FGR

Summary

FGR (FGR proto-oncogene, Src family tyrosine kinase, HGNC:3697) is a protein-coding gene on chromosome 1p35.3, encoding Tyrosine-protein kinase Fgr (P09769). Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to ext….

This gene is a member of the Src family of protein tyrosine kinases (PTKs). The encoded protein contains N-terminal sites for myristylation and palmitylation, a PTK domain, and SH2 and SH3 domains which are involved in mediating protein-protein interactions with phosphotyrosine-containing and proline-rich motifs, respectively. The protein localizes to plasma membrane ruffles, and functions as a negative regulator of cell migration and adhesion triggered by the beta-2 integrin signal transduction pathway. Infection with Epstein-Barr virus results in the overexpression of this gene. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 2268 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 68 total
• Druggable target: yes — 44 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_005248

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3697
Approved symbol	FGR
Name	FGR proto-oncogene, Src family tyrosine kinase
Location	1p35.3
Locus type	gene with protein product
Status	Approved
Aliases	c-fgr, p55c-fgr
Ensembl gene	ENSG00000000938
Ensembl biotype	protein_coding
OMIM	164940
Entrez	2268

Gene structure

Transcript identifiers

Ensembl transcripts: 32 — 30 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000374003, ENST00000374004, ENST00000374005, ENST00000399173, ENST00000457296, ENST00000468038, ENST00000475472, ENST00000859115, ENST00000859116, ENST00000859117, ENST00000859118, ENST00000859119, ENST00000859120, ENST00000859121, ENST00000859122, ENST00000859123, ENST00000859124, ENST00000859125, ENST00000859126, ENST00000859127, ENST00000859128, ENST00000859129, ENST00000859130, ENST00000859131, ENST00000968119, ENST00000968120, ENST00000968121, ENST00000968122, ENST00000968123, ENST00000968124, ENST00000968125, ENST00000968126

RefSeq mRNA: 3 — MANE Select: NM_005248 NM_001042729, NM_001042747, NM_005248

CCDS: CCDS305

Canonical transcript exons

ENST00000374005 — 13 exons

Exon	Start	End
ENSE00000761811	27623042	27623144
ENSE00000761813	27621559	27621657
ENSE00000761815	27617193	27617296
ENSE00000761817	27616857	27617006
ENSE00000761819	27615689	27615844
ENSE00000866729	27615434	27615613
ENSE00001410025	27625089	27625151
ENSE00001462133	27623691	27623929
ENSE00001462138	27635065	27635185
ENSE00001912718	27612064	27613122
ENSE00003309671	27614430	27614583
ENSE00003329774	27614850	27614926
ENSE00003384215	27613219	27613350

Expression profiles

Bgee: expression breadth ubiquitous, 199 present calls, max score 99.57.

FANTOM5 (CAGE): breadth broad, TPM avg 30.4578 / max 1551.5677, expressed in 502 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
11276	13.9208	426
11278	7.6107	348
11277	2.2439	256
11261	1.7505	229
11260	1.1996	201
11267	0.9832	95
11279	0.5838	189
11262	0.5658	147
11264	0.4506	110
11265	0.3855	97

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.57	gold quality
monocyte	CL:0000576	99.38	gold quality
mononuclear cell	CL:0000842	99.37	gold quality
leukocyte	CL:0000738	99.36	gold quality
blood	UBERON:0000178	98.92	gold quality
right lung	UBERON:0002167	98.09	gold quality
spleen	UBERON:0002106	97.34	gold quality
upper lobe of left lung	UBERON:0008952	97.09	gold quality
bone marrow cell	CL:0002092	97.04	gold quality
bone marrow	UBERON:0002371	96.64	gold quality
upper lobe of lung	UBERON:0008948	96.53	gold quality
trabecular bone tissue	UBERON:0002483	96.18	gold quality
vermiform appendix	UBERON:0001154	91.61	gold quality
left uterine tube	UBERON:0001303	90.95	gold quality
lower lobe of lung	UBERON:0008949	90.95	gold quality
lung	UBERON:0002048	89.77	gold quality
lymph node	UBERON:0000029	88.96	gold quality
omental fat pad	UBERON:0010414	88.60	gold quality
peritoneum	UBERON:0002358	88.53	gold quality
adipose tissue of abdominal region	UBERON:0007808	88.17	gold quality
subcutaneous adipose tissue	UBERON:0002190	86.72	gold quality
gall bladder	UBERON:0002110	86.31	gold quality
caecum	UBERON:0001153	86.21	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.94	gold quality
left coronary artery	UBERON:0001626	83.56	gold quality
adipose tissue	UBERON:0001013	83.33	gold quality
apex of heart	UBERON:0002098	83.13	gold quality
connective tissue	UBERON:0002384	82.53	gold quality
coronary artery	UBERON:0001621	82.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	82.24	gold quality

Single-cell (SCXA)

Detected in 12 experiment(s), a significant marker in 12.

