RALGAPA1Ral GTPase activating protein catalytic subunit alpha 1

Relevance to Autism

Whole exome sequencing of 75 Turkish patients diagnosed with ASD (based on DSM-5 criteria) identified a homozygous missense variant in the RALGAPA1 gene in a 10-year-old male presenting with ASD and developmental delay in Kayhan et al., 2026. Additional de novo variants in this gene, including a de novo loss-of-function variant and multiple de novo missense variants, have been reported in ASD probands from the Simons Simplex Collection, the SPARK cohort, the Autism Sequencing Consortium, and a Chinese ASD cohort (De Rubeis et al., 2014; Iossifov et al., 2014; Zhou et al., 2022; Fu et al., 2022; Yuan et al., 2023), while maternally-inherited loss-of-function variants in this gene were identified in two unrelated multiplex ASD families from the mAGRE cohort in Cirnigliaro et al., 2023.

Molecular Function

This gene encodes a major subunit of the RAL-GTPase activating protein. A similar protein in mouse binds E12, a transcriptional regulator of immunoglobulin genes. The mouse protein also functions in skeletal muscle by binding to the regulatory 14-3-3 proteins upon stimulation with insulin or muscle contraction. Biallelic variants in this gene are responsible for neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulation (NEDHRIT; OMIM 618797).

External Links

Gene CardOpen Targets PlatformgnomAD browserPubMed

Human

Entrez GeneOMIMUniProtHumanBaseVariCarta

SFARI Genomic Platforms

GPF browser SFARI genome browser