Relevance to Autism

Li et al., 2023 determined that a de novo coding-synonymous variant in the NPTN gene originally identified in an ASD proband from the Autism Sequencing Consortium in Satterstrom et al., 2020 was a non-canonical splicing variant; subsequent functional analysis by minigene splicing assays demonstrated that this variant resulted in loss of 180 base pairs from exon 6 of this gene. De novo missense variants have also been identified in two ASD probands from the SPARK cohort (Trost et al., 2022). Liang et al., 2026 reported eight individuals with heterozygous variants in NPTN (five loss-of-function variant and two missense variants, seven of which were de novo in origin) presenting with developmental delay and/or intellectual disability and a diagnosis of autism spectrum disorder in seven individuals; the two missense variants were experimentally shown to result in lower expression in HEK cells and failure to regulate cytosolic calcium transients in primary neurons. Furthermore, Liang et al., 2026 demonstrated that haploinsufficent Nptn +/- mice displayed reduced levels of neuroplastin (Np) and plasma membrane calcium ATPases (PMCA), as well as altered social behavior.

Molecular Function

This gene encodes a type I transmembrane protein belonging to the Ig superfamily. The protein is believed to be involved in cell-cell interactions or cell-substrate interactions.

External Links

References