PAK2
p21 (RAC1) activated kinase 2
Basic information
Region (hg38): 3:196739856-196832647
Links
Phenotypes
GenCC
Source:
- Knobloch syndrome 2 (Limited), mode of inheritance: Unknown
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Knobloch syndrome 2 | AD | Ophthalmologic | The condition can involve increased risk of retinal detachment, and awareness can allow early diagnosis and management | Dermatologic; Neurologic; Ophthalmologic | 33693784 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (11 variants)
- not specified (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PAK2 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 | 12 | 12 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 0 | |||||
| Total | 0 | 0 | 12 | 0 | 0 |
Variants in PAK2
This is a list of pathogenic ClinVar variants found in the PAK2 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 3-196782710-A-G | not specified | Uncertain significance (Oct 12, 2022) | ||
| 3-196803111-A-C | not specified | Uncertain significance (Jun 11, 2021) | ||
| 3-196803142-A-G | PAK2-related disorder | Likely benign (Jul 08, 2022) | ||
| 3-196806629-T-G | not specified | Uncertain significance (Aug 02, 2021) | ||
| 3-196806643-C-T | not specified | Uncertain significance (Mar 23, 2022) | ||
| 3-196806667-G-T | not specified | Uncertain significance (Jan 04, 2022) | ||
| 3-196807902-A-G | not specified | Uncertain significance (Dec 01, 2022) | ||
| 3-196810598-G-A | not specified | Uncertain significance (Jun 05, 2023) | ||
| 3-196812239-C-T | not specified | Uncertain significance (Aug 12, 2021) | ||
| 3-196812852-G-T | PAK2-related disorder | Uncertain significance (Nov 22, 2023) | ||
| 3-196814458-G-T | not specified | Uncertain significance (Aug 01, 2022) | ||
| 3-196814501-G-T | PAK2-related disorder | Uncertain significance (Nov 07, 2023) | ||
| 3-196820422-C-T | not specified | Uncertain significance (May 13, 2021) | ||
| 3-196820486-A-T | not specified | Uncertain significance (Feb 28, 2024) | ||
| 3-196820490-G-A | Knobloch syndrome 2 | Likely pathogenic (Feb 14, 2024) | ||
| 3-196820495-A-G | not specified | Uncertain significance (Apr 26, 2023) | ||
| 3-196820520-G-A | Knobloch syndrome | Pathogenic (Jan 01, 2004) | ||
| 3-196827296-A-T | not specified | Uncertain significance (Aug 02, 2021) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PAK2 | protein_coding | protein_coding | ENST00000327134 | 14 | 92791 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.972 | 0.0283 | 125741 | 0 | 5 | 125746 | 0.0000199 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 3.40 | 122 | 283 | 0.431 | 0.0000145 | 3426 |
| Missense in Polyphen | 28 | 116.46 | 0.24043 | 1371 | ||
| Synonymous | -0.0631 | 101 | 100 | 1.01 | 0.00000567 | 976 |
| Loss of Function | 4.27 | 4 | 28.6 | 0.140 | 0.00000151 | 357 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.00 | 0.00 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000463 | 0.0000462 |
| European (Non-Finnish) | 0.0000180 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000671 | 0.0000653 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell motility, cell cycle progression, apoptosis or proliferation. Acts as downstream effector of the small GTPases CDC42 and RAC1. Activation by the binding of active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Full-length PAK2 stimulates cell survival and cell growth. Phosphorylates MAPK4 and MAPK6 and activates the downstream target MAPKAPK5, a regulator of F-actin polymerization and cell migration. Phosphorylates JUN and plays an important role in EGF- induced cell proliferation. Phosphorylates many other substrates including histone H4 to promote assembly of H3.3 and H4 into nucleosomes, BAD, ribosomal protein S6, or MBP. Additionally, associates with ARHGEF7 and GIT1 to perform kinase-independent functions such as spindle orientation control during mitosis. On the other hand, apoptotic stimuli such as DNA damage lead to caspase-mediated cleavage of PAK2, generating PAK-2p34, an active p34 fragment that translocates to the nucleus and promotes cellular apoptosis involving the JNK signaling pathway. Caspase- activated PAK2 phosphorylates MKNK1 and reduces cellular translation. {ECO:0000269|PubMed:12853446, ECO:0000269|PubMed:15234964, ECO:0000269|PubMed:16617111, ECO:0000269|PubMed:19923322, ECO:0000269|PubMed:21177766, ECO:0000269|PubMed:21317288, ECO:0000269|PubMed:21724829, ECO:0000269|PubMed:9171063}.;
- 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);MAPK signaling pathway - Homo sapiens (human);EGF-Core;Integrin-mediated Cell Adhesion;Apoptosis-related network due to altered Notch3 in ovarian cancer;Focal Adhesion;Fas Ligand (FasL) pathway and Stress induction of Heat Shock Proteins (HSP) regulation;TGF-beta Signaling Pathway;MAPK Signaling Pathway;VEGFA-VEGFR2 Signaling Pathway;Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation;MET in type 1 papillary renal cell carcinoma;Ras Signaling;Regulation of Actin Cytoskeleton;Developmental Biology;Smooth Muscle Contraction;Disease;Signal Transduction;hiv-1 nef: negative effector of fas and tnf;VEGFA-VEGFR2 Pathway;mapkinase signaling pathway;Generation of second messenger molecules;Host Interactions of HIV factors;HIV Infection;MAPK6/MAPK4 signaling;TCR signaling;CD28 dependent Vav1 pathway;CD28 co-stimulation;Costimulation by the CD28 family;CD209 (DC-SIGN) signaling;C-type lectin receptors (CLRs);EPH-Ephrin signaling;FCERI mediated MAPK activation;Fc epsilon receptor (FCERI) signaling;Infectious disease;Innate Immune System;Immune System;Stimulation of the cell death response by PAK-2p34;Apoptotic execution phase;Regulation of PAK-2p34 activity by PS-GAP/RHG10;Regulation of Apoptosis;Apoptosis;Programmed Cell Death;Ephrin signaling;Adaptive Immune System;Activation of RAC1;fas signaling pathway (cd95);RHO GTPases activate PAKs;Muscle contraction;IL-7 signaling;RHO GTPase Effectors;Signaling by Rho GTPases;fc epsilon receptor i signaling in mast cells;Nef and signal transduction;agrin in postsynaptic differentiation;Sema3A PAK dependent Axon repulsion;MAPK family signaling cascades;Semaphorin interactions;JAK STAT pathway and regulation;The role of Nef in HIV-1 replication and disease pathogenesis;EPO signaling;Signaling by ROBO receptors;C-MYC pathway;Signaling by VEGF;Axon guidance;Signaling by Receptor Tyrosine Kinases;VEGF;RAC1 signaling pathway;CDC42 signaling events;Signaling events mediated by Hepatocyte Growth Factor Receptor (c-Met);Fc-epsilon receptor I signaling in mast cells;Regulation of p38-alpha and p38-beta;Signaling events mediated by VEGFR1 and VEGFR2;VEGFR2 mediated vascular permeability
(Consensus)
Recessive Scores
- pRec
- 0.274
Intolerance Scores
- loftool
- 0.249
- rvis_EVS
- -0.34
- rvis_percentile_EVS
- 30.07
Haploinsufficiency Scores
- pHI
- 0.806
- hipred
- Y
- hipred_score
- 0.783
- ghis
- 0.691
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- S
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Pak2
- Phenotype
- cellular phenotype; growth/size/body region phenotype; embryo 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); hematopoietic system phenotype; 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);
Zebrafish Information Network
- Gene name
- pak2a
- Affected structure
- cranial vasculature
- Phenotype tag
- abnormal
- Phenotype quality
- hemorrhagic
Gene ontology
- Biological process
- stimulatory C-type lectin receptor signaling pathway;protein phosphorylation;negative regulation of protein kinase activity;apoptotic process;signal transduction;phosphorylation;cell migration;peptidyl-serine phosphorylation;signal transduction by protein phosphorylation;stress-activated protein kinase signaling cascade;T cell costimulation;activation of protein kinase activity;interleukin-12-mediated signaling pathway;Fc-epsilon receptor signaling pathway;regulation of growth;negative regulation of apoptotic process;regulation of MAPK cascade;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;regulation of defense response to virus by virus;positive regulation of peptidyl-tyrosine phosphorylation;T cell receptor signaling pathway;dendritic spine development;positive regulation of protein tyrosine kinase activity;cellular response to organic cyclic compound;positive regulation of extrinsic apoptotic signaling pathway;negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
- Cellular component
- nucleus;cytoplasm;cytosol;plasma membrane;postsynaptic density;perinuclear region of cytoplasm;glutamatergic synapse
- Molecular function
- protein kinase activity;protein serine/threonine kinase activity;protein binding;ATP binding;protein kinase binding;protein tyrosine kinase activator activity;small GTPase binding;identical protein binding;cadherin binding;Rac GTPase binding