FES

Summary

FES (FES proto-oncogene, tyrosine kinase, HGNC:3657) is a protein-coding gene on chromosome 15q26.1, encoding Tyrosine-protein kinase Fes/Fps (P07332). 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.

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.

Source: NCBI Gene 2242 — RefSeq curated summary.

At a glance

• GWAS associations: 55
• Clinical variants (ClinVar): 150 total
• Druggable target: yes — 29 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002005

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3657
Approved symbol	FES
Name	FES proto-oncogene, tyrosine kinase
Location	15q26.1
Locus type	gene with protein product
Status	Approved
Aliases	FPS
Ensembl gene	ENSG00000182511
Ensembl biotype	protein_coding
OMIM	190030
Entrez	2242

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 53 protein_coding, 5 retained_intron, 2 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000328850, ENST00000394300, ENST00000394302, ENST00000414248, ENST00000416779, ENST00000443697, ENST00000444422, ENST00000448367, ENST00000452243, ENST00000462476, ENST00000464684, ENST00000470152, ENST00000481665, ENST00000494259, ENST00000496379, ENST00000497945, ENST00000559355, ENST00000907217, ENST00000907218, ENST00000907219, ENST00000907220, ENST00000907221, ENST00000907222, ENST00000907223, ENST00000907224, ENST00000907225, ENST00000907226, ENST00000907227, ENST00000907228, ENST00000907229, ENST00000907230, ENST00000907231, ENST00000907232, ENST00000907233, ENST00000907234, ENST00000907235, ENST00000907236, ENST00000907237, ENST00000907238, ENST00000939599, ENST00000939600, ENST00000963618, ENST00000963619, ENST00000963620, ENST00000963621, ENST00000963622, ENST00000963623, ENST00000963624, ENST00000963625, ENST00000963626, ENST00000963627, ENST00000963628, ENST00000963629, ENST00000963630, ENST00000963631, ENST00000963632, ENST00000963633, ENST00000963634, ENST00000963635, ENST00000963636, ENST00000963637

RefSeq mRNA: 4 — MANE Select: NM_002005 NM_001143783, NM_001143784, NM_001143785, NM_002005

CCDS: CCDS10365, CCDS45349, CCDS45350, CCDS45351

Canonical transcript exons

ENST00000328850 — 19 exons

Exon	Start	End
ENSE00001292079	90890982	90891191
ENSE00001297839	90885412	90885585
ENSE00001313735	90895416	90895776
ENSE00001641844	90889517	90889636
ENSE00001772963	90889306	90889443
ENSE00001802839	90893936	90894058
ENSE00001925529	90884504	90884544
ENSE00002144049	90885037	90885258
ENSE00003465171	90891554	90891676
ENSE00003467260	90886961	90887057
ENSE00003482425	90889840	90889962
ENSE00003501629	90890401	90890484
ENSE00003520158	90892707	90892825
ENSE00003582394	90887187	90887370
ENSE00003602818	90892058	90892111
ENSE00003606236	90893100	90893194
ENSE00003632717	90893654	90893811
ENSE00003674866	90890092	90890278
ENSE00003677915	90893291	90893414

Expression profiles

Bgee: expression breadth ubiquitous, 176 present calls, max score 96.93.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 7.5280 / max 172.6487, expressed in 1205 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
148501	4.4200	781
148500	2.1291	763
148499	0.5092	331
148498	0.2092	80
148503	0.1914	61
148502	0.0357	10
148504	0.0333	21

Top tissues by expression

291 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	96.93	gold quality
spleen	UBERON:0002106	96.77	gold quality
mononuclear cell	CL:0000842	96.23	gold quality
leukocyte	CL:0000738	95.92	gold quality
granulocyte	CL:0000094	95.84	gold quality
right lung	UBERON:0002167	94.25	gold quality
omental fat pad	UBERON:0010414	94.12	gold quality
peritoneum	UBERON:0002358	94.02	gold quality
upper lobe of left lung	UBERON:0008952	93.05	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.72	gold quality
blood	UBERON:0000178	92.31	gold quality
sural nerve	UBERON:0015488	92.30	gold quality
apex of heart	UBERON:0002098	92.04	gold quality
right lobe of liver	UBERON:0001114	91.83	gold quality
left uterine tube	UBERON:0001303	91.82	gold quality
upper lobe of lung	UBERON:0008948	91.28	gold quality
tibial nerve	UBERON:0001323	90.96	gold quality
body of uterus	UBERON:0009853	90.60	gold quality
gall bladder	UBERON:0002110	90.29	gold quality
right lobe of thyroid gland	UBERON:0001119	90.12	gold quality
endocervix	UBERON:0000458	89.88	gold quality
parotid gland	UBERON:0001831	89.56	gold quality
right coronary artery	UBERON:0001625	89.49	gold quality
left lobe of thyroid gland	UBERON:0001120	89.24	gold quality
right ovary	UBERON:0002118	88.80	gold quality
left coronary artery	UBERON:0001626	88.57	gold quality
descending thoracic aorta	UBERON:0002345	88.06	gold quality
saliva-secreting gland	UBERON:0001044	87.96	gold quality
subcutaneous adipose tissue	UBERON:0002190	87.96	gold quality
right atrium auricular region	UBERON:0006631	87.87	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	10.99
E-GEOD-70580	no	442.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RBPJ, SP1, SPI1

miRNA regulators (miRDB)

2 targeting FES, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4456	97.50	64.88	1678
HSA-MIR-558	97.50	67.16	977

Literature-anchored findings (GeneRIF, showing 26)

