MKNK2
protein-codingMAPK interacting serine/threonine kinase 2, the group of MAPK activated protein kinases
Gene summary
This gene encodes a member of the calcium/calmodulin-dependent protein kinases (CAMK) Ser/Thr protein kinase family, which belongs to the protein kinase superfamily. This protein contains conserved DLG (asp-leu-gly) and ENIL (glu-asn-ile-leu) motifs, and an N-terminal polybasic region which binds importin A and the translation factor scaffold protein eukaryotic initiation factor 4G (eIF4G). This protein is one of the downstream kinases activated by mitogen-activated protein (MAP) kinases. It phosphorylates the eukaryotic initiation factor 4E (eIF4E), thus playing important roles in the initiation of mRNA translation, oncogenic transformation and malignant cell proliferation. In addition to eIF4E, this protein also interacts with von Hippel-Lindau tumor suppressor (VHL), ring-box 1 (Rbx1) and Cullin2 (Cul2), which are all components of the CBC(VHL) ubiquitin ligase E3 complex. Multiple alternatively spliced transcript variants have been found, but the full-length nature and biological activity of only two variants are determined. These two variants encode distinct isoforms which differ in activity and regulation, and in subcellular localization. [provided by RefSeq, Aug 2011]
- GPRK7
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~13.8 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 MKNK2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_199054.3. 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 | 5 | 1 | 6 | |||
| missense | 66 | 1 | 67 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 81 | 2 | 0 | 83 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_951009.1 | 13 | MANE Select | |
| Ensembl | ENSP00000250896.3 | 13 | MANE Select | |
| RefSeq | NP_060042.2 | 13 | Standard | |
| Ensembl | ENSP00000309485.6 | 13 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- HIF-1 signaling pathway - Homo sapiens (human)
- MAPK signaling pathway - Homo sapiens (human)
- Insulin signaling pathway - Homo sapiens (human)
- EGF-Core
- Structural Pathway of Interleukin 1 (IL-1)
Biological Process
- regulation of translation
- protein phosphorylation
- cell surface receptor signaling pathway
- peptidyl-serine phosphorylation
- hemopoiesis
Molecular Function
- protein serine/threonine kinase activity
- calmodulin-dependent protein kinase activity
- protein binding
- calmodulin binding
- ATP binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- nuclear body
- PML body
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000250896
- Coding exons
- 13
- Length
- 13774
- Individuals with no LoFs
- 125697
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 50
- Defined
- 125747
- p
- 0.000199
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.885 | 232 | 273 | 0.849 | 0.0000168 | 2992 |
| Missense (PolyPhen) | 76 | 92.399 | 0.82252 | 946 | ||
| Synonymous | -2.29 | 147 | 116 | 1.27 | 0.00000798 | 859 |
| Loss of Function | 2.35 | 12 | 24.6 | 0.488 | 0.00000122 | 279 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000064 | 0.000062 | rare |
| Latino/Admixed American | 0.00054 | 0.00052 | rare |
| Ashkenazi Jewish | 0.00023 | 0.00020 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0.000099 | 0.000092 | rare |
| European (Non-Finnish) | 0.00012 | 0.00011 | rare |
| South Asian | 0.00010 | 0.000098 | rare |
| Other | 0.0014 | 0.0013 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Serine/threonine-protein kinase that phosphorylates SFPQ/PSF, HNRNPA1 and EIF4E. May play a role in the response to environmental stress and cytokines. Appears to regulate translation by phosphorylating EIF4E, thus increasing the affinity of this protein for the 7-methylguanosine-containing mRNA cap. Required for mediating PP2A-inhibition-induced EIF4E phosphorylation. Triggers EIF4E shuttling from cytoplasm to nucleus. Isoform 1 displays a high basal kinase activity, but isoform 2 exhibits a very low kinase activity. Acts as a mediator of the suppressive effects of IFNgamma on hematopoiesis. Negative regulator for signals that control generation of arsenic trioxide As(2)O(3)-dependent apoptosis and anti-leukemic responses. Involved in anti-apoptotic signaling in response to serum withdrawal. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:16111636, ECO:0000269|PubMed:17965020, ECO:0000269|PubMed:18299328, ECO:0000269|PubMed:20823271, ECO:0000269|PubMed:20927323, ECO:0000269|PubMed:21149447}.;
Recessive Scores
- pRec
- 0.148
Intolerance Scores
- LoFtool
- 0.735
- RVIS EVS
- -0.58
- RVIS percentile EVS
- 18.78
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |