PAK4
p21 (RAC1) activated kinase 4
Basic information
Region (hg38): 19:39125770-39182816
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAK4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 34 | 37 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 34 | 3 | 1 |
Variants in PAK4
This is a list of pathogenic ClinVar variants found in the PAK4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 19-39169567-G-C | not specified | Uncertain significance (Aug 13, 2021) | ||
| 19-39169576-G-A | not specified | Uncertain significance (Dec 03, 2024) | ||
| 19-39169590-G-T | not specified | Uncertain significance (Dec 22, 2023) | ||
| 19-39169591-C-T | not specified | Uncertain significance (May 24, 2023) | ||
| 19-39169614-G-A | Hereditary breast ovarian cancer syndrome | Uncertain significance (Aug 01, 2020) | ||
| 19-39169637-C-G | not specified | Uncertain significance (Sep 02, 2024) | ||
| 19-39169651-C-T | not specified | Uncertain significance (Dec 01, 2022) | ||
| 19-39169749-G-T | not specified | Uncertain significance (May 01, 2024) | ||
| 19-39169750-C-T | not specified | Uncertain significance (May 01, 2024) | ||
| 19-39172940-G-A | not specified | Uncertain significance (Nov 30, 2022) | ||
| 19-39172975-G-A | not specified | Uncertain significance (Jan 20, 2023) | ||
| 19-39173033-C-T | not specified | Uncertain significance (Sep 25, 2023) | ||
| 19-39173039-C-A | not specified | Uncertain significance (Aug 09, 2021) | ||
| 19-39173042-G-A | not specified | Uncertain significance (Aug 02, 2021) | ||
| 19-39173075-C-T | not specified | Uncertain significance (Dec 19, 2022) | ||
| 19-39173087-C-A | not specified | Uncertain significance (Nov 03, 2023) | ||
| 19-39173123-G-A | not specified | Uncertain significance (Mar 18, 2024) | ||
| 19-39173152-G-A | not specified | Likely benign (Jun 18, 2021) | ||
| 19-39173170-C-T | not specified | Uncertain significance (Oct 29, 2024) | ||
| 19-39173173-G-T | not specified | Uncertain significance (Oct 21, 2024) | ||
| 19-39173177-G-C | not specified | Uncertain significance (Jun 07, 2024) | ||
| 19-39173190-G-T | not specified | Uncertain significance (Aug 30, 2021) | ||
| 19-39173219-G-A | not specified | Uncertain significance (Aug 21, 2024) | ||
| 19-39173320-C-T | not specified | Uncertain significance (Jun 16, 2023) | ||
| 19-39173335-T-C | not specified | Uncertain significance (Oct 28, 2024) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PAK4 | protein_coding | protein_coding | ENST00000593690 | 8 | 57047 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000436 | 0.992 | 125732 | 0 | 13 | 125745 | 0.0000517 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.590 | 366 | 399 | 0.917 | 0.0000284 | 3710 |
| Missense in Polyphen | 128 | 161.98 | 0.79021 | 1445 | ||
| Synonymous | -0.420 | 189 | 182 | 1.04 | 0.0000136 | 1303 |
| Loss of Function | 2.35 | 11 | 23.2 | 0.474 | 0.00000141 | 225 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000121 | 0.000121 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000461 | 0.0000439 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000980 | 0.0000980 |
| Other | 0.000363 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, growth, 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 and inactivates the protein phosphatase SSH1, leading to increased inhibitory phosphorylation of the actin binding/depolymerizing factor cofilin. Decreased cofilin activity may lead to stabilization of actin filaments. Phosphorylates LIMK1, a kinase that also inhibits the activity of cofilin. Phosphorylates integrin beta5/ITGB5 and thus regulates cell motility. Phosphorylates ARHGEF2 and activates the downstream target RHOA that plays a role in the regulation of assembly of focal adhesions and actin stress fibers. Stimulates cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Alternatively, inhibits apoptosis by preventing caspase-8 binding to death domain receptors in a kinase independent manner. Plays a role in cell-cycle progression by controlling levels of the cell-cycle regulatory protein CDKN1A and by phosphorylating RAN. {ECO:0000269|PubMed:11278822, ECO:0000269|PubMed:11313478, ECO:0000269|PubMed:14560027, ECO:0000269|PubMed:15660133, ECO:0000269|PubMed:20507994, ECO:0000269|PubMed:20631255, ECO:0000269|PubMed:20805321, ECO:0000269|PubMed:26607847}.;
- Pathway
- 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);Axon guidance - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);Integrin-mediated Cell Adhesion;Focal Adhesion;MET in type 1 papillary renal cell carcinoma;Ras Signaling;Regulation of Actin Cytoskeleton;ErbB Signaling Pathway;Developmental Biology;Activation of RAC1;IL-7 signaling;agrin in postsynaptic differentiation;JAK STAT pathway and regulation;EPO signaling;Signaling by ROBO receptors;Axon guidance;VEGF;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);FGF signaling pathway
(Consensus)
Recessive Scores
- pRec
- 0.300
Intolerance Scores
- loftool
- 0.236
- rvis_EVS
- -0.49
- rvis_percentile_EVS
- 22.65
Haploinsufficiency Scores
- pHI
- 0.480
- hipred
- Y
- hipred_score
- 0.809
- ghis
- 0.472
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pak4
- Phenotype
- cellular phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); embryo phenotype;
Zebrafish Information Network
- Gene name
- pak4
- Affected structure
- myeloid leukocyte
- Phenotype tag
- abnormal
- Phenotype quality
- decreased amount
Gene ontology
- Biological process
- regulation of cell growth;apoptotic process;cytoskeleton organization;cell cycle;signal transduction;cell population proliferation;cell migration;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;regulation of MAPK cascade;positive regulation of angiogenesis;dendritic spine development;cellular response to organic cyclic compound;cell-cell adhesion;negative regulation of endothelial cell apoptotic process
- Cellular component
- cytoplasm;Golgi apparatus;cell-cell adherens junction;focal adhesion
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;Rac GTPase binding;cadherin binding involved in cell-cell adhesion