• Closing in on the biological functions of Fps/Fes and Fer. A review. (PMID:11994747)
• Fes naturally adopts an inactive conformation in vivo, and maintenance of the inactive structure requires the coiled-coil and SH2 domains. (PMID:12653561)
• Fps/Fes and Fer are expressed in human and mouse platelets, and are activated following stimulation with collagen and collagen-related peptide (CRP), suggesting a role in GPVI receptor signaling (PMID:12871378)
• Fes transduces inductive signals for terminal macrophage and granulocyte differentiation, and this biological activity is mediated through the activation of lineage-specific transcription factors. (PMID:15003822)
• FPS mediates enhanced sensitization to VEGF and PDGF signaling in ECs; this hypersensitization contributes to excessive angiogenic signaling and underlies the observed hypervascular phenotype of human myristoylated FPS expressed in transgenic mice. (PMID:15099290)
• c-Fes is a regulator of the tubulin cytoskeleton and may contribute to Fes-induced morphological changes in myeloid hematopoietic and neuronal cells (PMID:15485904)
• NMR assignment of the SH2 domain (PMID:15630569)
• PEDF downregulates Fyn through Fes, resulting in inhibition of FGF-2-induced capillary morphogenesis of endothelial cells (PMID:15713745)
• NMR analysis of Src homology 2 domain from the human feline sarcoma oncogene Fes (PMID:15929003)
• FES has a growth suppressive function in colorectal neoplasms. (PMID:16455651)
• A novel Fes-KAP-1 interaction is reported, suggesting a dual role for KAP-1 as both a Fes activator and downstream effector. (PMID:16792528)
• These novel results indicate the involvement of Fes in VEGF-A-induced cellular responses by cultured endothelial cells. (PMID:17521372)
• shows a major function of FES downstream of activated KIT receptor and thereby points to FES as a novel target in KIT-related pathologi (PMID:17595334)
• Ezrin/Fes interaction at cell-cell contacts plays an essential role in hepatocyte growth factor-induced cell scattering and implicates Fes in the cross-talk between cell-cell and cell-matrix adhesion. (PMID:18046454)
• The SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling. (PMID:18775312)
• study shows Fes phosphorylates C-terminal tyrosine residues in HS1 implicated in actin stabilization; coordinated action of F-BAR & SH2 domains of Fes allow for coupling to FcepsilonRI signaling & potential regulation of actin reorganization in mast cells (PMID:19001085)
• Study of promoter methylation as important mechanism responsible for downregulation of FES gene expression in colorectal cancer cells. Treatment with DNA methyltransferase inhibitor resulted in expression of functional FES transcripts in CRC cell lines. (PMID:19051325)
• Downregulation of the c-Fes protein-tyrosine kinase inhibits the proliferation of renal carcinoma. (PMID:19082481)
• c-Fes oligomerization is independent of activation; data suggest that conformational changes, rather than oligomerization, govern c-Fes kinase activation and downstream signaling in vivo. (PMID:19382747)
• FGF-2 activates Fes via the second coiled-coil domain, leading to lamellipodium formation and chemotaxis by endothelial cells (PMID:19885553)
• c-fes gene expression was found in myeloid leukemias, whereas low or no expression in lymphocytic leukemias. (PMID:20030920)
• FES kinase is a mediator of wild-type KIT signalling implicated in cell migration. (PMID:20117079)
• analysis of the JAK-Fes-phospholipase D signaling pathway that is enhanced in highly proliferative breast cancer cells (PMID:23404507)
• Identification of FES as a Novel Radiosensitizing Target in Human Cancers. (PMID:31573955)
• This study supports the critical role of FER and FES tyrosine kinase fusions in the pathogenesis of follicular T-cell lymphoma and provides additional evidence that these can drive follicular T-cell lymphoma in the absence of RHOA mutations. (PMID:31746983)
• The FES Gene at the 15q26 Coronary-Artery-Disease Locus Inhibits Atherosclerosis. (PMID:36321446)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fes	ENSDARG00000011449
mus_musculus	Fes	ENSMUSG00000053158
rattus_norvegicus	Fes	ENSRNOG00000011683

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase Fes/Fps — P07332 (reviewed: P07332)

Alternative names: Feline sarcoma/Fujinami avian sarcoma oncogene homolog, Proto-oncogene c-Fes, Proto-oncogene c-Fps, p93c-fes

All UniProt accessions (8): C9J3W6, P07332, E7EMJ7, E7ENM8, E9PGC7, E9PIJ7, H0YNN8, H0YNT6

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Homooligomer. Interacts with BCR. Interacts (when activated, via coiled coil domain) with TRIM28. Interacts (via SH2 domain) with phosphorylated EZR, MS4A2/FCER1B and HCLS1/HS1. Interacts with phosphorylated KIT. Interacts with FLT3. Interacts (via F-BAR domain) with soluble tubulin. Interacts (via SH2 domain) with microtubules.

Subcellular location. Cytoplasm. Cytosol. Cytoskeleton. Cell membrane. Cytoplasmic vesicle. Golgi apparatus. Cell junction. Focal adhesion.

Tissue specificity. Widely expressed. Detected in adult colon epithelium (at protein level). Expressed in melanocytes (at protein level).

Post-translational modifications. Autophosphorylated on Tyr-713. Phosphorylated by LYN in response to FCER1 activation. Phosphorylated by HCK.

Disease relevance. 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. Expression is absent in K562 leukemia cells; ectopic expression of FSP/FES restores myeloid differentiation. May function as tumor suppressor in colorectal cancer; expression is reduced or absent in samples from some colon cancer patients. May function as tumor suppressor in melanoma by preventing melanoma cell proliferation; expression is reduced or absent in samples from some melanoma patients. Ectopic expression of FSP/FES suppresses anchorage-independent growth in colon cancer cell lines. Up-regulated in prostate cancer, and might be a predictor of recurrence after radical surgery. May promote growth of renal carcinoma cells.

