YES1
protein-codingYES proto-oncogene 1, Src family tyrosine kinase, the group of Src family tyrosine kinases|SH2 domain containing
Gene summary
This gene is the cellular homolog of the Yamaguchi sarcoma virus oncogene. The encoded protein has tyrosine kinase activity and belongs to the src family of proteins. This gene lies in close proximity to thymidylate synthase gene on chromosome 18, and a corresponding pseudogene has been found on chromosome 22. [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 ~91.0 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 YES1 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_005433.4. 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 | ||||
| missense | 59 | 2 | 61 | |||
| nonsense | 0 | |||||
| start loss | 1 | 1 | ||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 6 | 6 | ||||
| Total | 0 | 0 | 68 | 2 | 0 | 70 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_005424.1 | 11 | MANE Select | |
| Ensembl | ENSP00000324740.4 | 11 | MANE Select | |
| Ensembl | ENSP00000464380.1 | 12 | Standard | |
| Ensembl | ENSP00000462468.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| yes1 | Danio rerio | Structure: epiboly Quality: arrested abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Adherens junction - Homo sapiens (human)
- Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway
- Interleukin-11 Signaling Pathway
- Developmental Biology
- RUNX2 regulates osteoblast differentiation
Biological Process
- cellular protein modification process
- transmembrane receptor protein tyrosine kinase signaling pathway
- regulation of glucose transmembrane transport
- cell differentiation
- T cell costimulation
Molecular Function
- phosphotyrosine residue binding
- protein tyrosine kinase activity
- non-membrane spanning protein tyrosine kinase activity
- signaling receptor binding
- epidermal growth factor receptor binding
Cellular Component
- Golgi apparatus
- microtubule organizing center
- cytosol
- actin filament
- plasma membrane
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000584307
- Coding exons
- 11
- Length
- 90960
- 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 | 1.16 | 232 | 287 | 0.807 | 0.0000141 | 3517 |
| Missense (PolyPhen) | 66 | 113.87 | 0.57961 | 1391 | ||
| Synonymous | -0.0900 | 101 | 99.9 | 1.01 | 0.00000503 | 1041 |
| Loss of Function | 3.09 | 13 | 31.8 | 0.409 | 0.00000186 | 378 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0.00040 | 0.00040 | rare |
| East Asian | 0.00016 | 0.00016 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.00014 | 0.00014 | rare |
| South Asian | 0.00012 | 0.000098 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Non-receptor protein tyrosine kinase that is involved in the regulation of cell growth and survival, apoptosis, cell-cell adhesion, cytoskeleton remodeling, and differentiation. Stimulation by receptor tyrosine kinases (RTKs) including EGRF, PDGFR, CSF1R and FGFR leads to recruitment of YES1 to the phosphorylated receptor, and activation and phosphorylation of downstream substrates. Upon EGFR activation, promotes the phosphorylation of PARD3 to favor epithelial tight junction assembly. Participates in the phosphorylation of specific junctional components such as CTNND1 by stimulating the FYN and FER tyrosine kinases at cell-cell contacts. Upon T-cell stimulation by CXCL12, phosphorylates collapsin response mediator protein 2/DPYSL2 and induces T-cell migration. Participates in CD95L/FASLG signaling pathway and mediates AKT-mediated cell migration. Plays a role in cell cycle progression by phosphorylating the cyclin-dependent kinase 4/CDK4 thus regulating the G1 phase. Also involved in G2/M progression and cytokinesis. {ECO:0000269|PubMed:11901164, ECO:0000269|PubMed:18479465, ECO:0000269|PubMed:19276087, ECO:0000269|PubMed:21566460, ECO:0000269|PubMed:21713032}.;
Recessive Scores
- pRec
- 0.513
Intolerance Scores
- LoFtool
- 0.451
- RVIS EVS
- -0.2
- RVIS percentile EVS
- 38.82
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- H
- Indispensability pred.
- E
- Indispensability score
- 0.994
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |