FYN

Summary

FYN (FYN proto-oncogene, Src family tyrosine kinase, HGNC:4037) is a protein-coding gene on chromosome 6q21, encoding Tyrosine-protein kinase Fyn (P06241). Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance.

This gene is a member of the protein-tyrosine kinase oncogene family. It encodes a membrane-associated tyrosine kinase that has been implicated in the control of cell growth. The protein associates with the p85 subunit of phosphatidylinositol 3-kinase and interacts with the fyn-binding protein. Alternatively spliced transcript variants encoding distinct isoforms exist.

Source: NCBI Gene 2534 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 53 total — 3 pathogenic
• Druggable target: yes — 120 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_002037

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4037
Approved symbol	FYN
Name	FYN proto-oncogene, Src family tyrosine kinase
Location	6q21
Locus type	gene with protein product
Status	Approved
Aliases	SYN, SLK, MGC45350
Ensembl gene	ENSG00000010810
Ensembl biotype	protein_coding
OMIM	137025
Entrez	2534

Gene structure

Transcript identifiers

Ensembl transcripts: 82 — 72 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined

ENST00000229471, ENST00000354650, ENST00000368667, ENST00000368678, ENST00000368682, ENST00000462598, ENST00000462856, ENST00000467899, ENST00000467921, ENST00000471959, ENST00000476769, ENST00000484067, ENST00000487824, ENST00000491885, ENST00000495927, ENST00000495935, ENST00000496864, ENST00000517419, ENST00000518295, ENST00000518630, ENST00000520518, ENST00000521062, ENST00000521361, ENST00000523238, ENST00000523322, ENST00000523570, ENST00000523574, ENST00000524310, ENST00000905530, ENST00000905531, ENST00000905532, ENST00000905533, ENST00000905534, ENST00000905535, ENST00000905536, ENST00000905537, ENST00000905538, ENST00000905539, ENST00000905540, ENST00000905541, ENST00000905542, ENST00000905543, ENST00000905544, ENST00000905545, ENST00000905546, ENST00000905547, ENST00000905548, ENST00000905549, ENST00000905550, ENST00000905551, ENST00000905552, ENST00000912314, ENST00000912315, ENST00000912316, ENST00000912317, ENST00000912318, ENST00000912319, ENST00000912320, ENST00000912321, ENST00000912322, ENST00000912323, ENST00000912324, ENST00000912325, ENST00000912326, ENST00000912327, ENST00000966561, ENST00000966562, ENST00000966563, ENST00000966564, ENST00000966565, ENST00000966566, ENST00000966567, ENST00000966568, ENST00000966569, ENST00000966570, ENST00000966571, ENST00000966572, ENST00000966573, ENST00000966574, ENST00000966575, ENST00000966576, ENST00000966577

RefSeq mRNA: 4 — MANE Select: NM_002037 NM_001370529, NM_002037, NM_153047, NM_153048

CCDS: CCDS5094, CCDS5095, CCDS5096

Canonical transcript exons

ENST00000354650 — 14 exons

Exon	Start	End
ENSE00001344307	111780566	111780635
ENSE00001344310	111846589	111846629
ENSE00001880540	111696277	111696456
ENSE00001902078	111872968	111873452
ENSE00001939766	111660332	111661947
ENSE00003467096	111707922	111708020
ENSE00003472114	111700104	111700268
ENSE00003481156	111703999	111704102
ENSE00003497339	111719805	111720062
ENSE00003504910	111674499	111674630
ENSE00003528595	111714347	111714443
ENSE00003601706	111694375	111694528
ENSE00003674937	111694628	111694704
ENSE00003791523	111702885	111703034

Expression profiles

Bgee: expression breadth ubiquitous, 296 present calls, max score 99.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 69.6147 / max 1552.0119, expressed in 1753 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
75142	62.2897	1750
75141	2.6409	746
75117	0.9727	100
75132	0.5264	88
75123	0.5093	113
75143	0.3680	170
75137	0.3463	110
75122	0.3426	48
75134	0.2976	72
75131	0.2685	57

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.23	gold quality
corpus callosum	UBERON:0002336	98.92	gold quality
granulocyte	CL:0000094	98.89	gold quality
olfactory bulb	UBERON:0002264	98.87	gold quality
lymph node	UBERON:0000029	98.50	gold quality
cortical plate	UBERON:0005343	98.46	gold quality
cranial nerve II	UBERON:0000941	98.44	gold quality
right lung	UBERON:0002167	98.38	gold quality
ventricular zone	UBERON:0003053	98.37	gold quality
amygdala	UBERON:0001876	98.32	gold quality
leukocyte	CL:0000738	98.10	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	98.08	gold quality
mononuclear cell	CL:0000842	98.05	gold quality
monocyte	CL:0000576	98.04	gold quality
temporal lobe	UBERON:0001871	98.04	gold quality
nucleus accumbens	UBERON:0001882	97.97	gold quality
thymus	UBERON:0002370	97.96	gold quality
lateral globus pallidus	UBERON:0002476	97.91	gold quality
caudate nucleus	UBERON:0001873	97.88	gold quality
hypothalamus	UBERON:0001898	97.86	gold quality
prefrontal cortex	UBERON:0000451	97.85	gold quality
trigeminal ganglion	UBERON:0001675	97.85	gold quality
medulla oblongata	UBERON:0001896	97.84	gold quality
putamen	UBERON:0001874	97.81	gold quality
ventral tegmental area	UBERON:0002691	97.78	gold quality
entorhinal cortex	UBERON:0002728	97.74	gold quality
peripheral nervous system	UBERON:0000010	97.70	gold quality
tibial nerve	UBERON:0001323	97.70	gold quality
right frontal lobe	UBERON:0002810	97.66	gold quality
Ammon’s horn	UBERON:0001954	97.65	gold quality

Single-cell (SCXA)

Detected in 20 experiment(s), a significant marker in 15.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	3848.49
E-GEOD-131882	yes	2090.03
E-ANND-2	yes	1772.86
E-CURD-122	yes	60.34
E-CURD-46	yes	49.64
E-HCAD-1	yes	48.50
E-CURD-88	yes	46.90
E-GEOD-135922	yes	32.36
E-CURD-119	yes	29.41
E-MTAB-6678	yes	28.00
E-HCAD-9	yes	20.10
E-ANND-3	yes	19.68
E-MTAB-8271	yes	15.07
E-MTAB-8410	yes	8.85
E-MTAB-9067	yes	5.23

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EGR1, FLCN, SP1

Literature-anchored findings (GeneRIF, showing 40)

• Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling (PMID:11943772)
• Src-kinase p59(fyn) play a role in anergy induction in CD8+ T cells. (PMID:12368035)
• the distinct potential of Fyn and Lck to phosphorylate Sam68 is likely controlled by the interaction of the kinase SH3 domain with the linker and Sam68, possibly on a competitive binding basis. (PMID:12370810)
• identification of novel isoform fynDelta7, in which exon 7 is absent (PMID:12408980)
• The Fyn but not the Lck tyrosine kinase SH3 domain competes with CD2BP2 GYF-domain binding to the same CD2 proline-rich sequence in vitro. CD2BP2 is replaced by Fyn SH3 after CD2 is translocated into lipid rafts upon CD2 ectodomain clustering. (PMID:12426371)
• High expression of FYN is restricted to low-stage tumors and predicts long-term survival. In culture, expression of active Fyn kinase induces differentiation and growth arrest of neuroblastoma cells. (PMID:12450793)
• Data show that the SLAM-associated protein (SAP) SH2 domain binds to the SH3 domain of FynT and directly couples FynT to SLAM. (PMID:12545174)
• There was an increase in both total area Fyn mRNA signal (17.7%, P<0.05) and cellular mRNA content (15.7%, P<0.05) in schizophrenic brains relative to controls. (PMID:12670706)
• p250GAP is phosphorylated by Fyn in oligodendrocytes. (PMID:12788081)
• upon ligation of integrin beta6 with fibronectin, beta6 complexed with Fyn and activated it, activating a pathway leading to activation of the matrix metalloproteinase-3 gene, and promoting oral SCC cell proliferation and experimental metastasis in vivo (PMID:12917446)
• tr-kit promotes the formation of a multimolecular complex composed of Fyn, PLCgamma1 and Sam68, which allows phosphorylation of PLCgamma1 by Fyn, and may modulate RNA metabolism. (PMID:14647465)
• Two Src kinases are selectively activated by TPO signaling in primary megakaryocytes, Fyn and Lyn, but only Fyn expression is significantly upregulated during MK differentiation, suggesting variable gene regulation. (PMID:14662334)
• Our results indicate a possible association of alcohol dependence with a genotype of the SNP T137346C of the PTK fyn, with C being the risk allele. (PMID:14675807)
• Tyrosine phosphorylated tau is distributed in Alzheimer disease brain differently from other phosphorylated tau. Evidence of differentially phosphorylated tau within degenerating neurons was found supporting a role for fyn in neurodegeneration (PMID:14999081)
• LYN and FYN are downregulated by CBL in osteoblast differentiation induced by constitutive FGFR2 activation (PMID:15190072)
• activation of Fyn is inhibited by NSAIDs and constitutively active Fyn reverses the NSAID-dependent stress kinase inhibition (PMID:15514010)
• determined that Fyn phosphorylated MAP-2c on tyrosine 67 (PMID:15536091)
• Fyn kinase plays a key role in the UVB-induced phosphorylation of histone H3 at serine 10 (PMID:15537652)
• Alterations in Fyn localization might be associated with neurofibrillary pathology and synapse loss in Alzheimer’s disease. (PMID:15708437)
• PEDF downregulates Fyn through Fes, resulting in inhibition of FGF-2-induced capillary morphogenesis of endothelial cells (PMID:15713745)
• calcium activates PLC-gamma1 via increased PIP3 formation mediated by c-src- and fyn-activated PI3K (PMID:15872086)
• the Fyn-tau interaction has a role in neurodegeneration (PMID:16115884)
• independent of one another Fyn and MAP-2c are able to induce process outgrowth and in concert can initiate and enhance process outgrowth in an additive manner. (PMID:16145685)
• Increased Fyn expression is sufficient to trigger prominent neuronal deficits in FYN/human amyloid precursor protein transgenic mice in the context of even relatively moderate Abeta levels. (PMID:16237174)
• Cells with single Src family kinase knockdown show that Src, Fyn and Yes kinases are all required for vascular endothelial growth factor (VEGF) mitogenic signaling in retinal microvascular endothelial cells. (PMID:16400523)
• Fibronectin rigidity response involves force-dependent Fyn phosphorylation of p130Cas with rigidity-dependent displacement. (PMID:16597701)
• Fyn suppresses the GTPase-activating protein (GAP) activity of wild-type brain-enriched Rho GTPase-activating protein TCGAP but not the Y406F mutant of TCGAP in a phosphorylation-dependent manner. (PMID:16777849)
• Staurosporine binds to the ATP-binding site of Fyn in a similar manner as in the Lck- and Csk-complexes (PMID:16782058)
• These results indicate that Fyn is activated by G-protein-coupled receptor stimulation and is responsible for transactivation of TrkA receptors on intracellular membranes. (PMID:16860569)
• extracellular matrix fragments produced by apoptotic EC initiate a state of resistance to apoptosis in fibroblasts via an alpha2beta1 integrin/SFK (Src and Fyn)/phosphatidylinositol 3-kinase (PI3K)-dependent pathway (PMID:16882656)
• Glucocorticoids causes dissociation of T-cell receptor associated protein complex containing LCK and FYN. (PMID:16888650)
• TNF-alpha regulates the pulmonary vascular endothelial paracellular pathway, in part, through fyn activation. (PMID:16891393)
• The extra-domain B binding D3 protein opens new biomedical opportunities for the in vivo imaging of solid tumorsand for the delivery of toxic agents to the tumoral vasculature. (PMID:17130124)
• Polymorphisms of the Fyn gene is related to the function of glutamatergic system, and a performance on neuropsychological test of prefrontal cortex activity in schizophrenic patients. (PMID:17417065)
• the mechanism of signal transduction by CD244 is to regulate FYN kinase recruitment and/or activity and the outcome of CD48/CD244 interactions is determined by which other receptors are engaged. (PMID:17599905)
• Fyn is weakly phosphorylated in normal B cells, but strongly phosphorylated in myeloma B cells. (PMID:17701175)
• The results of this study may suggest a relationship between the FYN gene polymorphisms and allergic asthma (PMID:17703099)
• Chromosomal deletion, promoter hypermethylation and downregulation of FYN is associated with prostate cancer (PMID:17943724)
• engagement of the SH2 domain on PAG renders FynT insensitive to Csk negative regulation (PMID:18056706)
• Fyn, due in part to its effects on Dab1, regulates the phosphorylation, trafficking, and processing of APP and apoEr2. (PMID:18089558)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	fyna	ENSDARG00000011370
danio_rerio	fynb	ENSDARG00000025319
mus_musculus	Fyn	ENSMUSG00000019843
rattus_norvegicus	Fyn	ENSRNOG00000000596

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), 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 Fyn — P06241 (reviewed: P06241)

Alternative names: Proto-oncogene Syn, Proto-oncogene c-Fyn, Src-like kinase, p59-Fyn

All UniProt accessions (14): P06241, E5RFM0, E5RFM4, E5RFM6, E5RFS5, E5RGM6, E5RGT0, E5RH71, E5RHF7, E5RHX7, E5RI25, E5RIX5, E5RJX7, E5RK23

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that plays a role in many biological processes including regulation of cell growth and survival, cell adhesion, integrin-mediated signaling, cytoskeletal remodeling, cell motility, immune response and axon guidance. Inactive FYN is phosphorylated on its C-terminal tail within the catalytic domain. Following activation by PKA, the protein subsequently associates with PTK2/FAK1, allowing PTK2/FAK1 phosphorylation, activation and targeting to focal adhesions. Involved in the regulation of cell adhesion and motility through phosphorylation of CTNNB1 (beta-catenin) and CTNND1 (delta-catenin). Regulates cytoskeletal remodeling by phosphorylating several proteins including the actin regulator WAS and the microtubule-associated proteins MAP2 and MAPT. Promotes cell survival by phosphorylating AGAP2/PIKE-A and preventing its apoptotic cleavage. Participates in signal transduction pathways that regulate the integrity of the glomerular slit diaphragm (an essential part of the glomerular filter of the kidney) by phosphorylating several slit diaphragm components including NPHS1, KIRREL1 and TRPC6. Plays a role in neural processes by phosphorylating DPYSL2, a multifunctional adapter protein within the central nervous system, ARHGAP32, a regulator for Rho family GTPases implicated in various neural functions, and SNCA, a small pre-synaptic protein. Involved in reelin signaling by mediating phosphorylation of DAB1 following reelin (RELN)-binding to its receptor. Participates in the downstream signaling pathways that lead to T-cell differentiation and proliferation following T-cell receptor (TCR) stimulation. Phosphorylates PTK2B/PYK2 in response to T-cell receptor activation. Also participates in negative feedback regulation of TCR signaling through phosphorylation of PAG1 and PDCD1. Phosphorylation of PAG1 promotes interaction between PAG1 and CSK and recruitment of CSK to lipid rafts. Phosphorylation of PDCD1 leads to the recruitment of PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules. CSK maintains LCK and FYN in an inactive form. Promotes CD28-induced phosphorylation of VAV1. In mast cells, phosphorylates CLNK after activation of immunoglobulin epsilon receptor signaling. Can also promote CD244-mediated NK cell activation.

Subunit / interactions. Interacts (via its SH3 domain) with PIK3R1 and PRMT8. Interacts with FYB1, PAG1, and SH2D1A. Interacts with CD79A (tyrosine-phosphorylated form); the interaction increases FYN activity. Interacts (via SH2 domain) with CSF1R (tyrosine phosphorylated). Interacts with TOM1L1 (phosphorylated form). Interacts with KDR (tyrosine phosphorylated). Interacts (via SH3 domain) with KLHL2 (via N-terminus). Interacts with SH2D1A and SLAMF1. Interacts with ITCH; the interaction phosphorylates ITCH and negatively regulates its activity. Interacts with FASLG. Interacts with RUNX3. Interacts with KIT. Interacts with EPHA8; possible downstream effector of EPHA8 in regulation of cell adhesion. Interacts with PTK2/FAK1; this interaction leads to PTK2/FAK1 phosphorylation and activation. Interacts with CAV1; this interaction couples integrins to the Ras-ERK pathway. Interacts with UNC119. Interacts (via SH2 domain) with PTPRH (phosphorylated form). Interacts with PTPRO (phosphorylated form). Interacts with PTPRB (phosphorylated form). Interacts with FYB2. Interacts with DSCAM. Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK. Interacts with NEDD9; in the presence of PTK2. (Microbial infection) Interacts (via its SH3 domain) with hepatitis E virus/HEV protein ORF3.

Subcellular location. Cytoplasm. Nucleus. Cell membrane. Perikaryon.

Tissue specificity. Isoform 1 is highly expressed in the brain. Isoform 2 is expressed in cells of hemopoietic lineages, especially T-lymphocytes.

Post-translational modifications. Autophosphorylated at Tyr-420. Phosphorylation on the C-terminal tail at Tyr-531 by CSK maintains the enzyme in an inactive state. PTPRC/CD45 dephosphorylates Tyr-531 leading to activation. Ultraviolet B (UVB) strongly increase phosphorylation at Thr-12 and kinase activity, and promotes translocation from the cytoplasm to the nucleus. Dephosphorylation at Tyr-420 by PTPN2 negatively regulates T-cell receptor signaling. Phosphorylated at tyrosine residues, which can be enhanced by NTN1. Palmitoylated. Palmitoylation at Cys-3 and Cys-6, probably by ZDHHC21, regulates subcellular location.

Activity regulation. Inhibited by phosphorylation of Tyr-531 by leukocyte common antigen and activated by dephosphorylation of this site.

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

Isoforms (3)

UniProt ID	Names	Canonical?
P06241-1	1, B	yes
P06241-2	2, T
P06241-3	3

RefSeq proteins (4): NP_001357458, NP_002028, NP_694592, NP_694593 (=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
IPR035750	Fyn/Yrk_SH3	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR047924	Fyn/Yrk_SH2	Domain
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 (76 total): strand 25, helix 16, turn 9, modified residue 6, sequence variant 4, lipid moiety-binding region 3, domain 3, splice variant 2, sequence conflict 2, binding site 2, initiator methionine 1, chain 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

53 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
7A2P	X-RAY DIFFRACTION	0.9
7A2X	X-RAY DIFFRACTION	0.92
7A2O	X-RAY DIFFRACTION	0.94
7A2Q	X-RAY DIFFRACTION	0.94
7A2Y	X-RAY DIFFRACTION	0.97
7A2W	X-RAY DIFFRACTION	0.99
8KDX	X-RAY DIFFRACTION	1.01
7A2S	X-RAY DIFFRACTION	1.02
7A2R	X-RAY DIFFRACTION	1.05
7A2Z	X-RAY DIFFRACTION	1.14
7A2T	X-RAY DIFFRACTION	1.22
6IPY	X-RAY DIFFRACTION	1.34
4U1P	X-RAY DIFFRACTION	1.4
6EDF	X-RAY DIFFRACTION	1.4
7A2N	X-RAY DIFFRACTION	1.4
9GHK	X-RAY DIFFRACTION	1.42
3UA7	X-RAY DIFFRACTION	1.5
7A2J	X-RAY DIFFRACTION	1.5
7A2K	X-RAY DIFFRACTION	1.5
7A2M	X-RAY DIFFRACTION	1.5
6IPZ	X-RAY DIFFRACTION	1.58
4EIK	X-RAY DIFFRACTION	1.6
7A2U	X-RAY DIFFRACTION	1.7
3H0H	X-RAY DIFFRACTION	1.76
7A2V	X-RAY DIFFRACTION	1.81
3UA6	X-RAY DIFFRACTION	1.85
1SHF	X-RAY DIFFRACTION	1.9
7A2L	X-RAY DIFFRACTION	1.9
4U17	X-RAY DIFFRACTION	1.99
4ZNX	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P06241-F1	81.62	0.59

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): 390 (proton acceptor)

Ligand- & substrate-binding residues (2): 277–285; 299

Post-translational modifications (9): 21, 26, 185, 420, 531, 2, 3, 6, 12

Function

Pathways and Gene Ontology

Reactome pathways

45 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1227986	Signaling by ERBB2
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1433559	Regulation of KIT signaling
R-HSA-164944	Nef and signal transduction
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-2029481	FCGR activation
R-HSA-210990	PECAM1 interactions
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer
R-HSA-2424491	DAP12 signaling
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-373753	Nephrin family interactions
R-HSA-375165	NCAM signaling for neurite out-growth
R-HSA-389356	Co-stimulation by CD28
R-HSA-389357	CD28 dependent PI3K/Akt signaling
R-HSA-389359	CD28 dependent Vav1 pathway
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928664	Ephrin signaling
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
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
R-HSA-4420097	VEGFA-VEGFR2 Pathway
R-HSA-5621480	Dectin-2 family
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5673001	RAF/MAP kinase cascade

MSigDB gene sets: 1113 (showing top): GOBP_REGULATION_OF_T_CELL_RECEPTOR_SIGNALING_PATHWAY, GOBP_DENDRITE_DEVELOPMENT, GOBP_REGULATION_OF_CELL_ACTIVATION, RNGTGGGC_UNKNOWN, GOBP_REGULATION_OF_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_RESPONSE_TO_ETHANOL, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_CYTOPLASMIC_MICROTUBULE_ORGANIZATION, WALLACE_PROSTATE_CANCER_RACE_UP, REACTOME_INNATE_IMMUNE_SYSTEM, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE_TO_ANTIGENIC_STIMULUS, GOBP_COGNITION, GOBP_BEHAVIOR, GOBP_REGULATION_OF_CELL_MORPHOGENESIS

GO Biological Process (70): response to singlet oxygen (GO:0000304), neuron migration (GO:0001764), stimulatory C-type lectin receptor signaling pathway (GO:0002223), adaptive immune response (GO:0002250), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), heart process (GO:0003015), calcium ion transport (GO:0006816), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), G protein-coupled glutamate receptor signaling pathway (GO:0007216), axon guidance (GO:0007411), learning (GO:0007612), feeding behavior (GO:0007631), regulation of cell shape (GO:0008360), response to xenobiotic stimulus (GO:0009410), gene expression (GO:0010467), negative regulation of gene expression (GO:0010629), negative regulation of hydrogen peroxide biosynthetic process (GO:0010730), positive regulation of neuron projection development (GO:0010976), negative regulation of angiogenesis (GO:0016525), protein ubiquitination (GO:0016567), peptidyl-tyrosine phosphorylation (GO:0018108), natural killer cell activation (GO:0030101), cell differentiation (GO:0030154), protein catabolic process (GO:0030163), forebrain development (GO:0030900), T cell costimulation (GO:0031295), negative regulation of protein ubiquitination (GO:0031397), intracellular signal transduction (GO:0035556), cellular response to platelet-derived growth factor stimulus (GO:0036120), reelin-mediated signaling pathway (GO:0038026), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), negative regulation of protein catabolic process (GO:0042177), response to cocaine (GO:0042220), negative regulation of neuron apoptotic process (GO:0043524), response to ethanol (GO:0045471), vascular endothelial growth factor receptor signaling pathway (GO:0048010), ephrin receptor signaling pathway (GO:0048013), dendrite morphogenesis (GO:0048813), activated T cell proliferation (GO:0050798), modulation of chemical synaptic transmission (GO:0050804)

GO Molecular Function (31): G protein-coupled receptor binding (GO:0001664), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), phospholipase activator activity (GO:0016004), enzyme binding (GO:0019899), type 5 metabotropic glutamate receptor binding (GO:0031802), T cell receptor binding (GO:0042608), CD4 receptor binding (GO:0042609), CD8 receptor binding (GO:0042610), identical protein binding (GO:0042802), alpha-tubulin binding (GO:0043014), phospholipase binding (GO:0043274), phosphatidylinositol 3-kinase binding (GO:0043548), transmembrane transporter binding (GO:0044325), metal ion binding (GO:0046872), ephrin receptor binding (GO:0046875), tau protein binding (GO:0048156), tau-protein kinase activity (GO:0050321), peptide hormone receptor binding (GO:0051428), growth factor receptor binding (GO:0070851), scaffold protein binding (GO:0097110), disordered domain specific binding (GO:0097718), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), tubulin binding (GO:0015631), kinase activity (GO:0016301), transferase activity (GO:0016740), protein-containing complex binding (GO:0044877)

GO Cellular Component (20): nucleus (GO:0005634), mitochondrion (GO:0005739), endosome (GO:0005768), cytosol (GO:0005829), actin filament (GO:0005884), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), dendrite (GO:0030425), perikaryon (GO:0043204), cell body (GO:0044297), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), perinuclear endoplasmic reticulum (GO:0097038), glial cell projection (GO:0097386), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), postsynaptic density, intracellular component (GO:0099092), cytoplasm (GO:0005737), membrane (GO:0016020), cell periphery (GO:0071944)

Reactome top-level categories

Rollup of top-16 pathways:

Category	Pathways
Signaling by Receptor Tyrosine Kinases	2
Axon guidance	2
Regulation of T cell activation by CD28 family	2
Co-stimulation by CD28	2
Platelet activation, signaling and aggregation	1
Intracellular signaling by second messengers	1
Signaling by SCF-KIT	1
The role of Nef in HIV-1 replication and disease pathogenesis	1
Hemostasis	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
PI3K/AKT Signaling in Cancer	1
DAP12 interactions	1
Fc epsilon receptor (FCERI) signaling	1
Cell-Cell communication	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	8
signaling receptor binding	5
protein binding	5
cytoplasm	3
intracellular membrane-bounded organelle	2
synapse	2
response to reactive oxygen species	1
cell migration	1
generation of neurons	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
immune response	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
circulatory system process	1
metal ion transport	1
enzyme-linked receptor protein signaling pathway	1
G protein-coupled receptor signaling pathway	1
glutamate receptor signaling pathway	1
G protein-coupled glutamate receptor activity	1
axonogenesis	1
neuron projection guidance	1
learning or memory	1
behavior	1
regulation of cell morphogenesis	1
regulation of biological quality	1
response to chemical	1
macromolecule biosynthetic process	1
gene expression	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
negative regulation of hydrogen peroxide metabolic process	1
regulation of hydrogen peroxide biosynthetic process	1
hydrogen peroxide biosynthetic process	1
negative regulation of reactive oxygen species biosynthetic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1

Protein interactions and networks

STRING

5014 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FYN	DLG4	P78352	992
FYN	LCP2	Q13094	981
FYN	LCK	P06239	981
FYN	GRIN2B	Q13224	981
FYN	CD4	P01730	978
FYN	LYN	P07948	965
FYN	GRB2	P29354	964
FYN	CBL	P22681	961
FYN	CD8A	P01732	960
FYN	MAPT	P10636	958
FYN	CD36	P16671	958
FYN	SYK	P43405	957
FYN	PTK2	Q05397	956
FYN	CAV1	Q03135	944
FYN	SCARB2	Q14108	942

IntAct

596 interactions, top by confidence:

A	B	Type	Score
FYN	FYB1	psi-mi:“MI:0915”(physical association)	0.820
FYN	BCAR1	psi-mi:“MI:0915”(physical association)	0.780
MED28	FYN	psi-mi:“MI:0915”(physical association)	0.740
FYN	MED28	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
FYN	MED28	psi-mi:“MI:0915”(physical association)	0.740
PRKCD	FYN	psi-mi:“MI:0915”(physical association)	0.740
PRKCD	FYN	psi-mi:“MI:0217”(phosphorylation reaction)	0.740
FYN	FYN	psi-mi:“MI:0217”(phosphorylation reaction)	0.720
FYN	ASAP1	psi-mi:“MI:0915”(physical association)	0.700
MED28	LCK	psi-mi:“MI:0914”(association)	0.690
EFS	FYN	psi-mi:“MI:0915”(physical association)	0.670
PRKCQ	FYN	psi-mi:“MI:0915”(physical association)	0.660
FYN	PRKCQ	psi-mi:“MI:0915”(physical association)	0.660
PRKCQ	FYN	psi-mi:“MI:0217”(phosphorylation reaction)	0.660
FYN	HTR6	psi-mi:“MI:0915”(physical association)	0.630
HTR6	FYN	psi-mi:“MI:0915”(physical association)	0.630
HTR6	FYN	psi-mi:“MI:0407”(direct interaction)	0.630

BioGRID (614): MAPT (Reconstituted Complex), MAPT (Biochemical Activity), FYN (Affinity Capture-Western), EFS (Two-hybrid), WBP11 (Two-hybrid), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Affinity Capture-MS), FYN (Two-hybrid), FYN (Two-hybrid)

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: A0A8I3NFE2, A0FI79, A0JNB0, A1Y2K1, A6QLK6, B2RZ59, B5KFD7, D3ZGS3, D7PF45, F1RDG9, G5ECJ6, O14306, O14796, O15357, O35324, O60880, O88890, O88900, P00519, P00520, P00521, P00522, P03949, P06239, P06241, P09851, P0CE43, P10447, P17713, P20936, P29350, P29351, P32019, P34370, P39688, P42684, P42685, P42686, P50904, P53356

SIGNOR signaling

149 interactions.

A	Effect	B	Mechanism
DOK4	up-regulates	FYN	binding
FYN	“down-regulates activity”	CAV1	phosphorylation
FYN	up-regulates	ITPR1	phosphorylation
FYN	down-regulates	MAPT	phosphorylation
FYN	“down-regulates activity”	H3-3A	phosphorylation
FYN	up-regulates	MAPK14	phosphorylation
FYN	down-regulates	SCN5A	phosphorylation
FYN	down-regulates	ARHGAP33	phosphorylation
FYN	up-regulates	AGAP2	phosphorylation
FYN	up-regulates	MED28	phosphorylation
FYN	up-regulates	LAT	phosphorylation
PTPRA	up-regulates	FYN	dephosphorylation
FYN	down-regulates	CHN2	phosphorylation
FYN	up-regulates	RPS6KA3	phosphorylation
PRKACA	up-regulates	FYN	phosphorylation
FYN	up-regulates	FYN	phosphorylation
PTPN2	down-regulates	FYN	dephosphorylation
SMO	up-regulates	FYN	phosphorylation
FYN	up-regulates	DLG4	phosphorylation
FYN	up-regulates	GRIN2A	phosphorylation
PTPRC	“up-regulates activity”	FYN	dephosphorylation
FYN	“up-regulates activity”	CDK5	phosphorylation
FYN	unknown	CTLA4	phosphorylation
FYN	“up-regulates quantity by stabilization”	CTLA4	phosphorylation
FYN	“up-regulates activity”	FYB1	phosphorylation
FYN	unknown	GRIN2B	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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
GPVI-mediated activation cascade	5	12.4×	5e-03
Fcgamma receptor (FCGR) dependent phagocytosis	5	11.2×	6e-03
FCGR3A-mediated phagocytosis	6	9.1×	5e-03
Regulation of actin dynamics for phagocytic cup formation	6	8.9×	5e-03
RHOG GTPase cycle	7	8.4×	4e-03
RAC2 GTPase cycle	7	7.2×	5e-03
RAC3 GTPase cycle	7	6.7×	6e-03
RAC1 GTPase cycle	13	6.4×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
integrin-mediated signaling pathway	8	8.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	17
Likely benign	3
Benign	6

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2681288	NM_002037.5(FYN):c.286C>G (p.Arg96Gly)	Pathogenic
2681289	NM_002037.5(FYN):c.286C>T (p.Arg96Trp)	Pathogenic
2681290	NM_002037.5(FYN):c.289A>G (p.Thr97Ala)	Pathogenic

SpliceAI

4120 predictions. Top by Δscore:

Variant	Effect	Δscore
6:111661943:CATGC:C	acceptor_gain	1.0000
6:111661945:TGC:T	acceptor_gain	1.0000
6:111661945:TGCC:T	acceptor_loss	1.0000
6:111661946:GCCT:G	acceptor_loss	1.0000
6:111661947:CCT:C	acceptor_loss	1.0000
6:111661948:C:CC	acceptor_gain	1.0000
6:111661948:CT:C	acceptor_loss	1.0000
6:111694372:CAC:C	donor_loss	1.0000
6:111694373:A:AT	donor_loss	1.0000
6:111694374:C:CA	donor_loss	1.0000
6:111694394:A:AC	donor_gain	1.0000
6:111694394:ATTGT:A	donor_gain	1.0000
6:111694524:GCCAC:G	acceptor_gain	1.0000
6:111694525:CCAC:C	acceptor_gain	1.0000
6:111694525:CCACC:C	acceptor_gain	1.0000
6:111694526:CAC:C	acceptor_gain	1.0000
6:111694526:CACC:C	acceptor_gain	1.0000
6:111694527:AC:A	acceptor_gain	1.0000
6:111694527:ACCT:A	acceptor_loss	1.0000
6:111694528:CC:C	acceptor_gain	1.0000
6:111694528:CCT:C	acceptor_loss	1.0000
6:111694529:C:CC	acceptor_gain	1.0000
6:111694529:C:CG	acceptor_loss	1.0000
6:111694530:T:G	acceptor_loss	1.0000
6:111694540:C:CT	acceptor_gain	1.0000
6:111694540:C:T	acceptor_gain	1.0000
6:111694624:CTAC:C	donor_loss	1.0000
6:111694625:TACC:T	donor_loss	1.0000
6:111694626:A:C	donor_loss	1.0000
6:111694701:CTTC:C	acceptor_gain	1.0000

AlphaMissense

3503 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:111661761:T:C	Y531C	1.000
6:111661762:A:G	Y531H	1.000
6:111661794:A:G	L520P	1.000
6:111661814:A:C	F513L	1.000
6:111661814:A:T	F513L	1.000
6:111661816:A:G	F513L	1.000
6:111661825:G:T	R510S	1.000
6:111661846:A:G	W503R	1.000
6:111661846:A:T	W503R	1.000
6:111661847:G:C	C502W	1.000
6:111661926:A:G	L476P	1.000
6:111674505:A:C	Y467D	1.000
6:111674505:A:G	Y467H	1.000
6:111674505:A:T	Y467N	1.000
6:111674507:G:C	P466R	1.000
6:111674507:G:T	P466Q	1.000
6:111674508:G:A	P466S	1.000
6:111674508:G:T	P466T	1.000
6:111674516:C:A	G463V	1.000
6:111674516:C:T	G463E	1.000
6:111674517:C:G	G463R	1.000
6:111674517:C:T	G463R	1.000
6:111674528:A:G	L459P	1.000
6:111674532:C:T	E458K	1.000
6:111674537:A:G	L456P	1.000
6:111674546:C:A	G453V	1.000
6:111674546:C:T	G453E	1.000
6:111674547:C:G	G453R	1.000
6:111674547:C:T	G453R	1.000
6:111674552:G:A	S451F	1.000

dbSNP variants (sampled 300 via entrez): RS1000012633 (6:111842872 G>A), RS1000028804 (6:111776554 A>C,T), RS1000056912 (6:111734012 G>A), RS1000058165 (6:111776149 T>C), RS1000066242 (6:111716903 G>A), RS1000075407 (6:111693490 T>C), RS1000084536 (6:111731528 C>G), RS1000087630 (6:111675808 A>G), RS1000097173 (6:111717198 T>C), RS1000163911 (6:111682083 G>A,C), RS1000188036 (6:111703607 A>C,G), RS1000217188 (6:111698538 T>C), RS1000231620 (6:111845800 A>T), RS1000250486 (6:111699852 T>C), RS1000259175 (6:111682330 A>G)

Disease associations

OMIM: gene MIM:137025 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001725_23	Inflammatory bowel disease	1.000000e-13
GCST002324_4	Anger	3.000000e-08
GCST002337_38	Amyotrophic lateral sclerosis (sporadic)	3.000000e-06
GCST004131_98	Inflammatory bowel disease	4.000000e-10
GCST004133_60	Ulcerative colitis	6.000000e-10
GCST004946_216	Schizophrenia	5.000000e-08
GCST005580_245	Intraocular pressure	7.000000e-16
GCST005580_32	Intraocular pressure	3.000000e-13
GCST006976_97	Macular thickness	9.000000e-09
GCST007201_9	Schizophrenia	8.000000e-09
GCST007267_187	Systolic blood pressure	4.000000e-09
GCST008103_102	Bipolar disorder	3.000000e-06
GCST008839_367	Height	4.000000e-08
GCST009325_41	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2.000000e-09
GCST009548_2	NASH resolution in nonalcoholic steatohepatitis	9.000000e-07
GCST010049_6	Parkinson’s disease	3.000000e-08
GCST010571_35	Autoimmune thyroid disease	8.000000e-10
GCST010796_4591	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4592	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4593	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_4594	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4595	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4596	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-10
GCST010991_23	Parkinson’s disease	2.000000e-07

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0003015	aggressive behavior
EFO:0004695	intraocular pressure measurement
EFO:0006335	systolic blood pressure
EFO:0009785	remission
EFO:0004327	electrocardiography

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL1841 (SINGLE PROTEIN), CHEMBL2363074 (PROTEIN FAMILY), CHEMBL6066563 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

120 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 813,521 (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
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL104	CLOTRIMAZOLE	4	56,325
CHEMBL11359	CISPLATIN	4
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1200528	CHROMIC CHLORIDE	4
CHEMBL1200679	ZINC CHLORIDE	4	411,454
CHEMBL1200748	CARBIDOPA	4	354
CHEMBL1201469	GRAMICIDIN	4
CHEMBL1221	SULCONAZOLE	4	12,121
CHEMBL1276308	MIFEPRISTONE	4	30,535
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1366	AURANOFIN	4
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1714574	TERCONAZOLE	4	21
CHEMBL17157	TERFENADINE	4	25,393
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4
CHEMBL2028663	DABRAFENIB	4
CHEMBL2103743	TOFACITINIB CITRATE	4
CHEMBL221959	TOFACITINIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL255863	NILOTINIB	4
CHEMBL288441	BOSUTINIB	4
CHEMBL296419	ASTEMIZOLE	4
CHEMBL305660	EBASTINE	4
CHEMBL3545311	BRIGATINIB	4

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

PharmGKB variants

2 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs706895	FYN		0.00	0
rs3730353	FYN		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (9 total), top 9:

Ligand	Action	Affinity	Parameter
compound 2 [PMID: 15546730]	Inhibition	9.0	pIC50
bosutinib	Inhibition	8.74	pIC50
eCF506	Inhibition	8.68	pIC50
PP2	Inhibition	8.3	pIC50
PP1	Inhibition	8.22	pIC50
ibrutinib	Inhibition	7.54	pIC50
pexmetinib	Inhibition	7.39	pIC50
compound 25 [PMID: 31260299]	Inhibition	6.78	pIC50
acalabrutinib	Inhibition	6.0	pEC50

Binding affinities (BindingDB)

79 measured of 237 human assays (267 total across all organisms); most potent 50 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-(3-(2-(5-((6-cyano-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-fluorophenyl)-4-((dimethylamino) methyl)-3-(trifluoromethyl)benzamide	IC50	1 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
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
N-(3-(5-(3-cyclopentylureido)-2-methylphenethyl)-1H-pyrazol-5-yl)-4-(4-methylpiperazin-1-yl)benzamide	IC50	2 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(5-((6-cyano-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-methylphenyl)-8-azaspiro [4.5] decane-8-carboxamide	IC50	2 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
N-(3-(5-(3-(4,4-dimethylcyclohexyl)ureido)-2-methylphenethyl)-1H-pyrazol-5-yl)-4-(1-methylpiperidin-4-yl)benzamide	IC50	3 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(5-((2-(2-hydroxyethyl)-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)amino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	4 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
3,3-diethyl-N-(4-methyl-3-(2-(5-((3-methylpyrazin-2-yl)amino)-1H-pyrazol-3-yl)ethyl)phenyl)pyrrolidine-1-carboxamide	IC50	5 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(5-(3-(4,4-dimethylcyclohexyl)ureido)-2-methylphenethyl)-1H-pyrazol-5-yl)-4-((1-isopropylazetidin-3-yl)oxy)benzamide	IC50	5 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
1-tert-butyl-3-(4-methylphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine	IC50	6 nM
2-(2-hydroxypropan-2-yl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)isonicotinamide	IC50	6 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(3-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl) benzamide	IC50	6 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(5-((2-acetyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-methylphenyl)-3-(trifluoromethyl) benzamide	IC50	6 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
3,3-diethyl-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)pyrrolidine-1-carboxamide	IC50	7 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(5-((2-ethyl-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-methylphenyl) -3-(trifluoromethyl)benzamide	IC50	8 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
4-(2-cyanopropan-2-yl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)picolinamide	IC50	8 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(2-fluoro-5-(2-(3-((6-(4-(2-hydroxyethyl)piperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl) ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	8 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
(4-chlorophenyl) N-(2-phenylethyl)carbamate	IC50	8 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
(S)-N-(3-(2-(3-((6-(3-(dimethylamino)pyrrolidin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)-4-fluorophenyl)-3-(trifluoromethyl)benzamide	IC50	9 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
2-(2-cyanopropan-2-yl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)isonicotinamide	IC50	10 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(3-((6-(((2S,6R)-2,6-dimethylmorpholino)methyl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)-4-fluorophenyl)-3-(trifluoromethyl)benzamide	IC50	10 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(3-((6-(3-hydroxyazetidin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	10 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
1-(1,2-oxazol-5-yl)-3-phenylurea	IC50	10 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
3-[(4-bromo-2,6-difluorophenyl)methoxy]-5-({[4-(pyrrolidin-1-yl)butyl]carbamoyl}amino)-1,2-thiazole-4-carboxamide	IC50	10.1 nM	US-9446026: Ocular formulations for drug-delivery to the posterior segment of the eye
N-(4-fluoro-3-(2-(3-((2-methyl-6-(morpholinomethyl)pyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	12 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(3-((6-(1-(2-hydroxyethyl)-1H-pyrazol-4-yl)-2-methylpyrimidin-4-yl) amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	13 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(5-(2-methyl-5-(3-(trifluoromethyl)benzamido)phenethyl)-1H-pyrazol-3-yl)picolinamide	IC50	15 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(3-((6-(4-ethylpiperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)-4-fluorophenyl)-3-(trifluoromethyl)benzamide	IC50	15 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-fluoro-5-(6-isobutylnicotinamido)phenethyl)-1H-pyrazol-5-yl)pyrimidine-2-carboxamide	IC50	16 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
3-(difluoromethyl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl) benzamide	IC50	16 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(3-((2-methyl-6-(pyrrolidin-1-ylmethyl)pyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	17 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-[3-[2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	18 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
N-(4-fluoro-3-(2-(5-((3-methylpyrazin-2-yl)amino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	18 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-methyl-3-(2-(5-((3-methylpyrazin-2-yl)amino)-1H-pyrazol-3-yl)ethyl)phenyl)-6-azaspiro[3.4]octane-6-carboxamide	IC50	18 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(2-fluoro-5-(2-(3-((6-(3-hydroxyazetidin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	18 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(2-fluoro-5-(2-(5-((2-methyl-6-morpholinopyrimidin-4-yl)amino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	19 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
4-(cyclopropylsulfonyl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)picolinamide	IC50	20 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
4-(1-(ethylamino)cyclopropyl)-N-(4-methyl-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)benzamide	IC50	21 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
2-(2-cyanopropan-2-yl)-N-(4-fluoro-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)isonicotinamide	IC50	21 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(5-(2-(3-((6-(4-ethylpiperazin-1-yl)-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-5-yl)ethyl)-2-fluorophenyl)-3-(trifluoromethyl) benzamide	IC50	22 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(methylsulfonyl)benzamide	IC50	24 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-chloro-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(trifluoromethyl)benzamide	IC50	24 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(5-((6-cyano-2-methylpyrimidin-4-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-methylphenyl)-3-(N,N-dimethylsulfamoyl)benzamide	IC50	24 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(4-fluoro-3-(2-(5-(pyrazin-2-ylamino)-1H-pyrazol-3-yl)ethyl)phenyl)-3-(trifluoromethyl) benzamide	IC50	26 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
BMS-354825	KD	27 nM
4-chloro-N-(2-thiophen-2-ylethyl)benzamide	IC50	27 nM	US-12509446: FYN and VEGFR2 kinase inhibitors
N-(3-(2-(5-((3,5-dimethylpyrazin-2-yl)amino)-1H-pyrazol-3-yl)ethyl)-4-fluorophenyl)-3-(trifluoromethyl)benzamide	IC50	31 nM	US-12509446: FYN and VEGFR2 kinase inhibitors