Activity regulation. Kinase activity is tightly regulated. Activated in response to signaling from a cell surface receptor. Activation probably requires binding of a substrate via the SH2 domain, plus autophosphorylation at Tyr-713. Present in an inactive form in the absence of activating stimuli.

Domain organisation. The coiled coil domains are important for regulating the kinase activity. They mediate homooligomerization and probably also interaction with other proteins. The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.

Miscellaneous. Cellular homolog of retroviral oncogenes. In contrast to the viral oncoproteins, the kinase activity of cellular FSP/FES is tightly regulated, and the kinase is inactive in normal cells in the absence of activating stimuli.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.

Isoforms (4)

UniProt ID	Names	Canonical?
P07332-1	1	yes
P07332-2	2, Variant 1
P07332-3	3, Variant 3
P07332-4	4, Variant 4

RefSeq proteins (4): NP_001137255, NP_001137256, NP_001137257, NP_001996* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001060	FCH_dom	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR016250	Tyr-prot_kinase_Fes/Fps	Family
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR027267	AH/BAR_dom_sf	Homologous_superfamily
IPR031160	F_BAR_dom	Domain
IPR035849	Fes/Fps/Fer_SH2	Domain
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00611, PF07714

Enzyme classification (BRENDA):

• EC 2.7.10.2 — non-specific protein-tyrosine kinase (BRENDA: 41 organisms, 396 substrates, 479 inhibitors, 43 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

6 substrates with measured Km, best-characterized 6. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.014–17.64	12
[KDSRC KINASE]-L-TYROSINE	0.0057–0.24	12
POLY(GLU4-TYR)	0.018–0.659	10
EEEEYIQ[DP]-8-HYDROXY-5-(N,N-DIMETHYLSULFONAMIDO	0.057	1
S1 PEPTIDE	0.037	1
EEEEY	—	0

Catalyzed reactions (Rhea), 1 shown:

• L-tyrosyl-[protein] + ATP = O-phospho-L-tyrosyl-[protein] + ADP + H(+) (RHEA:10596)

UniProt features (96 total): helix 33, strand 20, mutagenesis site 12, modified residue 8, turn 5, domain 3, sequence variant 3, binding site 2, splice variant 2, region of interest 2, coiled-coil region 2, chain 1, sequence conflict 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7T1K	X-RAY DIFFRACTION	1.25
7T1L	X-RAY DIFFRACTION	1.35
3CBL	X-RAY DIFFRACTION	1.75
3BKB	X-RAY DIFFRACTION	1.78
4E93	X-RAY DIFFRACTION	1.84
3CD3	X-RAY DIFFRACTION	1.98
6JMF	X-RAY DIFFRACTION	2
8XKP	X-RAY DIFFRACTION	2.05
4DYL	X-RAY DIFFRACTION	2.18
8X2T	X-RAY DIFFRACTION	2.9
1WQU	SOLUTION NMR
2DCR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07332-F1	89.63	0.78

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 683 (proton acceptor)

Ligand- & substrate-binding residues (2): 567–575; 590

Post-translational modifications (8): 64, 67, 261, 408, 411, 421, 713, 716

Mutagenesis-validated functional residues (12):

Position	Phenotype
113–114	reduced binding to membranes containing phosphoinositides.
145	constitutively activated kinase that can act as oncogene. promotes myeloid cell survival and proliferation.
334	abolishes autophosphorylation.
463	abolishes kinase activity.
483	abolishes ptyr binding. abolishes association with microtubules. abolishes autophosphorylation. reduced kinase activity.
590	abolishes kinase activity. fails to inhibit proliferation of melanoma cells.
704	reduced autophosphorylation and strongly reduced kinase activity.
706	negligible effect on autophosphorylation and kinase activity.
713	reduces kinase activity by over 90%.
743	strongly reduced autophosphorylation and kinase activity.
759	reduced autophosphorylation and strongly reduced kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-399954	Sema3A PAK dependent Axon repulsion
R-HSA-399955	SEMA3A-Plexin repulsion signaling by inhibiting Integrin adhesion
R-HSA-399956	CRMPs in Sema3A signaling

MSigDB gene sets: 413 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_PROTEIN_POLYMERIZATION, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_MICROTUBULE_BASED_PROCESS, GOBP_CELLULAR_RESPONSE_TO_LIPID, LFA1_Q6, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_GROWTH, GOBP_REGULATION_OF_EXOCYTOSIS, DARWICHE_SKIN_TUMOR_PROMOTER_DN, DARWICHE_PAPILLOMA_RISK_LOW_UP

GO Biological Process (25): microtubule bundle formation (GO:0001578), chemotaxis (GO:0006935), centrosome cycle (GO:0007098), cell adhesion (GO:0007155), regulation of cell shape (GO:0008360), positive regulation of neuron projection development (GO:0010976), peptidyl-tyrosine phosphorylation (GO:0018108), regulation of cell adhesion (GO:0030155), positive regulation of microtubule polymerization (GO:0031116), regulation of cell population proliferation (GO:0042127), regulation of mast cell degranulation (GO:0043304), regulation of cell differentiation (GO:0045595), positive regulation of myeloid cell differentiation (GO:0045639), positive regulation of monocyte differentiation (GO:0045657), protein autophosphorylation (GO:0046777), myoblast proliferation (GO:0051450), cardiac muscle cell proliferation (GO:0060038), regulation of vesicle-mediated transport (GO:0060627), cellular response to vitamin D (GO:0071305), regulation of cell motility (GO:2000145), protein phosphorylation (GO:0006468), positive regulation of protein polymerization (GO:0032273), positive regulation of cytoskeleton organization (GO:0051495), regulation of plasma membrane bounded cell projection organization (GO:0120035), positive regulation of supramolecular fiber organization (GO:1902905)

