PSD3 (Pleckstrin and Sec7 Domain Containing 3)
A guanine nucleotide exchange factor (GEF) for ADP-ribosylation factors (ARFs) involved in vesicle trafficking and cytoskeletal organization.
Gene Information Card
| Symbol | PSD3 |
|---|---|
| Full Name | Pleckstrin and Sec7 Domain Containing 3 |
| Gene Type | Protein-coding |
| Chromosomal Location | 8p22 |
| NCBI Gene ID | 23362 ncbi.nlm.nih.gov/gene/23362 |
| Ensembl ID | ENSG00000156052 |
| UniProt ID | Q9NYI0 |
| OMIM ID | 614083 |
| HGNC ID | 19095 |
| Aliases | EFA6R, KIAA0942, PSD-3, EFA6D |
Description
PSD3 encodes a member of the cytohesin family of guanine nucleotide exchange factors (GEFs) that specifically activate ADP-ribosylation factors (ARFs), small GTPases involved in vesicle trafficking, lipid metabolism, and actin cytoskeleton remodeling. The protein contains an N-terminal pleckstrin homology (PH) domain, a central Sec7 catalytic domain, and a C-terminal coiled-coil region. PSD3 is implicated in endocytosis, cell adhesion, and signal transduction. Alternative splicing generates multiple transcript variants.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | PSD3 overexpression may promote ARF6-mediated cell migration and invasion, contributing to metastasis. | COSMIC; PMID: 25691885 |
| Neurodevelopmental disorders | Rare copy number variants and missense mutations in PSD3 have been reported in patients with intellectual disability and autism spectrum disorder. | ClinVar; PMID: 27569548 |
| Obesity | Genome-wide association studies have linked PSD3 variants to body mass index and adiposity. | OMIM 614083; PMID: 25673412 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Lung | 8.3 | Low |
| Kidney | 6.1 | Low |
| Testis | 15.2 | Medium |
| Adipose tissue | 4.7 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 10.1 | Embryonic kidney cells |
| SH-SY5Y | 14.3 | Neuroblastoma cells |
| MCF7 | 7.8 | Breast cancer cells |
| A549 | 5.2 | Lung carcinoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.187C>T (p.Arg63Trp) | Missense | <0.01% | Unknown; reported in ClinVar as variant of uncertain significance |
| c.1024G>A (p.Glu342Lys) | Missense | <0.01% | Predicted damaging; associated with neurodevelopmental phenotypes |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.01% | Loss of function; observed in breast cancer (COSMIC) |
Mutation functional classification
Loss of Function (LOF)
Frameshift and nonsense mutations that truncate the Sec7 domain or PH domain are predicted to abolish GEF activity.
Gain of Function (GOF)
Not well characterized; some missense mutations may increase ARF6 activation, potentially promoting oncogenic signaling.
Dominant Negative (DN)
Mutations in the Sec7 domain that disrupt catalytic activity but retain PH domain-mediated membrane binding may act as dominant negatives.
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) |
| • regulation of ARF protein signal transduction (GO:0032012) | • positive regulation of GTPase activity (GO:0043547) |
Pathways
• ARF6 signaling pathway (Reactome: R-HSA-8873719)
• Clathrin-mediated endocytosis (Reactome: R-HSA-199991)
• Vesicle-mediated transport (Reactome: R-HSA-5653656)
Protein Summary
PSD3 (Pleckstrin and Sec7 Domain Containing 3) is a 1009-amino acid protein that functions as a guanine nucleotide exchange factor (GEF) for ARF GTPases, particularly ARF6. It localizes to the plasma membrane and endosomal compartments, where it regulates endocytic recycling, cell adhesion, and actin dynamics. The protein is highly expressed in brain and testis, with moderate levels in other tissues. Dysregulation of PSD3 has been implicated in cancer metastasis and neurodevelopmental disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PSD3 Knockout HEK293 Cell Line | EDJ-KQ7989 | Human | 23362 | Details Get a Quote |
| PSD3 Knockout A-549 Cell Line | EDJ-KQ33714 | Human | 23362 | Details Get a Quote |
| PSD3 Knockout HCT 116 Cell Line | EDJ-KQ33715 | Human | 23362 | Details Get a Quote |
| PSD3 Knockout HeLa Cell Line | EDJ-KQ33716 | Human | 23362 | Details Get a Quote |
