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): 55 total — 3 pathogenic
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈33% of expected missense variation)
• GTEx eGene: eQTL in 12 tissues, sQTL in 26 (q < 0.05)
• Drug target: yes — 1 curated mechanism-of-action drug, 5 via a complex or family; 120 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 1 — Dasatinib Anhydrous (SRC)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.21 (highly constrained)
• MANE Select transcript: NM_002037
• Interaction hub: 3,339 STRING partners (top 2% of genes corpus-wide)
• Notable: 55 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 87 — 75 protein_coding, 8 retained_intron, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

MANE Select: ENST00000354650

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 4, TSL 3: 2, TSL 4: 5, TSL 5: 15

ENST00000354650, ENST00000229471, 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, ENST00001016292, ENST00001016293, ENST00001099098, ENST00001112802, ENST00001134049

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.

Highest expression (Bgee): ganglionic eminence, corpus callosum, granulocyte, olfactory bulb, lymph node.

Genetic regulation across tissues (GTEx eQTL / sQTL)

FYN is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 12 tissues and its splicing (sQTL) in 26 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 38 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	1.9e-34	-0.69	6:111777061:A:G
Adipose Subcutaneous	sqtl	3.1e-19	+1.13	6:111709043:T:C
Thyroid	sqtl	4.0e-17	-2.13	6:111813888:C:T
Skin Sun Exposed Lower leg	sqtl	4.0e-15	-0.51	6:111777061:A:G
Artery Tibial	sqtl	7.5e-13	-1.54	6:111813888:C:T
Artery Tibial	eqtl	9.6e-12	+0.20	6:112045183:C:T
Cells Cultured fibroblasts	eqtl	7.0e-11	+0.26	6:112054441:G:A
Esophagus Muscularis	sqtl	1.3e-10	-1.85	6:111813888:C:T
Breast Mammary Tissue	sqtl	1.3e-09	-1.30	6:111708331:T:C
Lung	sqtl	7.0e-09	-0.46	6:111777061:A:G
Brain Cerebellum	sqtl	3.5e-06	-2.21	6:111813888:C:T
Skin Not Sun Exposed Suprapubic	sqtl	2.6e-05	-0.82	6:111709043:T:C
Heart Left Ventricle	sqtl	2.9e-05	-1.46	6:111813888:C:T
Brain Putamen basal ganglia	eqtl	4.6e-05	-0.21	6:111908951:T:C
Brain Cerebellar Hemisphere	sqtl	1.4e-04	-1.70	6:111813888:C:T
Testis	sqtl	4.0e-04	-0.48	6:111750224:A:G
Brain Anterior cingulate cortex BA24	eqtl	4.2e-04	-0.20	6:111793105:C:T
Artery Aorta	eqtl	5.7e-04	+0.14	6:112046015:A:G
Brain Nucleus accumbens basal ganglia	eqtl	7.9e-04	-0.18	6:111908738:C:T
Brain Caudate basal ganglia	eqtl	9.8e-04	-0.20	6:111830772:T:A