GO Molecular Function (12): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), microtubule binding (GO:0008017), immunoglobulin receptor binding (GO:0034987), phosphatidylinositol binding (GO:0035091), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), lipid binding (GO:0008289), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), focal adhesion (GO:0005925), cytoplasmic side of plasma membrane (GO:0009898), microtubule cytoskeleton (GO:0015630), cytoplasmic vesicle (GO:0031410), cytoskeleton (GO:0005856), membrane (GO:0016020), anchoring junction (GO:0070161)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Semaphorin interactions	3
Signaling by Receptor Tyrosine Kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	5
cellular anatomical structure	3
cytoplasm	3
protein phosphorylation	2
cell population proliferation	2
binding	2
microtubule cytoskeleton organization	1
response to chemical	1
taxis	1
cell cycle process	1
microtubule organizing center organization	1
cellular process	1
regulation of cell morphogenesis	1
regulation of biological quality	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
peptidyl-tyrosine modification	1
cell adhesion	1
positive regulation of microtubule polymerization or depolymerization	1
regulation of microtubule polymerization	1
positive regulation of protein polymerization	1
microtubule polymerization	1
positive regulation of supramolecular fiber organization	1
regulation of myeloid leukocyte mediated immunity	1
regulation of leukocyte degranulation	1
mast cell degranulation	1
cell differentiation	1
regulation of developmental process	1
myeloid cell differentiation	1
positive regulation of cell differentiation	1
regulation of myeloid cell differentiation	1
positive regulation of myeloid leukocyte differentiation	1
monocyte differentiation	1
regulation of monocyte differentiation	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
vesicle-mediated transport	1
regulation of transport	1
response to vitamin D	1

Protein interactions and networks

STRING

1770 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FES	TRIP10	Q15642	917
FES	AMPH	P49418	793
FES	BIN1	O00499	766
FES	EZR	P15311	721
FES	PACSIN2	Q9UNF0	598
FES	PACSIN3	Q9UKS6	556
FES	FARP2	O94887	555
FES	PLXNA1	Q9UIW2	553
FES	PACSIN1	Q9BY11	534
FES	HSP90AA1	P07900	517
FES	WAS	P42768	506
FES	FNBP1	Q96RU3	505
FES	HSP90AB1	P08238	489
FES	PSTPIP1	O43586	482
FES	FEZF1	A0PJY2	475

IntAct

41 interactions, top by confidence:

A	B	Type	Score
EZR	FES	psi-mi:“MI:0915”(physical association)	0.680
FES	EZR	psi-mi:“MI:0915”(physical association)	0.680
FES	EZR	psi-mi:“MI:0407”(direct interaction)	0.680
EZR	FES	psi-mi:“MI:0403”(colocalization)	0.680
FES	EZR	psi-mi:“MI:0914”(association)	0.680
DSP	FES	psi-mi:“MI:0915”(physical association)	0.560
FES	DSP	psi-mi:“MI:0914”(association)	0.560
TERF1	FES	psi-mi:“MI:0915”(physical association)	0.510
MDFI	FES	psi-mi:“MI:0915”(physical association)	0.490
FES	NSF	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FES	EGFR	psi-mi:“MI:0407”(direct interaction)	0.440
FES	ABI1	psi-mi:“MI:0407”(direct interaction)	0.440
FES	AR	psi-mi:“MI:0407”(direct interaction)	0.440
FES	GAB1	psi-mi:“MI:0407”(direct interaction)	0.440
FES	KIT	psi-mi:“MI:0407”(direct interaction)	0.440
FES	MET	psi-mi:“MI:0407”(direct interaction)	0.440
HSP90AB1	FES	psi-mi:“MI:0915”(physical association)	0.400
FES	POT1	psi-mi:“MI:0915”(physical association)	0.370
PDE4DIP	FES	psi-mi:“MI:0915”(physical association)	0.370
FES	ZNF746	psi-mi:“MI:0915”(physical association)	0.370
FES	ZNF775	psi-mi:“MI:0915”(physical association)	0.370
FES		psi-mi:“MI:0915”(physical association)	0.370

BioGRID (51): DSP (Affinity Capture-MS), FES (Reconstituted Complex), Bcar1 (Reconstituted Complex), Bcar1 (Affinity Capture-Western), Bcar1 (Biochemical Activity), FES (Reconstituted Complex), FES (Biochemical Activity), FES (Two-hybrid), FES (Affinity Capture-MS), BCR (Affinity Capture-Western), FES (Affinity Capture-Western), HSP90AA1 (Reconstituted Complex), HSPA4 (Reconstituted Complex), FKBP4 (Reconstituted Complex), FKBP5 (Reconstituted Complex)

ESM2 similar proteins: A1IGU3, A1IGU4, A1IGU5, A6QP29, B1AVH7, B2RUP2, B5DFA1, D2H0G5, D3ZFJ3, O15068, O55043, P00530, P07332, P14238, P16879, P55194, P98171, Q0GNC1, Q14155, Q15052, Q27J81, Q3U5C8, Q3UMR0, Q58EX7, Q5VV41, Q5XXR3, Q5ZLR6, Q60I26, Q63406, Q64096, Q6PFY1, Q6PGG2, Q70J99, Q7TNH6, Q80TT2, Q80VK6, Q86WN1, Q8C2K1, Q8C6B2, Q8CJ00

Diamond homologs: A1Z9X0, A2CI34, A2CI35, A8KBH6, A8XW88, F1M7Y5, O70146, P00542, P00543, P04409, P05126, P05128, P05129, P05696, P05771, P05772, P07332, P09215, P0CD62, P10102, P10829, P13678, P14238, P16054, P16879, P17252, P20444, P21137, P22612, P23298, P24723, P28867, P32866, P41743, P43057, P48562, P50527, P57078, P63318, P63319

