DOCK8
Dedicator of Cytokinesis 8
Gene Information Card
| Symbol | DOCK8 |
|---|---|
| Full Name | Dedicator of cytokinesis 8 |
| Gene Type | Protein coding |
| Chromosomal Location | 9p24.3 |
| NCBI Gene ID | 81704 ncbi.nlm.nih.gov/gene/81704 |
| Ensembl ID | ENSG00000107099 |
| UniProt ID | Q8NF50 |
| OMIM ID | 611432 |
| HGNC ID | 19191 |
| Aliases | ZIR8, MRD2, HEL-205 |
Description
DOCK8 encodes a member of the DOCK family of guanine nucleotide exchange factors (GEFs) that activate Rho GTPases, particularly Cdc42 and Rac1. The protein plays a critical role in cytoskeletal rearrangements, cell migration, and immune synapse formation. Loss-of-function mutations cause autosomal recessive hyper-IgE syndrome (HIES) with combined immunodeficiency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Autosomal recessive hyper-IgE syndrome (HIES) | Loss-of-function mutations impair DOCK8 GEF activity, leading to defective actin polymerization, impaired T-cell migration, and reduced immune synapse formation. | ClinVar, OMIM |
| Combined immunodeficiency | DOCK8 deficiency disrupts lymphocyte homing and survival, resulting in recurrent infections, severe allergies, and autoimmunity. | NCBI Gene, OMIM |
| Mental retardation, autosomal dominant 2 (MRD2) | Heterozygous missense mutations may alter DOCK8 function, affecting neuronal development. | OMIM |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 8.2 | Medium |
| Lung | 4.1 | Low |
| Brain | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| B-lymphocytes (GM12878) | 15.6 | High expression |
| T-lymphocytes (Jurkat) | 14.2 | High expression |
| NK cells (NK-92) | 13.0 | High expression |
| HeLa | 3.5 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.513C>T (p.Arg171*) | Nonsense | Rare | Loss-of-function; truncation of DOCK8 protein |
| c.1672delC (p.Leu558Trpfs*12) | Frameshift | Rare | Loss-of-function; premature stop codon |
| c.3973G>A (p.Glu1325Lys) | Missense | Rare | Impaired GEF activity; reduced Cdc42 activation |
Mutation functional classification
Loss of Function (LOF)
Most DOCK8 mutations are loss-of-function, leading to reduced or absent protein expression and impaired Rho GTPase activation, causing immunodeficiency.
Gain of Function (GOF)
No gain-of-function mutations have been reported in DOCK8.
Dominant Negative (DN)
Some missense mutations may exert dominant-negative effects by interfering with wild-type DOCK8 function, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • Rho guanyl-nucleotide exchange factor activity |
| • actin cytoskeleton organization | • cell migration |
| • immune response | • T cell chemotaxis |
Pathways
• Rho GTPase cycle
• Cdc42 signaling
• Rac1 signaling
• Immune system (R-HSA-168256)
Protein Summary
DOCK8 is a 2070-amino acid protein containing a DHR2 (DOCK homology region 2) domain responsible for GEF activity toward Cdc42 and Rac1. It localizes to the cytoplasm and cell membrane, regulating actin dynamics essential for lymphocyte migration, adhesion, and immune synapse formation. Loss of DOCK8 leads to severe combined immunodeficiency.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| DOCK8 Knockout HEK293 Cell Line | EDJ-KQ3085 | Human | 81704 | Details Get a Quote |
| DOCK8 Knockout A-549 Cell Line | EDJ-KQ24390 | Human | 81704 | Details Get a Quote |
| DOCK8 Knockout HeLa Cell Line | EDJ-KQ57409 | Human | 81704 | Details Get a Quote |
| DOCK8 Knockout HCT 116 Cell Line | EDJ-KQ74343 | Human | 81704 | Details Get a Quote |
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