PSD4: Pleckstrin and Sec7 Domain Containing 4
A guanine nucleotide exchange factor (GEF) for ADP-ribosylation factor (ARF) GTPases involved in vesicle trafficking and immune regulation.
Gene Information Card
| Symbol | PSD4 |
|---|---|
| Full Name | pleckstrin and Sec7 domain containing 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 2q31.1 |
| NCBI Gene ID | 23550 ncbi.nlm.nih.gov/gene/23550 |
| Ensembl ID | ENSG00000115956 |
| UniProt ID | Q8NDX1 |
| OMIM ID | 614446 |
| HGNC ID | 19094 |
| Aliases | KIAA0440, TIC, EFA6B |
Description
PSD4 (pleckstrin and Sec7 domain containing 4) encodes a guanine nucleotide exchange factor (GEF) that specifically activates ADP-ribosylation factor (ARF) GTPases, particularly ARF6. The protein contains a Sec7 domain responsible for catalytic activity and a pleckstrin homology (PH) domain that mediates membrane localization. PSD4 is involved in endocytic recycling, cell adhesion, actin cytoskeleton remodeling, and immune synapse formation. It is widely expressed, with highest levels in lymphoid tissues and the brain.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Immunodeficiency | PSD4 mutations impair ARF6 activation, disrupting immune cell trafficking and synapse formation | ClinVar: pathogenic variants reported in patients with recurrent infections |
| Cancer (breast, lung) | Altered PSD4 expression may affect cell migration and invasion via ARF6 signaling | COSMIC: somatic mutations and copy number alterations observed in multiple tumor types |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | High |
| Spleen | 11.8 | High |
| Brain (cortex) | 8.3 | Medium |
| Lung | 6.1 | Medium |
| Liver | 2.4 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 9.7 | Embryonic kidney; high expression |
| Jurkat | 14.2 | T-cell line; very high expression |
| HeLa | 7.5 | Cervical carcinoma; moderate expression |
| A549 | 5.3 | Lung carcinoma; moderate expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.148C>T (p.Arg50*) | Nonsense | Rare | Loss of function; truncation of Sec7 domain |
| c.625G>A (p.Gly209Arg) | Missense | Rare | Likely damaging; disrupts catalytic activity |
| c.1021_1023del (p.Lys341del) | In-frame deletion | Rare | Alters PH domain; reduced membrane localization |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated protein or nonsense-mediated decay; missense mutations in the Sec7 domain that abolish GEF activity.
Gain of Function (GOF)
Not well documented; no recurrent activating mutations reported in COSMIC or ClinVar.
Dominant Negative (DN)
Potential for missense mutations that retain membrane binding but lack catalytic activity, interfering with wild-type function.
View complete mutation data：
Gene Ontology (GO)
| • ARF guanyl-nucleotide exchange factor activity (GO:0005086) | • protein binding (GO:0005515) |
| • phosphatidylinositol-4 (GO:0005546) | • cytoplasm (GO:0005737) |
| • plasma membrane (GO:0005886) | • endocytosis (GO:0006897) |
| • actin cytoskeleton organization (GO:0030036) | • positive regulation of GTPase activity (GO:0043547) |
Pathways
• ARF6 signaling pathway
• Endocytosis and vesicle recycling
• Immune synapse formation
• Cell adhesion and migration
Protein Summary
PSD4 (EFA6B) is a 1029-amino acid protein that functions as a guanine nucleotide exchange factor (GEF) for ARF6. It contains an N-terminal coiled-coil region, a central Sec7 catalytic domain, and a C-terminal pleckstrin homology (PH) domain. The PH domain binds phosphatidylinositol-4,5-bisphosphate (PIP2), targeting the protein to the plasma membrane. PSD4 regulates endocytic recycling, cell spreading, and immune cell polarization. It is highly expressed in lymphoid tissues and the brain. Mutations in PSD4 are associated with primary immunodeficiency and have been implicated in cancer metastasis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSD4 Knockout HEK293 Cell Line | EDJ-KQ8063 | Human | 23550 | Details Get a Quote |
| PSD4 Knockout HeLa Cell Line | EDJ-KQ32545 | Human | 23550 | Details Get a Quote |
| PSD4 Knockout A-549 Cell Line | EDJ-KQ33883 | Human | 23550 | Details Get a Quote |
| PSD4 Knockout HCT 116 Cell Line | EDJ-KQ33884 | Human | 23550 | Details Get a Quote |