Experiment	Marker?	Max mean expression
E-MTAB-8498	yes	887.96
E-GEOD-84465	yes	687.64
E-CURD-122	yes	67.94
E-MTAB-9221	yes	28.64
E-MTAB-6678	yes	27.86
E-MTAB-6701	yes	27.67
E-HCAD-10	yes	26.71
E-CURD-112	yes	23.04
E-MTAB-9067	yes	19.64
E-MTAB-8410	yes	13.64
E-MTAB-9801	yes	8.01
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

35 targeting FGR, 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-3686	99.90	70.53	2432
HSA-MIR-6756-5P	99.82	67.97	2466
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-6766-5P	99.68	67.70	2325
HSA-MIR-378A-5P	99.65	66.33	1311
HSA-MIR-4328	99.57	71.06	4094
HSA-MIR-12117	99.50	67.57	868
HSA-MIR-4519	99.48	66.10	859
HSA-MIR-3123	99.47	67.15	2693
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-5701	98.97	69.54	1502
HSA-MIR-3154	98.94	66.55	1455
HSA-MIR-6846-5P	98.81	65.86	1121
HSA-MIR-6848-5P	98.81	65.49	1126
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-4700-5P	98.63	67.43	1915
HSA-MIR-603	98.58	68.28	1603
HSA-MIR-31-5P	98.58	68.35	1239
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-18B-3P	98.05	65.55	595
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-4469	97.93	65.81	1319
HSA-MIR-1279	97.83	67.50	1898
HSA-MIR-8089	97.74	66.21	1698
HSA-MIR-4667-5P	97.61	66.67	1683
HSA-MIR-3189-5P	97.55	66.71	655

Literature-anchored findings (GeneRIF, showing 12)

• Substitution of two relevant serines with glutamic acid residues in urokinase prevents urokinase activation of p55fgr needed for cell migration and adhesion. (PMID:11928806)
• Recruitment of the coactivator, SRC2, is coupled to cooperative DNA binding by the progesterone receptor. (PMID:17845055)
• Fgr plays a biologically significant role in ovarian cancer growth and might represent an important target (PMID:21300758)
• Data indicate that combined treatment using SFK (LYN, HCK, or FGR) and c-KIT inhibitor dasatinib dasatinib and chemotherapy provides a novel approach to increasing p53 activity and enhancing targeting of acute myeloid leukemia (AML) stem cells. (PMID:23896410)
• we provide evidence for involvement of HCK and FGR in FCRL4-mediated immunoregulation and for the functional importance of posttranslational modifications of the FCRL4 molecule. (PMID:25972488)
• the Src tyrosine kinase Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog (FGR) is associated with suberoylanilide hydroxamic acid resistance. (PMID:27324824)
• Weighted gene co-expression network analysis of gene modules for the prognosis of esophageal cancer yielded PTAFR and FGR as the most important hub genes for predicting patient survival. (PMID:28585144)
• Fgr protein is overexpressed in acute myelogenous leukemia. (PMID:29763550)
• Fgr is a transforming oncoprotein that functions independently of SH3-SH2 domain regulation (PMID:30352950)
• These studies show that Hck and Fgr expression influences inhibitor sensitivity and the pathway to acquired resistance in Flt3-ITD+ AML. (PMID:31790499)
• A Model for the Signal Initiation Complex Between Arrestin-3 and the Src Family Kinase Fgr. (PMID:34902430)
• Variants in PSMB9 and FGR differentially affect Parkinson’s disease risk in GBA and LRRK2 mutation carriers. (PMID:37116292)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	yrk	ENSDARG00000004378
mus_musculus	Fgr	ENSMUSG00000028874
rattus_norvegicus	Fgr	ENSRNOG00000009912

Paralogs (32): 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), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase Fgr — P09769 (reviewed: P09769)

Alternative names: Gardner-Rasheed feline sarcoma viral (v-fgr) oncogene homolog, Proto-oncogene c-Fgr, p55-Fgr, p58-Fgr, p58c-Fgr

