Molecular Characteristics
UNC80 is located at 2q34 and encodes a protein necessary for bridging UNC79 and NALCN and the formation of UNC79-UNC80-NALCN channel complex, a voltage-insensitive and non-selective cation channel. Shamseldin et al. found that Unc80 murine ortholog expression was nearly exclusive to the brain.
Mutations and pathophysiology
Shamseldin et al. identified two truncating variants, c.3793C >T (p.Arg1265*) (GenBank: NM_032504.1) and c.1078C >T (p.Arg360*), and one missense variant, c.565G >A (p.Val189Met) (GenBank: XM_005246476.1), in 6 children from 4 unrelated consanguineous families. Stray-Pedersen et al. identified a homozygous c.5098C>T transition (GenBank: NM_032504.1) resulting in a pro1700-to-ser. Individuals with missense variants seem to display a relatively milder phenotype than those with truncating variants.
UNC80 mutations produce a phenotypic pattern remarkably similar to NALCN-related encephalopathy, as described in the previous sections.