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
EZR	up-regulates	FES	relocalization
FES	“down-regulates activity”	BCR	phosphorylation
FES	“up-regulates activity”	PECAM1	phosphorylation
FES	“up-regulates activity”	STAT3	phosphorylation
FES	up-regulates	FES	phosphorylation
FES	down-regulates	BCR	phosphorylation
FES	“up-regulates activity”	FES	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 22 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by Aberrant PI3K in Cancer	5	39.6×	2e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	30.2×	4e-05
PIP3 activates AKT signaling	6	25.0×	2e-05
Signaling by Receptor Tyrosine Kinases	5	16.1×	5e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

150 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	120
Likely benign	6
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

3161 predictions. Top by Δscore:

Variant	Effect	Δscore
15:90884477:G:GT	donor_gain	1.0000
15:90885582:CAAGG:C	donor_loss	1.0000
15:90885586:G:GG	donor_gain	1.0000
15:90885587:T:G	donor_loss	1.0000
15:90886958:TA:T	acceptor_loss	1.0000
15:90886959:A:AG	acceptor_gain	1.0000
15:90886959:A:AT	acceptor_loss	1.0000
15:90886960:G:GG	acceptor_gain	1.0000
15:90887035:C:T	donor_gain	1.0000
15:90887045:G:GT	donor_gain	1.0000
15:90887054:AAAG:A	donor_loss	1.0000
15:90887058:G:GA	donor_loss	1.0000
15:90887181:T:TA	acceptor_gain	1.0000
15:90887354:G:GT	donor_gain	1.0000
15:90887366:ATCCT:A	donor_gain	1.0000
15:90887367:TCCT:T	donor_gain	1.0000
15:90887368:CCTGT:C	donor_loss	1.0000
15:90887369:CT:C	donor_gain	1.0000
15:90887370:TGTA:T	donor_loss	1.0000
15:90887371:G:GA	donor_loss	1.0000
15:90887371:G:GG	donor_gain	1.0000
15:90887372:T:A	donor_loss	1.0000
15:90889302:GCA:G	acceptor_loss	1.0000
15:90889303:CAG:C	acceptor_loss	1.0000
15:90889304:AGGAA:A	acceptor_loss	1.0000
15:90889305:G:A	acceptor_loss	1.0000
15:90889412:GC:G	donor_gain	1.0000
15:90889438:G:GG	donor_gain	1.0000
15:90889441:TGGG:T	donor_loss	1.0000
15:90889442:GG:G	donor_gain	1.0000

AlphaMissense

5337 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:90892713:T:C	F572L	1.000
15:90892715:T:A	F572L	1.000
15:90892715:T:G	F572L	1.000
15:90892767:A:G	K590E	1.000
15:90892769:G:C	K590N	1.000
15:90892769:G:T	K590N	1.000
15:90892810:T:C	F604S	1.000
15:90893177:T:A	V635D	1.000
15:90893390:T:C	L674P	1.000
15:90893414:G:C	R682P	1.000
15:90893656:A:C	D683A	1.000
15:90893656:A:G	D683G	1.000
15:90893656:A:T	D683V	1.000
15:90893659:T:C	L684P	1.000
15:90893672:C:A	N688K	1.000
15:90893672:C:G	N688K	1.000
15:90893709:G:C	D701H	1.000
15:90893710:A:C	D701A	1.000
15:90893710:A:G	D701G	1.000
15:90893710:A:T	D701V	1.000
15:90893711:C:A	D701E	1.000
15:90893711:C:G	D701E	1.000
15:90893784:T:A	W726R	1.000
15:90893784:T:C	W726R	1.000
15:90893786:G:C	W726C	1.000
15:90893786:G:T	W726C	1.000
15:90893962:T:A	W744R	1.000
15:90893962:T:C	W744R	1.000
15:90893965:A:C	S745R	1.000
15:90893967:C:A	S745R	1.000

dbSNP variants (sampled 300 via entrez): RS1000197988 (15:90893878 C>G,T), RS1000277544 (15:90884664 C>G,T), RS1000401581 (15:90889127 A>C), RS1000519788 (15:90889900 G>A), RS1000584990 (15:90884133 C>T), RS1000836183 (15:90888875 T>G), RS1001241513 (15:90892836 A>C), RS1001480196 (15:90887709 A>G), RS1001549606 (15:90883464 T>C), RS1001580580 (15:90883253 C>T), RS1002243837 (15:90891665 G>C), RS1002275129 (15:90891360 A>G,T), RS1002427101 (15:90895581 T>C), RS1002476082 (15:90895784 G>A), RS1003072570 (15:90886081 A>G)

Disease associations

OMIM: gene MIM:190030 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

55 associations (top):

