DOCK1

dedicator of cytokinesis 1, the group of Armadillo like helical domain containing|DOCK family Rho GEFs

Basic information

Region (hg38): 10:126905408-127452517

Links

ENSG00000150760 ∙ NCBI:1793 ∙ OMIM:601403 ∙ HGNC:2987 ∙ Uniprot:Q14185 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK1 gene.

• Inborn genetic diseases (80 variants)
• not provided (4 variants)
• DOCK1 related disorder (1 variants)
• Temporomandibular joint disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK1 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				3		3
missense			70	1		71
nonsense			1			1
start loss						0
frameshift		1				1
inframe indel			1			1
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			5	2		7
Total	0	1	77	6	0

Variants in DOCK1

This is a list of pathogenic ClinVar variants found in the DOCK1 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-126981957-A-G		not specified	Uncertain significance (Feb 03, 2023)
10-126987579-C-G		not specified	Uncertain significance (Feb 08, 2023)
10-126990477-G-A		not specified	Uncertain significance (Oct 03, 2023)
10-126990479-A-G		not specified	Uncertain significance (May 10, 2023)
10-126990483-T-G		not specified	Uncertain significance (Feb 17, 2024)
10-126990486-G-A		not specified	Uncertain significance (Dec 21, 2022)
10-126990507-T-C		not specified	Uncertain significance (Apr 28, 2023)
10-126990516-G-A		not specified	Uncertain significance (Feb 03, 2022)
10-126990564-TGAA-T		Inborn genetic diseases	Uncertain significance (May 17, 2017)
10-126996851-A-G		not specified	Uncertain significance (May 03, 2023)
10-126998122-C-G		not specified	Uncertain significance (Mar 22, 2022)
10-126999361-T-C		not specified	Uncertain significance (Oct 05, 2023)
10-127000184-A-G		not specified	Uncertain significance (Jan 17, 2024)
10-127000197-G-T		not specified	Uncertain significance (Sep 20, 2023)
10-127000238-C-T		not specified	Uncertain significance (May 16, 2022)
10-127000256-A-G		not specified	Uncertain significance (Dec 06, 2022)
10-127000278-C-T		not specified	Uncertain significance (Jan 23, 2024)
10-127012360-A-G		not specified	Uncertain significance (Jan 16, 2024)
10-127018757-C-G		not specified	Uncertain significance (May 23, 2023)
10-127018784-A-G		not specified	Uncertain significance (Dec 08, 2023)
10-127023221-A-G		not specified	Uncertain significance (Dec 18, 2023)
10-127023230-T-C		not specified	Uncertain significance (Mar 01, 2023)
10-127024685-C-T		not specified	Uncertain significance (Nov 17, 2022)
10-127024717-G-A			Likely benign (Feb 01, 2023)
10-127024763-C-T		not specified	Uncertain significance (Jan 23, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK1	protein_coding	protein_coding	ENST00000280333	52	656804

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00681	0.993	124792	2	353	125147	0.00142

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.41	808	1.03e+3	0.788	0.0000600	12276
Missense in Polyphen		105	140.93	0.74507		1388
Synonymous	0.0211	399	400	0.999	0.0000267	3325
Loss of Function	7.49	29	116	0.250	0.00000667	1336

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0131	0.0131
Ashkenazi Jewish	0.000706	0.000695
East Asian	0.000228	0.000220
Finnish	0.000792	0.000788
European (Non-Finnish)	0.000455	0.000450
Middle Eastern	0.000228	0.000220
South Asian	0.00127	0.00121
Other	0.00150	0.00148

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in cytoskeletal rearrangements required for phagocytosis of apoptotic cells and cell motility. Along with DOCK1, mediates CRK/CRKL regulation of epithelial and endothelial cell spreading and migration on type IV collagen (PubMed:19004829). Functions as a guanine nucleotide exchange factor (GEF), which activates Rac Rho small GTPases by exchanging bound GDP for free GTP. Its GEF activity may be enhanced by ELMO1 (PubMed:8657152). {ECO:0000269|PubMed:19004829, ECO:0000269|PubMed:8657152}.
• Pathway: Focal adhesion - Homo sapiens (human);Regulation of actin cytoskeleton - Homo sapiens (human);Bacterial invasion of epithelial cells - Homo sapiens (human);Shigellosis - Homo sapiens (human);Integrin-mediated Cell Adhesion;Androgen Receptor Network in Prostate Cancer;Focal Adhesion;Signaling of Hepatocyte Growth Factor Receptor;Regulation of Actin Cytoskeleton;Developmental Biology;Signaling by PTK6;Signal Transduction;VEGFA-VEGFR2 Pathway;Factors involved in megakaryocyte development and platelet production;Fcgamma receptor (FCGR) dependent phagocytosis;HGF;Innate Immune System;Immune System;DCC mediated attractive signaling;Integrin;EGFR1;Regulation of RAC1 activity;Hemostasis;Regulation of actin dynamics for phagocytic cup formation;PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases;Signaling by Non-Receptor Tyrosine Kinases;Netrin-1 signaling;Signaling by VEGF;Axon guidance;Signaling by Receptor Tyrosine Kinases;Neurotrophic factor-mediated Trk receptor signaling;Netrin-mediated signaling events;Signaling events mediated by focal adhesion kinase;Urokinase-type plasminogen activator (uPA) and uPAR-mediated signaling;Alpha4 beta1 integrin signaling events (Consensus)

Recessive Scores

• pRec: 0.197

Haploinsufficiency Scores

• pHI: 0.116
• hipred: Y
• hipred_score: 0.538
• ghis: 0.563

Essentials

• essential_gene_CRISPR2: N
• essential_gene_gene_trap: H
• gene_indispensability_pred: E
• gene_indispensability_score: 0.700

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dock1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; craniofacial phenotype; muscle phenotype; homeostasis/metabolism phenotype; immune system phenotype; cellular phenotype; respiratory system phenotype; embryo phenotype; neoplasm; 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; 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); renal/urinary system phenotype; skeleton phenotype

Zebrafish Information Network

• Gene name: dock1
• Affected structure: fast muscle cell
• Phenotype tag: abnormal
• Phenotype quality: mononucleate

Gene ontology

• Biological process: phagocytosis, engulfment;apoptotic process;cytoskeleton organization;signal transduction;integrin-mediated signaling pathway;small GTPase mediated signal transduction;blood coagulation;positive regulation of epithelial cell migration;cell migration;Fc-gamma receptor signaling pathway involved in phagocytosis;positive regulation of GTPase activity;vascular endothelial growth factor receptor signaling pathway;positive regulation of substrate adhesion-dependent cell spreading
• Cellular component: nucleus;cytoplasm;cytosol;membrane;nuclear speck;guanyl-nucleotide exchange factor complex
• Molecular function: guanyl-nucleotide exchange factor activity;Rho guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;SH3 domain binding