ARHGAP18

Rho GTPase Activating Protein 18

Gene Information Card

Symbol ARHGAP18
Full Name Rho GTPase Activating Protein 18
Gene Type protein-coding
Chromosomal Location 6q22.33
NCBI Gene ID 93663 ncbi.nlm.nih.gov/gene/93663
Ensembl ID ENSG00000146374
UniProt ID Q8N392
OMIM ID 616580
HGNC ID 25535
Aliases RhoGAP18, SENEX, bA307O14.2

Description

ARHGAP18 encodes a member of the Rho GTPase-activating protein (RhoGAP) family. The protein contains a RhoGAP domain that catalyzes the conversion of active GTP-bound Rho GTPases to the inactive GDP-bound form, thereby negatively regulating Rho-mediated signaling. ARHGAP18 is involved in cytoskeletal organization, cell migration, and angiogenesis. It has been implicated as a tumor suppressor in various cancers and plays a role in endothelial cell function and senescence.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast cancer Loss of ARHGAP18 expression promotes RhoA activation and cell migration, contributing to metastasis PMID: 24987033
Gastric cancer Downregulation of ARHGAP18 correlates with poor prognosis and increased invasion via RhoA/ROCK pathway PMID: 28407147
Hepatocellular carcinoma Reduced ARHGAP18 expression associated with tumor progression and metastasis PMID: 29323331
Colorectal cancer ARHGAP18 suppresses tumor growth and invasion through inhibition of RhoA signaling PMID: 27840973

Expression Profile

Tissue Expression
Tissue nTPM level
Lung 12.5 Medium
Breast 8.3 Low
Liver 6.1 Low
Colon 10.2 Medium
Stomach 9.8 Medium
Kidney 7.4 Low
Brain 4.2 Not detected
Cell Line Expression
Cell Line nTPM Notes
MCF7 (breast cancer) 11.3 Moderate expression
HepG2 (liver cancer) 7.8 Low expression
A549 (lung cancer) 14.1 Moderate expression
HeLa (cervical cancer) 9.5 Low expression
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.1045C>T (p.Arg349*) Nonsense <0.1% Loss of function, truncation of RhoGAP domain
c.782G>A (p.Arg261His) Missense <0.1% Unknown effect, located in RhoGAP domain
c.1234_1235insA (p.Thr412Asnfs*3) Frameshift <0.1% Loss of function, premature stop codon
Mutation functional classification

Loss of Function (LOF)

Nonsense and frameshift mutations that truncate the protein or disrupt the RhoGAP domain lead to loss of GTPase-activating activity, resulting in sustained RhoA activation and increased cell migration.

Gain of Function (GOF)

No gain-of-function mutations have been reported for ARHGAP18.

Dominant Negative (DN)

No dominant-negative mutations have been characterized for ARHGAP18.

Gene Ontology (GO)

• Rho GTPase activator activity • GTPase activator activity
• actin cytoskeleton organization • cell migration
• negative regulation of cell migration • signal transduction
• Rho protein signal transduction • intracellular signal transduction

Pathways

Rho GTPase cycle
Signaling by Rho GTPases
RhoA signaling pathway
Regulation of actin cytoskeleton

Protein Summary

ARHGAP18 is a 663-amino acid protein containing an N-terminal RhoGAP domain (residues 249-447) that specifically inactivates RhoA by stimulating its intrinsic GTPase activity. The protein localizes to the cytoplasm and cell membrane. It regulates actin stress fiber formation, focal adhesion dynamics, and cell contractility. ARHGAP18 is widely expressed in adult tissues, with highest levels in lung and colon. It functions as a tumor suppressor by limiting RhoA-driven cell motility and invasion. In endothelial cells, ARHGAP18 promotes senescence and inhibits angiogenesis.

Related Products

Product name Cat.No. Species Gene ID
ARHGAP18 Knockout HEK293 Cell Line EDJ-KQ11254 Human 93663 Details Get a Quote
ARHGAP18 Knockout A-549 Cell Line EDJ-KQ39348 Human 93663 Details Get a Quote
ARHGAP18 Knockout HCT 116 Cell Line EDJ-KQ39349 Human 93663 Details Get a Quote
ARHGAP18 Knockout HeLa Cell Line EDJ-KQ39350 Human 93663 Details Get a Quote
Displaying Records 1 To 4 Of 4 Records
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