MKNK1
protein-codingMAPK interacting serine/threonine kinase 1, the group of MAPK activated protein kinases
Gene summary
This gene encodes a Ser/Thr protein kinase that interacts with, and is activated by ERK1 and p38 mitogen-activated protein kinases, and thus may play a role in the response to environmental stress and cytokines. This kinase may also regulate transcription by phosphorylating eIF4E via interaction with the C-terminal region of eIF4G. Alternatively spliced transcript variants have been noted for this gene. [provided by RefSeq, Jan 2012]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~59.4 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 MKNK1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001135553.4. 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 | 2 | 2 | 4 | |||
| missense | 50 | 1 | 51 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 58 | 3 | 0 | 61 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001129025.2 | 11 | MANE Select | |
| Ensembl | ENSP00000361013.5 | 11 | MANE Select | |
| RefSeq | NP_001364266.1 | 12 | Standard | |
| RefSeq | NP_001364267.1 | 12 | 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
- peptidyl-serine phosphorylation
- intracellular signal transduction
- protein autophosphorylation
Molecular Function
- protein serine/threonine kinase activity
- calmodulin-dependent protein kinase activity
- protein binding
- calmodulin binding
- ATP binding
Cellular Component
- nucleus
- nucleoplasm
- cytoplasm
- cytosol
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000371946
- Coding exons
- 13
- Length
- 59426
- Individuals with no LoFs
- 125718
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 30
- Defined
- 125748
- p
- 0.000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.44 | 197 | 263 | 0.750 | 0.0000152 | 3029 |
| Missense (PolyPhen) | 55 | 78.131 | 0.70394 | 847 | ||
| Synonymous | 0.155 | 104 | 106 | 0.981 | 0.00000660 | 915 |
| Loss of Function | 1.43 | 18 | 25.9 | 0.696 | 0.00000142 | 295 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.000087 | 0.000087 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00015 | 0.00015 | rare |
| South Asian | 0.00016 | 0.00016 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: 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. {ECO:0000269|PubMed:11463832, ECO:0000269|PubMed:15350534, ECO:0000269|PubMed:9155018, ECO:0000269|PubMed:9878069}.;
Recessive Scores
- pRec
- 0.144
Intolerance Scores
- LoFtool
- 0.916
- RVIS EVS
- 0.33
- RVIS percentile EVS
- 73.41
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.999
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |