DLC1 Gene

HGNC Family	Rho GTPase activating proteins (ARHGAP), StAR-related lipid transfer (START) domain containing (STARD)
Name	DLC1 Rho GTPase activating protein
Description	This gene encodes a GTPase-activating protein (GAP) that is a member of the rhoGAP family of proteins which play a role in the regulation of small GTP-binding proteins. GAP family proteins participate in signaling pathways that regulate cell processes involved in cytoskeletal changes. This gene functions as a tumor suppressor gene in a number of common cancers, including prostate, lung, colorectal, and breast cancers. Multiple transcript variants due to alternative promoters and alternative splicing have been found for this gene.[provided by RefSeq, Apr 2010]
Summary	{"type": "root", "children": [{"type": "t", "text": "<head>\n <meta charset=\"UTF-8\">\n <title>DLC1 Function Summary</title>\n </head>\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Deleted in Liver Cancer 1 (DLC1) is a multi‐domain tumor suppressor that encodes a Rho GTPase–activating protein (RhoGAP) critically involved in the negative regulation of Rho family members (e.g. RhoA, RhoB, and RhoC). Through its GAP activity, DLC1 governs actin cytoskeletal organization, focal adhesion dynamics, and cell migration. Loss or downregulation of DLC1, resulting from genetic deletion, aberrant promoter methylation, microRNA‐mediated repression, or enhanced ubiquitin–dependent degradation, is frequently observed in hepatocellular, breast, prostate, lung, and nasopharyngeal carcinomas."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "9"}]}, {"type": "t", "text": " Consequently, re‐expression of DLC1 in tumor cells not only suppresses growth and colony formation but also induces apoptosis and diminishes invasiveness by inhibiting Rho/ROCK signaling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}, {"type": "fg_fs", "start_ref": "10", "end_ref": "12"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n DLC1 function is further modulated through its interactions with several focal adhesion proteins that determine its subcellular localization and full tumor suppressive activity. For instance, binding to tensin, talin, and focal adhesion kinase (FAK) via conserved motifs facilitates proper recruitment of DLC1 to adhesion sites; in addition, interactions with regulators such as p120Ras–GAP and elongation factor 1A1 integrate DLC1 activity with Ras signaling and cytoskeletal remodeling."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "21"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, DLC1 activity is tightly controlled by intramolecular autoinhibition via its sterile alpha motif (SAM) domain and by post‐translational modifications. Phosphorylation events mediated by kinases such as CDK5—as well as the binding of 14–3–3 adaptor proteins—relieve autoinhibition and promote DLC1 localization to focal adhesions, thereby enhancing its RhoGAP activity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "22"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its canonical roles in cytoskeletal regulation and adhesion, DLC1 also modulates signaling pathways involved in tumor progression. Its loss has been linked to aberrant TGF–β responses and enhanced osteolytic metastasis in breast cancer, while the consequent dependency on the RhoA pathway offers opportunities for targeted therapeutic intervention."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}, {"type": "fg_fs", "start_ref": "24", "end_ref": "27"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings establish DLC1 as a central regulator of cytoskeletal organization and cell motility whose loss contributes to oncogenic transformation and metastasis. The multifaceted regulation of DLC1—ranging from genetic and epigenetic inactivation to complex control by interacting proteins and phosphorylation—underscores its potential as a promising therapeutic target in malignancies driven by deregulated Rho signaling.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Wen Xue, Alexander Krasnitz, Robert Lucito, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "ERK5 promotes Src-induced podosome formation by limiting Rho activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200801078"}], "href": "https://doi.org/10.1083/jcb.200801078"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18573916"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18573916"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Hansoo Park, Sung-Yup Cho, Hyerim Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genomic alterations in BCL2L1 and DLC1 contribute to drug sensitivity in gastric cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1507491112"}], "href": "https://doi.org/10.1073/pnas.1507491112"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26401016"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26401016"}]}]}]}
Synonyms	P122-RHOGAP, ARHGAP7, STARD12
Proteins	RHG07_HUMAN
NCBI Gene ID	10395
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

DLC1 has 10,760 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 118 datasets.

Click the + buttons to view associations for DLC1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

DLC1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DLC1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of DLC1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of DLC1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of DLC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of DLC1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of DLC1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving DLC1 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of DLC1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DLC1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of DLC1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of DLC1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of DLC1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of DLC1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with DLC1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DLC1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of DLC1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with DLC1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of DLC1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing DLC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing DLC1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing DLC1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing DLC1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with DLC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with DLC1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of DLC1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with DLC1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with DLC1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with DLC1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with DLC1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by DLC1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with DLC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with DLC1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with DLC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with DLC1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with DLC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with DLC1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at DLC1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of DLC1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of DLC1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing DLC1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.