ChEMBL bioactivities

1972 potent at pChembl≥5 of 2151 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.70	IC50	0.2	nM	DASATINIB
9.52	IC50	0.3	nM	CHEMBL45177
9.50	Ki	0.3162	nM	CHEMBL1969102
9.44	IC50	0.36	nM	PONATINIB
9.40	Kd	0.4	nM	CHEMBL249097
9.40	Ki	0.3981	nM	CHEMBL1994938
9.20	Ki	0.631	nM	CHEMBL1982476
9.10	Kd	0.8	nM	DASATINIB
9.10	Kd	0.79	nM	DASATINIB
9.00	IC50	1	nM	CHEMBL364623
9.00	IC50	1	nM	CHEMBL515414
9.00	IC50	1	nM	CHEMBL285063
9.00	Ki	1	nM	CHEMBL1970879
8.96	Ki	1.1	nM	CHEMBL432189
8.96	IC50	1.1	nM	STAUROSPORINE
8.90	Ki	1.259	nM	CHEMBL1976376
8.86	IC50	1.38	nM	STAUROSPORINE
8.80	IC50	1.6	nM	DASATINIB
8.80	Ki	1.585	nM	PD-0166285
8.74	IC50	1.8	nM	BOSUTINIB
8.70	IC50	2	nM	CHEMBL3335371
8.70	IC50	2	nM	STAUROSPORINE
8.70	Ki	1.995	nM	CHEMBL1993243
8.69	IC50	2.06	nM	STAUROSPORINE
8.68	IC50	2.1	nM	CHEMBL3824089
8.66	IC50	2.17	nM	CHEMBL1997924
8.62	Ki	2.4	nM	CHEMBL312933
8.60	Ki	2.512	nM	CHEMBL1999749
8.57	IC50	2.68	nM	DASATINIB
8.52	IC50	3	nM	CHEMBL272888
8.52	IC50	3	nM	CHEMBL4787515
8.52	IC50	3	nM	CHEMBL1221769
8.50	Ki	3.162	nM	CHEMBL1996979
8.43	Kd	3.715	nM	DASATINIB ANHYDROUS
8.40	IC50	4	nM	CHEMBL88009
8.40	Kd	4	nM	DASATINIB
8.40	Kd	4	nM	DASATINIB ANHYDROUS
8.40	Ki	3.981	nM	CHEMBL1989267
8.36	IC50	4.4	nM	STAUROSPORINE
8.31	Kd	4.9	nM	CHEMBL386051
8.30	IC50	5	nM	CHEMBL3426225
8.30	IC50	5	nM	CHEMBL470808
8.30	Kd	5	nM	CHEMBL3991931
8.30	IC50	5	nM	STAUROSPORINE
8.30	IC50	5	nM	CHEMBL406845
8.30	IC50	5	nM	CHEMBL1163016
8.30	IC50	5	nM	CHEMBL1221699
8.30	Ki	5.012	nM	CHEMBL1982466
8.30	Ki	5.012	nM	CHEMBL508928
8.22	IC50	6	nM	CHEMBL4798527

