PTK6
protein-codingprotein tyrosine kinase 6, the group of SH2 domain containing|PTK6 family tyrosine kinases
Gene summary
The protein encoded by this gene is a cytoplasmic nonreceptor protein kinase which may function as an intracellular signal transducer in epithelial tissues. Overexpression of this gene in mammary epithelial cells leads to sensitization of the cells to epidermal growth factor and results in a partially transformed phenotype. Expression of this gene has been detected at low levels in some breast tumors but not in normal breast tissue. The encoded protein has been shown to undergo autophosphorylation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.4 kbGenCC 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 PTK6 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005975.4. 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.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | 1 | 3 | ||
| missense | 83 | 2 | 85 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 84 | 3 | 1 | 88 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005966.1 | 8 | MANE Select | |
| Ensembl | ENSP00000442460.2 | 8 | MANE Select | |
| RefSeq | NP_001243287.1 | 3 | Standard | |
| Ensembl | ENSP00000217185.3 | 3 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal Adhesion
- Signaling by PTK6
- EGF-EGFR Signaling Pathway
- Signaling by PTK6
- Signal Transduction
Biological Process
- protein phosphorylation
- transmembrane receptor protein tyrosine kinase signaling pathway
- tyrosine phosphorylation of STAT protein
- negative regulation of signal transduction
- positive regulation of neuron projection development
Molecular Function
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- signaling receptor binding
- protein binding
- ATP binding
Cellular Component
- ruffle
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000217185
- Coding exons
- 8
- Length
- 8946
- Individuals with no LoFs
- 125503
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 232
- Defined
- 125735
- p
- 0.000923
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.394 | 270 | 289 | 0.935 | 0.0000196 | 2904 |
| Missense (PolyPhen) | 84 | 101.77 | 0.8254 | 1105 | ||
| Synonymous | -0.762 | 148 | 137 | 1.08 | 0.0000101 | 900 |
| Loss of Function | 0.329 | 20 | 21.7 | 0.924 | 0.00000117 | 212 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.0022 | 0.0019 | notable |
| Latino/Admixed American | 0.0018 | 0.0018 | notable |
| Ashkenazi Jewish | 0.00020 | 0.00020 | rare |
| East Asian | 0.00099 | 0.00092 | rare |
| Finnish | 0.00011 | 0.000092 | rare |
| European (Non-Finnish) | 0.00088 | 0.00084 | rare |
| South Asian | 0.00049 | 0.00049 | rare |
| Other | 0.0016 | 0.0015 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein kinase implicated in the regulation of a variety of signaling pathways that control the differentiation and maintenance of normal epithelia, as well as tumor growth. Function seems to be context dependent and differ depending on cell type, as well as its intracellular localization. A number of potential nuclear and cytoplasmic substrates have been identified. These include the RNA-binding proteins: KHDRBS1/SAM68, KHDRBS2/SLM1, KHDRBS3/SLM2 and SFPQ/PSF; transcription factors: STAT3 and STAT5A/B and a variety of signaling molecules: ARHGAP35/p190RhoGAP, PXN/paxillin, BTK/ATK, STAP2/BKS. Associates also with a variety of proteins that are likely upstream of PTK6 in various signaling pathways, or for which PTK6 may play an adapter-like role. These proteins include ADAM15, EGFR, ERBB2, ERBB3 and IRS4. In normal or non-tumorigenic tissues, PTK6 promotes cellular differentiation and apoptosis. In tumors PTK6 contributes to cancer progression by sensitizing cells to mitogenic signals and enhancing proliferation, anchorage- independent survival and migration/invasion. Association with EGFR, ERBB2, ERBB3 may contribute to mammary tumor development and growth through enhancement of EGF-induced signaling via BTK/AKT and PI3 kinase. Contributes to migration and proliferation by contributing to EGF-mediated phosphorylation of ARHGAP35/p190RhoGAP, which promotes association with RASA1/p120RasGAP, inactivating RhoA while activating RAS. EGF stimulation resulted in phosphorylation of PNX/Paxillin by PTK6 and activation of RAC1 via CRK/CrKII, thereby promoting migration and invasion. PTK6 activates STAT3 and STAT5B to promote proliferation. Nuclear PTK6 may be important for regulating growth in normal epithelia, while cytoplasmic PTK6 might activate oncogenic signaling pathways.;
Recessive Scores
- pRec
- 0.174
Intolerance Scores
- LoFtool
- 0.281
- RVIS EVS
- -1.04
- RVIS percentile EVS
- 7.77
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.997
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |