PLEKHG4: Pleckstrin Homology and RhoGEF Domain Containing G4
A gene encoding a guanine nucleotide exchange factor (GEF) for Rho GTPases, implicated in cytoskeletal dynamics and genetic disorders.
Gene Information Card
| Symbol | PLEKHG4 |
|---|---|
| Full Name | Pleckstrin homology and RhoGEF domain containing G4 |
| Gene Type | Protein coding |
| Chromosomal Location | 16q22.1 |
| NCBI Gene ID | 25894 ncbi.nlm.nih.gov/gene/25894 |
| Ensembl ID | ENSG00000140987 |
| UniProt ID | Q58EX7 |
| OMIM ID | 609526 |
| HGNC ID | 20285 |
| Aliases | FLJ00012, KIAA1386, PURATLAS |
Description
PLEKHG4 encodes a protein containing a pleckstrin homology (PH) domain and a Rho guanine nucleotide exchange factor (RhoGEF) domain. The protein functions as a GEF for Rho GTPases, activating signaling pathways that regulate cytoskeletal organization, cell migration, and adhesion. Mutations in this gene are associated with autosomal recessive spinocerebellar ataxia and other neurological disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Spinocerebellar ataxia, autosomal recessive 32 (SCAR32) | Loss-of-function mutations impair RhoGEF activity, disrupting neuronal cytoskeletal dynamics and leading to cerebellar degeneration. | PMID: 32860008; ClinVar |
| Hereditary spastic paraplegia (HSP) | Missense variants in PLEKHG4 may alter GEF activity, affecting axonal transport and motor neuron function. | PMID: 31006510; ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Cerebellum | 15.2 | Medium |
| Testis | 8.3 | Low |
| Heart | 5.1 | Low |
| Liver | 2.0 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 14.8 | Neuronal model |
| HeLa (cervical carcinoma) | 6.2 | Epithelial |
| HEK293 (embryonic kidney) | 4.5 | Transformed |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.2236C>T (p.Arg746*) | Nonsense | <0.01% | Loss of function; truncation of RhoGEF domain |
| c.2870G>A (p.Arg957Gln) | Missense | <0.01% | Impaired GEF activity; associated with SCAR32 |
| c.1012_1013del (p.Leu338Glufs*12) | Frameshift | <0.01% | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations leading to truncated or unstable protein, reducing RhoGEF activity.
Gain of Function (GOF)
Not reported.
Dominant Negative (DN)
Not reported.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Rho GTPase cycle (Reactome: R-HSA-194840)
• Signaling by Rho family GTPases (Reactome: R-HSA-194315)
Protein Summary
The PLEKHG4 protein (UniProt Q58EX7) is 1,200 amino acids long and contains an N-terminal pleckstrin homology (PH) domain and a central RhoGEF domain. It catalyzes the exchange of GDP for GTP on Rho family GTPases (e.g., RhoA, Rac1), activating downstream effectors that regulate actin dynamics, cell shape, and migration. The protein is predominantly expressed in neural tissues, consistent with its role in neuronal development and maintenance.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PLEKHG4 Knockout HEK293 Cell Line | EDJ-KQ8286 | Human | 25894 | Details Get a Quote |
| PLEKHG4B Knockout HEK293 Cell Line | EDJ-KQ11504 | Human | 153478 | Details Get a Quote |
| PLEKHG4 Knockout HCT 116 Cell Line | EDJ-KQ32927 | Human | 25894 | Details Get a Quote |
| PLEKHG4 Knockout A-549 Cell Line | EDJ-KQ34241 | Human | 25894 | Details Get a Quote |
| PLEKHG4 Knockout HeLa Cell Line | EDJ-KQ34242 | Human | 25894 | Details Get a Quote |
| PLEKHG4B Knockout HeLa Cell Line | EDJ-KQ58725 | Human | 153478 | Details Get a Quote |
| PLEKHG4B Knockout A-549 Cell Line | EDJ-KQ67208 | Human | 153478 | Details Get a Quote |
| PLEKHG4B Knockout HCT 116 Cell Line | EDJ-KQ75612 | Human | 153478 | Details Get a Quote |
Displaying Records 1 To 8 Of 8 Records
