DOCK4: Dedicator of Cytokinesis 4
A guanine nucleotide exchange factor (GEF) for Rac1 and Rho GTPases involved in cell migration, adhesion, and neuronal development.
Gene Information Card
| Symbol | DOCK4 |
|---|---|
| Full Name | Dedicator of cytokinesis 4 |
| Gene Type | Protein coding |
| Chromosomal Location | 7q31.1 |
| NCBI Gene ID | 9732 ncbi.nlm.nih.gov/gene/9732 |
| Ensembl ID | ENSG00000128512 |
| UniProt ID | Q8N1I0 |
| OMIM ID | 607679 |
| HGNC ID | 19192 |
| Aliases | KIAA0716, MGC138207, MGC138209 |
Description
DOCK4 (Dedicator of cytokinesis 4) encodes a member of the DOCK family of guanine nucleotide exchange factors (GEFs) that activate small GTPases of the Rho family, particularly Rac1. The protein contains a DOCK homology region 2 (DHR2) domain responsible for GEF activity and a DHR1 domain that binds phospholipids. DOCK4 is involved in cell migration, adhesion, neurite outgrowth, and phagocytosis. Mutations and altered expression of DOCK4 have been implicated in autism spectrum disorders, schizophrenia, and various cancers, including ovarian and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autism spectrum disorder | Missense and frameshift mutations in DOCK4 disrupt Rac1 activation, impairing neuronal connectivity and synaptic function. | PMID: 16936731; ClinVar |
| Schizophrenia | Rare copy number variants and SNPs in DOCK4 are associated with increased risk, possibly through altered dendritic spine morphology. | PMID: 21926972; OMIM |
| Ovarian cancer | DOCK4 overexpression promotes cell migration and invasion via Rac1 signaling; loss of heterozygosity at 7q31.1 is frequent. | PMID: 22952450; COSMIC |
| Colorectal cancer | DOCK4 mutations (e.g., R1197X) lead to loss of GEF activity and reduced cell adhesion, contributing to metastasis. | PMID: 19252532; COSMIC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.3 | Medium |
| Lung | 8.7 | Low |
| Ovary | 15.2 | Medium |
| Colon | 9.1 | Low |
| Testis | 18.5 | High |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 14.6 | Embryonic kidney; moderate expression |
| HeLa | 11.2 | Cervical carcinoma; moderate expression |
| SH-SY5Y | 22.1 | Neuroblastoma; high expression |
| OVCAR-3 | 19.8 | Ovarian cancer; high expression |
| HCT116 | 8.4 | Colorectal carcinoma; low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| R1197X | Nonsense | <1% | Loss of GEF activity; truncated protein; associated with colorectal cancer |
| E1118K | Missense | <0.5% | Impaired Rac1 binding; linked to autism |
| c.2074delC | Frameshift | <0.1% | Premature stop; loss of function; autism spectrum disorder |
| Gln1138His | Missense | <0.3% | Reduced Rac1 activation; reported in schizophrenia |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., R1197X, c.2074delC) result in truncated or unstable protein, reducing Rac1-GEF activity and impairing cell migration and adhesion.
Gain of Function (GOF)
Not well documented; overexpression in ovarian cancer may act as a gain-of-function by enhancing Rac1 signaling and promoting invasion.
Dominant Negative (DN)
Missense mutations (e.g., E1118K) may produce a dominant-negative effect by sequestering Rac1 or disrupting DOCK4 dimerization, leading to reduced downstream signaling.
View complete mutation data：
Gene Ontology (GO)
| • Rho guanyl-nucleotide exchange factor activity (GO:0005089) | • regulation of Rho protein signal transduction (GO:0035023) |
| • cell migration (GO:0016477) | • cell adhesion (GO:0007155) |
| • actin cytoskeleton organization (GO:0030036) | • positive regulation of GTPase activity (GO:0043547) |
| • plasma membrane (GO:0005886) |
Pathways
• Rac1 signaling pathway (Reactome: R-HSA-9012999)
• Rho GTPase cycle (Reactome: R-HSA-194840)
• Signaling by Rho family GTPases (Reactome: R-HSA-194315)
• Cell migration and adhesion (KEGG: hsa04510)
Protein Summary
DOCK4 is a 1,982-amino-acid protein (UniProt Q8N1I0) that functions as a guanine nucleotide exchange factor (GEF) specifically for Rac1, but not for Cdc42 or RhoA. It contains an N-terminal DHR1 domain that binds phosphatidylinositol (3,4,5)-trisphosphate (PIP3), targeting the protein to the plasma membrane, and a C-terminal DHR2 domain that catalyzes nucleotide exchange on Rac1. DOCK4 also interacts with ELMO proteins to enhance GEF activity. The protein is critical for cytoskeletal remodeling during cell migration, neurite outgrowth, and phagocytosis. Alternative splicing produces multiple isoforms, and post-translational modifications include phosphorylation and ubiquitination.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOCK4 Knockout HEK293 Cell Line | EDJ-KQ1285 | Human | 9732 | Details Get a Quote |
| DOCK4 Knockout A-549 Cell Line | EDJ-KQ19338 | Human | 9732 | Details Get a Quote |
| DOCK4 Knockout HCT 116 Cell Line | EDJ-KQ20685 | Human | 9732 | Details Get a Quote |
| DOCK4 Knockout HeLa Cell Line | EDJ-KQ20686 | Human | 9732 | Details Get a Quote |
