TNK2

tyrosine kinase non receptor 2, the group of MicroRNA protein coding host genes|TNK family tyrosine kinases

Basic information

Region (hg38): 3:195863363-195911945

Links

ENSG00000061938 ∙ NCBI:10188 ∙ OMIM:606994 ∙ HGNC:19297 ∙ Uniprot:Q07912 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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 ClinVar and linked to the TNK2 gene.

• not provided (173 variants)
• Inborn genetic diseases (66 variants)
• not specified (15 variants)
• Parkinson disease (4 variants)
• Early infantile epileptic encephalopathy with suppression bursts (1 variants)
• Infantile epilepsy (1 variants)
• Autosomal recessive infantile epilepsy (1 variants)
• TNK2-associated Epilepsy syndrome (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.

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				42	27	69
missense			115	9	8	132
nonsense			2			2
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)			1			1
splice region			2	1	2	5
non coding			5	11	3	19
Total	0	0	125	62	38

Variants in TNK2

This is a list of pathogenic ClinVar variants found in the TNK2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
3-195864185-C-T		not specified	Benign (Jan 29, 2024)
3-195864186-G-A		not specified	Uncertain significance (Jan 16, 2024)
3-195866930-G-A			Likely benign (Jul 01, 2022)
3-195866951-G-T			Likely benign (Jun 10, 2022)
3-195866984-G-A			Likely benign (Jun 13, 2023)
3-195866990-C-A			Likely benign (Oct 05, 2022)
3-195867005-G-A			Likely benign (Jan 01, 2023)
3-195867028-G-C			Likely benign (Feb 06, 2022)
3-195867033-C-T			Likely benign (Feb 14, 2023)
3-195867034-G-A			Likely benign (Dec 11, 2023)
3-195867180-G-A		Early infantile epileptic encephalopathy with suppression bursts	Uncertain significance (May 26, 2020)
3-195867221-G-A		Parkinson disease	Uncertain significance (Jan 01, 2016)
3-195867255-T-A		not specified	Uncertain significance (Nov 21, 2016)
3-195867344-C-G			Likely benign (Oct 30, 2022)
3-195867350-T-A			Likely benign (Jan 15, 2023)
3-195867370-C-G			Benign (Dec 18, 2023)
3-195867379-T-C			Likely benign (May 12, 2023)
3-195867383-C-T		not specified	Uncertain significance (Nov 03, 2022)
3-195867384-G-A			Uncertain significance (Jan 06, 2024)
3-195867389-G-A		not specified	Uncertain significance (Feb 16, 2023)
3-195867428-C-T			Uncertain significance (Jul 03, 2022)
3-195867429-G-A			Uncertain significance (Aug 17, 2023)
3-195867434-G-C		See cases • not specified	Uncertain significance (May 25, 2022)
3-195867442-C-T			Likely benign (Apr 27, 2023)
3-195867445-G-A			Likely benign (Oct 03, 2023)

GnomAD

Source: gnomAD

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: dbNSFP

• 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

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