FANTOM5 promoters

showing 10 of 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

showing 100 of 300 tissues 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
inferior olivary complex	UBERON:0002127	97.63	gold quality
telencephalon	UBERON:0001893	97.62	gold quality
spleen	UBERON:0002106	97.62	gold quality
superior vestibular nucleus	UBERON:0007227	97.62	gold quality
CA1 field of hippocampus	UBERON:0003881	97.60	gold quality
cingulate cortex	UBERON:0003027	97.58	gold quality
spinal cord	UBERON:0002240	97.56	gold quality
anterior cingulate cortex	UBERON:0009835	97.56	gold quality
sural nerve	UBERON:0015488	97.55	gold quality
frontal cortex	UBERON:0001870	97.53	gold quality
frontal lobe	UBERON:0016525	97.53	gold quality
omental fat pad	UBERON:0010414	97.52	gold quality
neocortex	UBERON:0001950	97.51	gold quality
peritoneum	UBERON:0002358	97.51	gold quality
cerebral cortex	UBERON:0000956	97.47	gold quality
substantia nigra pars reticulata	UBERON:0001966	97.46	gold quality
subcutaneous adipose tissue	UBERON:0002190	97.46	gold quality
dorsal root ganglion	UBERON:0000044	97.45	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.45	gold quality
inferior vagus X ganglion	UBERON:0005363	97.44	gold quality
midbrain	UBERON:0001891	97.43	gold quality
substantia nigra	UBERON:0002038	97.43	gold quality
adipose tissue of abdominal region	UBERON:0007808	97.43	gold quality
subthalamic nucleus	UBERON:0001906	97.38	gold quality
upper lobe of left lung	UBERON:0008952	97.35	gold quality
upper lobe of lung	UBERON:0008948	97.30	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.30	gold quality
substantia nigra pars compacta	UBERON:0001965	97.25	gold quality
calcaneal tendon	UBERON:0003701	97.21	gold quality
forebrain	UBERON:0001890	97.20	gold quality
synovial joint	UBERON:0002217	97.20	gold quality
embryo	UBERON:0000922	97.15	gold quality
pericardium	UBERON:0002407	97.15	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.14	gold quality
central nervous system	UBERON:0001017	97.12	gold quality
brain	UBERON:0000955	97.10	gold quality
parietal lobe	UBERON:0001872	97.01	gold quality
blood	UBERON:0000178	97.00	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.98	gold quality
gall bladder	UBERON:0002110	96.91	gold quality
adipose tissue	UBERON:0001013	96.84	gold quality
postcentral gyrus	UBERON:0002581	96.84	gold quality
vermiform appendix	UBERON:0001154	96.81	gold quality
pons	UBERON:0000988	96.79	gold quality
colonic epithelium	UBERON:0000397	96.77	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.73	gold quality
globus pallidus	UBERON:0001875	96.68	gold quality
connective tissue	UBERON:0002384	96.67	gold quality
smooth muscle tissue	UBERON:0001135	96.64	gold quality
decidua	UBERON:0002450	96.62	gold quality
superior frontal gyrus	UBERON:0002661	96.62	gold quality
endocervix	UBERON:0000458	96.60	gold quality
cerebellum	UBERON:0002037	96.58	gold quality
pylorus	UBERON:0001166	96.53	gold quality
renal glomerulus	UBERON:0000074	96.52	gold quality
cerebellar cortex	UBERON:0002129	96.50	gold quality
cerebellar hemisphere	UBERON:0002245	96.48	gold quality
stromal cell of endometrium	CL:0002255	96.47	gold quality
mucosa of stomach	UBERON:0001199	96.43	gold quality
cerebellar vermis	UBERON:0004720	96.42	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.42	gold quality
occipital lobe	UBERON:0002021	96.40	gold quality
metanephric glomerulus	UBERON:0004736	96.40	gold quality
medial globus pallidus	UBERON:0002477	96.36	gold quality
paraflocculus	UBERON:0005351	96.35	gold quality
caecum	UBERON:0001153	96.34	gold quality
body of uterus	UBERON:0009853	96.32	gold quality
superficial temporal artery	UBERON:0001614	96.29	gold quality
lower lobe of lung	UBERON:0008949	96.24	gold quality
oocyte	CL:0000023	96.17	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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Hippocampus	tissue	196.1	not detected
Locus coeruleus	tissue	170.8
Nucleus accumbens	tissue	163.4
Postcentral gyrus	tissue	125.8
Lymph node	tissue	105.6	high
Caudate putamen	tissue	98.7
Frontal cortex	tissue	98.1
Olfactory bulb	tissue	88.2
Thymus	tissue	86.2
Spinal cord	tissue	84.8
Thalamus	tissue	81.6
Midbrain	tissue	74.7
Cerebral cortex	tissue	73.1	medium
Corpus callosum	tissue	73.1
Somatosensory cortex	tissue	73.1
Hippocampal formation	tissue	72.5
Superior colliculi	tissue	71.4
Substantia nigra	tissue	71.3
Medulla oblongata	tissue	70.7
Putamen	tissue	69.6
Occipital cortex	tissue	69.3
Spleen	tissue	69.2	low
Pons	tissue	68.7
Septum	tissue	68.3
Prefrontal cortex	tissue	68.0
Ventral forebrain	tissue	67.8
Amygdala	tissue	67.4
Motor cortex	tissue	67.3
Hypothalamus	tissue	66.9
Temporal cortex	tissue	66.9
Entorhinal cortex	tissue	66.2
Tonsil	tissue	65.6	high
Periaqueductal gray	tissue	62.9
Retrosplenial and cingulate cortex	tissue	62.0
Basal ganglia	tissue	61.8	not detected
Retrosplenial cortex	tissue	61.4
Insular cortex	tissue	59.3
Cerebellum	tissue	54.5	not detected
Choroid plexus	tissue	52.4
Appendix	tissue	51.8	medium
Fallopian tube	tissue	48.4	high
Adipose tissue	tissue	47.5	not detected
Thyroid gland	tissue	42.8	medium
Cervix	tissue	37.0	not detected
Smooth muscle	tissue	36.0	not detected
Urinary bladder	tissue	34.9	not detected
Heart muscle	tissue	34.3	not detected
Lung	tissue	33.9	not detected
Ovary	tissue	33.5	not detected
Endometrium 1	tissue	33.3	not detected
Vagina	tissue	31.8	not detected
Epididymis	tissue	31.6	low
Bone marrow	tissue	31.1	medium
Gallbladder	tissue	30.2	low
Placenta	tissue	28.4	not detected
Retina	tissue	25.2
Stomach 1	tissue	24.8	not detected
Small intestine	tissue	22.2	not detected
Pituitary gland	tissue	21.1
Skin 1	tissue	20.7	not detected

