Two de novo variants in the UNC80 gene (one nonsense variant, one missense variant predicted to be damaging) were identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014). An additional de novo loss-of-function (LoF) variant in the UNC80 gene was identified in a proband from the SAGE cohort in Stessman et al., 2017; while no phenotypic information was provided for the SAGE proband in this report, UNC80 was identified as one of eight genes showing a bias for autism versus intellectual disability (two one-tailed binomial tests, P<0.025 for either ASD or ID/DD cases).
Molecular Function
Component of the NALCN sodium channel complex, required for channel regulation. This complex is a cation channel activated by neuropeptides substance P, neurotensin, and extracellular calcium that regulates neuronal excitability by controlling the sizes of NALCN-dependent sodium-leak current. UNC80 is essential for NALCN sensitivity to extracellular calcium. Biallelic variants in UNC80 are responsible for infantile hypotonia with psychomotor retardation and characteristic facies-2 (IHPRF2; OMIM 616801).
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
The contribution of de novo coding mutations to autism spectrum disorder
