PTK2B
protein tyrosine kinase 2 beta, the group of FERM domain containing|Minor histocompatibility antigens|PTK2 family tyrosine kinases|MicroRNA protein coding host genes
Basic information
Region (hg38): 8:27311481-27459391
Previous symbols: [ "FAK2" ]
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn genetic diseases (34 variants)
- not provided (11 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the PTK2B 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 | 6 | |||||
| missense | 35 | 38 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region ? | 0 | |||||
| non coding ? | 1 | |||||
| Total | 0 | 0 | 35 | 6 | 4 |
Variants in PTK2B
This is a list of pathogenic ClinVar variants found in the PTK2B region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-27397592-G-A | not specified | Uncertain significance (Aug 02, 2022) | ||
| 8-27397634-G-A | not specified | Uncertain significance (Jun 16, 2023) | ||
| 8-27397636-C-T | not specified | Uncertain significance (Jun 12, 2023) | ||
| 8-27397646-G-A | not specified | Uncertain significance (Sep 25, 2023) | ||
| 8-27397646-G-C | not specified | Uncertain significance (Feb 01, 2023) | ||
| 8-27397649-C-T | not specified | Uncertain significance (Apr 28, 2022) | ||
| 8-27397661-T-C | not specified | Uncertain significance (May 30, 2023) | ||
| 8-27420047-G-A | Likely benign (Apr 02, 2018) | |||
| 8-27420057-G-A | not specified | Uncertain significance (Nov 22, 2023) | ||
| 8-27422326-G-A | Likely benign (Mar 01, 2022) | |||
| 8-27422364-C-T | Benign (Jun 18, 2018) | |||
| 8-27422366-G-A | Benign (May 24, 2018) | |||
| 8-27430144-C-A | not specified | Uncertain significance (Sep 17, 2021) | ||
| 8-27430961-A-G | not specified | Uncertain significance (Aug 23, 2021) | ||
| 8-27430978-G-A | not specified | Uncertain significance (Jan 31, 2022) | ||
| 8-27430997-C-A | Likely benign (Jun 08, 2018) | |||
| 8-27432282-A-C | not specified | Uncertain significance (Jun 13, 2023) | ||
| 8-27432351-G-T | Uncertain significance (Nov 01, 2022) | |||
| 8-27433522-C-G | Likely benign (Aug 20, 2018) | |||
| 8-27434104-C-T | not specified | Uncertain significance (May 23, 2023) | ||
| 8-27434527-G-A | not specified | Uncertain significance (Nov 18, 2022) | ||
| 8-27434536-A-G | not specified | Uncertain significance (Oct 14, 2021) | ||
| 8-27435782-G-A | not specified | Uncertain significance (Apr 08, 2022) | ||
| 8-27435789-C-T | Benign (Jul 31, 2018) | |||
| 8-27435790-G-A | not specified | Uncertain significance (Sep 06, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| PTK2B | protein_coding | protein_coding | ENST00000397501 | 30 | 147905 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.935 | 0.0646 | 125719 | 0 | 29 | 125748 | 0.000115 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.50 | 517 | 623 | 0.830 | 0.0000395 | 6615 |
| Missense in Polyphen | 148 | 217.25 | 0.68124 | 2280 | ||
| Synonymous | -0.404 | 253 | 245 | 1.03 | 0.0000156 | 1895 |
| Loss of Function | 6.05 | 13 | 66.0 | 0.197 | 0.00000353 | 709 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000116 | 0.000116 |
| Ashkenazi Jewish | 0.0000992 | 0.0000992 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.0000924 | 0.0000924 |
| European (Non-Finnish) | 0.000168 | 0.000167 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.00 | 0.00 |
| Other | 0.000326 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor protein-tyrosine kinase that regulates reorganization of the actin cytoskeleton, cell polarization, cell migration, adhesion, spreading and bone remodeling. Plays a role in the regulation of the humoral immune response, and is required for normal levels of marginal B-cells in the spleen and normal migration of splenic B-cells. Required for normal macrophage polarization and migration towards sites of inflammation. Regulates cytoskeleton rearrangement and cell spreading in T- cells, and contributes to the regulation of T-cell responses. Promotes osteoclastic bone resorption; this requires both PTK2B/PYK2 and SRC. May inhibit differentiation and activity of osteoprogenitor cells. Functions in signaling downstream of integrin and collagen receptors, immune receptors, G-protein coupled receptors (GPCR), cytokine, chemokine and growth factor receptors, and mediates responses to cellular stress. Forms multisubunit signaling complexes with SRC and SRC family members upon activation; this leads to the phosphorylation of additional tyrosine residues, creating binding sites for scaffold proteins, effectors and substrates. Regulates numerous signaling pathways. Promotes activation of phosphatidylinositol 3-kinase and of the AKT1 signaling cascade. Promotes activation of NOS3. Regulates production of the cellular messenger cGMP. Promotes activation of the MAP kinase signaling cascade, including activation of MAPK1/ERK2, MAPK3/ERK1 and MAPK8/JNK1. Promotes activation of Rho family GTPases, such as RHOA and RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Acts as a scaffold, binding to both PDPK1 and SRC, thereby allowing SRC to phosphorylate PDPK1 at 'Tyr-9, 'Tyr-373', and 'Tyr-376'. Promotes phosphorylation of NMDA receptors by SRC family members, and thereby contributes to the regulation of NMDA receptor ion channel activity and intracellular Ca(2+) levels. May also regulate potassium ion transport by phosphorylation of potassium channel subunits. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ASAP1, NPHP1, KCNA2 and SHC1. Promotes phosphorylation of ASAP2, RHOU and PXN; this requires both SRC and PTK2/PYK2. {ECO:0000269|PubMed:10022920, ECO:0000269|PubMed:12771146, ECO:0000269|PubMed:12893833, ECO:0000269|PubMed:14585963, ECO:0000269|PubMed:15050747, ECO:0000269|PubMed:15166227, ECO:0000269|PubMed:17634955, ECO:0000269|PubMed:18086875, ECO:0000269|PubMed:18339875, ECO:0000269|PubMed:18587400, ECO:0000269|PubMed:18765415, ECO:0000269|PubMed:19086031, ECO:0000269|PubMed:19207108, ECO:0000269|PubMed:19244237, ECO:0000269|PubMed:19428251, ECO:0000269|PubMed:19648005, ECO:0000269|PubMed:19880522, ECO:0000269|PubMed:20001213, ECO:0000269|PubMed:20381867, ECO:0000269|PubMed:20521079, ECO:0000269|PubMed:21357692, ECO:0000269|PubMed:21533080, ECO:0000269|PubMed:7544443, ECO:0000269|PubMed:8670418, ECO:0000269|PubMed:8849729}.;
- Disease
- DISEASE: Note=Aberrant PTK2B/PYK2 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. Elevated PTK2B/PYK2 expression is seen in gliomas, hepatocellular carcinoma, lung cancer and breast cancer.;
- Pathway
- GnRH signaling pathway - Homo sapiens (human);Chemokine signaling pathway - Homo sapiens (human);Calcium signaling pathway - Homo sapiens (human);Natural killer cell mediated cytotoxicity - Homo sapiens (human);Phospholipase D signaling pathway - Homo sapiens (human);Hepatitis B - Homo sapiens (human);Leukocyte transendothelial migration - Homo sapiens (human);IL-7 Signaling Pathway;Androgen Receptor Network in Prostate Cancer;Oncostatin M Signaling Pathway;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Nifedipine Activity;Apoptosis-related network due to altered Notch3 in ovarian cancer;Signaling of Hepatocyte Growth Factor Receptor;VEGFA-VEGFR2 Signaling Pathway;Chemokine signaling pathway;EGF-EGFR Signaling Pathway;IL-2 Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Signal Transduction;Signaling by Interleukins;bioactive peptide induced signaling pathway;links between pyk2 and map kinases;il-7 signal transduction;angiotensin ii mediated activation of jnk pathway via pyk2 dependent signaling;VEGFA-VEGFR2 Pathway;thrombin signaling and protease-activated receptors;calcium signaling by hbx of hepatitis b virus;Cytokine Signaling in Immune system;TCR;Oncostatin_M;Immune System;Interleukin-2 family signaling;BCR;IL-7 signaling;role of nicotinic acetylcholine receptors in the regulation of apoptosis;BDNF;EGFR1;CXCR4-mediated signaling events;Coregulation of Androgen receptor activity;JAK STAT pathway and regulation;IL2;EPO signaling;IL2-mediated signaling events;Signaling by VEGF;Interleukin-2 signaling;IL5;IL6;IL-7;Signaling by Receptor Tyrosine Kinases;Signal regulatory protein family interactions;VEGF;Cell-Cell communication;Osteopontin-mediated events;LPA receptor mediated events;Alpha-synuclein signaling;Alpha4 beta1 integrin signaling events;Endothelins;FGF signaling pathway;Signaling events mediated by VEGFR1 and VEGFR2;Integrins in angiogenesis
(Consensus)
Recessive Scores
- pRec
- 0.743
Intolerance Scores
- loftool
- 0.170
- rvis_EVS
- -1.28
- rvis_percentile_EVS
- 5.19
Haploinsufficiency Scores
- pHI
- 0.349
- hipred
- Y
- hipred_score
- 0.694
- ghis
- 0.566
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.942
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ptk2b
