PAK3: p21 (RAC1) Activated Kinase 3
A key regulator of neuronal development, synaptic plasticity, and intellectual disability
Gene Information Card
| Symbol | PAK3 |
|---|---|
| Full Name | p21 (RAC1) Activated Kinase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | Xq23 |
| NCBI Gene ID | 5063 ncbi.nlm.nih.gov/gene/5063 |
| Ensembl ID | ENSG00000170264 |
| UniProt ID | O75914 |
| OMIM ID | 300142 |
| HGNC ID | 8592 |
| Aliases | PAK3beta, PAK3gamma, bPAK, hPAK3, MRX30, MRX47, OPHN3 |
Description
PAK3 (p21 (RAC1) Activated Kinase 3) encodes a member of the PAK family of serine/threonine protein kinases. These kinases are effectors of the small GTPases CDC42 and RAC1 and play critical roles in cytoskeletal dynamics, cell motility, and signal transduction. PAK3 is highly expressed in the brain and is essential for neuronal development, dendritic spine morphogenesis, and synaptic plasticity. Mutations in PAK3 cause X-linked intellectual disability (XLID) and have been associated with autism spectrum disorder.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| X-linked intellectual disability (XLID) | Loss-of-function mutations impair PAK3 kinase activity, disrupting downstream signaling pathways (e.g., LIMK1/cofilin) required for actin cytoskeleton remodeling and dendritic spine formation. | ClinVar, OMIM #300142 |
| Autism spectrum disorder (ASD) | Rare missense variants in PAK3 may alter synaptic protein interactions and neuronal connectivity. | ClinVar, literature (e.g., PMID: 23453855) |
| Non-syndromic intellectual disability | Deletions or truncating mutations in PAK3 lead to reduced protein expression and impaired cognitive function. | OMIM #300142, HGNC |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 25.6 | High |
| Testis | 8.3 | Medium |
| Lung | 4.1 | Low |
| Heart | 3.5 | Low |
| Liver | 1.2 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| SH-SY5Y (neuroblastoma) | 18.4 | High expression; used for neuronal differentiation studies |
| HeLa (cervical carcinoma) | 6.7 | Moderate expression |
| HEK293 (embryonic kidney) | 5.2 | Moderate expression |
| HepG2 (hepatocellular carcinoma) | 2.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.419G>A (p.Arg140Gln) | Missense | Rare | Reduced kinase activity; associated with XLID |
| c.1045C>T (p.Arg349*) | Nonsense | Rare | Premature truncation; loss of function |
| c.124_125del (p.Leu42Valfs*5) | Frameshift | Rare | Loss of protein function |
| c.1013A>G (p.Tyr338Cys) | Missense | Rare | Impaired interaction with CDC42/RAC1 |
Mutation functional classification
Loss of Function (LOF)
Most PAK3 mutations associated with intellectual disability are loss-of-function, including nonsense, frameshift, and missense variants that reduce kinase activity or protein stability.
Gain of Function (GOF)
No confirmed gain-of-function mutations reported in PAK3.
Dominant Negative (DN)
Some missense mutations (e.g., p.Arg140Gln) may act in a dominant-negative manner by interfering with wild-type PAK3 signaling in heterozygotes (X-linked inheritance).
View complete mutation data：
Gene Ontology (GO)
Pathways
• RAC1/CDC42-PAK signaling pathway
• Regulation of actin cytoskeleton (KEGG: hsa04810)
• Axon guidance (KEGG: hsa04360)
• Neurotrophin signaling pathway (KEGG: hsa04722)
• Focal adhesion (KEGG: hsa04510)
Protein Summary
PAK3 is a 559-amino acid serine/threonine kinase with an N-terminal p21-binding domain (PBD) that binds activated CDC42 and RAC1, and a C-terminal kinase domain. Autoinhibition is relieved upon GTPase binding, leading to kinase activation. PAK3 phosphorylates substrates including LIMK1, which inactivates cofilin to stabilize actin filaments. In neurons, PAK3 regulates dendritic spine morphology, synaptic plasticity, and learning. Loss of PAK3 function underlies X-linked intellectual disability.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| PAK3 Knockout HEK293 Cell Line | EDJ-KQ1239 | Human | 5063 | Details Get a Quote |
| PAK3 Knockout HeLa Cell Line | EDJ-KQ54076 | Human | 5063 | Details Get a Quote |
| PAK3 Knockout A-549 Cell Line | EDJ-KQ62564 | Human | 5063 | Details Get a Quote |
| PAK3 Knockout HCT 116 Cell Line | EDJ-KQ71034 | Human | 5063 | Details Get a Quote |
