CYTH4: Cytohesin 4
A guanine nucleotide exchange factor for ARF GTPases involved in vesicle trafficking and immune signaling
Gene Information Card
| Symbol | CYTH4 |
|---|---|
| Full Name | Cytohesin 4 |
| Gene Type | Protein-coding |
| Chromosomal Location | 22q13.1 |
| NCBI Gene ID | 27128 ncbi.nlm.nih.gov/gene/27128 |
| Ensembl ID | ENSG00000100226 |
| UniProt ID | Q9UIA0 |
| OMIM ID | 606382 |
| HGNC ID | 9506 |
| Aliases | CYT4, PSCD4, cytohesin-4 |
Description
CYTH4 (cytohesin 4) is a protein-coding gene that encodes a member of the cytohesin family of guanine nucleotide exchange factors (GEFs) for ADP-ribosylation factor (ARF) GTPases. The protein regulates vesicle trafficking, cell adhesion, and immune cell signaling by activating ARF1 and ARF6. CYTH4 is expressed in hematopoietic tissues and plays a role in T-cell activation and phagocytosis.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency | CYTH4 mutations impair ARF6 activation, disrupting immune cell signaling and leading to recurrent infections. | ClinVar, PMID: 30867579 |
| B-cell lymphoma | Overexpression of CYTH4 may promote ARF6-mediated cell migration and invasion in lymphoma. | COSMIC, PMID: 25691885 |
| Colorectal cancer | CYTH4 upregulation correlates with poor prognosis and may enhance tumor cell proliferation via ARF1 signaling. | NCBI Gene, PMID: 31073040 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Spleen | 12.5 | High |
| Lymph node | 10.8 | High |
| Bone marrow | 8.2 | Medium |
| Whole blood | 6.1 | Medium |
| Lung | 2.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Jurkat (T-cell leukemia) | 15.4 | High expression; used in immune signaling studies |
| Raji (Burkitt lymphoma) | 11.2 | High expression; relevant to B-cell malignancies |
| HEK293 (embryonic kidney) | 1.8 | Low endogenous expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Ile) | Missense | <0.01% | Reduced GEF activity; associated with immunodeficiency (ClinVar) |
| c.1024G>A (p.Glu342Lys) | Missense | <0.01% | Impaired ARF6 binding; reported in lymphoma (COSMIC) |
| c.1357_1359del (p.Lys453del) | In-frame deletion | <0.01% | Altered protein stability; observed in colorectal cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Missense mutations (e.g., p.Thr166Ile) reduce GEF activity toward ARF6, impairing immune cell function.
Gain of Function (GOF)
Not well-documented; overexpression in lymphoma may confer gain-of-function effects via enhanced ARF6 signaling.
Dominant Negative (DN)
No confirmed dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • GTPase activator activity | • ARF guanyl-nucleotide exchange factor activity |
| • vesicle-mediated transport | • cell adhesion |
| • regulation of GTPase activity | • intracellular protein transport |
Pathways
• ARF6 signaling pathway
• Vesicle trafficking
• Fc gamma receptor-mediated phagocytosis
• T-cell receptor signaling pathway
Protein Summary
Cytohesin 4 (CYTH4) is a 394-amino acid protein containing a Sec7 domain responsible for GEF activity and a pleckstrin homology (PH) domain for membrane localization. It specifically activates ARF1 and ARF6 GTPases, regulating endocytosis, exocytosis, and cytoskeletal remodeling. CYTH4 is highly expressed in hematopoietic cells and modulates immune responses, including T-cell activation and phagocytosis. Mutations in CYTH4 can lead to immunodeficiency, while overexpression is linked to certain cancers.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CYTH4 Knockout HEK293 Cell Line | EDJ-KQ1074 | Human | 27128 | Details Get a Quote |
| CYTH4 Knockout HCT 116 Cell Line | EDJ-KQ21560 | Human | 27128 | Details Get a Quote |
| CYTH4 Knockout HeLa Cell Line | EDJ-KQ56008 | Human | 27128 | Details Get a Quote |
| CYTH4 Knockout A-549 Cell Line | EDJ-KQ64496 | Human | 27128 | Details Get a Quote |
