De novo missense variants that were predicted in silico to be damaging were identified in the DPYSL2 gene in an ASD proband from the Autism Sequencing Consortium (De Rubeis et al., 2014) and the Simons Simplex Collection (Iossifov et al., 2014). TADA-Denovo analysis using a combined dataset of previously published cohorts from the Simons Simplex Collection and the Autism Sequencing Consortium, as well as a novel cohort of 262 Japanese ASD trios, in Takata et al., 2018 identified DPYSL2 as a gene significantly enriched in damaging de novo mutations in ASD cases (pBH < 0.05). Multiple studies have reported an association between the DPYSL2 gene and schizophrenia (Nakata et al., 2003; Fallin et al., 2005; Fallin et al., 2011; Liu et al., 2014; Lee et al., 2015), as well as evidence suggesting that the DPYSL2 gene links mTOR signaling and schizophrenia (Liu et al., 2014; Pham et al., 2016).
Molecular Function
This gene encodes a member of the collapsin response mediator protein family. Collapsin response mediator proteins form homo- and hetero-tetramers and facilitate neuron guidance, growth and polarity. The encoded protein promotes microtubule assembly and is required for Sema3A-mediated growth cone collapse, and also plays a role in synaptic signaling through interactions with calcium channels. This gene has been implicated in multiple neurological disorders, and hyperphosphorylation of the encoded protein may play a key role in the development of Alzheimer's disease.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
De novo non-synonymous DPYSL2 (CRMP2) variants in two patients with intellectual disabilities and documentation of functional relevance through zebrafish rescue and cellular transfection experiments