PubChem BioAssay actives

340 with measured affinity, of 1914 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-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	271967: Inhibition of Fyn	ic50	0.0002	uM
7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1407822: Inhibition of Fyn (unknown origin) using Src-family kinase bisamide rhodamine 110 peptide substrate after 1 hr by fluorescence assay	ic50	0.0003	uM
Ponatinib	1716399: Binding affinity to human FYN using poly[Glu:Tyr] (4:1) as substrate by radiometric hotspot kinase assay	ic50	0.0004	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389066: Binding affinity to human FYN	kd	0.0004	uM
1-tert-butyl-3-(4-chlorophenyl)pyrazolo[3,4-d]pyrimidin-4-amine	1803322: In Vitor Src Tyrosine Kinase Activity Assay from Article 10.3109/14756366.2012.715288: “Synthesis, biological evaluation and docking studies of new pyrrolo[2,3-d] pyrimidine derivatives as Src family-selective tyrosine kinase inhibitors.”	ic50	0.0005	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	240651: inhibitory activity against Fyn protein kinase	ic50	0.0010	uM
N-[4-(3-bromoanilino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0010	uM
1-[4-amino-7-(3-hydroxypropyl)-5-(4-methylphenyl)pyrrolo[2,3-d]pyrimidin-6-yl]-2-fluoroethanone	394244: Inhibition of FYN Val285Cys mutant expressed in Escherichia coli	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	1715337: Inhibition of human FYN using poly[Glu:Tyr] (4:1) as substrate by [gamma-33P]-ATP assay	ic50	0.0011	uM
N-(2-chloro-6-methylphenyl)-2-[[6-methyl-2-(oxolan-2-ylmethylamino)pyrimidin-4-yl]amino]-1,3-benzothiazole-6-carboxamide	72282: Inhibition of Fyn protein kinase	ki	0.0011	uM
Bosutinib	507435: Inhibition of FYN	ic50	0.0018	uM
N-[4-[2-(3-tert-butylanilino)-1-methylbenzimidazol-5-yl]oxy-2-pyridinyl]acetamide	1255121: Inhibition of FYN (unknown origin)	ic50	0.0020	uM
tert-butyl N-[4-[4-amino-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-3-yl]-2-methoxyphenyl]carbamate	1310126: Inhibition of human FYN using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P]ATP	ic50	0.0021	uM
2-N-benzyl-4-N-(5-cyclopropyl-1H-pyrazol-3-yl)thieno[3,2-d]pyrimidine-2,4-diamine	1899931: Inhibition of human Fyn using Cdc2 peptide as substrate incubated for 40 mins in presence of [gamma-33P]-ATP by radiometric scintillation assay	ic50	0.0022	uM
N-(2-chloro-6-methylphenyl)-2-[[6-(2-hydroxyethylamino)-2-pyridinyl]amino]-1,3-benzothiazole-6-carboxamide	72282: Inhibition of Fyn protein kinase	ki	0.0024	uM
N-[4-(naphthalen-2-ylamino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0030	uM
2-methyl-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	326715: Inhibition of Fyn by HTRF assay	ic50	0.0030	uM
Dasatinib	2148406: Binding affinity to human FYN incubated for 45 mins by Kinobead based pull down assay	kd	0.0037	uM
N-(2-chloro-6-methylphenyl)-2-[[2-(2-hydroxyethylamino)-6-methylpyrimidin-4-yl]amino]-1,3-benzothiazole-6-carboxamide	72277: Inhibition of Fyn protein kinase	ic50	0.0040	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624727: Binding constant for FYN kinase domain	kd	0.0049	uM
N-(4-anilinoquinazolin-6-yl)prop-2-enamide	502963: Inhibition of Fyn S349C mutant in expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0050	uM
3-[2-(4-amino-1-ethylpyrazolo[3,4-d]pyrimidin-3-yl)ethynyl]-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	1206222: Inhibition of human Fyn	ic50	0.0050	uM
4-[2-(3-tert-butylanilino)-1-methylbenzimidazol-5-yl]oxy-N-methylpyridine-2-carboxamide	1255121: Inhibition of FYN (unknown origin)	ic50	0.0050	uM
46179972	446589: Inhibition of Fyn	ic50	0.0050	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1425008: 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	0.0050	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734746: Inhibition of human full length recombinant FYN using Cdc2 peptide as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0060	uM
1-tert-butyl-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-4-amine	1799456: Inhibition Assay from Article 10.1016/s1074-5521(99)80118-5: “Structural basis for selective inhibition of Src family kinases by PP1.”	ic50	0.0060	uM
N-[3-[2-[4-(4-ethylpiperazin-1-yl)anilino]thieno[3,2-d]pyrimidin-7-yl]phenyl]methanesulfonamide	1779449: Inhibition of Fyn (unknown origin)	ic50	0.0077	uM
N-(2-chloro-6-methylphenyl)-2-[[6-(methylamino)pyrimidin-4-yl]amino]-1,3-benzothiazole-6-carboxamide	72282: Inhibition of Fyn protein kinase	ki	0.0088	uM
N,N-dicyclopropyl-7-[(4,5-dimethyl-1,3-thiazol-2-yl)amino]-10-ethyl-3-methyl-3,5,8,10-tetrazatricyclo[7.3.0.02,6]dodeca-1,4,6,8,11-pentaene-11-carboxamide	1249773: Inhibition of recombinant Fyn (unknown origin) using fluoresceinated peptide as substrate after 60 mins by HTRF assay	ic50	0.0100	uM
8-cyclopentyl-2-[4-(4-methylpiperazin-1-yl)anilino]-7-oxopyrido[2,3-d]pyrimidine-6-carbonitrile	1845570: Inhibition of FYN (unknown origin)	ic50	0.0110	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168208: Inhibition of human wild type FYN 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	0.0120	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	1721753: Inhibition of FYN (unknown origin)	ic50	0.0180	uM
N-[4-(4-bromoanilino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0190	uM
7-(2,6-dimethylphenyl)-5-methyl-N-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1,2,4-benzotriazin-3-amine	276186: Inhibition of Fyn	ic50	0.0230	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1425008: 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	0.0230	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	1425008: 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	0.0240	uM
N-[4-(4-tert-butylanilino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0240	uM
4-[(4-methyl-1H-indol-5-yl)amino]-2-[(E)-3-oxo-3-pyrrolidin-1-ylprop-1-enyl]thieno[2,3-b]pyridine-5-carbonitrile	341659: Inhibition of FYN	ic50	0.0250	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	2167985: Inhibition of human FYN assessed as inhibition constant in presence of ATP	ki	0.0260	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	624727: Binding constant for FYN kinase domain	kd	0.0280	uM
2-[(6-hydroxy-6-methylheptan-2-yl)amino]-4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyridine-3-carbonitrile;hydrochloride	598156: Inhibition of Fyn	ki	0.0280	uM
Ibrutinib	2188598: Inhibition of recombinant FYN (unknown origin) preincubated for 1 hr in presence of ATP by Z-Lyte assay	ic50	0.0290	uM
N-[4-(naphthalen-1-ylamino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0300	uM
N-[4-(4-propan-2-ylanilino)quinazolin-6-yl]prop-2-enamide	502964: Inhibition of Fyn T342G/S349C double mutant expressed in Escherichia coli C43 by radioactive phosphotransfer assay	ic50	0.0320	uM
1-[2-[4-[(dimethylamino)methyl]piperidin-1-yl]ethyl]-3-(1H-pyrrolo[2,3-b]pyridin-5-yl)pyrazolo[3,4-d]pyrimidin-4-amine	1310126: Inhibition of human FYN using poly[Glu,Tyr]4:1 as substrate in presence of [gamma-33P]ATP	ic50	0.0380	uM
Fedratinib	624727: Binding constant for FYN kinase domain	kd	0.0380	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573282: Binding affinity to FYN in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0380	uM
N-(3-tert-butylphenyl)-5-[[2-(1H-imidazol-2-yl)-4-pyridinyl]oxy]-1-methylbenzimidazol-2-amine	1255121: Inhibition of FYN (unknown origin)	ic50	0.0400	uM
2-[[N-[2-[3-ethylsulfonyl-4-(4-methylpiperazin-1-yl)anilino]-5-fluoropyrimidin-4-yl]-5-(hydroxymethyl)-2-methylanilino]methyl]benzonitrile	1326076: Inhibition of N-Terminal His6-tagged full length recombinant human FYN expressed in baculovirus expression system	ic50	0.0450	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	7
sodium arsenite	increases phosphorylation, increases reaction, decreases expression, increases abundance, increases expression	6
trichostatin A	affects cotreatment, increases expression, affects expression	4
Benzo(a)pyrene	affects methylation, decreases expression	4
Decitabine	affects expression, increases expression	3
Tretinoin	decreases expression	3
chromium hexavalent ion	decreases reaction, increases activity, increases expression, increases reaction, increases phosphorylation	2
Acetaminophen	decreases expression, increases expression	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Cisplatin	decreases expression, increases reaction	2
Doxorubicin	decreases expression, increases expression, affects reaction	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
Aflatoxin B1	affects expression, decreases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
methyleugenol	decreases expression	1
triphenyl phosphate	affects expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases methylation	1
methylselenic acid	increases expression	1
salinomycin	decreases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	increases reaction, decreases expression	1
tobacco tar	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	1
oxophenylarsine	affects localization	1

ChEMBL screening assays

651 unique, capped per target: 636 binding, 8 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1011430	Binding	Inhibition of FYN	Identification and SAR of squarate inhibitors of mitogen activated protein kinase-activated protein kinase 2 (MK-2). — Bioorg Med Chem
CHEMBL1963817	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: FYN	PubChem BioAssay data set
CHEMBL4335777	ADMET	Inhibition of human full-length recombinant FYN using KVEKIGEGTYGVVYK as substrate measured after 40 mins in presence of [gamma-33P]-ATP by scintillation counting analysis	Discovery of 4-Aminoquinoline-3-carboxamide Derivatives as Potent Reversible Bruton’s Tyrosine Kinase Inhibitors for the Treatment of Rheumatoid Arthritis. — J Med Chem

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2XF	Abcam HEK293T FYN KO	Transformed cell line	Female
CVCL_B9VY	Abcam HEK293 FYN KO	Transformed cell line	Female
CVCL_D9F5	Ubigene HEK293 FYN KO	Transformed cell line	Female
CVCL_E0DF	Ubigene HeLa FYN KO	Cancer cell line	Female
CVCL_SP07	HAP1 FYN (-) 1	Cancer cell line	Male
CVCL_SP08	HAP1 FYN (-) 2	Cancer cell line	Male
CVCL_SP09	HAP1 FYN (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists