DOCK2

dedicator of cytokinesis 2, the group of DOCK family Rho GEFs|Armadillo like helical domain containing|MicroRNA protein coding host genes

Basic information

Region (hg38): 5:169637268-170083382

Links

ENSG00000134516

∙ NCBI:1794 ∙ OMIM:603122 ∙ HGNC:2988 ∙ Uniprot:Q92608 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

DOCK2 deficiency (Strong), mode of inheritance: AR
DOCK2 deficiency (Supportive), mode of inheritance: AR
DOCK2 deficiency (Definitive), mode of inheritance: AR
DOCK2 deficiency (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Immunodeficiency 40	AR	Allergy/Immunology/Infectious	Individuals are susceptible to frequent and severe infections, and antiinfectious prophylaxis and early and aggressive treatment of infections may be beneficial; BMT has been described	Allergy/Immunology/Infectious	26083206

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the DOCK2 gene.

DOCK2_deficiency (1038 variants)
Inborn_genetic_diseases (162 variants)
not_specified (82 variants)
not_provided (52 variants)
DOCK2-related_disorder (24 variants)
See_cases (3 variants)
Prostate_cancer (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the DOCK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000004946.3. 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	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	313 clinvar	19 clinvar	336
missense	1 clinvar	1 clinvar	417 clinvar	20 clinvar	9 clinvar	448
nonsense	5 clinvar	2 clinvar	1 clinvar			8
start loss						0
frameshift	8 clinvar	2 clinvar				10
splice donor/acceptor (+/-2bp)	1 clinvar	11 clinvar				12
Total	15	16	422	333	28

Highest pathogenic variant AF is 0.000004789344

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
DOCK2	protein_coding	protein_coding	ENST00000256935	52	446136

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.00	0.000310	125716	0	32	125748	0.000127

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	3.94	678	1.03e+3	0.655	0.0000580	12231
Missense in Polyphen		118	283.66	0.41598		3402
Synonymous	0.388	381	391	0.975	0.0000232	3246
Loss of Function	8.02	20	111	0.180	0.00000560	1298

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000213	0.000213
Ashkenazi Jewish	0.00	0.00
East Asian	0.0000544	0.0000544
Finnish	0.000231	0.000231
European (Non-Finnish)	0.000185	0.000176
Middle Eastern	0.0000544	0.0000544
South Asian	0.0000660	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Involved in cytoskeletal rearrangements required for lymphocyte migration in response of chemokines. Activates RAC1 and RAC2, but not CDC42, by functioning as a guanine nucleotide exchange factor (GEF), which exchanges bound GDP for free GTP. May also participate in IL2 transcriptional activation via the activation of RAC2. {ECO:0000269|PubMed:21613211}.;
Disease: DISEASE: Immunodeficiency 40 (IMD40) [MIM:616433]: A form of combined immunodeficiency characterized by lymphopenia, and defective T-cell, B-cell, and NK-cell responses. Patients suffer from severe invasive bacterial and viral infections in early childhood and may die without bone marrow transplantation. {ECO:0000269|PubMed:26083206}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Fc gamma R-mediated phagocytosis - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Chemokine signaling pathway;Neutrophil degranulation;Disease;Host Interactions of HIV factors;HIV Infection;Factors involved in megakaryocyte development and platelet production;TCR;Infectious disease;Innate Immune System;Immune System;Integrin;Nef and signal transduction;Regulation of RAC1 activity;Hemostasis;The role of Nef in HIV-1 replication and disease pathogenesis;IL8- and CXCR2-mediated signaling events (Consensus)

Recessive Scores

pRec: 0.110

Intolerance Scores

loftool: 0.335
rvis_EVS: -1.16
rvis_percentile_EVS: 6.1

Haploinsufficiency Scores

pHI: 0.504
hipred: Y
hipred_score: 0.639
ghis: 0.551

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.684

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Dock2
Phenotype: cellular phenotype; homeostasis/metabolism phenotype; immune system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic system phenotype; hearing/vestibular/ear 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); renal/urinary system phenotype;

Gene ontology

Biological process: membrane raft polarization;establishment of T cell polarity;immunological synapse formation;myeloid dendritic cell activation involved in immune response;chemotaxis;small GTPase mediated signal transduction;actin cytoskeleton organization;neutrophil degranulation;positive regulation of GTPase activity;macropinocytosis;positive thymic T cell selection;negative thymic T cell selection;alpha-beta T cell proliferation;regulation of defense response to virus by virus;positive regulation of phagocytosis
Cellular component: extracellular region;cytosol;cytoskeleton;membrane;specific granule lumen;extracellular exosome
Molecular function: GTPase activator activity;protein binding;Rac guanyl-nucleotide exchange factor activity;T cell receptor binding