Relevance to Autism

Biallelic variants in the KPTN gene were found to cosegregate with the disease phenotype in nine family members from four nuclear families from the Amish community of Ohio presenting with an inherited variable form of neurodevelopmental delay (most consistent features were global developmental delay, macrocephaly with frontal bossing, high levels of anxiety, and some features suggestive of pervasive developmental disorder, such as stereotypies and/or repetitive speech) in Baple et al., 2013. A homozygous frameshift variant in the KPTN gene was identified in two adult siblings from Estonia presenting with moderate intellectual disability and macrocephaly in Pajusalu et al., 2015; the male sibling also presented with behavioral problems, including autistic features. Rawlins et al., 2026 reported the genotype and clinical phenotype of 71 individuals with KPTN-related disorder, including 48 newly identified individuals, and observed that behavioral features were a common (85%; 55/65 individuals) but variable feature and included stereotypy (51%; 30/59 individuals) and repetitive speech (34%; 17/50 individuals); in the same study, the authors found that Kptn -/- mice displayed increased cortical mTOR signaling and heterotopic neurons in the subcortical white matter.

Molecular Function

This gene encodes a filamentous-actin-associated protein, which is involved in actin dynamics and plays an important role in neuromorphogenesis. This protein is part of the KICSTOR protein complex that localizes to lysosomes. Mutations in this gene result in an autosomal recessive form of intellectual disability.

External Links

References