ARHGAP35

Chr 19

Rho GTPase activating protein 35

Also known as: GRF-1, GRLF1, P190-A, P190A, p190ARhoGAP, p190RhoGAP

NCBI Gene: 2909 ENSG00000160007 UniProt: Q9NRY4

The protein functions as a Rho GTPase-activating protein that regulates cell adhesion, migration, and morphogenesis, playing critical roles in retinal development, neural tube fusion, cerebral hemisphere midline fusion, and axon outgrowth and guidance. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and structural brain abnormalities, inherited in an autosomal dominant pattern. The gene is extremely intolerant to loss-of-function variants, indicating that proper protein dosage is critical for normal neurodevelopment.

ResearchSummary from RefSeq, UniProt

The human glucocorticoid receptor DNA binding factor, which associates with the promoter region of the glucocorticoid receptor gene (hGR gene), is a repressor of glucocorticoid receptor transcription. The amino acid sequence deduced from the cDNA sequences show the presence of three sequence motifs characteristic of a zinc finger and one motif suggestive of a leucine zipper in which 1 cysteine is found instead of all leucines. The GRLF1 enhances the homologous down-regulation of wild-type hGR gene expression. Biochemical analysis suggests that GRLF1 interaction is sequence specific and that transcriptional efficacy of GRLF1 is regulated through its interaction with specific sequence motif. The level of expression is regulated by glucocorticoids. [provided by RefSeq, Jul 2008]

ResearchGenerating clinical summary…

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)

—

P/LP submissions

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P/LP missense

0.06

LOEUF· LoF intol.

LOF

Mechanism· G2P

Some data sources returned errors (1)

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