DOCK6

dedicator of cytokinesis 6, the group of DOCK family Rho GEFs

Basic information

Region (hg38): 19:11199295-11262524

Links

ENSG00000130158

∙ NCBI:57572 ∙ OMIM:614194 ∙ HGNC:19189 ∙ Uniprot:Q96HP0 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

Adams-Oliver syndrome 2 (Strong), mode of inheritance: AR
Adams-Oliver syndrome 2 (Strong), mode of inheritance: AR
Adams-Oliver syndrome (Supportive), mode of inheritance: AD
Adams-Oliver syndrome (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Adams-Oliver syndrome 2	AR	Cardiovascular	The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Dermatologic; Musculoskeletal; Neurologic; Ophthalmologic	3354597; 21820096; 25132448; 25824905

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK6 gene.

not provided (24 variants)
Adams-Oliver syndrome 2 (11 variants)
DOCK6-related disorder (2 variants)
Inborn genetic diseases (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK6 gene is commonly pathogenic or not. These statistics are base on transcript: . 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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1 clinvar	304 clinvar	28 clinvar	333
missense			523 clinvar	21 clinvar	7 clinvar	551
nonsense	10 clinvar	7 clinvar				17
start loss			1			1
frameshift	17 clinvar	6 clinvar	1 clinvar			24
splice donor/acceptor (+/-2bp)	4 clinvar	18 clinvar	1 clinvar		1 clinvar	24
Total	31	31	527	325	36

Highest pathogenic variant AF is 0.000184031

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK6	protein_coding	protein_coding	ENST00000294618	48	63187

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.26e-26	1.00	122041	170	2594	124805	0.0111

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.43	1160	1.31e+3	0.888	0.0000901	13118
Missense in Polyphen		295	360.25	0.81888		3591
Synonymous	0.723	545	567	0.961	0.0000407	4257
Loss of Function	3.96	59	102	0.577	0.00000547	1112

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.157	0.153
Ashkenazi Jewish	0.00241	0.00239
East Asian	0.000785	0.000779
Finnish	0.000289	0.000278
European (Non-Finnish)	0.00213	0.00205
Middle Eastern	0.000785	0.000779
South Asian	0.00119	0.00118
Other	0.00449	0.00429

dbNSFP

Source: dbNSFP

Function: FUNCTION: Acts as guanine nucleotide exchange factor (GEF) for CDC42 and RAC1 small GTPases. Through its activation of CDC42 and RAC1, may regulate neurite outgrowth (By similarity). {ECO:0000250, ECO:0000269|PubMed:17196961}.;
Disease: DISEASE: Adams-Oliver syndrome 2 (AOS2) [MIM:614219]: A disorder characterized by the congenital absence of skin (aplasia cutis congenita) in combination with transverse limb defects. Aplasia cutis congenita can be located anywhere on the body, but in the vast majority of the cases, it is present on the posterior parietal region where it is often associated with an underlying defect of the parietal bones. Limb abnormalities are typically limb truncation defects affecting the distal phalanges or entire digits (true ectrodactyly). Only rarely, metatarsals/metacarpals or more proximal limb structures are also affected. Apart from transverse limb defects, syndactyly, most commonly of second and third toes, can also be observed. The clinical features are highly variable and can also include cardiovascular malformations, brain abnormalities and vascular defects such as cutis marmorata and dilated scalp veins. {ECO:0000269|PubMed:21820096}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Factors involved in megakaryocyte development and platelet production;Integrin;Regulation of RAC1 activity;Hemostasis;Regulation of CDC42 activity (Consensus)

Recessive Scores

pRec: 0.100

Intolerance Scores

loftool: 0.931
rvis_EVS: -0.94
rvis_percentile_EVS: 9.42

Haploinsufficiency Scores

pHI: 0.157
hipred: N
hipred_score: 0.466
ghis: 0.518

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.719

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dock6
Phenotype

Gene ontology

Biological process: small GTPase mediated signal transduction;blood coagulation
Cellular component: cytosol;perinuclear region of cytoplasm
Molecular function: guanyl-nucleotide exchange factor activity