Molecular Characteristics
The NECAP1 (Necap Endocytosis-Associated Protein 1) gene is located at 12p13.31 and encodes a clathrin-accessory protein, which regulates clathrin-mediated endocytosis in neuronal synapses.
Mutations and pathophysiology
Mutations in NECAP1 trigger nonsense-mediated mRNA decay and result in significant impairment of clathrin-mediated endocytosis. One consanguineous family with a pathogenic variant has been reported to date.
Alazami et al. (2014) reported a homozygous c.142C>T mutation in NECAP1 (NM_015509.3), resulting in premature truncation of the protein (p.R48*) near its N terminus. The four affected children came from a consanguineous Saudi family and displayed the phenotypical features of EIEE.