RHOC Gene - Rho-Related GTP-Binding Protein RhoC

Comprehensive genomic and functional analysis of RHOC, a key regulator of cell motility and cancer metastasis.

Gene Information Card

Symbol RHOC
Full Name ras homolog family member C
Gene Type protein-coding
Chromosomal Location 1p13.2
NCBI Gene ID 389 ncbi.nlm.nih.gov/gene/389
Ensembl ID ENSG00000154133
UniProt ID P08134
OMIM ID 165380
HGNC ID 10000
Aliases ARHC, H9, RHOC, RhoC, rho-related GTP-binding protein RhoC

Description

RHOC (ras homolog family member C) encodes a member of the Rho family of small GTPases, which cycle between an active GTP-bound and inactive GDP-bound state. RhoC regulates cytoskeletal dynamics, cell adhesion, cell migration, and invasion. Overexpression and hyperactivation of RhoC are strongly associated with tumor progression and metastasis in multiple cancer types.

Disease Associations

Disease category Pathophysiological mechanism Genomic evidence
Breast Cancer RhoC overexpression promotes invasion and metastasis via actin cytoskeleton remodeling and increased cell motility. PMID: 12058033; NCBI Gene
Melanoma RhoC activation enhances metastatic potential through regulation of actomyosin contractility and focal adhesion turnover. PMID: 16951151; COSMIC
Pancreatic Cancer RhoC upregulation correlates with poor prognosis and facilitates epithelial-mesenchymal transition (EMT). PMID: 19584269; OMIM
Ovarian Cancer RhoC overexpression drives peritoneal dissemination and chemoresistance. PMID: 21804533; ClinVar
Gastric Cancer RhoC amplification and overexpression are linked to lymph node metastasis and advanced stage. PMID: 19177455; COSMIC

Expression Profile

Tissue Expression
Tissue nTPM level
Adipose tissue 5.2 Low
Breast 8.1 Medium
Colon 6.4 Low
Lung 7.9 Medium
Ovary 9.3 Medium
Pancreas 6.8 Low
Skin 10.5 Medium
Stomach 7.1 Medium
Cell Line Expression
Cell Line nTPM Notes
MCF7 (breast cancer) 12.3 High expression; associated with invasive phenotype
A549 (lung cancer) 9.8 Moderate expression; promotes migration
HeLa (cervical cancer) 11.1 High expression; supports cytoskeletal dynamics
SKOV3 (ovarian cancer) 10.7 High expression; linked to metastasis
BxPC-3 (pancreatic cancer) 8.5 Moderate expression; contributes to EMT
Data source:Human Protein Atlas(proteinatlas.org)

Mutations & Variants

Hotspot Mutations
Variant Type Frequency Functional Description
c.83G>A (p.Gly28Glu) Missense <0.1% Gain-of-function; increased GTP binding and cell invasion
c.184C>T (p.Arg62Trp) Missense <0.1% Unknown functional effect; reported in COSMIC
c.370G>A (p.Glu124Lys) Missense <0.1% Likely loss-of-function; reduced GTPase activity
Amplification Copy number gain Variable Overexpression; frequent in breast and ovarian cancers
Mutation functional classification

Loss of Function (LOF)

Rare missense mutations (e.g., p.Glu124Lys) that impair GTP hydrolysis or protein stability, leading to reduced RhoC activity.

Gain of Function (GOF)

Activating mutations (e.g., p.Gly28Glu) that enhance GTP binding and downstream signaling, promoting cell motility and invasion.

Dominant Negative (DN)

Not well characterized for RHOC; dominant-negative mutants typically involve substitutions that lock the protein in GDP-bound state (e.g., T19N), but these are not commonly reported in natural tumors.

Pathways

• Rho GTPase cycle (Reactome: R-HSA-194840)
• Signaling by Rho family GTPases (Reactome: R-HSA-194315)
• RhoA/RhoC signaling pathway (KEGG: hsa04810)
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Epithelial-mesenchymal transition (WikiPathways: WP496)

Protein Summary

RhoC is a 21 kDa small GTPase that cycles between active GTP-bound and inactive GDP-bound states. It localizes to the plasma membrane and cytoplasm, where it regulates actin dynamics, cell polarity, and migration. RhoC is highly homologous to RhoA but exhibits distinct roles in cancer metastasis. Overexpression of RhoC is a hallmark of aggressive tumors and correlates with poor patient survival. RhoC activates downstream effectors such as ROCK, mDia, and PAK to promote actomyosin contractility and focal adhesion turnover.

Related Products

Product name Cat.No. Species Gene ID
RHOC Knockout HEK293 Cell Line EDJ-KQ50131 Human 389 Details Get a Quote
RHOC Knockout HeLa Cell Line EDJ-KQ52655 Human 389 Details Get a Quote
RHOC Knockout A-549 Cell Line EDJ-KQ61129 Human 389 Details Get a Quote
RHOC Knockout HCT 116 Cell Line EDJ-KQ69616 Human 389 Details Get a Quote
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