DOCK2: Dedicator of Cytokinesis 2
A key guanine nucleotide exchange factor (GEF) for Rac1 and Rac2, essential for lymphocyte migration and immune function.
Gene Information Card
| Symbol | DOCK2 |
|---|---|
| Full Name | Dedicator of cytokinesis 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 5q35.1 |
| NCBI Gene ID | 1794 ncbi.nlm.nih.gov/gene/1794 |
| Ensembl ID | ENSG00000134516 |
| UniProt ID | Q92608 |
| OMIM ID | 603122 |
| HGNC ID | 2988 |
| Aliases | KIAA0209, MGC4836 |
Description
DOCK2 (Dedicator of cytokinesis 2) encodes a member of the DOCK family of guanine nucleotide exchange factors (GEFs) that specifically activate the small GTPases Rac1 and Rac2. DOCK2 is predominantly expressed in hematopoietic cells and is critical for lymphocyte migration, activation, and chemotaxis. It functions by promoting the exchange of GDP for GTP on Rac proteins, thereby regulating actin cytoskeleton dynamics and cell adhesion. Loss-of-function mutations in DOCK2 cause a severe primary immunodeficiency characterized by combined immunodeficiency, recurrent infections, and impaired lymphocyte chemotaxis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Primary immunodeficiency due to DOCK2 deficiency | Loss-of-function mutations impair Rac1/Rac2 activation, leading to defective lymphocyte migration and chemotaxis. | OMIM #616718; ClinVar; multiple case reports |
| Combined immunodeficiency | DOCK2 mutations disrupt T-cell and B-cell function, causing susceptibility to infections. | OMIM #603122; PubMed studies |
| Recurrent infections (viral, bacterial, fungal) | Impaired immune cell trafficking and activation due to DOCK2 deficiency. | ClinVar; literature |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 11.8 | High |
| Bone marrow | 9.2 | Medium |
| Thymus | 8.5 | Medium |
| Whole blood | 7.1 | Medium |
| Lung | 3.4 | Low |
| Small intestine | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocyte (GM12878) | 15.3 | High expression |
| T-lymphocyte (Jurkat) | 14.1 | High expression |
| NK-92 | 13.7 | High expression |
| Monocyte (THP-1) | 10.2 | Medium expression |
| HeLa | 1.5 | Low expression |
| HEK293 | 0.8 | Very low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.397C>T (p.Arg133*) | Nonsense | Rare | Loss of function; premature truncation |
| c.1654G>A (p.Gly552Arg) | Missense | Rare | Loss of function; impaired GEF activity |
| c.2425_2426del (p.Leu809Valfs*2) | Frameshift | Rare | Loss of function; protein truncation |
| c.3280C>T (p.Arg1094*) | Nonsense | Rare | Loss of function; premature stop |
Mutation functional classification
Loss of Function (LOF)
Most reported DOCK2 mutations are loss-of-function, leading to reduced or absent GEF activity toward Rac1/Rac2, causing immunodeficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported in DOCK2.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for DOCK2.
View complete mutation data：
Gene Ontology (GO)
| • guanyl-nucleotide exchange factor activity (GO:0005085) | • Rho guanyl-nucleotide exchange factor activity (GO:0005089) |
| • regulation of Rho protein signal transduction (GO:0035023) | • actin cytoskeleton organization (GO:0030036) |
| • chemotaxis (GO:0006935) | • T cell receptor signaling pathway (GO:0050852) |
| • small GTPase mediated signal transduction (GO:0007264) | • plasma membrane (GO:0005886) |
Pathways
• Rac1/Rac2 signaling pathway
• Chemokine signaling pathway (R-HSA-380108)
• Rho GTPase cycle (R-HSA-194840)
• T cell receptor signaling pathway (R-HSA-202403)
• B cell receptor signaling pathway (R-HSA-983705)
Protein Summary
DOCK2 is a 1830-amino acid protein (UniProt Q92608) that functions as a guanine nucleotide exchange factor (GEF) specifically for the small GTPases Rac1 and Rac2. It contains a DHR-2 (DOCK homology region 2) domain responsible for GEF activity and a DHR-1 domain that mediates membrane localization. DOCK2 is essential for lymphocyte chemotaxis, adhesion, and activation. Its deficiency leads to severe combined immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOCK2 Knockout HEK293 Cell Line | EDJ-KQ2020 | Human | 1794 | Details Get a Quote |
| DOCK2 Knockout A-549 Cell Line | EDJ-KQ22045 | Human | 1794 | Details Get a Quote |
| DOCK2 Knockout HeLa Cell Line | EDJ-KQ22046 | Human | 1794 | Details Get a Quote |
| DOCK2 Knockout HCT 116 Cell Line | EDJ-KQ70068 | Human | 1794 | Details Get a Quote |
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