TNK1
protein-codingtyrosine kinase non receptor 1, the group of TNK family tyrosine kinases
Gene summary
The protein encoded by this gene belongs to the tyrosine protein kinase family. Tyrosine protein kinases are important regulators of intracellular signal transduction pathways, mediating cellular proliferation, survival, and development. This gene is highly expressed in fetal tissues and at lower levels in few adult tissues, thus may function in signaling pathways utilized broadly during fetal development, and more selectively in adult tissues. It plays a negative regulatory role in the Ras-Raf1-MAPK pathway, and knockout mice have been shown to develop spontaneous tumors, suggesting a role as a tumor suppressor gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~9.2 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 TNK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003985.6. 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 | 3 | 4 | 5 | 12 | ||
| missense | 95 | 8 | 4 | 107 | ||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 5 | 5 | ||||
| Total | 0 | 0 | 104 | 12 | 9 | 125 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003976.2 | 12 | MANE Select | |
| Ensembl | ENSP00000509611.1 | 12 | MANE Select | |
| RefSeq | NP_001238831.1 | 12 | Standard | |
| Ensembl | ENSP00000458834.1 | 12 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Focal Adhesion
Biological Process
- protein phosphorylation
- cell differentiation
- negative regulation of cell growth
- peptidyl-tyrosine autophosphorylation
- regulation of cell population proliferation
Molecular Function
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- protein binding
- ATP binding
Cellular Component
- cytoplasm
- cytosol
- membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000576812
- Coding exons
- 12
- Length
- 9241
- Individuals with no LoFs
- 109295
- Homozygous LoFs
- 792
- Heterozygous LoFs
- 14603
- Defined
- 124690
- p
- 0.0638
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.00 | 328 | 383 | 0.856 | 0.0000220 | 4158 |
| Missense (PolyPhen) | 112 | 132.11 | 0.8478 | 1620 | ||
| Synonymous | 1.73 | 129 | 157 | 0.824 | 0.00000875 | 1464 |
| Loss of Function | 1.77 | 16 | 25.7 | 0.623 | 0.00000124 | 294 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.010 | 0.0092 | notable |
| Latino/Admixed American | 0.12 | 0.11 | notable |
| Ashkenazi Jewish | 0.069 | 0.066 | notable |
| East Asian | 0.18 | 0.16 | notable |
| Finnish | 0.045 | 0.042 | notable |
| European (Non-Finnish) | 0.055 | 0.051 | notable |
| South Asian | 0.048 | 0.043 | notable |
| Other | 0.067 | 0.064 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Involved in negative regulation of cell growth. Has tumor suppressor properties. Plays a negative regulatory role in the Ras-MAPK pathway. May function in signaling pathways utilized broadly during fetal development and more selectively in adult tissues and in cells of the lymphohematopoietic system. Could specifically be involved in phospholipid signal transduction. {ECO:0000269|PubMed:10873601, ECO:0000269|PubMed:18974114}.;
Recessive Scores
- pRec
- 0.181
Intolerance Scores
- LoFtool
- 0.623
- RVIS EVS
- 0.09
- RVIS percentile EVS
- 60.57
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Indispensability pred.
- N
- Indispensability score
- 0.328
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |