Relevance to Autism

A de novo loss-of-function (LoF) variant in the SRCAP gene was first identified in an ASD proband from the Simons Simplex Collection (Iossifov et al., 2014). A second ASD-associated de novo LOF variant was identified in a proband from the Autism Simplex Collection (TASC) in Stessman et al., 2017. A third de novo LoF variant in SRACP was identified in an ASD proband from a simplex family by whole genome sequencing in Yuen et al., 2017. Additional de novo loss-of-function and missense variants in the SRCAP gene were observed in ASD probands from the Autism Sequencing Consortium, the MSSNG cohort, and the SPARK cohort in Zhou et al., 2022; furthermore, a two-stage analysis of rare de novo and inherited coding variants in 42,607 ASD cases, including 35,130 new cases from the SPARK cohort, in this report identified SRCAP as a gene reaching exome-wide significance (P < 2.5E-06). Rots et al., 2021 reported 33 unrelated individuals with truncating SRCAP variants proximal (n=28) or distal (n=5) to the locus for Floating-Harbor syndrome who presented with a distinct neurodevelopmental disorder characterized by developmental delay with or without intellectual disability, behavioral and psychiatric abnormalities, non-specific facial features, musculoskeletal abnormalities, and hypotonia; autism spectrum disorder was observed in individuals with both proximal SRCAP variants (10/24; 41.67%) and distal SRCAP variants (2/5; 40%) in this report.

Molecular Function

This gene encodes the core catalytic component of the multiprotein chromatin-remodeling SRCAP complex. The encoded protein is an ATPase that is necessary for the incorporation of the histone variant H2A.Z into nucleosomes. It can function as a transcriptional activator in Notch-mediated, CREB-mediated and steroid receptor-mediated transcription. Mutations in this gene cause Floating-Harbor syndrome (OMIM 136140), a rare disorder characterized by short stature, language deficits and dysmorphic facial features.

External Links

References