Brain sub-regions (HPA Brain Atlas): detected in 190; highest nTPM — Area postrema (274.1), Supraoptic nucleus (242.8), Corticomedial amygdala (224.9), Basal amygdala (217.8), Cervical spinal cord, dorsal horn (214.7).

Regulation

Is transcription factor: no

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

Functional genomics

gnomAD constraint: pLI 1, LOEUF 0.215, missense Z 5.24 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000354650 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈33% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
6:111,661,742–111,694,663	64 / 223.0	0.29	yes (p 1.8e-26)
6:111,694,664–111,696,282	15 / 16.0	0.94	no
6:111,696,283–111,707,931	112 / 250.2	0.45	no
6:111,707,932–111,720,051	128 / 183.9	0.70	no

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

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	fyna	ENSDARG00000011370
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)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:95602) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 110 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal dentate gyrus morphology	2
abnormal myelination	2
thick epidermis	2
epidermal hyperplasia	2
reduced long-term potentiation	2
decreased IgE level	2
abnormal keratinocyte morphology	2
oligozoospermia	2
increased fear-related response	2
abnormal thymocyte activation	2
decreased T cell proliferation	2
abnormal hippocampus pyramidal cell layer	2
decreased interleukin-2 secretion	2
abnormal hippocampus pyramidal cell morphology	2
abnormal cranium morphology	1
abnormal spleen morphology	1
abnormal filiform papillae morphology	1
decreased corpus callosum size	1
abnormal cerebral cortex lamination	1
abnormal hippocampus morphology	1
abnormal hippocampus layer morphology	1
abnormal olfactory bulb morphology	1
abnormal hypothalamus morphology	1
abnormal somatosensory cortex morphology	1
small seminiferous tubules	1

+85 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Paracoccidioides brasiliensis Pb03	C0S7Q7	100.0%	Diamond
Paracoccidioides brasiliensis Pb18	C1GJ63	100.0%	Diamond
Trichophyton benhamiae CBS 112371	D4ARB8	100.0%	Diamond
Trichophyton verrucosum HKI 0517	D4DA58	100.0%	Diamond
Gallus gallus	P00523	100.0%	Diamond
Coturnix japonica	P34908	100.0%	Diamond
Drosophila melanogaster	Q08012	100.0%	Diamond
Bos taurus	A0JNB0	99.6%	Diamond
Sus scrofa	A1Y2K1	99.4%	Diamond
Felis catus	P14238	98.7%	Diamond
Xenopus laevis	P87379	98.7%	Diamond
Calliphora vicina	P11681	98.6%	Diamond
Canis lupus familiaris	A0A8I3NFE2	95.9%	Diamond
Saccharomyces cerevisiae YJM789	A6ZKU1	95.9%	Diamond
Avian retrovirus IC10	P10533	100.0%	Diamond
Avian sarcoma virus PR2257	P15054	100.0%	Diamond
Rous-associated virus type 1	P27966	100.0%	Diamond
Avian sarcoma virus S2	P14085	99.8%	Diamond
Avian sarcoma virus S1	P14084	99.6%	Diamond
Feline sarcoma virus (STRAIN HARDY-ZUCKERMAN 2)	P10447	99.3%	Diamond
Gardner-Arnstein feline sarcoma virus	P00542	99.1%	Diamond
Snyder-Theilen feline sarcoma virus	P00543	99.1%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin A)	P00524	99.0%	Diamond
Avian sarcoma virus RASV1441	P00525	99.0%	Diamond
Rous sarcoma virus - Prague C	P00526	99.0%	Diamond
Rous sarcoma virus (strain H-19)	P25020	99.0%	Diamond
Rous sarcoma virus (strain Schmidt-Ruppin E)	P63185	99.0%	Diamond
Y73 sarcoma virus	P00527	98.9%	Diamond
Avian carcinoma Mill Hill virus 2	P00531	98.9%	Diamond
Murine sarcoma virus 3611	P00532	98.8%	Diamond
Abelson murine leukemia virus	P00521	98.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
LINC02527	ncRNA	105377946
TRAF3IP2	protein-coding	10758
TRAF3IP2-AS1	ncRNA	643749
CCN6	protein-coding	8838
TUBE1	protein-coding	51175
REV3L	protein-coding	5980

