DOCK4

dedicator of cytokinesis 4, the group of DOCK family Rho GEFs

Basic information

Region (hg38): 7:111726109-112206407

Links

ENSG00000128512 ∙ NCBI:9732 ∙ OMIM:607679 ∙ HGNC:19192 ∙ Uniprot:Q8N1I0 ∙ 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 DOCK4 gene.

• Inborn genetic diseases (50 variants)
• not provided (30 variants)
• Neurodevelopmental disorder (11 variants)
• DOCK4-related condition (2 variants)
• Autism spectrum disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK4 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				8	6	14
missense		3	58	6	4	71
nonsense		2				2
start loss						0
frameshift		1				1
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region				1	2	3
non coding				1	1	2
Total	0	6	59	15	11

Variants in DOCK4

This is a list of pathogenic ClinVar variants found in the DOCK4 region.

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

Position	Type	Phenotype	Significance	ClinVar
7-111728289-C-A		Neurodevelopmental disorder	Uncertain significance (Feb 12, 2024)
7-111728294-G-A		not specified	Uncertain significance (Nov 10, 2022)
7-111728329-C-T		not specified	Uncertain significance (Nov 23, 2021)
7-111728333-G-A		not specified	Uncertain significance (Aug 08, 2023)
7-111728388-G-A			Likely benign (Mar 30, 2018)
7-111728398-G-A		DOCK4-related disorder	Benign (Feb 13, 2023)
7-111728425-G-A			Likely benign (Dec 31, 2019)
7-111728464-C-T		DOCK4-related disorder	Likely benign (Apr 21, 2022)
7-111728470-G-A		not specified	Uncertain significance (Jul 19, 2023)
7-111728635-T-C		not specified	Uncertain significance (Apr 04, 2023)
7-111728696-A-G		not specified	Uncertain significance (Dec 28, 2023)
7-111728698-G-A		DOCK4-related disorder	Uncertain significance (Nov 09, 2022)
7-111728711-G-T			Benign (Dec 31, 2019)
7-111732243-C-T		not specified	Uncertain significance (Mar 12, 2024)
7-111732245-G-A		not specified	Uncertain significance (Apr 05, 2023)
7-111732257-G-T		not specified	Uncertain significance (Jul 17, 2023)
7-111732269-G-A		not specified	Uncertain significance (Dec 06, 2021)
7-111735055-A-T		DOCK4-related disorder	Likely benign (Sep 16, 2021)
7-111735084-G-A		not specified	Uncertain significance (May 09, 2023)
7-111735107-G-A		not specified	Uncertain significance (Apr 28, 2022)
7-111735123-C-G		not specified	Uncertain significance (Sep 13, 2023)
7-111735158-G-A		not specified	Uncertain significance (Aug 28, 2023)
7-111735159-G-A		not specified	Uncertain significance (Jul 13, 2022)
7-111739179-C-G		not specified	Uncertain significance (Apr 21, 2022)
7-111741606-C-T		not specified	Uncertain significance (Dec 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK4	protein_coding	protein_coding	ENST00000437633	52	480301

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.826	0.174	124611	0	48	124659	0.000193

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.52	826	1.06e+3	0.782	0.0000599	12859
Missense in Polyphen		207	333.14	0.62136		4153
Synonymous	0.654	380	397	0.958	0.0000233	3623
Loss of Function	7.83	25	116	0.216	0.00000642	1366

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000570	0.000568
Ashkenazi Jewish	0.00	0.00
East Asian	0.000111	0.000111
Finnish	0.000139	0.000139
European (Non-Finnish)	0.000182	0.000177
Middle Eastern	0.000111	0.000111
South Asian	0.000198	0.000196
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Involved in regulation of adherens junction between cells. Plays a role in cell migration. Functions as a guanine nucleotide exchange factor (GEF), which activates Rap1 small GTPase by exchanging bound GDP for free GTP. {ECO:0000269|PubMed:12628187, ECO:0000269|PubMed:20679435}.
• Pathway: Rap1 signaling pathway - Homo sapiens (human);Factors involved in megakaryocyte development and platelet production;Integrin;EGFR1;Hemostasis;PDGFR-beta signaling pathway (Consensus)

Recessive Scores

• pRec: 0.0997

Intolerance Scores

• loftool: 0.717
• rvis_EVS: -0.83
• rvis_percentile_EVS: 11.53

Haploinsufficiency Scores

• pHI: 0.358
• hipred: Y
• hipred_score: 0.652
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.943

Mouse Genome Informatics

• Gene name: Dock4
• Phenotype: neoplasm; 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); 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)

Zebrafish Information Network

• Gene name: dock4a
• Affected structure: erythroid progenitor cell
• Phenotype tag: abnormal
• Phenotype quality: decreased amount

Gene ontology

• Biological process: small GTPase mediated signal transduction;positive regulation of GTPase activity;cell chemotaxis;negative regulation of vascular smooth muscle contraction;positive regulation of vascular associated smooth muscle cell migration
• Cellular component: nucleolus;Golgi apparatus;cytosol;plasma membrane;membrane;stereocilium;stereocilium bundle
• Molecular function: guanyl-nucleotide exchange factor activity;GTPase activator activity;protein binding;SH3 domain binding;PDZ domain binding;receptor tyrosine kinase binding;Rac GTPase binding