TNK2
tyrosine kinase non receptor 2, the group of MicroRNA protein coding host genes|TNK family tyrosine kinases
Basic information
Region (hg38): 3:195863364-195911945
Links
Phenotypes
GenCC
Source:
- infantile-onset mesial temporal lobe epilepsy with severe cognitive regression (Supportive), mode of inheritance: AR
ClinVar
This is a list of variants' phenotypes submitted to
- not_provided (244 variants)
- not_specified (230 variants)
- TNK2-related_disorder (20 variants)
- Parkinson_disease (4 variants)
- Abnormality_of_neuronal_migration (2 variants)
- Epileptic_encephalopathy (1 variants)
- Autosomal_recessive_infantile_epilepsy (1 variants)
- TNK2-associated_Epilepsy_syndrome (1 variants)
- Infantile_epilepsy (1 variants)
- Developmental_and_epileptic_encephalopathy (1 variants)
- See_cases (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the TNK2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_001382273.1. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 69 | 25 | 94 | |||
| missense | 263 | 18 | 289 | |||
| nonsense | 2 | |||||
| start loss | 0 | |||||
| frameshift | 3 | |||||
| splice donor/acceptor (+/-2bp) | 1 | |||||
| Total | 1 | 0 | 269 | 87 | 32 |
Highest pathogenic variant AF is 0.00000371889
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| TNK2 | protein_coding | protein_coding | ENST00000381916 | 15 | 48582 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 8.22e-12 | 0.993 | 125678 | 0 | 70 | 125748 | 0.000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | -0.202 | 710 | 695 | 1.02 | 0.0000479 | 6863 |
| Missense in Polyphen | 225 | 259.45 | 0.86722 | 2555 | ||
| Synonymous | -4.89 | 416 | 307 | 1.36 | 0.0000218 | 2358 |
| Loss of Function | 2.61 | 25 | 43.6 | 0.574 | 0.00000229 | 448 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000756 | 0.000730 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.000167 | 0.000163 |
| Finnish | 0.0000961 | 0.0000924 |
| European (Non-Finnish) | 0.000343 | 0.000325 |
| Middle Eastern | 0.000167 | 0.000163 |
| South Asian | 0.000328 | 0.000327 |
| Other | 0.000330 | 0.000326 |
dbNSFP
Source:
- Function
- FUNCTION: Non-receptor tyrosine-protein and serine/threonine- protein kinase that is implicated in cell spreading and migration, cell survival, cell growth and proliferation. Transduces extracellular signals to cytosolic and nuclear effectors. Phosphorylates AKT1, AR, MCF2, WASL and WWOX. Implicated in trafficking and clathrin-mediated endocytosis through binding to epidermal growth factor receptor (EGFR) and clathrin. Binds to both poly- and mono-ubiquitin and regulates ligand-induced degradation of EGFR, thereby contributing to the accumulation of EGFR at the limiting membrane of early endosomes. Downstream effector of CDC42 which mediates CDC42-dependent cell migration via phosphorylation of BCAR1. May be involved both in adult synaptic function and plasticity and in brain development. Activates AKT1 by phosphorylating it on 'Tyr-176'. Phosphorylates AR on 'Tyr-267' and 'Tyr-363' thereby promoting its recruitment to androgen-responsive enhancers (AREs). Phosphorylates WWOX on 'Tyr- 287'. Phosphorylates MCF2, thereby enhancing its activity as a guanine nucleotide exchange factor (GEF) toward Rho family proteins. Contributes to the control of AXL receptor levels. Confers metastatic properties on cancer cells and promotes tumor growth by negatively regulating tumor suppressor such as WWOX and positively regulating pro-survival factors such as AKT1 and AR. Phosphorylates WASP (PubMed:20110370). {ECO:0000269|PubMed:10652228, ECO:0000269|PubMed:11278436, ECO:0000269|PubMed:16247015, ECO:0000269|PubMed:16257963, ECO:0000269|PubMed:16472662, ECO:0000269|PubMed:17038317, ECO:0000269|PubMed:18262180, ECO:0000269|PubMed:18435854, ECO:0000269|PubMed:19815557, ECO:0000269|PubMed:20110370, ECO:0000269|PubMed:20333297, ECO:0000269|PubMed:20383201}.;
- Pathway
- Focal Adhesion;Oxidative Damage;EGF-EGFR Signaling Pathway;G13 Signaling Pathway;EGFR1;CDC42 signaling events
(Consensus)
Recessive Scores
- pRec
- 0.423
Intolerance Scores
- loftool
- 0.779
- rvis_EVS
- -0.72
- rvis_percentile_EVS
- 14.28
Haploinsufficiency Scores
- pHI
- 0.412
- hipred
- Y
- hipred_score
- 0.610
- ghis
- 0.616
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.990
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Tnk2
- Phenotype
Gene ontology
- Biological process
- endocytosis;cell surface receptor signaling pathway;small GTPase mediated signal transduction;phosphorylation;cell differentiation;negative regulation of GTPase activity;peptidyl-tyrosine autophosphorylation;regulation of cell population proliferation;positive regulation of peptidyl-tyrosine phosphorylation;regulation of clathrin-dependent endocytosis
- Cellular component
- nucleus;cytoplasm;endosome;plasma membrane;clathrin-coated pit;adherens junction;membrane;clathrin-coated vesicle;cytoplasmic vesicle membrane;perinuclear region of cytoplasm;Grb2-EGFR complex;cytoophidium
- Molecular function
- protein serine/threonine kinase activity;protein serine/threonine/tyrosine kinase activity;protein tyrosine kinase activity;non-membrane spanning protein tyrosine kinase activity;GTPase inhibitor activity;epidermal growth factor receptor binding;protein binding;ATP binding;ubiquitin protein ligase binding;identical protein binding;metal ion binding;WW domain binding