RALGAPA1

Chr 14AR

Ral GTPase activating protein catalytic subunit alpha 1

Also known as: GARNL1, GRIPE, NEDHRIT, RalGAPalpha1, TULIP1, p240

NCBI Gene: 253959 ENSG00000174373 UniProt: Q6GYQ0 OMIM: 608884

This gene encodes the catalytic subunit of RalGAP1 complex, which acts as a GTPase activator for the small GTPases RALA and RALB that regulate cellular processes including vesicle trafficking and cytoskeletal organization. Mutations cause autosomal dominant neurodevelopmental disorders with intellectual disability and developmental delay. The gene is highly constrained against loss-of-function variants, indicating that such mutations are likely to be pathogenic.

OMIM ResearchSummary from RefSeq, UniProt

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. A pseudogene of this gene has been identified on chromosome 9. [provided by RefSeq, Oct 2016]

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Neurodevelopmental disorder with hypotonia, neonatal respiratory insufficiency, and thermodysregulationMIM #618797

Clinical highlights

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.23

LOEUF· LoF intol.

LOF

Mechanism· G2P