the NALCN channel that contributes to the Ca(2+) sensitivity of the channel. [GeneCards, UNC79; 2023.12.20]
One to one: 1 human gene to 1 Drosophila gene.
High-scoring ortholog of human UNC79 (1 Drosophila to 1 human).