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)

• 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)

showing 30 of 53 structures by resolution:

PDB	Title	Method	Resolution (Å)
7A2P	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 5.0 …	X-RAY DIFFRACTION	0.9
7A2X	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant in complex …	X-RAY DIFFRACTION	0.92
7A2O	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 4.5	X-RAY DIFFRACTION	0.94
7A2Q	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 3.0 …	X-RAY DIFFRACTION	0.94
7A2Y	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant in complex …	X-RAY DIFFRACTION	0.97
7A2W	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant in complex …	X-RAY DIFFRACTION	0.99
8KDX	Tau-S214 Phosphorylation Inhibits Fyn Kinase Interaction and Increases the Decay Time of …	X-RAY DIFFRACTION	1.01
7A2S	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 5.0	X-RAY DIFFRACTION	1.02
7A2R	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 6.0	X-RAY DIFFRACTION	1.05
7A2Z	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant in complex …	X-RAY DIFFRACTION	1.14
7A2T	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E121L-R123H mutant at pH 4.0	X-RAY DIFFRACTION	1.22
6IPY	His-tagged Fyn SH3 domain R96I mutant	X-RAY DIFFRACTION	1.34
4U1P	Human Fyn-SH2 domain in complex with a synthetic high-affinity phospho-peptide	X-RAY DIFFRACTION	1.4
6EDF	Fragment of a tyrosine-protein kinase	X-RAY DIFFRACTION	1.4
7A2N	Crystal structure of the Fyn SH3 domain A95S-D99T mutant in space group P21	X-RAY DIFFRACTION	1.4
9GHK	Crystal structure of Fyn SH3 domain/tau 214-220 peptide complex	X-RAY DIFFRACTION	1.42
3UA7	Crystal Structure of the Human Fyn SH3 domain in complex with a peptide from the …	X-RAY DIFFRACTION	1.5
7A2J	Crystal structure of the Fyn SH3 domain in space group C21 at pH 7.5	X-RAY DIFFRACTION	1.5
7A2K	Crystal structure of the Fyn SH3 domain in space group P1 at pH 7.5	X-RAY DIFFRACTION	1.5
7A2M	Crystal structure of the Fyn SH3 domain A95S-D99T mutant in C21 space group	X-RAY DIFFRACTION	1.5
6IPZ	Fyn SH3 domain R96W mutant, crystallized with 18-crown-6	X-RAY DIFFRACTION	1.58
4EIK	Crystal Structure of the Human Fyn SH3 domain in complex with the synthetic peptide VSL12	X-RAY DIFFRACTION	1.6
7A2U	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T at pH 4.5	X-RAY DIFFRACTION	1.7
3H0H	human Fyn SH3 domain R96I mutant, crystal form I	X-RAY DIFFRACTION	1.76
7A2V	Crystal structure of the Fyn SH3 domain L112V-S114N-S115T-E129Q at pH 4.0	X-RAY DIFFRACTION	1.81
3UA6	Crystal Structure of the Human Fyn SH3 domain	X-RAY DIFFRACTION	1.85
1SHF	CRYSTAL STRUCTURE OF THE SH3 DOMAIN IN HUMAN FYN; COMPARISON OF THE THREE-DIMENSIONAL …	X-RAY DIFFRACTION	1.9
7A2L	Crystal structure of the Fyn SH3 domain mutant E129Q in space group C21 at pH 4.0	X-RAY DIFFRACTION	1.9
4U17	Swapped dimer of the human Fyn-SH2 domain	X-RAY DIFFRACTION	1.99
4ZNX	Crystal structure of the Fyn-SH3 domain in complex with the high affinity peptide APP12	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Kinases, Tyr protein kinases, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): plasma membrane; cytosol

Antibody reliability (HPA): IH approved · IF supported

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)

Position	Role
390	proton acceptor

Ligand- & substrate-binding residues (2)

Position	Role
277–285	ATP
299	ATP

Post-translational modifications (9)

Type	Positions
Phosphoserine	21, 26
Phosphotyrosine	185, 420, 531
N-myristoyl glycine	2
S-palmitoyl cysteine	3, 6
Phosphothreonine	12

Function

Pathways and Gene Ontology

Reactome pathways

26 curated (TAS) of 90; 19 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 90 pathways:

