Relevance to Autism

De novo damaging missense variants in the CHMP1A gene were identifed in ASD probands from the Simons Simplex Collection and the Autism Sequencing Consortium (De Rubeis et al., 2014; Iossifov et al., 2014). Rare inherited loss-of-function variants in this gene were observed in ASD probands from the Simons Simplex Collection (Krumm et al., 2015) and in a cohort of Chinese ASD probands (Guo et al., 2017). Transmission and De Novo Association (TADA) analysis of a combined cohort consisting of 536 Chinese ASD probands and 1457 Chinese controls, as well as ASD probands and controls from the Simons Simplex Collection and the Autism Sequencing Consortium, in Guo et al., 2017 identified CHMP1A as an ASD candidate gene with a PTADA of 0.001528.

Molecular Function

Probable peripherally associated component of the endosomal sorting required for transport complex III (ESCRT-III) which is involved in multivesicular bodies (MVBs) formation and sorting of endosomal cargo proteins into MVBs. MVBs contain intraluminal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome and mostly are delivered to lysosomes enabling degradation of membrane proteins, such as stimulated growth factor receptors, lysosomal enzymes and lipids. Homozygous mutations in the CHMP1A gene are associated with pontocerebellar hypoplasia type 8 (PCH8; OMIM 614961), a neurodevelopmental disorder characterized by severe psychomotor retardation, abnormal movements, hypotonia, spasticity, and variable visual defects (Mochida et al., 2012).

External Links

References