DOCK3

dedicator of cytokinesis 3, the group of Armadillo like helical domain containing|MicroRNA protein coding host genes|DOCK family Rho GEFs

Basic information

Region (hg38): 3:50674927-51384198

Links

ENSG00000088538 ∙ NCBI:1795 ∙ OMIM:603123 ∙ HGNC:2989 ∙ Uniprot:Q8IZD9 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• syndromic intellectual disability (Supportive), mode of inheritance: AD
• neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Neurodevelopmental disorder with impaired intellectual development, hypotonia, and ataxia	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Craniofacial; Musculoskeletal; Neurologic	28195318; 29130632

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK3 gene.

• Inborn_genetic_diseases (196 variants)
• not_provided (44 variants)
• DOCK3-related_disorder (31 variants)
• Neurodevelopmental_disorder_with_impaired_intellectual_development,_hypotonia,_and_ataxia (16 variants)
• not_specified (5 variants)
• Hypotonia (2 variants)
• Global_developmental_delay (2 variants)
• EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK3 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004947.5. 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			2	29	1	32
missense			203	7	1	211
nonsense	1	1				2
start loss						0
frameshift	4	2	2			8
splice donor/acceptor (+/-2bp)		2	1			3
Total	5	5	208	36	2

Highest pathogenic variant AF is 6.8567164e-7

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK3	protein_coding	protein_coding	ENST00000266037	53	708958

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	2.56e-11	124654	0	19	124673	0.0000762

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.94	766	1.14e+3	0.672	0.0000670	13368
Missense in Polyphen		264	458.3	0.57604		5325
Synonymous	-0.000292	426	426	1.00	0.0000245	3787
Loss of Function	9.00	11	115	0.0954	0.00000624	1320

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000261	0.000252
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000986	0.0000973
Middle Eastern	0.00	0.00
South Asian	0.000104	0.0000980
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Potential guanine nucleotide exchange factor (GEF). GEF proteins activate some small GTPases by exchanging bound GDP for free GTP. Its interaction with presenilin proteins as well as its ability to stimulate Tau/MAPT phosphorylation suggest that it may be involved in Alzheimer disease. Ectopic expression in nerve cells decreases the secretion of amyloid-beta APBA1 protein and lowers the rate of cell-substratum adhesion, suggesting that it may affect the function of some small GTPase involved in the regulation of actin cytoskeleton or cell adhesion receptors (By similarity). {ECO:0000250}.
• Disease: DISEASE: Note=A chromosomal aberration involving DOCK3 has been found in a family with early-onset behavioral/developmental disorder with features of attention deficit-hyperactivity disorder and intellectual disability. Inversion inv(3)(p14:q21). The inversion disrupts DOCK3 and SLC9A9. {ECO:0000269|PubMed:14569117}.
• Pathway: Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Factors involved in megakaryocyte development and platelet production;Integrin;Hemostasis (Consensus)

Recessive Scores

• pRec: 0.132

Intolerance Scores

• loftool: 0.544
• rvis_EVS: -1.88
• rvis_percentile_EVS: 2.01

Haploinsufficiency Scores

• pHI: 0.269
• hipred: Y
• hipred_score: 0.708
• ghis: 0.628

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.125

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Dock3
• Phenotype: immune 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); hematopoietic system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); muscle phenotype

Gene ontology

• Biological process: small GTPase mediated signal transduction;positive regulation of non-membrane spanning protein tyrosine kinase activity
• Cellular component: cytosol
• Molecular function: protein binding;SH3 domain binding;Rac guanyl-nucleotide exchange factor activity