GeneBe

PTK2

protein-coding

protein tyrosine kinase 2, the group of PTK2 family tyrosine kinases|Protein phosphatase 1 regulatory subunits|MicroRNA protein coding host genes|FERM domain containing

Gene summary

This gene encodes a cytoplasmic protein tyrosine kinase which is found concentrated in the focal adhesions that form between cells growing in the presence of extracellular matrix constituents. The encoded protein is a member of the FAK subfamily of protein tyrosine kinases but lacks significant sequence similarity to kinases from other subfamilies. Activation of this gene may be an important early step in cell growth and intracellular signal transduction pathways triggered in response to certain neural peptides or to cell interactions with the extracellular matrix. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jun 2017]

MANE transcript

NM_001352702.2

Inheritance

—

ClinVar variants

U:126B:20

Top phenotype

Shallow orbits

gnomAD constraint

pLI —, LoF o/e 0.14

Max pathogenic AF

—

Genomic locus

chr8:140,657,900-141,002,216

External References & Databases

Ensembl (ENSG00000169398)NCBI Gene (5747)OMIM (600758)HGNC:9611GenCCUniProt (Q05397)AlphaFoldClinVar (PTK2)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~344.3 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PTK2 variants in ClinVar

13 Conditions Cataloged
not specifiedTotal: 93
not providedTotal: 24
Shallow orbitsTotal: 1
HypertoniaTotal: 1
Bulbous noseTotal: 1
EpicanthusTotal: 1
Mandibular prognathiaTotal: 1
AutismTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001352702.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
3
clinvar
11
clinvar
7
clinvar
 21
missense
102
clinvar
2
clinvar
 104
nonsense
2
clinvar
 2
start loss
0
frameshift
1
clinvar
 1
splice donor/acceptor (+/-2bp)
18
clinvar
 18
Total00126137146
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 336 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001352702.2RefSeqNP_001339631.134MANE Select
ENST00000696786.1EnsemblENSP00000512868.134MANE Select
NM_001199649.2RefSeqNP_001186578.131Standard
NM_001316342.2RefSeqNP_001303271.132Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
ptk2abDanio rerio

Structure: lens

Quality: separated from

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • PI3K-Akt signaling pathway - Homo sapiens (human)
  • Focal adhesion - Homo sapiens (human)
  • VEGF signaling pathway - Homo sapiens (human)
  • Small cell lung cancer - Homo sapiens (human)
  • ErbB signaling pathway - Homo sapiens (human)

Biological Process

  • MAPK cascade
  • microtubule cytoskeleton organization
  • angiogenesis
  • vasculogenesis
  • neuron migration

Molecular Function

  • actin binding
  • protein kinase activity
  • protein tyrosine kinase activity
  • non-membrane spanning protein tyrosine kinase activity
  • Ras guanyl-nucleotide exchange factor activity

Cellular Component

  • stress fiber
  • nucleus
  • cytoplasm
  • microtubule organizing center
  • cytosol

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000340930
Coding exons
31
Length
344317
Individuals with no LoFs
125734
Homozygous LoFs
0
Heterozygous LoFs
14
Defined
125748
p
0.0000557
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense3.443585940.6030.00003166992
Missense (PolyPhen)95237.520.399962701
Synonymous-0.3732182111.030.00001181959
Loss of Function6.621069.70.1440.00000376804

Population LoF Frequency

PopulationCAFp-valueStatus
African0.000120.00012rare
Latino/Admixed American0.0000290.000029rare
Ashkenazi Jewish00.0absent
East Asian0.000110.00011rare
Finnish0.0000940.000092rare
European (Non-Finnish)0.0000260.000026rare
South Asian0.000130.00013rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Non-receptor protein-tyrosine kinase that plays an essential role in regulating cell migration, adhesion, spreading, reorganization of the actin cytoskeleton, formation and disassembly of focal adhesions and cell protrusions, cell cycle progression, cell proliferation and apoptosis. Required for early embryonic development and placenta development. Required for embryonic angiogenesis, normal cardiomyocyte migration and proliferation, and normal heart development. Regulates axon growth and neuronal cell migration, axon branching and synapse formation; required for normal development of the nervous system. Plays a role in osteogenesis and differentiation of osteoblasts. Functions in integrin signal transduction, but also in signaling downstream of numerous growth factor receptors, G-protein coupled receptors (GPCR), EPHA2, netrin receptors and LDL receptors. 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 the AKT1 signaling cascade. Promotes activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling cascade. Promotes localized and transient activation of guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and thereby modulates the activity of Rho family GTPases. Signaling via CAS family members mediates activation of RAC1. Recruits the ubiquitin ligase MDM2 to P53/TP53 in the nucleus, and thereby regulates P53/TP53 activity, P53/TP53 ubiquitination and proteasomal degradation. Phosphorylates SRC; this increases SRC kinase activity. Phosphorylates ACTN1, ARHGEF7, GRB7, RET and WASL. Promotes phosphorylation of PXN and STAT1; most likely PXN and STAT1 are phosphorylated by a SRC family kinase that is recruited to autophosphorylated PTK2/FAK1, rather than by PTK2/FAK1 itself. Promotes phosphorylation of BCAR1; GIT2 and SHC1; this requires both SRC and PTK2/FAK1. Promotes phosphorylation of BMX and PIK3R1. Isoform 6 (FRNK) does not contain a kinase domain and inhibits PTK2/FAK1 phosphorylation and signaling. Its enhanced expression can attenuate the nuclear accumulation of LPXN and limit its ability to enhance serum response factor (SRF)-dependent gene transcription. {ECO:0000269|PubMed:10655584, ECO:0000269|PubMed:11331870, ECO:0000269|PubMed:11980671, ECO:0000269|PubMed:15166238, ECO:0000269|PubMed:15561106, ECO:0000269|PubMed:15895076, ECO:0000269|PubMed:16919435, ECO:0000269|PubMed:16927379, ECO:0000269|PubMed:17395594, ECO:0000269|PubMed:17431114, ECO:0000269|PubMed:17968709, ECO:0000269|PubMed:18006843, ECO:0000269|PubMed:18206965, ECO:0000269|PubMed:18256281, ECO:0000269|PubMed:18292575, ECO:0000269|PubMed:18497331, ECO:0000269|PubMed:18677107, ECO:0000269|PubMed:19138410, ECO:0000269|PubMed:19147981, ECO:0000269|PubMed:19224453, ECO:0000269|PubMed:20332118, ECO:0000269|PubMed:20495381, ECO:0000269|PubMed:21454698}.;
Disease
DISEASE: Note=Aberrant PTK2/FAK1 expression may play a role in cancer cell proliferation, migration and invasion, in tumor formation and metastasis. PTK2/FAK1 overexpression is seen in many types of cancer.;

Intolerance Scores

LoFtool
0.286
RVIS EVS
-1.51
RVIS percentile EVS
3.54

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
E
Essential (gene trap)
H
Indispensability pred.
E
Indispensability score
0.965

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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