All UniProt accessions (2): P09769, Q5TGY6

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors devoid of kinase activity and contributes to the regulation of immune responses, including neutrophil, monocyte, macrophage and mast cell functions, cytoskeleton remodeling in response to extracellular stimuli, phagocytosis, cell adhesion and migration. Promotes mast cell degranulation, release of inflammatory cytokines and IgE-mediated anaphylaxis. Acts downstream of receptors that bind the Fc region of immunoglobulins, such as MS4A2/FCER1B, FCGR2A and/or FCGR2B. Acts downstream of ITGB1 and ITGB2, and regulates actin cytoskeleton reorganization, cell spreading and adhesion. Depending on the context, activates or inhibits cellular responses. Functions as a negative regulator of ITGB2 signaling, phagocytosis and SYK activity in monocytes. Required for normal ITGB1 and ITGB2 signaling, normal cell spreading and adhesion in neutrophils and macrophages. Functions as a positive regulator of cell migration and regulates cytoskeleton reorganization via RAC1 activation. Phosphorylates SYK (in vitro) and promotes SYK-dependent activation of AKT1 and MAP kinase signaling. Phosphorylates PLD2 in antigen-stimulated mast cells, leading to PLD2 activation and the production of the signaling molecules lysophosphatidic acid and diacylglycerol. Promotes activation of PIK3R1. Phosphorylates FASLG, and thereby regulates its ubiquitination and subsequent internalization. Phosphorylates ABL1. Promotes phosphorylation of CBL, CTTN, PIK3R1, PTK2/FAK1, PTK2B/PYK2 and VAV2. Phosphorylates HCLS1 that has already been phosphorylated by SYK, but not unphosphorylated HCLS1. Together with CLNK, it acts as a negative regulator of natural killer cell-activating receptors and inhibits interferon-gamma production.

Subunit / interactions. Interacts with ITGB1, ITGB2, MS4A2/FCER1B, FCER1G, FCGR2A and/or FCGR2B. Interacts (via SH2 domain) with SYK (tyrosine phosphorylated). Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with PTK2/FAK1. Interacts (via SH2 domain) with HCLS1 (tyrosine phosphorylated by SYK). Interacts with SIRPA and PTPNS1. Interacts (not phosphorylated on tyrosine residues) with CBL; FGR tyrosine phosphorylation promotes dissociation. Interacts with PIK3R1 and FASLG. Interacts with CLNK.

Subcellular location. Cell membrane. Cell projection. Ruffle membrane. Cytoplasm. Cytosol. Cytoskeleton. Mitochondrion inner membrane. Mitochondrion intermembrane space.

Tissue specificity. Detected in neutrophils, monocytes and natural killer cells (at protein level). Detected in monocytes and large lymphocytes.

Post-translational modifications. Ubiquitinated. Becomes ubiquitinated in response to ITGB2 signaling; this does not lead to degradation. Phosphorylated. Autophosphorylated on tyrosine residues. Becomes phosphorylated in response to FCGR2A and/or FCGR2B engagement, cell adhesion and signaling by ITGB2. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412.

Disease relevance. Mutations that cause aberrant kinase activation can confer oncogene activity and promote aberrant cell proliferation.

Activity regulation. Activated by autophosphorylation. Prior phosphorylation at Tyr-523 by SRC inhibits ulterior autophosphorylation at Tyr-412. Activated by phorbol myristate acetate, phosphatidic acid and poly-Lys. Binding (via SH2 domain) of HCLS1 that is already phosphorylated by SYK strongly increases kinase activity.

Similarity. Belongs to the protein kinase superfamily. Tyr protein kinase family. SRC subfamily.

RefSeq proteins (3): NP_001036194, NP_001036212, NP_005239* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035693	Fgr_SH2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, 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 (67 total): strand 25, helix 19, modified residue 5, turn 4, lipid moiety-binding region 3, domain 3, sequence variant 2, binding site 2, initiator methionine 1, chain 1, mutagenesis site 1, active site 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7JT9	X-RAY DIFFRACTION	1.93
7UY0	X-RAY DIFFRACTION	2.55
7UY3	X-RAY DIFFRACTION	2.99

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09769-F1	83.00	0.65

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): 382 (proton acceptor)

Ligand- & substrate-binding residues (2): 269–277; 291

Post-translational modifications (8): 218, 412, 523, 2, 3, 6, 34, 208

Mutagenesis-validated functional residues (1):

Position	Phenotype
523	strongly increased catalytic activity. functions as oncogene.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2029481	FCGR activation
R-HSA-432142	Platelet sensitization by LDL
R-HSA-6798695	Neutrophil degranulation
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 424 (showing top): GOBP_REGULATION_OF_CELL_ACTIVATION, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, MYOGENIN_Q6, GOBP_REGULATION_OF_CELL_MORPHOGENESIS, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_INFLAMMATORY_RESPONSE, GOCC_SECRETORY_GRANULE, GOBP_POSITIVE_REGULATION_OF_LEUKOCYTE_DEGRANULATION, GCANCTGNY_MYOD_Q6, MODULE_45, MODULE_64, AREB6_03, BIOCARTA_BARRESTIN_SRC_PATHWAY