- Phenotype
- immune system phenotype; 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); hematopoietic system phenotype; homeostasis/metabolism phenotype; cellular phenotype; muscle phenotype;
Gene ontology
- Biological process
- MAPK cascade;angiogenesis;oocyte maturation;response to hypoxia;positive regulation of cell-matrix adhesion;sprouting angiogenesis;adaptive immune response;marginal zone B cell differentiation;protein phosphorylation;apoptotic process;cellular defense response;response to osmotic stress;signal transduction;cell surface receptor signaling pathway;signal complex assembly;epidermal growth factor receptor signaling pathway;positive regulation of cytosolic calcium ion concentration;integrin-mediated signaling pathway;positive regulation of cell population proliferation;negative regulation of cell population proliferation;regulation of cell shape;response to mechanical stimulus;response to hormone;response to glucose;response to lithium ion;positive regulation of endothelial cell migration;negative regulation of muscle cell apoptotic process;regulation of cGMP-mediated signaling;regulation of macrophage chemotaxis;positive regulation of neuron projection development;glial cell proliferation;peptidyl-tyrosine phosphorylation;cell differentiation;regulation of cell adhesion;positive regulation of cell growth;positive regulation of cell migration;negative regulation of bone mineralization;positive regulation of actin filament polymerization;neuron projection development;regulation of inositol trisphosphate biosynthetic process;tumor necrosis factor-mediated signaling pathway;ionotropic glutamate receptor signaling pathway;response to immobilization stress;peptidyl-tyrosine autophosphorylation;interleukin-2-mediated signaling pathway;regulation of cell population proliferation;response to cocaine;response to hydrogen peroxide;activation of Janus kinase activity;negative regulation of apoptotic process;stress fiber assembly;negative regulation of potassium ion transport;positive regulation of JUN kinase activity;negative regulation of neuron apoptotic process;blood vessel endothelial cell migration;positive regulation of phosphatidylinositol 3-kinase activity;positive regulation of nitric oxide biosynthetic process;bone resorption;response to ethanol;negative regulation of myeloid cell differentiation;positive regulation of translation;positive regulation of angiogenesis;positive regulation of protein kinase activity;positive regulation of JNK cascade;protein autophosphorylation;vascular endothelial growth factor receptor signaling pathway;focal adhesion assembly;regulation of synaptic plasticity;positive regulation of peptidyl-tyrosine phosphorylation;regulation of calcium-mediated signaling;positive regulation of nitric-oxide synthase activity;regulation of release of sequestered calcium ion into cytosol;response to cAMP;response to calcium ion;positive regulation of synaptic transmission, glutamatergic;long-term synaptic potentiation;long-term synaptic depression;protein-containing complex assembly;chemokine-mediated signaling pathway;positive regulation of ERK1 and ERK2 cascade;cellular response to retinoic acid;cellular response to fluid shear stress;activation of GTPase activity;regulation of ubiquitin-dependent protein catabolic process;positive regulation of ubiquitin-dependent protein catabolic process;regulation of establishment of cell polarity;regulation of actin cytoskeleton reorganization;regulation of NMDA receptor activity;positive regulation of excitatory postsynaptic potential;positive regulation of B cell chemotaxis;positive regulation of DNA biosynthetic process
- Cellular component
- nucleus;cytoplasm;cytosol;cytoskeleton;focal adhesion;cell cortex;postsynaptic density;NMDA selective glutamate receptor complex;lamellipodium;dendrite;growth cone;extrinsic component of cytoplasmic side of plasma membrane;neuronal cell body;dendritic spine;cell body;membrane raft;perinuclear region of cytoplasm;apical dendrite;glutamatergic synapse
- Molecular function
- calmodulin-dependent protein kinase activity;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;NMDA glutamate receptor activity;protein binding;ATP binding;protein C-terminus binding;ubiquitin protein ligase binding;3-phosphoinositide-dependent protein kinase binding;protein-containing complex binding