ID	Pathway	Evidence
R-HSA-2219530	Constitutive Signaling by Aberrant PI3K in Cancer ⚕	curated
R-HSA-9664323	FCGR3A-mediated IL10 synthesis ⚕	curated
R-HSA-9664422	FCGR3A-mediated phagocytosis ⚕	curated
R-HSA-164944	Nef and signal transduction ⚕	curated
R-HSA-9670439	Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants ⚕	curated
R-HSA-5621575	CD209 (DC-SIGN) signaling	curated
R-HSA-389357	CD28 dependent PI3K/Akt signaling	curated
R-HSA-389359	CD28 dependent Vav1 pathway	curated
R-HSA-202733	Cell surface interactions at the vascular wall	curated
R-HSA-389513	Co-inhibition by CTLA4	curated
R-HSA-389356	Co-stimulation by CD28	curated
R-HSA-5621480	Dectin-2 family	curated
R-HSA-9766229	Degradation of CDH1	curated
R-HSA-3928665	EPH-ephrin mediated repulsion of cells	curated
R-HSA-2029481	FCGR activation	curated
R-HSA-114604	GPVI-mediated activation cascade	curated
R-HSA-210990	PECAM1 interactions	curated
R-HSA-6811558	PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	curated
R-HSA-1257604	PIP3 activates AKT signaling	curated
R-HSA-75892	Platelet Adhesion to exposed collagen	curated
R-HSA-5673001	RAF/MAP kinase cascade	curated
R-HSA-8866376	Reelin signalling pathway	curated
R-HSA-1433559	Regulation of KIT signaling	curated
R-HSA-399954	Sema3A PAK dependent Axon repulsion	curated
R-HSA-1227986	Signaling by ERBB2	curated
R-HSA-4420097	VEGFA-VEGFR2 Pathway	curated
R-HSA-9662851	Anti-inflammatory response favouring Leishmania parasite infection ⚕	—
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-162906	HIV Infection ⚕	—
R-HSA-162909	Host Interactions of HIV factors ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9658195	Leishmania infection ⚕	—
R-HSA-9664433	Leishmania parasite growth and survival ⚕	—
R-HSA-9664417	Leishmania phagocytosis ⚕	—
R-HSA-2219528	PI3K/AKT Signaling in Cancer ⚕	—
R-HSA-9664407	Parasite infection ⚕	—
R-HSA-9824443	Parasitic Infection Pathways ⚕	—
R-HSA-9669938	Signaling by KIT in disease ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-9032500	Activated NTRK2 signals through FYN	electronic
R-HSA-1280218	Adaptive Immune System	—
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers	electronic
R-HSA-422475	Axon guidance	—
R-HSA-5621481	C-type lectin receptors (CLRs)	—
R-HSA-399956	CRMPs in Sema3A signaling	electronic
R-HSA-1500931	Cell-Cell communication	—
R-HSA-9855142	Cellular responses to mechanical stimuli	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-2172127	DAP12 interactions	—
R-HSA-2424491	DAP12 signaling	electronic
R-HSA-418885	DCC mediated attractive signaling	electronic
R-HSA-1266738	Developmental Biology	—
R-HSA-2682334	EPH-Ephrin signaling	electronic
R-HSA-3928663	EPHA-mediated growth cone collapse	electronic
R-HSA-3928662	EPHB-mediated forward signaling	electronic
R-HSA-3928664	Ephrin signaling	electronic
R-HSA-9607240	FLT3 Signaling	—
R-HSA-9706374	FLT3 signaling through SRC family kinases	electronic

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 (50): response to singlet oxygen (GO:0000304), 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), negative regulation of gene expression (GO:0010629), negative regulation of hydrogen peroxide biosynthetic process (GO:0010730), negative regulation of angiogenesis (GO:0016525), peptidyl-tyrosine phosphorylation (GO:0018108), natural killer cell activation (GO:0030101), cell differentiation (GO:0030154), T cell costimulation (GO:0031295), intracellular signal transduction (GO:0035556), reelin-mediated signaling pathway (GO:0038026), Fc-gamma receptor signaling pathway involved in phagocytosis (GO:0038096), response to cocaine (GO:0042220), negative regulation of neuron apoptotic process (GO:0043524), vascular endothelial growth factor receptor signaling pathway (GO:0048010), ephrin receptor signaling pathway (GO:0048013), modulation of chemical synaptic transmission (GO:0050804), T cell receptor signaling pathway (GO:0050852), negative regulation of T cell receptor signaling pathway (GO:0050860), negative regulation of T cell activation (GO:0050868), leukocyte migration (GO:0050900), positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051897), cellular response to hydrogen peroxide (GO:0070301), cellular response to growth factor stimulus (GO:0071363), cellular response to peptide hormone stimulus (GO:0071375), positive regulation of protein targeting to membrane (GO:0090314), dendritic spine maintenance (GO:0097062), regulation of glutamate receptor signaling pathway (GO:1900449), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176), negative regulation of dendritic spine maintenance (GO:1902951), response to amyloid-beta (GO:1904645), cellular response to amyloid-beta (GO:1904646), cellular response to L-glutamate (GO:1905232), cellular response to glycine (GO:1905430), positive regulation of protein localization to membrane (GO:1905477), regulation of calcium ion import across plasma membrane (GO:1905664), negative regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001240), immune system process (GO:0002376), protein phosphorylation (GO:0006468)