GO Biological Process (24): positive regulation of cytokine production (GO:0001819), immune response-regulating cell surface receptor signaling pathway (GO:0002768), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), protein phosphorylation (GO:0006468), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), integrin-mediated signaling pathway (GO:0007229), regulation of cell shape (GO:0008360), response to virus (GO:0009615), peptidyl-tyrosine phosphorylation (GO:0018108), cell differentiation (GO:0030154), bone mineralization (GO:0030282), positive regulation of cell migration (GO:0030335), negative regulation of natural killer cell activation (GO:0032815), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), positive regulation of mast cell degranulation (GO:0043306), innate immune response (GO:0045087), regulation of innate immune response (GO:0045088), regulation of protein kinase activity (GO:0045859), protein autophosphorylation (GO:0046777), skeletal system morphogenesis (GO:0048705), regulation of phagocytosis (GO:0050764), defense response to Gram-positive bacterium (GO:0050830), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), immune system process (GO:0002376)

GO Molecular Function (13): phosphotyrosine residue binding (GO:0001784), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), protein kinase binding (GO:0019901), immunoglobulin receptor binding (GO:0034987), Fc-gamma receptor I complex binding (GO:0034988), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (15): extracellular region (GO:0005576), mitochondrial inner membrane (GO:0005743), mitochondrial intermembrane space (GO:0005758), cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), aggresome (GO:0016235), ruffle membrane (GO:0032587), secretory granule lumen (GO:0034774), extracellular exosome (GO:0070062), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytoskeleton (GO:0005856), membrane (GO:0016020), cell projection (GO:0042995)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Fcgamma receptor (FCGR) dependent phagocytosis	1
Platelet homeostasis	1
Innate Immune System	1
Anti-inflammatory response favouring Leishmania parasite infection	1
Leishmania phagocytosis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	5
cell surface receptor signaling pathway	2
protein phosphorylation	2
protein kinase activity	2
cytoplasm	2
cytokine production	1
regulation of cytokine production	1
positive regulation of gene expression	1
positive regulation of multicellular organismal process	1
immune response-regulating signaling pathway	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1
negative regulation of immune response	1
phosphorylation	1
protein modification process	1
enzyme-linked receptor protein signaling pathway	1
regulation of cell morphogenesis	1
regulation of biological quality	1
response to other organism	1
peptidyl-tyrosine modification	1
cellular developmental process	1
ossification	1
biomineral tissue development	1
cell migration	1
regulation of cell migration	1
positive regulation of cell motility	1
natural killer cell activation	1
regulation of natural killer cell activation	1
negative regulation of lymphocyte activation	1
Fc receptor mediated stimulatory signaling pathway	1
phagocytosis	1
Fc-gamma receptor signaling pathway	1
positive regulation of leukocyte degranulation	1
mast cell degranulation	1
regulation of mast cell degranulation	1
immune response	1
defense response to symbiont	1
regulation of response to biotic stimulus	1
regulation of defense response	1

Protein interactions and networks

STRING

3104 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FGR	ARRB2	P32121	707
FGR	CBL	P22681	648
FGR	LCP2	Q13094	641
FGR	FUCA1	P04066	593
FGR	EYA3	Q99504	550
FGR	CCKBR	P32239	550
FGR	CRKL	P46109	539
FGR	SHC1	P29353	538
FGR	ABL1	P00519	533
FGR	WAS	P42768	518
FGR	HSP90AA1	P07900	515
FGR	HSP90AB1	P08238	510
FGR	BLNK	Q8WV28	506
FGR	SYK	P43405	505
FGR	PLCG2	P16885	502

IntAct

44 interactions, top by confidence:

A	B	Type	Score
HSP90AB1	FGR	psi-mi:“MI:0915”(physical association)	0.640
FGR	HSP90AB1	psi-mi:“MI:0915”(physical association)	0.640
EGFR	FGR	psi-mi:“MI:0915”(physical association)	0.630
FGR	EGFR	psi-mi:“MI:0915”(physical association)	0.630
YES1	AIP	psi-mi:“MI:0914”(association)	0.530
YES1	SERPINB2	psi-mi:“MI:0914”(association)	0.530
CDK4	GUSB	psi-mi:“MI:0914”(association)	0.530
EEF1A2	FGR	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	ERBB2	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	ABI1	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	WAS	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	ALOX5	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
ALOX5	FGR	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
FGR	AR	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	KIT	psi-mi:“MI:0407”(direct interaction)	0.440
FGR	MET	psi-mi:“MI:0407”(direct interaction)	0.440
	FGR	psi-mi:“MI:0915”(physical association)	0.400
NR1I2	FGR	psi-mi:“MI:0915”(physical association)	0.370
FGR	STAT3	psi-mi:“MI:0915”(physical association)	0.370
FGR	ALK	psi-mi:“MI:0915”(physical association)	0.370
SYK	FGR	psi-mi:“MI:0915”(physical association)	0.370
	SGK1	psi-mi:“MI:0914”(association)	0.350
CDK18	MTA2	psi-mi:“MI:0914”(association)	0.350

