PLEKHG3: Pleckstrin Homology and RhoGEF Domain Containing G3
A Rho guanine nucleotide exchange factor implicated in cytoskeletal dynamics and neurodevelopmental disorders.
Gene Information Card
| Symbol | PLEKHG3 |
|---|---|
| Full Name | Pleckstrin Homology and RhoGEF Domain Containing G3 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q23.3 |
| NCBI Gene ID | 26007 ncbi.nlm.nih.gov/gene/26007 |
| Ensembl ID | ENSG00000100823 |
| UniProt ID | Q9H0W5 |
| OMIM ID | 611893 |
| HGNC ID | 29233 |
| Aliases | FLJ00018, KIAA0599 |
Description
PLEKHG3 encodes a Rho guanine nucleotide exchange factor (RhoGEF) that activates small GTPases such as Rac1 and Cdc42, regulating actin cytoskeleton reorganization, cell migration, and neurite outgrowth. Mutations in PLEKHG3 have been associated with autosomal recessive intellectual disability and other neurodevelopmental phenotypes.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Intellectual disability, autosomal recessive | Loss-of-function variants impair RhoGEF activity, disrupting neuronal actin dynamics and synaptic function | ClinVar, OMIM #611893 |
| Neurodevelopmental disorder with hypotonia and dysmorphic features | Missense mutations affecting GEF domain reduce Rac1 activation | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Lung | 6.1 | Low |
| Kidney | 5.4 | Low |
| Liver | 3.2 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 15.2 | High expression |
| HEK293 (embryonic kidney) | 9.8 | Moderate |
| HeLa (cervical carcinoma) | 7.1 | Low |
| A549 (lung carcinoma) | 5.6 | Low |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1543C>T (p.Arg515*) | Nonsense | <0.01% | Loss of function; truncated protein |
| c.2021G>A (p.Arg674His) | Missense | <0.01% | Reduced GEF activity; associated with intellectual disability |
| c.2870_2871del (p.Leu957fs) | Frameshift | <0.01% | Loss of function; likely pathogenic |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations lead to truncated or absent protein, impairing RhoGEF activity and downstream signaling.
Gain of Function (GOF)
Not reported in PLEKHG3.
Dominant Negative (DN)
Not reported in PLEKHG3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rho GTPase cycle (Reactome R-HSA-194840)
• Signaling by Rho family GTPases (Reactome R-HSA-194315)
• Rac1/Pak1/p38/MMP2 pathway
Protein Summary
PLEKHG3 is a 1,058-amino acid protein containing a pleckstrin homology (PH) domain and a Dbl homology (DH) domain characteristic of RhoGEFs. It localizes to the cytoplasm and promotes nucleotide exchange on Rac1 and Cdc42, influencing cell morphology and migration. The protein is highly expressed in brain tissues and is critical for normal neuronal development.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLEKHG3 Knockout HEK293 Cell Line | EDJ-KQ8359 | Human | 26030 | Details Get a Quote |
| PLEKHG3 Knockout A-549 Cell Line | EDJ-KQ34393 | Human | 26030 | Details Get a Quote |
| PLEKHG3 Knockout HCT 116 Cell Line | EDJ-KQ34394 | Human | 26030 | Details Get a Quote |
| PLEKHG3 Knockout HeLa Cell Line | EDJ-KQ34395 | Human | 26030 | Details Get a Quote |
Displaying Records 1 To 4 Of 4 Records