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 (19): 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), cell periphery (GO:0071944)

Reactome top-level categories

16 top-level categories:

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
EPH-Ephrin signaling	1

GO top-level categories

showing 60 of 74 GO namespaces:

Category	Terms
cellular anatomical structure	7
signaling receptor binding	5
protein binding	5
cytoplasm	3
intracellular membrane-bounded organelle	2
synapse	2
response to reactive oxygen species	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
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
angiogenesis	1
regulation of angiogenesis	1
negative regulation of blood vessel morphogenesis	1
protein phosphorylation	1
lymphocyte activation	1
cellular developmental process	1
lymphocyte costimulation	1
positive regulation of T cell activation	1
protein kinase activity	1
protein tyrosine kinase activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
glycerophospholipase activity	1
lipase activator activity	1
G protein-coupled glutamate receptor binding	1
protein-containing complex binding	1
tubulin binding	1
enzyme binding	1
cation binding	1
cytoskeletal protein binding	1
protein serine/threonine kinase activity	1
endomembrane system	1
cytoplasmic vesicle	1
actin cytoskeleton	1
polymeric cytoskeletal fiber	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 24 of 100 annotations. The rest are phylogenetic / computational / electronic (IEA).

24 experimentally-supported GO terms:

GO term	NS	Evidence
G protein-coupled glutamate receptor signaling pathway	BP	direct assay
T cell receptor signaling pathway	BP	direct assay
cellular response to amyloid-beta	BP	mutant phenotype
heart process	BP	genetic interaction
intracellular signal transduction	BP	mutant phenotype
natural killer cell activation	BP	direct assay
negative regulation of T cell activation	BP	direct assay
negative regulation of T cell receptor signaling pathway	BP	direct assay
cytosol	CC	direct assay
dendrite	CC	direct assay
endosome	CC	direct assay
membrane raft	CC	direct assay
plasma membrane	CC	direct assay
G protein-coupled receptor binding	MF	physical interaction
disordered domain specific binding	MF	physical interaction
enzyme binding	MF	physical interaction
ephrin receptor binding	MF	physical interaction
growth factor receptor binding	MF	physical interaction
identical protein binding	MF	physical interaction
non-membrane spanning protein tyrosine kinase activity	MF	direct assay
phospholipase activator activity	MF	direct assay
phospholipase binding	MF	physical interaction
protein tyrosine kinase activity	MF	direct assay
scaffold protein binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,339 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
FYN	CRK	P46108	788
FYN	LCP2	Q13094	784
FYN	GRIN2B	Q13224	777
FYN	PAG1	Q9NWQ8	765
FYN	SHC1	P29353	742
FYN	SKAP1	Q86WV1	724
FYN	PRNP	P04156	724
FYN	NCKIPSD	Q9NZQ3	719
FYN	BCAR1	P56945	707
FYN	CAV1	Q03135	685
FYN	CD79A	P11912	672
FYN	FCER1G	P30273	665
FYN	FYB1	O15117	665
FYN	CD247	P20963	659
FYN	CD79B	P40259	655

IntAct

Human interaction partners of FYN in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 290 partners by confidence:

Partner	Interaction type	MIscore	Records
KHDRBS1	physical association	0.850	7
FYB1	physical association	0.820	7
CBL	physical association	0.800	6
HSP90AA1	physical association	0.800	4
CDC37	physical association	0.800	1
BCAR1	physical association	0.780	4
MED28	physical association	0.740	5
PRKCD	physical association	0.740	5
HSP90AB1	physical association	0.720	2
PTK2B	association	0.700	4
WAS	phosphorylation reaction	0.700	4
ASAP1	physical association	0.700	3
MAPT	physical association	0.680	16
ATXN1	physical association	0.670	8
PDCD6IP	physical association	0.670	6
EFS	physical association	0.670	4
SRC	physical association	0.670	1
PRKCQ	physical association	0.660	7
PDGFRB	association	0.640	3
HTR6	physical association	0.630	7
ARHGAP32	physical association	0.630	4
PAG1	association	0.620	5
ADAM15	physical association	0.590	2
CD2	phosphorylation reaction	0.570	3
CD2AP	physical association	0.570	2
FASLG	direct interaction	0.570	2
NCKIPSD	physical association	0.570	2
GP6	association	0.560	4
AKT1	physical association	0.560	3
APBB2	physical association	0.560	3