BioGRID (106): FGR (Two-hybrid), FGR (Affinity Capture-MS), FGR (Affinity Capture-MS), FGR (PCA), FGR (Affinity Capture-Luminescence), FGR (Biochemical Activity), FGR (Affinity Capture-MS), FGR (Affinity Capture-MS), FGR (Affinity Capture-MS), FGR (Affinity Capture-MS), FGR (Affinity Capture-MS), FGR (Affinity Capture-Western), SKAP2 (PCA), WAS (Affinity Capture-Western), WAS (Reconstituted Complex)

ESM2 similar proteins: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, P00523, P00524, P00525, P00526, P00527, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08631, P09324, P09769, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P17713, P25020, P27446, P27447, P31693, P39688, P42683, P50545, P63185, Q01621, Q02977, Q04736

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
FGR	“down-regulates activity”	IKBKG	phosphorylation
FGR	“up-regulates activity”	KCND3	phosphorylation
FGR	“down-regulates activity”	TBK1	phosphorylation
FGR	“up-regulates activity”	SYK	phosphorylation
FGR	up-regulates	PTK2	phosphorylation
CSK	“down-regulates activity”	FGR	phosphorylation
FGR	“up-regulates activity”	FGR	phosphorylation
FGR	unknown	HCLS1	phosphorylation
FGR	unknown	SRC	phosphorylation
midostaurin	“down-regulates activity”	FGR	“chemical inhibition”
FGR	unknown	ACO2	phosphorylation
FGR	unknown	SDHA	phosphorylation
FGR	“up-regulates activity”	GLO1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 33 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
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	99.8×	3e-07
Signaling by SCF-KIT	5	47.7×	3e-06
FCGR3A-mediated phagocytosis	6	43.2×	6e-07
Constitutive Signaling by Aberrant PI3K in Cancer	6	29.3×	3e-06
MAPK1/MAPK3 signaling	5	25.2×	4e-05
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	6	22.3×	1e-05
Intracellular signaling by second messengers	6	21.1×	1e-05
PIP3 activates AKT signaling	8	20.6×	5e-07

GO biological processes:

GO term	Partners	Fold	FDR
cell surface receptor protein tyrosine kinase signaling pathway	6	35.9×	9e-06
positive regulation of MAPK cascade	6	16.7×	1e-04
negative regulation of apoptotic process	7	8.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	47
Likely benign	4
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2385 predictions. Top by Δscore:

Variant	Effect	Δscore
1:27613118:CATGC:C	acceptor_gain	1.0000
1:27613120:TGC:T	acceptor_gain	1.0000
1:27613121:GC:G	acceptor_gain	1.0000
1:27613122:CC:C	acceptor_gain	1.0000
1:27613123:C:CC	acceptor_gain	1.0000
1:27613123:CTGAA:C	acceptor_loss	1.0000
1:27613214:CAAA:C	donor_loss	1.0000
1:27613215:AAACC:A	donor_loss	1.0000
1:27613216:AAC:A	donor_loss	1.0000
1:27613217:ACC:A	donor_loss	1.0000
1:27613218:C:CA	donor_loss	1.0000
1:27613351:C:CC	acceptor_gain	1.0000
1:27613351:C:CG	acceptor_loss	1.0000
1:27613360:A:AC	acceptor_gain	1.0000
1:27613360:A:C	acceptor_gain	1.0000
1:27614445:A:AC	donor_gain	1.0000
1:27614446:C:CC	donor_gain	1.0000
1:27614449:A:AC	donor_gain	1.0000
1:27614449:ATCGT:A	donor_gain	1.0000
1:27614453:T:TA	donor_gain	1.0000
1:27614593:C:CT	acceptor_gain	1.0000
1:27614597:G:GC	acceptor_gain	1.0000
1:27614922:GCTGC:G	acceptor_loss	1.0000
1:27614923:CTGC:C	acceptor_gain	1.0000
1:27614924:TGC:T	acceptor_gain	1.0000
1:27614927:C:CC	acceptor_gain	1.0000
1:27614927:C:G	acceptor_loss	1.0000
1:27614928:T:C	acceptor_loss	1.0000
1:27615427:T:TA	donor_gain	1.0000
1:27615430:TGAC:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000393479 (1:27632531 A>T), RS1000501558 (1:27612240 G>A,C), RS1000575758 (1:27613761 G>A), RS1000802619 (1:27631546 C>T), RS1000870575 (1:27632752 CG>C), RS1000914107 (1:27625261 C>A), RS1001012717 (1:27618836 C>A,T), RS1001063561 (1:27619028 G>A), RS1001204486 (1:27630178 G>A,T), RS1001256922 (1:27630287 T>C,G), RS1001400231 (1:27617603 T>C), RS1001465360 (1:27624129 C>A,G,T), RS1001472068 (1:27631351 AC>A), RS1001535055 (1:27625475 C>G,T), RS1001735580 (1:27635772 G>C)

Disease associations

OMIM: gene MIM:164940 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST004904_218	Body mass index	2.000000e-08
GCST006628_27	Systolic blood pressure	1.000000e-10

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006335	systolic blood pressure

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL4454 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

44 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 487,632 (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
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL939	GEFITINIB	4
CHEMBL941	IMATINIB	4
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL572881	MOTESANIB	3
CHEMBL603469	LESTAURTINIB	3
CHEMBL103667	DORAMAPIMOD	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (6 total), top 6:

Ligand	Action	Affinity	Parameter
eCF506	Inhibition	9.3	pIC50
compound 2 [PMID: 15546730]	Inhibition	9.0	pIC50
compound 2c [PMID: 24900538]	Inhibition	8.66	pIC50
RIPK3 inhibitor 18	Inhibition	7.92	pIC50
P505-15	Inhibition	7.09	pIC50
apitolisib	Inhibition	6.16	pIC50

Binding affinities (BindingDB)

24 measured of 43 human assays (43 total across all organisms); most potent 24 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
Staurosporine	KD	1.7 nM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
3-[[2-[3-(morpholin-4-ylmethyl)phenyl]thieno[3,2-b]pyridin-7-yl]amino]phenol	IC50	5.1 nM	US-9062066: Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same
BIIB-057	IC50	10.5 nM
BMS-354825	KD	27 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
AMG 706	KD	300 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
3-[4-(benzylamino)-3-methoxyphenyl]-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-4-amine	IC50	550 nM	US-10294227: Compounds
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
5-[(Z)-(5-fluoranyl-2-oxidanylidene-1H-indol-3-ylidene)methyl]-2,4-dimethyl-N-[(2S)-3-morpholin-4-yl-2-oxidanyl-propyl]-1H-pyrrole-3-carboxamide	KD	2600 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
1-Acyl-1H-[1,2,4]triazole-3,5-diamine Analogue 3b	KD	3100 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

167 potent at pChembl≥5 of 175 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.52	Kd	0.3	nM	CHEMBL249097
9.40	IC50	0.4	nM	CHEMBL3647967
9.30	Kd	0.5	nM	DASATINIB
9.18	IC50	0.658	nM	STAUROSPORINE
9.10	IC50	0.8	nM	CHEMBL364623
9.10	IC50	0.794	nM	STAUROSPORINE
8.96	IC50	1.1	nM	BOSUTINIB
8.94	IC50	1.15	nM	STAUROSPORINE
8.74	IC50	1.82	nM	IBRUTINIB
8.66	IC50	2.2	nM	CHEMBL2151321
8.64	IC50	2.3	nM	IBRUTINIB
8.62	Kd	2.4	nM	CHEMBL386051
8.48	IC50	3.3	nM	IBRUTINIB
8.43	IC50	3.7	nM	CHEMBL2336005
8.30	Kd	5	nM	DASATINIB
8.27	IC50	5.36	nM	CHEMBL4877846
8.20	Kd	6.3	nM	BOSUTINIB
8.15	Kd	7	nM	CHEMBL450519
8.10	IC50	8	nM	IBRUTINIB
8.03	IC50	9.3	nM	CHEMBL5598020
7.82	IC50	15	nM	CHEMBL3928976
7.82	Ki	15	nM	PF-03758309
7.77	Kd	17	nM	STAUROSPORINE
7.66	IC50	22	nM	CHEMBL4077588
7.63	IC50	23.4	nM	PF-03758309
7.58	IC50	26	nM	CHEMBL4749037
7.57	IC50	27	nM	CHEMBL5750990
7.55	IC50	28	nM	CHEMBL4076024
7.55	IC50	28	nM	CHEMBL4525187
7.52	Kd	30	nM	STAUROSPORINE
7.48	IC50	33	nM	CHEMBL3116050
7.48	Kd	33	nM	R-406
7.47	IC50	34	nM	CHEMBL4108687
7.43	IC50	37	nM	CHEMBL4103954
7.42	Kd	38	nM	PONATINIB
7.42	IC50	38	nM	REBASTINIB
7.41	IC50	39	nM	CHEMBL4060757
7.40	Kd	40	nM	FORETINIB
7.39	IC50	41	nM	CHEMBL3586447
7.39	IC50	41	nM	CHEMBL4862806
7.37	IC50	43	nM	CHEMBL386637
7.28	IC50	52	nM	CHEMBL5794154
7.28	Kd	52	nM	LESTAURTINIB
7.26	IC50	55	nM	CHEMBL4799627
7.26	IC50	55	nM	CHEMBL3823861
7.26	IC50	55	nM	CHEMBL6018546
7.26	IC50	55	nM	CHEMBL3823255
7.26	IC50	55	nM	CHEMBL3823711
7.21	Kd	62	nM	PLX-4720
7.19	IC50	65	nM	CHEMBL3753341

PubChem BioAssay actives

144 with measured affinity, of 967 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
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389067: Binding affinity to human FGR	kd	0.0003	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435798: Binding constant for FGR kinase domain	kd	0.0005	uM
6-[7-methoxy-6-(1-methylpyrazol-4-yl)imidazo[1,2-a]pyridin-3-yl]-N-pyrrolidin-3-ylpyridin-2-amine	1894588: Inhibition of FGR (unknown origin)	ic50	0.0005	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	1715343: Inhibition of human FGR using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0007	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	271956: Inhibition of Fgr	ic50	0.0008	uM
Bosutinib	507433: Inhibition of FGR	ic50	0.0011	uM
Ibrutinib	1615371: Inhibition of human FGR using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	ic50	0.0018	uM
N-[(1S)-1-(5-fluoro-2-pyridinyl)ethyl]-3-(3-propan-2-yloxy-1H-pyrazol-5-yl)imidazo[4,5-b]pyridin-5-amine	692411: Inhibition of Fgr	ic50	0.0022	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	625011: Binding constant for FGR kinase domain	kd	0.0024	uM
3-tert-butyl-N-[(5R)-2-[2-(3,5-dimethyl-1-propan-2-ylpyrazol-4-yl)-1H-imidazo[4,5-b]pyridin-7-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-5-yl]-1,2,4-oxadiazole-5-carboxamide	1763492: Inhibition of human FGR	ic50	0.0054	uM
3-(4-amino-7-piperidin-4-ylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	389067: Binding affinity to human FGR	kd	0.0070	uM
2-amino-5-[2-[(3R)-3-aminopyrrolidin-1-yl]-6-fluoro-4-pyridinyl]-3-(3-hydroxy-2,6-dimethylphenyl)benzamide	2122459: Inhibition of Fgr (unknown origin)	ic50	0.0093	uM
N-[(1S)-2-(dimethylamino)-1-phenylethyl]-6,6-dimethyl-3-[(2-methylthieno[3,2-d]pyrimidin-4-yl)amino]-1,4-dihydropyrrolo[3,4-d]pyrazole-5-carboxamide	2167996: Inhibition of human FGR assessed as inhibition constant in presence of ATP	ki	0.0150	uM
3-chloro-4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	1678396: Inhibition of FGR (unknown origin)	ic50	0.0150	uM
4-[8-amino-3-[(3R)-1-(oxan-4-yl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488580: Inhibition of FGR (unknown origin)	ic50	0.0220	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721751: Inhibition of FGR (unknown origin)	ic50	0.0260	uM
7-[[(2R)-1-[[(2R)-oxiran-2-yl]methyl]pyrrolidin-2-yl]methyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1549556: Inhibition of human recombinant FGR using Ulight-TK peptide as substrate measured after 60 mins in the presence of ATP by LANCE method	ic50	0.0280	uM
4-[8-amino-3-[(3R)-1-(2-methoxyacetyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488580: Inhibition of FGR (unknown origin)	ic50	0.0280	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	625011: Binding constant for FGR kinase domain	kd	0.0330	uM
2-N-[(1S)-1-(5-fluoropyrimidin-2-yl)ethyl]-4-N-(1-methylimidazol-4-yl)-7H-pyrrolo[2,3-d]pyrimidine-2,4-diamine	1067927: Inhibition of human Fgr	ic50	0.0330	uM
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721751: Inhibition of FGR (unknown origin)	ic50	0.0340	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711657: Inhibition of human FGR	ic50	0.0370	uM
Ponatinib	1425005: 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	0.0380	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168206: Inhibition of human wild type FGR 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	0.0380	uM
4-[8-amino-3-[(2R)-4-(oxan-4-yl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488580: Inhibition of FGR (unknown origin)	ic50	0.0390	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	625011: Binding constant for FGR kinase domain	kd	0.0400	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-[3,5-bis(trifluoromethyl)phenyl]-4-methylbenzamide	1780011: Inhibition of human recombinant FGR (456 to 770) radiometric scintillation counting analysis	ic50	0.0410	uM
4-amino-8-(5-methyl-1H-indazol-6-yl)cinnoline-3-carboxamide	1230684: Inhibition of human recombinant Fgr	ic50	0.0410	uM
5-[2-(2-aminopyrimidin-5-yl)ethynyl]-N-[2-[(3S)-3-(dimethylamino)piperidin-1-yl]-5-(trifluoromethyl)phenyl]-2-fluorobenzamide	277457: Inhibition of FGR	ic50	0.0430	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	507950: Binding affinity to FGR	kd	0.0520	uM
4-[8-amino-3-[(3R)-1-(3-methyloxetane-3-carbonyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711657: Inhibition of human FGR	ic50	0.0550	uM
N-[3-(5-chloro-1H-pyrrolo[2,3-b]pyridine-3-carbonyl)-2,4-difluorophenyl]propane-1-sulfonamide	625011: Binding constant for FGR kinase domain	kd	0.0620	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-3-methoxy-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721751: Inhibition of FGR (unknown origin)	ic50	0.0640	uM
3-(5-cyclopropyl-1,2-oxazol-3-yl)-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-4-amine	1271645: Inhibition of recombinant human FGR by radiometric assay in presence of [gamma-33P]-ATP	ic50	0.0650	uM
4-[8-amino-3-[(2R)-4-(2-methoxyacetyl)morpholin-2-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488580: Inhibition of FGR (unknown origin)	ic50	0.0690	uM
Fedratinib	625011: Binding constant for FGR kinase domain	kd	0.0820	uM
3-(3,4-dimethoxyphenyl)-5-(1-methylpiperidin-4-yl)oxy-6-phenylpyrazolo[1,5-a]pyrimidin-7-amine	1648950: Inhibition of FGR (unknown origin) transfected in mouse Ba/F3 cells assessed as reduction in cell viability incubated for 48 hrs by brightglo-luciferase reporter gene assay	ic50	0.0980	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	1526212: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged FGR (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1010	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	1526212: Binding affinity to recombinant full-length N-terminal His-FLAG-tagged FGR (unknown origin) expressed in baculovirus infected Sf9 insect cells incubated for 1 hr by TR-FRET assay	kd	0.1190	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	625011: Binding constant for FGR kinase domain	kd	0.1200	uM
5-(1,3-benzodioxol-5-yl)-7-[[(2R)-1-ethenylsulfonylpyrrolidin-2-yl]methyl]pyrrolo[2,3-d]pyrimidin-4-amine	1488753: Inhibition of recombinant human N-terminal His6-tagged FGR (2 to end residues) expressed in baculovirus Sf21 insect cells preincubated for 5 mins followed by substrate addition after 30 to 60 mins in presence of ATP by fluorescence assay	ic50	0.1333	uM
N-[(2S,3R,4R,6R,18S)-18-hydroxy-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]-N-methylbenzamide	507950: Binding affinity to FGR	kd	0.1400	uM
Zanubrutinib	1615371: Inhibition of human FGR using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	ic50	0.1550	uM
2-(4-amino-1-propan-2-ylpyrazolo[3,4-d]pyrimidin-3-yl)-1H-indol-5-ol	625011: Binding constant for FGR kinase domain	kd	0.1600	uM
6-cyclopropyl-8-fluoro-2-[2-(hydroxymethyl)-3-[1-methyl-5-[[5-(4-methylpiperazin-1-yl)-2-pyridinyl]amino]-6-oxo-3-pyridinyl]phenyl]isoquinolin-1-one	1763492: Inhibition of human FGR	ic50	0.1800	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435798: Binding constant for FGR kinase domain	kd	0.1900	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	435798: Binding constant for FGR kinase domain	kd	0.1900	uM
4-[8-amino-3-[(3R)-1-(2-methylpropanoyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488580: Inhibition of FGR (unknown origin)	ic50	0.2030	uM
4-[[9-chloro-7-(2,6-difluorophenyl)-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	435798: Binding constant for FGR kinase domain	kd	0.2200	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	625011: Binding constant for FGR kinase domain	kd	0.2200	uM

