DLC1

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

Basic information

Region (hg38): 8:13083361-13604610

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 (376 variants)
• Colorectal_cancer (259 variants)
• not_specified (242 variants)
• DLC1-related_disorder (58 variants)
• Neural_tube_defect (2 variants)
• Carcinoma_of_colon (1 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. These statistics are base on transcript: NM_000182643.3. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			20	80	10	110
missense	1		510	36	11	558
nonsense			5			5
start loss						0
frameshift			1			1
splice donor/acceptor (+/-2bp)			2			2
Total	1	0	538	116	21

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
		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

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

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