PAK5
protein-codingp21 (RAC1) activated kinase 5
Gene summary
The protein encoded by this gene is a member of the PAK family of Ser/Thr protein kinases. PAK family members are known to be effectors of Rac/Cdc42 GTPases, which have been implicated in the regulation of cytoskeletal dynamics, proliferation, and cell survival signaling. This kinase contains a CDC42/Rac1 interactive binding (CRIB) motif, and has been shown to bind CDC42 in the presence of GTP. This kinase is predominantly expressed in brain. It is capable of promoting neurite outgrowth, and thus may play a role in neurite development. This kinase is associated with microtubule networks and induces microtubule stabilization. The subcellular localization of this kinase is tightly regulated during cell cycle progression. Alternatively spliced transcript variants encoding the same protein have been described. [provided by RefSeq, Jul 2008]
- PAK7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~301.7 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to PAK5 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_177990.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 1 | 4 | 7 | ||
| missense | 89 | 1 | 90 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 93 | 2 | 4 | 99 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_817127.1 | 8 | MANE Select | |
| Ensembl | ENSP00000322957.5 | 8 | MANE Select | |
| RefSeq | NP_065074.1 | 8 | Standard | |
| Ensembl | ENSP00000367679.1 | 8 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal adhesion - Homo sapiens (human)
- T cell receptor signaling pathway - Homo sapiens (human)
- Renal cell carcinoma - Homo sapiens (human)
- ErbB signaling pathway - Homo sapiens (human)
- Regulation of actin cytoskeleton - Homo sapiens (human)
Biological Process
- regulation of cell growth
- apoptotic process
- cytoskeleton organization
- signal transduction
- learning
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- Rac GTPase binding
Cellular Component
- nucleoplasm
- cytoplasm
- mitochondrion
- synapse
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000378429
- Coding exons
- 8
- Length
- 301654
- Individuals with no LoFs
- 125724
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 24
- Defined
- 125748
- p
- 0.0000954
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.47 | 329 | 413 | 0.796 | 0.0000239 | 4727 |
| Missense (PolyPhen) | 151 | 230.67 | 0.65461 | 2605 | ||
| Synonymous | 0.391 | 168 | 175 | 0.962 | 0.0000120 | 1400 |
| Loss of Function | 4.76 | 1 | 28.4 | 0.0352 | 0.00000128 | 356 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0.0022 | 0.00042 | notable |
| European (Non-Finnish) | 0.00041 | 0.00011 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00098 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions. {ECO:0000269|PubMed:12897128, ECO:0000269|PubMed:16014608, ECO:0000269|PubMed:16581795, ECO:0000269|PubMed:18465753, ECO:0000269|PubMed:20564219}.;
Recessive Scores
- pRec
- 0.233
Intolerance Scores
- RVIS EVS
- -0.22
- RVIS percentile EVS
- 37.6
Essentials
- Essential (gene trap)
- N