GeneBe

FES

protein-coding

FES proto-oncogene, tyrosine kinase, the group of SH2 domain containing|F-BAR domain containing |Fes family tyrosine kinases

Gene summary

This gene encodes the human cellular counterpart of a feline sarcoma retrovirus protein with transforming capabilities. The gene product has tyrosine-specific protein kinase activity and that activity is required for maintenance of cellular transformation. Its chromosomal location has linked it to a specific translocation event identified in patients with acute promyelocytic leukemia but it is also involved in normal hematopoiesis as well as growth factor and cytokine receptor signaling. Alternative splicing results in multiple variants encoding different isoforms.[provided by RefSeq, Jan 2009]

MANE transcript

NM_002005.4

Inheritance

—

ClinVar variants

U:130B:9

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.63

Max pathogenic AF

—

Genomic locus

chr15:90,883,695-90,895,776

External References & Databases

Ensembl (ENSG00000182511)NCBI Gene (2242)OMIM (190030)HGNC:3657GenCCUniProt (P07332)AlphaFoldClinVar (FES)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~12.1 kb
Loading mutation effect viewer...

GenCC 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 FES variants in ClinVar

2 Conditions Cataloged
not specifiedTotal: 126
not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002005.4. 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.

EffectPLPVUSLBBSum
synonymous
2
clinvar
1
clinvar
2
clinvar
 5
missense
124
clinvar
5
clinvar
1
clinvar
 130
nonsense
1
clinvar
 1
start loss
0
frameshift
0
splice donor/acceptor (+/-2bp)
3
clinvar
 3
Total0013063139
Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 133 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_002005.4RefSeqNP_001996.118MANE Select
ENST00000328850.8EnsemblENSP00000331504.318MANE Select
NM_001143783.1RefSeqNP_001137255.117Standard
NM_001143784.1RefSeqNP_001137256.117Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • Axon guidance - Homo sapiens (human)
  • Thymic Stromal LymphoPoietin (TSLP) Signaling Pathway
  • Interleukin-11 Signaling Pathway
  • IL-4 Signaling Pathway
  • Developmental Biology

Biological Process

  • microtubule bundle formation
  • protein phosphorylation
  • chemotaxis
  • centrosome cycle
  • cell adhesion

Molecular Function

  • protein tyrosine kinase activity
  • non-membrane spanning protein tyrosine kinase activity
  • protein binding
  • ATP binding
  • microtubule binding

Cellular Component

  • cytoplasm
  • Golgi apparatus
  • cytosol
  • focal adhesion
  • microtubule cytoskeleton

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000328850
Coding exons
18
Length
12082
Individuals with no LoFs
125692
Homozygous LoFs
0
Heterozygous LoFs
56
Defined
125748
p
0.000223
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.763935040.7790.00003255279
Missense (PolyPhen)117173.470.674461842
Synonymous-0.6192192081.050.00001271647
Loss of Function2.443149.50.6260.00000281484

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American0.000170.00017rare
Ashkenazi Jewish0.0000990.000099rare
East Asian0.000160.00016rare
Finnish0.000140.00014rare
European (Non-Finnish)0.000320.00032rare
South Asian0.000230.00023rare
Other00.0absent

dbNSFP Gene Annotations

Source: dbNSFP

Function
FUNCTION: Tyrosine-protein kinase that acts downstream of cell surface receptors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, cell attachment and cell spreading. Plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Acts down- stream of the activated FCER1 receptor and the mast/stem cell growth factor receptor KIT. Plays a role in the regulation of mast cell degranulation. Plays a role in the regulation of cell differentiation and promotes neurite outgrowth in response to NGF signaling. Plays a role in cell scattering and cell migration in response to HGF-induced activation of EZR. Phosphorylates BCR and down-regulates BCR kinase activity. Phosphorylates HCLS1/HS1, PECAM1, STAT3 and TRIM28. {ECO:0000269|PubMed:11509660, ECO:0000269|PubMed:15302586, ECO:0000269|PubMed:15485904, ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:17595334, ECO:0000269|PubMed:18046454, ECO:0000269|PubMed:19001085, ECO:0000269|PubMed:19051325, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:2656706, ECO:0000269|PubMed:8955135}.;
Disease
DISEASE: Note=Has been shown to act as proto-oncogene in some types of cancer, possibly due to abnormal activation of the kinase. Has been shown to act as tumor suppressor in other types of cancer. Expressed and present as activated kinase in a subset of acute myeloid leukemia patients; promotes survival of leukemia cells (PubMed:20111072). Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation (PubMed:2656706). May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients (PubMed:16455651). Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines (PubMed:16455651). Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery (PubMed:21563194). May promote growth of renal carcinoma cells (PubMed:19082481). {ECO:0000269|PubMed:16455651, ECO:0000269|PubMed:19082481, ECO:0000269|PubMed:20111072, ECO:0000269|PubMed:21563194, ECO:0000269|PubMed:2656706}.;

Recessive Scores

pRec
0.400

Intolerance Scores

LoFtool
0.285
RVIS EVS
-0.92
RVIS percentile EVS
9.77

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
0.965

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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