WEE1
protein-codingWEE1 G2 checkpoint kinase
Gene summary
This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase. [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 ~19.8 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 WEE1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003390.4. 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 | 1 | 1 | ||||
| missense | 73 | 1 | 74 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 75 | 0 | 1 | 76 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003381.1 | 11 | MANE Select | |
| Ensembl | ENSP00000402084.2 | 11 | MANE Select | |
| RefSeq | NP_001137448.1 | 10 | Standard | |
| Ensembl | ENSP00000299613.5 | 10 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| wee1 | Danio rerio | Structure: whole organism Quality: viability abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Cell cycle - Homo sapiens (human)
- Cell Cycle
- Retinoblastoma (RB) in Cancer
- G1 to S cell cycle control
- cdc25 and chk1 regulatory pathway in response to dna damage
Biological Process
- G2/M transition of mitotic cell cycle
- microtubule cytoskeleton organization
- mitotic cell cycle checkpoint
- peptidyl-tyrosine phosphorylation
- establishment of cell polarity
Molecular Function
- magnesium ion binding
- protein kinase activity
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000450114
- Coding exons
- 11
- Length
- 19777
- Individuals with no LoFs
- 125370
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 2
- Defined
- 125372
- p
- 0.00000798
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.64 | 153 | 277 | 0.553 | 0.0000141 | 4167 |
| Missense (PolyPhen) | 56 | 126.2 | 0.44373 | 1625 | ||
| Synonymous | 1.15 | 83 | 97.5 | 0.852 | 0.00000511 | 1274 |
| Loss of Function | 4.72 | 1 | 27.9 | 0.0358 | 0.00000164 | 362 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.000062 | 0.000062 | rare |
| Latino/Admixed American | 0.000032 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0 | 0.0 | absent |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Acts as a negative regulator of entry into mitosis (G2 to M transition) by protecting the nucleus from cytoplasmically activated cyclin B1-complexed CDK1 before the onset of mitosis by mediating phosphorylation of CDK1 on 'Tyr-15'. Specifically phosphorylates and inactivates cyclin B1-complexed CDK1 reaching a maximum during G2 phase and a minimum as cells enter M phase. Phosphorylation of cyclin B1-CDK1 occurs exclusively on 'Tyr-15' and phosphorylation of monomeric CDK1 does not occur. Its activity increases during S and G2 phases and decreases at M phase when it is hyperphosphorylated. A correlated decrease in protein level occurs at M/G1 phase, probably due to its degradation.;
Recessive Scores
- pRec
- 0.243
Intolerance Scores
- RVIS EVS
- 0.5
- RVIS percentile EVS
- 79.89
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |