Molecular characteristics
The NPTNgene is located on 15q24.1 of chromosome 15. NPTNconsists of eight coding exons, one non-encoding 3'UTR exon, and exon 2 that can be spliced out by alternative splicing of the gene transcripts. Additionally, the splicing isoforms may display an alternative aminoacidic insert (DDEP) encoded by exon 7. hNp65 is 394 or 398 amino acids long, contains a signal peptide sequence, three extracellular Ig-like domains (Ig-like I-III) encoded by exons 1-6, a single transmembrane domain (TM) encoded by exon 6, and a 34 or 38.
The hNps are enriched in human neuronal synapses (1, reference list in Professionals - Publications) and expressed early during the neurodevelopment at 19-24 post-coital weeks (PCW) across fetal brain regions (2), with peak levels in the brains of 18-year-old individuals (1-3). NPTNhas been related to several neuropsychiatric diseases (4).
NPTN mutations
Identified pathogenic missense variants are c.403T>A, p.(Trp135Arg) and c.1025C>T, p.(Pro342Leu). Nonsense variants are c.14C>A, p.(Ser5*), c.284C>G, p.(Ser95*), and c.342C>G, p.(Tyr114*). Frameshift variants producing a stop codon are c.902del, p.(Asn301Thrfs*3) and c.218_219del, p.(Glu73Valfs*53).
NPTN