Relevance to Autism

Whole genome and/or whole exome sequencing of 435 individuals in 116 ASD families in Viggiano et al., 2024 identified a de novo nonsense variant in the RAP1A gene in a male ASD proband who also presented with absent speech, moderate intellectual disability, and focal epilepsy. A rare damaging de novo missense variant in this gene had previously been reported in a male ASD proband from a multiplex family from the MSSNG cohort in Yuen et al., 2017. Woike et al., 2024 reported that the binding of RAP1A to the Shank/ProSAP N-terminal (SPN) domain of SHANK3 can differentially regulate its localization in dendrites.

Molecular Function

This gene encodes a member of the Ras family of small GTPases. The encoded protein undergoes a change in conformational state and activity, depending on whether it is bound to GTP or GDP. This protein is activated by several types of guanine nucleotide exchange factors (GEFs), and inactivated by two groups of GTPase-activating proteins (GAPs). The activation status of the encoded protein is therefore affected by the balance of intracellular levels of GEFs and GAPs. The encoded protein regulates signaling pathways that affect cell proliferation and adhesion, and may play a role in tumor malignancy. The protein encoded by the RAP1A gene also plays a role in nerve growth factor (NGF)-induced neurite outgrowth (Mochizuki et al., 2001).

External Links

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