Single nucleotide variations encoding missense mutations in G
protein-coupled receptors may contribute to autism.
Abstract
Autism is a neurodevelopmental condition with a range of symptoms that
vary in intensity and severity from person to person. Genetic sequencing
has identified thousands of genes containing mutations in autistic
individuals, which may contribute to the development of autistic
symptoms. Several of these genes encode G protein-coupled receptors
(GPCRs) which are cell surface expressed proteins that transduce
extracellular messages to the intracellular space. Mutations in GPCRs
can impact their function, resulting in aberrant signalling within
cells, and across neurotransmitter systems in the brain. This review
summarises the current knowledge on autism-associated single nucleotide
variations encoding missense mutations in GPCRs, and the impact of these
genetic mutations on GPCR function. For some autism-associated
mutations, changes in GPCR expression levels, ligand affinity, potency
and efficacy have been observed; however, for many the functional
consequences remain unknown. Thus, further work to characterise the
functional impacts of the genetically identified mutations is required.