PAK6

p21 (RAC1) activated kinase 6

Basic information

Region (hg38): 15:40217428-40277487

Links

ENSG00000137843 ∙ NCBI:56924 ∙ OMIM:608110 ∙ HGNC:16061 ∙ Uniprot:Q9NQU5 ∙ 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 PAK6 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAK6 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						0
missense			46	1	4	51
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding			3			3
Total	0	0	49	1	4

Variants in PAK6

This is a list of pathogenic ClinVar variants found in the PAK6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
15-40217496-A-G		Mosaic variegated aneuploidy syndrome 1 • Inborn genetic diseases	Conflicting classifications of pathogenicity (Feb 20, 2024)
15-40217498-T-A		Mosaic variegated aneuploidy syndrome 1 • Inborn genetic diseases	Uncertain significance (Aug 16, 2023)
15-40217499-C-G		Inborn genetic diseases	Uncertain significance (Jan 31, 2023)
15-40217502-C-T		Inborn genetic diseases	Likely benign (Feb 27, 2022)
15-40217503-G-A		See cases	Uncertain significance (Sep 14, 2019)
15-40217503-G-T		Inborn genetic diseases	Uncertain significance (Aug 29, 2023)
15-40217507-C-G		Inborn genetic diseases	Uncertain significance (Nov 14, 2023)
15-40217508-C-T		Inborn genetic diseases	Likely benign (Dec 02, 2023)
15-40217510-A-G		Mosaic variegated aneuploidy syndrome 1 • Inborn genetic diseases	Uncertain significance (May 02, 2024)
15-40217511-T-C		Inborn genetic diseases	Likely benign (Dec 09, 2019)
15-40217513-A-G		Inborn genetic diseases	Uncertain significance (Dec 22, 2023)
15-40217520-C-T		Inborn genetic diseases • Mosaic variegated aneuploidy syndrome 1	Likely benign (Oct 23, 2022)
15-40217523-G-C		Mosaic variegated aneuploidy syndrome 1	Uncertain significance (Jun 11, 2023)
15-40217523-G-T		Inborn genetic diseases	Uncertain significance (Aug 13, 2023)
15-40217525-A-G		Inborn genetic diseases • Mosaic variegated aneuploidy syndrome 1	Uncertain significance (Feb 18, 2022)
15-40217528-A-G		Inborn genetic diseases	Uncertain significance (May 25, 2023)
15-40217534-C-T		Inborn genetic diseases	Uncertain significance (May 22, 2024)
15-40217546-T-A		Mosaic variegated aneuploidy syndrome 1	Uncertain significance (Aug 16, 2023)
15-40217552-T-C		Inborn genetic diseases	Uncertain significance (Apr 22, 2022)
15-40217554-T-G		Mosaic variegated aneuploidy syndrome 1	Uncertain significance (May 24, 2022)
15-40217562-T-A		Mosaic variegated aneuploidy syndrome 1 • Inborn genetic diseases	Uncertain significance (Oct 08, 2023)
15-40217562-T-C		Inborn genetic diseases	Likely benign (Jul 24, 2022)
15-40217563-G-A		Inborn genetic diseases	Uncertain significance (Aug 02, 2021)
15-40217564-T-C		Inborn genetic diseases	Uncertain significance (Nov 11, 2023)
15-40217565-T-G		Inborn genetic diseases	Likely benign (May 07, 2020)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
PAK6	protein_coding	protein_coding	ENST00000560346	8	60060

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000431	0.998	125710	0	34	125744	0.000135

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.469	400	427	0.936	0.0000268	4367
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000188	0.000185
Ashkenazi Jewish	0.0000998	0.0000992
East Asian	0.000168	0.000163
Finnish	0.00	0.00
European (Non-Finnish)	0.000189	0.000185
Middle Eastern	0.000168	0.000163
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• 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}.
• 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);Androgen receptor signaling pathway;Integrin-mediated Cell Adhesion;Focal Adhesion;MET in type 1 papillary renal cell carcinoma;Ras Signaling;Regulation of Actin Cytoskeleton;Developmental Biology;Activation of RAC1;AndrogenReceptor;IL-7 signaling;agrin in postsynaptic differentiation;JAK STAT pathway and regulation;EPO signaling;Signaling by ROBO receptors;Axon guidance;VEGF (Consensus)

Recessive Scores

• pRec: 0.219

Intolerance Scores

• loftool: 0.634
• rvis_EVS: 0.74
• rvis_percentile_EVS: 86.34

Haploinsufficiency Scores

• pHI: 0.240
• hipred: Y
• hipred_score: 0.704
• ghis: 0.472

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.989

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Pak6
• Phenotype: 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); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); normal phenotype

Gene ontology

• Biological process: regulation of transcription, DNA-templated;apoptotic process;cytoskeleton organization;cell migration;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;activation of protein kinase activity;regulation of MAPK cascade
• Cellular component: fibrillar center;nucleus;cytoplasm;cell junction
• Molecular function: protein serine/threonine kinase activity;protein binding;ATP binding;cadherin binding;Rac GTPase binding