BioGRID (616 interactions; top human partners by supporting records in a sample of 600 records): CBL (Two-hybrid; 26 records), MAPT (Reconstituted Complex; 16 records), KHDRBS1 (Affinity Capture-Western; 9 records), FYB (Two-hybrid; 7 records), PRKCQ (Reconstituted Complex; 7 records), GRIN2A (Affinity Capture-Western; 6 records), PTK2B (Affinity Capture-Western; 6 records), SRC (Affinity Capture-MS; 6 records), WAS (Affinity Capture-Western; 6 records), BCAR1 (Two-hybrid; 5 records), FASLG (Co-localization; 5 records), HSP90AA1 (Affinity Capture-MS; 5 records), NPHS1 (Affinity Capture-Western; 5 records), SNCA (Affinity Capture-Western; 5 records), CDC37 (Affinity Capture-MS; 4 records)

SIGNOR signaling

showing 51 of 149 signaling 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
FYN	“up-regulates activity”	KIRREL1	phosphorylation
FYN	unknown	“Histone H3”	phosphorylation
FYN	“up-regulates activity”	PGD	phosphorylation
FYN	“up-regulates activity”	BCR-Mk	phosphorylation
FYN	“up-regulates activity”	BCR-Ml	phosphorylation
FYN	“up-regulates activity”	BCR-Dk	phosphorylation
FYN	“up-regulates activity”	BCR-Dl	phosphorylation
FYN	“up-regulates activity”	BSG	phosphorylation
FYN	“up-regulates activity”	CLIC5	phosphorylation
FYN	“down-regulates activity”	IKBKG	phosphorylation
FYN	“up-regulates activity”	PTPRJ	phosphorylation
FYN	“up-regulates activity”	KCND3	phosphorylation
FYN	“up-regulates quantity”	LRP8	phosphorylation
FYN	“down-regulates quantity”	NFE2L2	phosphorylation
FYN	“up-regulates quantity”	APP	phosphorylation
FYN	“up-regulates activity”	PTK2	phosphorylation
FYN	“down-regulates activity”	DAB1	phosphorylation
FYN	“down-regulates activity”	STK11	phosphorylation
FYN	“up-regulates activity”	ZAP70	phosphorylation
FYN	“up-regulates activity”	WAS	phosphorylation
FYN	“up-regulates activity”	BCAR1	phosphorylation
FYN	“up-regulates activity”	NTRK1	phosphorylation
FYN	“up-regulates activity”	KHDRBS1	phosphorylation
FYN	“up-regulates activity”	NPHS1	phosphorylation
FYN	“up-regulates activity”	SCN9A	phosphorylation

Protein complexes (CORUM) (21)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

21 complexes by size:

Complex	Subunits	Members
★ CBL-FGFR2-FYN-LYN complex	4	CBL, FGFR2, FYN, LYN
★ FYN-LYN-RASA1-YES1 complex	4	FYN, LYN, RASA1, YES1
★ FYN-LCK-LYN-MS4A1 complex	4	FYN, LCK, LYN, MS4A1
★ FYN-PAG1-KHDRBS1-RASA1 complex	4	FYN, KHDRBS1, PAG1, RASA1
★ AKAP9-FYN-PRKACA complex	3	AKAP9, FYN, PRKACA
★ FYN-PDE4DIP-PRKACA complex	3	PDE4DIP, PRKACA, FYN
★ CDK5RAP2-FYN-PRKACA complex	3	CDK5RAP2, FYN, PRKACA
★ FCER1G-FYN-GP6 complex	3	FCER1G, FYN, GP6
★ FYN-ITGA6-ITGB4 complex	3	ITGB4, FYN, ITGA6
★ FN1-FYN-ITGB6 complex	3	FYN, ITGB6, FN1
★ FYN-LCK-MS4A1 complex	3	FYN, LCK, MS4A1
★ DLG4-FYN-GRIN2A complex	3	DLG4, FYN, GRIN2A
★ FYN-KHDRBS1-PLCG1 complex	3	FYN, KHDRBS1, PLCG1
★ CSK-FYN-PAG1 complex	3	PAG1, CSK, FYN
★ FYN-KHDRBS1-PAG1 complex	3	PAG1, FYN, KHDRBS1
★ FYN-MAPT complex	2	FYN, MAPT
★ FLT1-FYN complex	2	FLT1, FYN
★ FYN-HTR6 complex	2	FYN, HTR6
★ CD36-FYN complex	2	CD36, FYN
★ FYN-PDGFRB complex	2	FYN, PDGFRB
★ FYN-PAG1 complex	2	FYN, PAG1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 290 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Constitutive Signaling by EGFRvIII	6	20.3×	3e-05
Signaling by ERBB2 ECD mutants	6	19.1×	4e-05
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	6	16.2×	9e-05
Integrin signaling	8	16.0×	9e-06
Signal regulatory protein family interactions	5	15.9×	5e-04
Interleukin-2 family signaling	5	15.0×	7e-04
Signaling by ERBB2	8	13.1×	2e-05
RIPK1-mediated regulated necrosis	6	13.0×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
synaptic vesicle priming	5	14.4×	3e-03
vascular endothelial growth factor receptor signaling pathway	8	13.9×	3e-05
peptidyl-tyrosine phosphorylation	9	13.6×	8e-06
epidermal growth factor receptor signaling pathway	14	12.5×	1e-08
membrane protein ectodomain proteolysis	5	11.7×	5e-03
positive regulation of Rac protein signal transduction	5	11.7×	5e-03
cellular response to vascular endothelial growth factor stimulus	5	10.1×	8e-03
cell surface receptor protein tyrosine kinase signaling pathway	15	9.4×	7e-08

