DLC1

Chr 8

DLC1 Rho GTPase activating protein

ENSG00000164741 UniProt: Q96QB1 OMIM: 604258

This protein functions as a GTPase-activating protein that terminates signaling of small GTPases including RHOA, RHOB, RHOC and CDC42, regulating cytoskeletal reorganization and cell migration. Mutations cause colorectal cancer with somatic inheritance pattern. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.26), indicating intolerance to protein-disrupting mutations.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

Functions as a GTPase-activating protein for the small GTPases RHOA, RHOB, RHOC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. Also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. Required for growth factor-induced epithelial cell migration; in resting cells, interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex but growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85 (PubMed:26166433). The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RHOA while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote RAC1 activation (PubMed:26166433)

OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Colorectal cancer, somaticMIM #114500

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

0.26

LOEUF· LoF intol.

LOF

Mechanism· predicted

Some data sources returned errors (1)

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