CTD chemical–gene interactions

38 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Tretinoin	increases expression, increases reaction, affects cotreatment	5
sodium arsenite	decreases expression	2
Arsenic Trioxide	affects cotreatment, increases expression	2
Estradiol	affects binding, increases expression	2
N-Formylmethionine Leucyl-Phenylalanine	affects cotreatment, decreases reaction, increases activity, increases phosphorylation	2
Nickel	increases expression, decreases expression	2
Silicon Dioxide	increases expression	2
Cadmium Chloride	decreases expression, increases expression	2
triphenyl phosphate	affects expression	1
bisphenol A	affects cotreatment, decreases expression	1
dihydrocytochalasin B	affects cotreatment, decreases reaction, increases activity	1
aflatoxin B2	increases methylation	1
tamibarotene	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
abrine	increases expression	1
ponatinib	decreases activity	1
(+)-JQ1 compound	decreases expression	1
Dasatinib	affects binding	1
Rosiglitazone	increases expression	1
Acetaminophen	increases expression	1
Air Pollutants, Occupational	decreases expression	1
Aspirin	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Cisplatin	increases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Diethylstilbestrol	increases expression	1
Dust	increases expression	1
Endosulfan	decreases expression	1
Indomethacin	decreases expression, affects cotreatment	1
Phosphatidic Acids	increases activity	1

ChEMBL screening assays

358 unique, capped per target: 357 binding, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5719121	Binding	Inhibition of Src family in human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma. — Oncotarget
CHEMBL4414921	ADMET	Inhibition of human FGR using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. — J Med Chem

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A1U1	SEES3-1V human FGR, clone1	Embryonic stem cell	Male
CVCL_A1U2	SEES3-1V human FGR, clone2	Embryonic stem cell	Male
CVCL_A1U3	SEES3-1V human FGR, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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