DLC1: A Key Tumor Suppressor in Rho GTPase Signaling
Comprehensive genomic and functional analysis of DLC1 (Deleted in Liver Cancer 1)
Gene Information Card
| Symbol | DLC1 |
|---|---|
| Full Name | Deleted in Liver Cancer 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 8p22 |
| NCBI Gene ID | 10395 ncbi.nlm.nih.gov/gene/10395 |
| Ensembl ID | ENSG00000164741 |
| UniProt ID | Q96QB1 |
| OMIM ID | 604259 |
| HGNC ID | 2895 |
| Aliases | ARHGAP7, STARD12, p122-RhoGAP |
Description
DLC1 (Deleted in Liver Cancer 1) encodes a Rho GTPase-activating protein (RhoGAP) that negatively regulates RhoA, Rac1, and Cdc42 signaling. It functions as a tumor suppressor frequently inactivated by deletion or promoter hypermethylation in hepatocellular carcinoma and other cancers. DLC1 also contains a sterile alpha motif (SAM) domain and a START lipid-binding domain, contributing to its role in cell adhesion, migration, and proliferation.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Hepatocellular carcinoma | Loss of DLC1 expression via deletion or methylation leads to RhoA activation and increased cell motility | Frequent deletion at 8p22 in HCC; re-expression suppresses tumor growth (PMID: 10700184) |
| Breast cancer | DLC1 downregulation correlates with poor prognosis; re-expression inhibits invasion | Reduced DLC1 mRNA in breast tumors (PMID: 15604238) |
| Lung cancer | Promoter hypermethylation silences DLC1 in non-small cell lung cancer | Methylation detected in 40% of NSCLC (PMID: 15604238) |
| Prostate cancer | DLC1 loss associated with metastatic progression | Deletion and reduced expression in prostate cancer cell lines (PMID: 15604238) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 8.5 | Medium |
| Lung | 6.2 | Low |
| Breast | 4.1 | Low |
| Prostate | 3.8 | Low |
| Brain | 2.5 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 12.3 | Hepatocellular carcinoma cell line |
| A549 | 5.7 | Lung adenocarcinoma cell line |
| MCF7 | 3.2 | Breast cancer cell line |
| PC3 | 2.1 | Prostate cancer cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | Rare | Loss of start codon; likely loss of function |
| c.124C>T (p.Arg42*) | Nonsense | Rare | Premature stop; loss of function |
| c.1453G>A (p.Glu485Lys) | Missense | Rare | Unknown; predicted damaging |
| Deletion of 8p22 | Copy number loss | Common in HCC | Loss of heterozygosity; reduced DLC1 expression |
Mutation functional classification
Loss of Function (LOF)
Most DLC1 mutations are loss-of-function, including nonsense, frameshift, and deletions that impair RhoGAP activity or protein stability.
Gain of Function (GOF)
No gain-of-function mutations reported; DLC1 is a tumor suppressor.
Dominant Negative (DN)
No dominant-negative mutations described; loss of one allele via deletion is common.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rho GTPase cycle (R-HSA-194840)
• Signaling by Rho GTPases (R-HSA-194315)
• RhoA signaling pathway (WP198)
Protein Summary
DLC1 is a 1091-amino acid protein containing an N-terminal SAM domain, a central RhoGAP domain, and a C-terminal START domain. The RhoGAP domain catalyzes GTP hydrolysis on RhoA, Rac1, and Cdc42, thereby inactivating these small GTPases. DLC1 localizes to focal adhesions and regulates actin cytoskeleton dynamics, cell migration, and proliferation. Loss of DLC1 function promotes oncogenic transformation and metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DLC1 Knockout HEK293 Cell Line | EDJ-KQ3908 | Human | 10395 | Details Get a Quote |
| DLC1 Knockout A-549 Cell Line | EDJ-KQ26128 | Human | 10395 | Details Get a Quote |
| DLC1 Knockout HeLa Cell Line | EDJ-KQ55399 | Human | 10395 | Details Get a Quote |
| DLC1 Knockout HCT 116 Cell Line | EDJ-KQ72337 | Human | 10395 | Details Get a Quote |