Study	Trait	p-value
GCST001227_15	Systolic blood pressure	5.000000e-19
GCST001228_12	Diastolic blood pressure	2.000000e-15
GCST001236_7	Blood pressure	3.000000e-08
GCST001238_9	Hypertension	7.000000e-07
GCST002539_79	Schizophrenia	8.000000e-14
GCST003116_43	Coronary artery disease	3.000000e-07
GCST003117_19	Myocardial infarction	2.000000e-07
GCST003272_4	Systolic blood pressure	6.000000e-08
GCST003518_37	Daytime sleep phenotypes	9.000000e-06
GCST004279_42	Systolic blood pressure	1.000000e-09
GCST004521_101	Autism spectrum disorder or schizophrenia	2.000000e-08
GCST004521_95	Autism spectrum disorder or schizophrenia	1.000000e-10
GCST004776_67	Systolic blood pressure	1.000000e-12
GCST004777_54	Diastolic blood pressure	1.000000e-13
GCST004787_62	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	7.000000e-13
GCST005146_41	Birth weight	1.000000e-08
GCST005194_13	Coronary artery disease	2.000000e-25
GCST006166_40	Diastolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-31
GCST006167_15	Mean arterial pressure x alcohol consumption interaction (2df test)	5.000000e-19
GCST006167_69	Mean arterial pressure x alcohol consumption interaction (2df test)	7.000000e-19
GCST006168_19	Pulse pressure x alcohol consumption interaction (2df test)	4.000000e-19
GCST006169_10	Diastolic blood pressure x alcohol consumption (light vs heavy) interaction (2df test)	2.000000e-19
GCST006172_32	Mean arterial pressure x alcohol consumption (light vs heavy) interaction (2df test)	6.000000e-23
GCST006187_42	Diastolic blood pressure (cigarette smoking interaction)	3.000000e-40
GCST006188_46	Systolic blood pressure (cigarette smoking interaction)	6.000000e-45
GCST006258_53	Diastolic blood pressure	2.000000e-17
GCST006259_12	Systolic blood pressure	3.000000e-20
GCST006434_46	Systolic blood pressure x alcohol consumption interaction (2df test)	8.000000e-41
GCST006803_31	Schizophrenia	3.000000e-12
GCST007094_38	Diastolic blood pressure	2.000000e-22

EFO canonical traits (17, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006340	mean arterial pressure
EFO:0007828	daytime rest measurement
EFO:0004344	birth weight
EFO:0004329	alcohol drinking
EFO:0005763	pulse pressure measurement
EFO:0006527	smoking status measurement
EFO:0009929	Beta blocking agent use measurement
EFO:0009928	Diuretic use measurement
EFO:0009930	Calcium channel blocker use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0005939	parental genotype effect measurement
EFO:0006781	coffee consumption measurement
EFO:0007796	parental longevity
EFO:0004346	neuroimaging measurement
EFO:0004980	appendicular lean mass

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5455 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

29 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 177,970 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL180022	NERATINIB	4	9,404
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3286830	LORLATINIB	4	3,598
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL223360	LINIFANIB	3	3,925
CHEMBL3545308	ROCILETINIB	3	1,729
CHEMBL603469	LESTAURTINIB	3
CHEMBL1230609	FORETINIB	2	3,096
CHEMBL1738757	REBASTINIB	2	1,478
CHEMBL402548	DANUSERTIB	2	1,928
CHEMBL475251	R-406	2	762
CHEMBL513909	BI-2536	2	895
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL574737	UCN-01	2
CHEMBL575448	BMS-754807	2
CHEMBL607707	PELITINIB	2
CHEMBL1908397	KW-2449	1
CHEMBL2041933	AZD-7762	1
CHEMBL2140408	AMG-900	1
CHEMBL3545360	ASP-3026	1
CHEMBL4289017	PF-03814735	1
CHEMBL574738	AST-487	1

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Fer family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 8e [PMID: 24432909]	Inhibition	8.3	pIC50
lorlatinib	Inhibition	8.22	pIC50
compound 25b [PMID: 22564207]	Inhibition	7.0	pIC50

Binding affinities (BindingDB)

4 measured of 5 human assays (5 total across all organisms); most potent 4 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
Staurosporine	KD	1.7 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM

ChEMBL bioactivities

146 potent at pChembl≥5 of 147 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.00	IC50	1	nM	CHEMBL459850
8.82	IC50	1.52	nM	STAUROSPORINE
8.80	IC50	1.59	nM	STAUROSPORINE
8.68	IC50	2.08	nM	STAUROSPORINE
8.46	IC50	3.5	nM	BRIGATINIB
8.32	Kd	4.8	nM	TAE-684
8.31	IC50	4.9	nM	CHEMBL4846921
8.30	IC50	5	nM	CHEMBL3128069
8.22	IC50	6	nM	LORLATINIB
8.22	Ki	6	nM	LORLATINIB
8.22	IC50	6	nM	CHEMBL5712062
8.15	Kd	7.04	nM	CHEMBL3752910
8.12	IC50	7.5	nM	CHEMBL6165880
8.10	Ki	7.943	nM	CHEMBL244378
8.09	IC50	8.1	nM	STAUROSPORINE
8.00	Ki	10	nM	CHEMBL396523
8.00	Ki	10	nM	CHEMBL243088
7.94	Kd	11.51	nM	CHEMBL5653589
7.90	Ki	12.59	nM	CHEMBL1983111
7.72	ED50	19.05	nM	CHEMBL3752910
7.70	Ki	19.95	nM	CHEMBL1981047
7.64	Kd	23	nM	STAUROSPORINE
7.51	ED50	31.14	nM	CHEMBL5653589
7.50	Ki	31.62	nM	CHEMBL1988163
7.40	Ki	39.81	nM	CHEMBL1987034
7.30	Ki	50.12	nM	CHEMBL1989708
7.30	Ki	50.12	nM	CHEMBL1825138
7.29	IC50	50.8	nM	CHEMBL5705846
7.28	Kd	52	nM	CHEMBL464552
7.16	IC50	69.7	nM	CHEMBL5705830
7.10	Ki	79.43	nM	SP-600125
7.00	IC50	99	nM	CHEMBL2064666
6.97	Kd	106	nM	CHEMBL4465866
6.96	Kd	110	nM	FORETINIB
6.94	Kd	114	nM	CHEMBL4576489
6.90	Kd	127	nM	AMG-900
6.90	Ki	125.9	nM	CHEMBL1986263
6.90	Ki	125.9	nM	CHEMBL1990885
6.90	Ki	125.9	nM	CHEMBL458997
6.83	Kd	149	nM	HESPERADIN
6.83	IC50	148	nM	CHEMBL466397
6.80	IC50	160	nM	REBASTINIB
6.80	Ki	158.5	nM	CHEMBL1978448
6.80	Ki	158.5	nM	CHEMBL1989708
6.80	Ki	158.5	nM	CHEMBL1974664
6.75	Kd	179	nM	CHEMBL3688339
6.70	Kd	200	nM	R-406
6.70	Ki	199.5	nM	CHEMBL1967720
6.60	IC50	252	nM	CHEMBL5705821
6.60	Ki	251.2	nM	CHEMBL1993941

PubChem BioAssay actives

66 with measured affinity, of 1129 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-[3-(7-amino-1-methyl-2-oxo-4H-pyrimido[4,5-d]pyrimidin-3-yl)-4-methylphenyl]-3-(trifluoromethyl)benzamide	383101: Inhibition of Fes	ic50	0.0010	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1531693: Inhibition of human FES using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0015	uM
Brigatinib	2182796: Inhibition of human FES using poly (Glu, Tyr)4:1 as substrate in presence of [gamma33P]-ATP by HotSpot assay	ic50	0.0035	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624852: Binding constant for FES kinase domain	kd	0.0048	uM
N-[3-[2-[4-(4-ethylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-7-yl]phenyl]methanesulfonamide	1779443: Inhibition of Fes (unknown origin)	ic50	0.0049	uM
(2R)-2-[5-[6-amino-5-[(1R)-1-[5-fluoro-2-(triazol-2-yl)phenyl]ethoxy]-3-pyridinyl]-4-methyl-1,3-thiazol-2-yl]propane-1,2-diol	1074703: Inhibition of FES (unknown origin) using Km levels of ATP	ic50	0.0050	uM
(16R)-19-amino-13-fluoro-4,8,16-trimethyl-9-oxo-17-oxa-4,5,8,20-tetrazatetracyclo[16.3.1.02,6.010,15]docosa-1(22),2,5,11,13,18,20-heptaene-3-carbonitrile	2187699: Inhibition of His-tagged recombinant full length FES (unknown origin) expressed in baculovirus expression system	ic50	0.0060	uM
Lorlatinib	1153112: Inhibition of FES (unknown origin) by TR-FRET-based Z’-LYTE assay	ic50	0.0060	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148383: Binding affinity to human FES incubated for 45 mins by Kinobead based pull down assay	kd	0.0070	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148383: Binding affinity to human FES incubated for 45 mins by Kinobead based pull down assay	kd	0.0115	uM
3-(6,7-dimethoxyquinazolin-4-yl)oxy-N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methylbenzamide	2180189: Inhibition of FES (unknown origin) by KiNativ Profiling analysis	ic50	0.0508	uM
2-[[2-[[1-[2-(dimethylamino)acetyl]-5-methoxy-2,3-dihydroindol-6-yl]amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]-6-fluoro-N-methylbenzamide	624852: Binding constant for FES kinase domain	kd	0.0520	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[(6-methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]benzamide	2180189: Inhibition of FES (unknown origin) by KiNativ Profiling analysis	ic50	0.0697	uM
(1S,2S,3R,4R)-3-[[5-chloro-2-[[(7S)-4-methoxy-7-morpholin-4-yl-6,7,8,9-tetrahydro-5H-benzo[7]annulen-3-yl]amino]pyrimidin-4-yl]amino]bicyclo[2.2.1]hept-5-ene-2-carboxamide	676090: Inhibition of human Fes	ic50	0.0990	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]amino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526230: Binding affinity to recombinant full-length N-terminal His-tagged FES (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1060	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624852: Binding constant for FES kinase domain	kd	0.1100	uM
3-(2,2-difluoro-10,12-dimethyl-1-aza-3-azonia-2-boranuidatricyclo[7.3.0.03,7]dodeca-3,5,7,9,11-pentaen-4-yl)-N-[2-[2-[2-[2-[[(2S,3R,4R,6R)-3-methoxy-2-methyl-16-oxo-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-4-yl]-methylamino]ethoxy]ethoxy]ethoxy]ethyl]propanamide	1526230: Binding affinity to recombinant full-length N-terminal His-tagged FES (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1140	uM
N-[4-[[3-(2-aminopyrimidin-4-yl)-2-pyridinyl]oxy]phenyl]-4-(4-methylthiophen-2-yl)phthalazin-1-amine	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1270	uM
N-(2,6-difluorophenyl)-5-[3-[2-[5-ethyl-2-methoxy-4-[4-(4-methylsulfonylpiperazin-1-yl)piperidin-1-yl]anilino]pyrimidin-4-yl]imidazo[1,2-a]pyridin-2-yl]-2-methoxybenzamide	2167073: Inhibition of N-terminal His6-tagged recombinant full length human Fes expressed in baculovirus infected Sf21 cells by filter binding assay	ic50	0.1480	uM
N-[2-hydroxy-3-[C-phenyl-N-[4-(piperidin-1-ylmethyl)phenyl]carbonimidoyl]-1H-indol-5-yl]ethanesulfonamide	389051: Binding affinity to human FES	kd	0.1490	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168236: Inhibition of human wild type FES using PolyEY as substrate preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.1600	uM
1-[6-(3,5-dichloro-4-hydroxyphenyl)-4-[[4-[(dimethylamino)methyl]cyclohexyl]amino]-1,5-naphthyridin-3-yl]ethanone	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.1790	uM
6-[[5-fluoro-2-(3,4,5-trimethoxyanilino)pyrimidin-4-yl]amino]-2,2-dimethyl-4H-pyrido[3,2-b][1,4]oxazin-3-one	624852: Binding constant for FES kinase domain	kd	0.2000	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[6-(methylamino)pyrimidin-4-yl]oxybenzamide	2180189: Inhibition of FES (unknown origin) by KiNativ Profiling analysis	ic50	0.2520	uM
1-[3-tert-butyl-1-(4-chlorophenyl)pyrazol-5-yl]-3-[4-[(6,6-dimethyl-7-oxo-8H-pyrimido[5,4-b][1,4]oxazin-4-yl)amino]-3-methylphenyl]urea	1822456: Inhibition of human FES in presence of ATP by radiometric assay	ic50	0.2690	uM
3-(carbamoylamino)-5-(3-fluorophenyl)-N-[(3S)-piperidin-3-yl]thiophene-2-carboxamide	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.3190	uM
