MATK
protein-codingmegakaryocyte-associated tyrosine kinase, the group of Csk family tyrosine kinases|SH2 domain containing
Gene summary
The protein encoded by this gene has amino acid sequence similarity to Csk tyrosine kinase and has the structural features of the CSK subfamily: SRC homology SH2 and SH3 domains, a catalytic domain, a unique N terminus, lack of myristylation signals, lack of a negative regulatory phosphorylation site, and lack of an autophosphorylation site. This protein is thought to play a significant role in the signal transduction of hematopoietic cells. It is able to phosphorylate and inactivate Src family kinases, and may play an inhibitory role in the control of T-cell proliferation. This protein might be involved in signaling in some cases of breast cancer. Three alternatively spliced transcript variants that encode different isoforms have been described for this gene. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~24.2 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 MATK variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_139355.3. 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 | 3 | 1 | 5 | ||
| missense | 65 | 3 | 68 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 66 | 6 | 1 | 73 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_647612.1 | 13 | MANE Select | |
| Ensembl | ENSP00000308734.5 | 13 | MANE Select | |
| RefSeq | NP_001427506.1 | 13 | Standard | |
| RefSeq | NP_001427507.1 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neurotrophin signaling pathway - Homo sapiens (human)
- Kit receptor signaling pathway
- Signal Transduction
- KitReceptor
- Downregulation of ERBB2 signaling
Biological Process
- protein phosphorylation
- mesoderm development
- cell population proliferation
- positive regulation of cell population proliferation
- peptidyl-tyrosine phosphorylation
Molecular Function
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- protein binding
- ATP binding
Cellular Component
- cytosol
- extrinsic component of cytoplasmic side of plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000395045
- Coding exons
- 13
- Length
- 24157
- Individuals with no LoFs
- 125725
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 21
- Defined
- 125746
- p
- 0.0000835
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.81 | 249 | 343 | 0.725 | 0.0000238 | 3234 |
| Missense (PolyPhen) | 84 | 146.53 | 0.57327 | 1330 | ||
| Synonymous | 0.0814 | 153 | 154 | 0.992 | 0.0000116 | 1047 |
| Loss of Function | 2.53 | 14 | 28.6 | 0.490 | 0.00000155 | 291 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00015 | 0.00014 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00028 | 0.00027 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000073 | 0.000070 | rare |
| South Asian | 0.000065 | 0.000065 | rare |
| Other | 0.00017 | 0.00016 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Could play a significant role in the signal transduction of hematopoietic cells. May regulate tyrosine kinase activity of SRC-family members in brain by specifically phosphorylating their C-terminal regulatory tyrosine residue which acts as a negative regulatory site. It may play an inhibitory role in the control of T-cell proliferation. {ECO:0000269|PubMed:9171348}.;
Intolerance Scores
- LoFtool
- 0.294
- RVIS EVS
- -0.55
- RVIS percentile EVS
- 19.8
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.975
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |