DLC1

DLC1 Rho GTPase activating protein, the group of StAR related lipid transfer domain containing|Rho GTPase activating proteins

Basic information

Region (hg38): 8:13083360-13604610

Links

ENSG00000164741 ∙ NCBI:10395 ∙ OMIM:604258 ∙ HGNC:2897 ∙ Uniprot:Q96QB1 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• colorectal cancer (No Known Disease Relationship), mode of inheritance: Unknown
• congenital heart defects, multiple types (Limited), mode of inheritance: AD

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DLC1 gene.

• not provided (248 variants)
• Inborn genetic diseases (66 variants)
• Colorectal cancer (12 variants)
• DLC1-related condition (9 variants)
• not specified (2 variants)
• Neural tube defect (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DLC1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				29	13	42
missense			143	17	17	177
nonsense						0
start loss						0
frameshift						0
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region			8	5	2	15
non coding			1	7	60	68
Total	0	0	145	53	90

Variants in DLC1

This is a list of pathogenic ClinVar variants found in the DLC1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
8-13085576-AT-A			Benign (May 11, 2021)
8-13085801-G-C		DLC1-related disorder	Likely benign (Sep 08, 2021)
8-13085815-C-T		not specified	Uncertain significance (Nov 07, 2022)
8-13085816-T-A		not specified	Uncertain significance (Aug 06, 2022)
8-13085818-G-A		not specified	Uncertain significance (Feb 14, 2023)
8-13085856-G-A		DLC1-related disorder	Likely benign (Mar 26, 2019)
8-13085861-C-T		not specified	Uncertain significance (Jun 30, 2023)
8-13085873-C-T		DLC1-related disorder	Benign/Likely benign (Aug 30, 2023)
8-13085885-C-A		not specified	Uncertain significance (Sep 15, 2021)
8-13085893-T-C			Uncertain significance (Jun 27, 2022)
8-13085908-G-A		not specified	Uncertain significance (Mar 24, 2023)
8-13085910-G-A			Likely benign (Aug 17, 2022)
8-13086116-C-G			Benign (May 11, 2021)
8-13086182-C-T			Benign (May 11, 2021)
8-13086280-C-G			Likely benign (Apr 17, 2022)
8-13086281-A-G			Likely benign (Dec 20, 2023)
8-13086282-G-C			Likely benign (Jun 28, 2022)
8-13086286-A-T		DLC1-related disorder	Conflicting classifications of pathogenicity (May 25, 2022)
8-13086307-C-A			Uncertain significance (Apr 26, 2023)
8-13086342-G-A			Uncertain significance (Sep 03, 2020)
8-13086346-A-C		not specified	Conflicting classifications of pathogenicity (Jun 27, 2022)
8-13086396-C-T			Uncertain significance (Sep 23, 2022)
8-13086405-G-C			Uncertain significance (Jun 08, 2022)
8-13086442-G-A			Likely benign (Jul 24, 2022)
8-13086463-T-C			Uncertain significance (Jul 21, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DLC1	protein_coding	protein_coding	ENST00000276297	17	432298

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.999	0.000519	125732	0	15	125747	0.0000596

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-2.93	1123	879	1.28	0.0000523	10086
Missense in Polyphen		418	378.12	1.1055		4304
Synonymous	-4.52	467	358	1.30	0.0000233	2978
Loss of Function	6.38	10	65.9	0.152	0.00000376	734

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000615	0.0000615
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000972	0.0000967
Middle Eastern	0.00	0.00
South Asian	0.0000984	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: 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. {ECO:0000269|PubMed:18786931, ECO:0000269|PubMed:19170769, ECO:0000269|PubMed:19710422}.
• Pathway: Signal Transduction;phospholipase c delta in phospholipid associated cell signaling;Rho GTPase cycle;Signaling by Rho GTPases;Regulation of RhoA activity (Consensus)

Recessive Scores

• pRec: 0.0951

Intolerance Scores

• loftool: 0.517
• rvis_EVS: -0.44
• rvis_percentile_EVS: 24.64

Haploinsufficiency Scores

• pHI: 0.213
• hipred: Y
• hipred_score: 0.756
• ghis: 0.522

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.518

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Dlc1
• Phenotype: embryo phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); homeostasis/metabolism phenotype; growth/size/body region phenotype; craniofacial phenotype; cellular phenotype

Gene ontology

• Biological process: neural tube closure;heart morphogenesis;apoptotic process;activation of cysteine-type endopeptidase activity involved in apoptotic process;signal transduction;negative regulation of cell population proliferation;regulation of cell shape;hindbrain morphogenesis;actin cytoskeleton organization;negative regulation of cell migration;forebrain development;regulation of actin cytoskeleton organization;negative regulation of Rho protein signal transduction;positive regulation of protein dephosphorylation;positive regulation of GTPase activity;focal adhesion assembly;regulation of small GTPase mediated signal transduction;negative regulation of stress fiber assembly;negative regulation of focal adhesion assembly;positive regulation of execution phase of apoptosis
• Cellular component: nucleus;cytoplasm;cytosol;caveola;focal adhesion;cortical actin cytoskeleton;ruffle membrane
• Molecular function: GTPase activator activity;protein binding;lipid binding;SH2 domain binding