PAK4

p21 (RAC1) activated kinase 4

Basic information

Region (hg38): 19:39125769-39182816

Links

ENSG00000130669 ∙ NCBI:10298 ∙ OMIM:605451 ∙ HGNC:16059 ∙ Uniprot:O96013 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the PAK4 gene.

• Inborn genetic diseases (25 variants)
• not provided (3 variants)
• Hereditary breast ovarian cancer syndrome (1 variants)

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		1
missense			26	1	1	28
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	26	2	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)
19-39169590-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)
19-39169651-C-T		not specified	Uncertain significance (Dec 01, 2022)
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)
19-39173152-G-A		not specified	Likely benign (Jun 18, 2021)
19-39173190-G-T		not specified	Uncertain significance (Aug 30, 2021)
19-39173320-C-T		not specified	Uncertain significance (Jun 16, 2023)
19-39173366-G-A		not specified	Uncertain significance (May 31, 2023)
19-39173372-C-T		not specified	Uncertain significance (Jul 28, 2021)
19-39173581-G-C		not specified	Uncertain significance (Mar 27, 2023)
19-39173595-C-T		not specified	Uncertain significance (Dec 21, 2022)
19-39173600-A-G		not specified	Uncertain significance (Nov 13, 2023)
19-39173607-C-T		not specified	Uncertain significance (Jan 30, 2024)
19-39173621-C-G		not specified	Uncertain significance (Feb 22, 2023)
19-39173643-C-T		not specified	Uncertain significance (Feb 10, 2022)
19-39173652-C-T		not specified	Uncertain significance (Nov 14, 2023)
19-39173730-C-A		not specified	Uncertain significance (Jun 21, 2022)

GnomAD

Source: gnomAD

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: dbNSFP

• 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