Bosutinib	624852: Binding constant for FES kinase domain	kd	0.3300	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435161: Binding constant for FES kinase domain	kd	0.3600	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	507944: Binding affinity to FES	kd	0.3700	uM
Crizotinib	624852: Binding constant for FES kinase domain	kd	0.4500	uM
1-[3-methoxy-4-[[4-(2-propan-2-ylsulfonylanilino)-1H-pyrazolo[5,4-d]pyrimidin-6-yl]amino]phenyl]piperidin-4-ol	1562811: Inhibition of FES (unknown origin)	ic50	0.4940	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide	1562811: Inhibition of FES (unknown origin)	ic50	0.5270	uM
Fedratinib	624852: Binding constant for FES kinase domain	kd	0.5300	uM
Neratinib	624852: Binding constant for FES kinase domain	kd	0.5900	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.5940	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624852: Binding constant for FES kinase domain	kd	0.6800	uM
1-(2-hydroxy-2-methylpropyl)-N-[5-(7-methoxyquinolin-4-yl)oxy-2-pyridinyl]-5-methyl-3-oxo-2-phenylpyrazole-4-carboxamide	343275: Inhibition of FES	ic50	0.7060	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624852: Binding constant for FES kinase domain	kd	0.7500	uM
5-[2-(2-aminopyrimidin-5-yl)ethynyl]-N-[2-[(3S)-3-(dimethylamino)piperidin-1-yl]-5-(trifluoromethyl)phenyl]-2-fluorobenzamide	277461: Inhibition of Fes	ic50	0.9100	uM
Sunitinib	435161: Binding constant for FES kinase domain	kd	0.9600	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624852: Binding constant for FES kinase domain	kd	1.1000	uM
2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)-1,3,5-triazine-2,4-diamine	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1220	uM
N-[3-[[2-[4-(4-acetylpiperazin-1-yl)-2-methoxyanilino]-5-(trifluoromethyl)pyrimidin-4-yl]amino]phenyl]prop-2-enamide	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.1940	uM
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624852: Binding constant for FES kinase domain	kd	1.2000	uM
N-[2-[4-[[4-(cyclobutylamino)-5-(trifluoromethyl)pyrimidin-2-yl]amino]-11-azatricyclo[6.2.1.02,7]undeca-2(7),3,5-trien-11-yl]-2-oxoethyl]acetamide	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.2340	uM
Pazopanib	624852: Binding constant for FES kinase domain	kd	1.4000	uM
Ceritinib	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7420	uM
(2S)-1-[4-[(5-cyclopropyl-1H-pyrazol-3-yl)amino]pyrrolo[2,1-f][1,2,4]triazin-2-yl]-N-(6-fluoro-3-pyridinyl)-2-methylpyrrolidine-2-carboxamide	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	1.7690	uM
4-[[(7R)-8-cyclopentyl-7-ethyl-5-methyl-6-oxo-7H-pteridin-2-yl]amino]-3-methoxy-N-(1-methylpiperidin-4-yl)benzamide	624852: Binding constant for FES kinase domain	kd	1.9000	uM
(2S,3R,4R,6R,18S)-18-hydroxy-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	1425003: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	2.3140	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tobacco Smoke Pollution	decreases expression, increases expression	2
Valproic Acid	increases expression, increases methylation	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
pentanal	increases expression	1
tamibarotene	affects expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
Aerosols	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	affects methylation	1
Caffeine	increases phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Dexamethasone	increases expression, affects cotreatment	1
Indomethacin	affects cotreatment, increases expression	1
Methylnitronitrosoguanidine	increases expression	1
Ozone	increases abundance, affects expression	1
Testosterone	decreases expression	1
Tetrachlorodibenzodioxin	affects expression	1
Tretinoin	increases expression	1
Urethane	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1
Aflatoxin B1	decreases expression	1

ChEMBL screening assays

325 unique, capped per target: 324 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1004488	Binding	Binding affinity to human recombinant FES expressed in Escherichia coli assessed as thermal shift by differential scanning fluorimetry	Discovery of a potent and selective inhibitor for human carbonyl reductase 1 from propionate scanning applied to the macrolide zearalenone. — Bioorg Med Chem
CHEMBL1963758	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FES	PubChem BioAssay data set

Cellosaurus cell lines

8 cell lines: 5 spontaneously immortalized cell line, 3 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_0F01	C166-lacZ	Spontaneously immortalized cell line	Sex unspecified
CVCL_6581	C166	Spontaneously immortalized cell line	Sex unspecified
CVCL_6582	C166-GFP	Spontaneously immortalized cell line	Sex unspecified
CVCL_E2VL	Rat-F	Spontaneously immortalized cell line	Male
CVCL_E2VM	Rat-MF	Spontaneously immortalized cell line	Male
CVCL_SN43	HAP1 FES (-) 1	Cancer cell line	Male
CVCL_SN44	HAP1 FES (-) 2	Cancer cell line	Male
CVCL_SN45	HAP1 FES (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.