A de novo nonsense variant in the PRKAR1B gene was identified in an ASD proband from the Autism Sequencing Consortium in De Rubeis et al., 2014, while de novo missense variants in this gene have been identified in ASD probands from the Simons Simplex Collection (Iossifov et al., 2014) and the iHART cohort (Ruzzo et al., 2019). Two separate studies used TADA analysis to identify PRKAR1B as an ASD candidate gene with a q-value < 0.1 (Du et al., 2019; Ruzzo et al., 2019). Marbach et al., 2021 characterized six individuals with PRKAR1B missense variants (five of which were confirmed de novo), all of whom were diagnosed with autism spectrum disorder and presented with global developmental delay, speech delay and/or regression, and dyspraxia/apraxia; functional analysis of PRKAR1B missense variants identified in this cohort demonstrated significantly reduced basal activity in cells transfected with mutant PRKAR1B compared to wild-type protein.
Molecular Function
The protein encoded by this gene is a regulatory subunit of cyclic AMP-dependent protein kinase A (PKA), which is involved in the signaling pathway of the second messenger cAMP. Two regulatory and two catalytic subunits form the PKA holoenzyme, disbands after cAMP binding. The holoenzyme is involved in many cellular events, including ion transport, metabolism, and transcription.
External Links
References
Type
Title
Type of Disorder
Associated Disorders
Author, Year
Primary
Synaptic, transcriptional and chromatin genes disrupted in autism.
