PAK6
protein-codingp21 (RAC1) activated kinase 6
Gene summary
This gene encodes a member of a family of p21-stimulated serine/threonine protein kinases, which contain an amino-terminal Cdc42/Rac interactive binding (CRIB) domain and a carboxyl-terminal kinase domain. These kinases function in a number of cellular processes, including cytoskeleton rearrangement, apoptosis, and the mitogen-activated protein (MAP) kinase signaling pathway. The protein encoded by this gene interacts with androgen receptor (AR) and translocates to the nucleus, where it is involved in transcriptional regulation. Changes in expression of this gene have been linked to prostate cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2015]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~60.1 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 PAK6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001395430.1. 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 | 1 | 1 | 2 | |||
| missense | 117 | 2 | 3 | 122 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 118 | 3 | 3 | 124 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001382359.1 | 8 | MANE Select | |
| Ensembl | ENSP00000453858.1 | 8 | MANE Select | |
| RefSeq | NP_001263646.1 | 8 | Standard | |
| RefSeq | NP_001263647.1 | 7 | 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 transcription, DNA-templated
- apoptotic process
- cytoskeleton organization
- cell migration
- signal transduction by protein phosphorylation
Molecular Function
- protein serine/threonine kinase activity
- protein binding
- ATP binding
- cadherin binding
- Rac GTPase binding
Cellular Component
- fibrillar center
- nucleus
- cytoplasm
- cell junction
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000560346
- Coding exons
- 8
- Length
- 60060
- Individuals with no LoFs
- 125710
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 34
- Defined
- 125744
- p
- 0.000135
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.469 | 400 | 427 | 0.936 | 0.0000268 | 4367 |
| Missense (PolyPhen) | 155 | 191.94 | 0.80755 | 1925 | ||
| Synonymous | -1.49 | 205 | 180 | 1.14 | 0.0000110 | 1458 |
| Loss of Function | 2.75 | 12 | 27.6 | 0.435 | 0.00000152 | 269 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00019 | 0.00018 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00010 | 0.000099 | rare |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00019 | 0.00018 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0.00016 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine protein kinase that plays a role in the regulation of gene transcription. The kinase activity is induced by various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the DNA-binding domain of androgen receptor/AR and thereby inhibits AR-mediated transcription. Inhibits also ESR1-mediated transcription. May play a role in cytoskeleton regulation by interacting with IQGAP1. May protect cells from apoptosis through phosphorylation of BAD. {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}.;
Recessive Scores
- pRec
- 0.219
Intolerance Scores
- LoFtool
- 0.634
- RVIS EVS
- 0.74
- RVIS percentile EVS
- 86.34
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.989
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |