ARHGAP26

Chr 5

Rho GTPase activating protein 26

Also known as: GRAF, GRAF1, OPHN1L, OPHN1L1

NCBI Gene: 23092 ENSG00000145819 UniProt: Q9UNA1

The protein is a GTPase-activating protein that regulates RhoA and Cdc42 activity and facilitates mitochondrial quality control by promoting autophagosome recruitment to damaged mitochondria. Mutations cause juvenile myelomonocytic leukemia (JMML), a childhood blood cancer with somatic inheritance pattern. The gene is highly constrained against loss-of-function variants, indicating that heterozygous loss is likely not tolerated in the general population.

ResearchSummary from RefSeq, OMIM, UniProt

Interaction of a cell with the extracellular matrix triggers integrin cell surface receptors to begin signaling cascades that regulate the organization of the actin-cytoskeleton. One of the proteins involved in these cascades is focal adhesion kinase. The protein encoded by this gene is a GTPase activating protein that binds to focal adhesion kinase and mediates the activity of the GTP binding proteins RhoA and Cdc42. Defects in this gene are a cause of juvenile myelomonocytic leukemia (JMML). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2017]

ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtLeukemia, juvenile myelomonocytic

Clinical highlights

Interpreting a novel variant

This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.

Active trials

Pubs (1 yr)

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P/LP submissions

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P/LP missense

0.28

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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