Disease & clinical

Genetic variants

Variant evidence for FYN: 55 ClinVar records (3 pathogenic / likely pathogenic); 24 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	19
Likely benign	3
Benign	6

Top pathogenic / likely-pathogenic (3)

Showing all 3 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2681288	NM_002037.5(FYN):c.286C>G (p.Arg96Gly)	Pathogenic	no assertion criteria provided	1
2681289	NM_002037.5(FYN):c.286C>T (p.Arg96Trp)	Pathogenic	no assertion criteria provided	1
2681290	NM_002037.5(FYN):c.289A>G (p.Thr97Ala)	Pathogenic	no assertion criteria provided	1

Per-variant reference — Sugi Variant

Explore FYN’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,290):

Position(s)	Effect	Δscore	Sites
6:111661948	acceptor_loss	1.0000	2
6:111694373–111694374	donor_loss	1.0000	5
6:111694529–111694530	acceptor_loss	1.0000	5
6:111694540	acceptor_gain	1.0000
6:111694626–111694627	donor_loss	1.0000	5
6:111694705–111694706	acceptor_loss	1.0000	4
6:111694713	acceptor_gain	1.0000
6:111696275–111696276	donor_loss	1.0000	2
6:111703997–111703998	donor_loss	1.0000	5
6:111704103–111704104	acceptor_loss	1.0000	2

AlphaMissense

2,345 missense substitutions predicted likely pathogenic (of 3,503 scored), across 453 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M378	9	0.994	1.000
M318	9	0.990	1.000
M306	9	0.987	0.999
M470	9	0.958	0.999
M485	9	0.941	0.999
M345	9	0.920	0.995
M499	9	0.912	0.996
H388	8	1.000	1.000
D390	8	1.000	1.000
D408	8	1.000	1.000
D448	8	1.000	1.000
H202	8	0.999	1.000
N395	8	0.999	1.000
F409	8	0.999	1.000
F428	8	0.999	1.000
F311	8	0.998	1.000
D191	8	0.997	0.999
F443	8	0.997	1.000
D100	8	0.996	0.999
F282	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Cancer enhanced (Glioblastoma Multiforme)

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

4 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	1.08e-05
Kidney Renal Clear Cell Carcinoma (validation)	favorable	3.7e-05
Liver Hepatocellular Carcinoma (validation)	favorable	5.08e-05
Liver Hepatocellular Carcinoma (TCGA)	favorable	0.000738

Disease associations

OMIM: gene MIM:137025 | disease phenotypes:

GWAS associations

24 associations:

Study	Trait	p-value
GCST005580_100	Intraocular pressure	7e-16
GCST001725_23	Inflammatory bowel disease	1e-13
GCST005580_302	Intraocular pressure	3e-13
GCST010796_2064	Electrocardiogram morphology (amplitude at temporal datapoints)	1e-10
GCST004131_98	Inflammatory bowel disease	4e-10
GCST004133_36	Ulcerative colitis	6e-10
GCST010571_4	Autoimmune thyroid disease	8e-10
GCST009325_40	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2e-9
GCST007267_287	Systolic blood pressure	4e-9
GCST010796_2061	Electrocardiogram morphology (amplitude at temporal datapoints)	4e-9
GCST007201_9	Schizophrenia	8e-9
GCST006976_122	Macular thickness	9e-9
GCST010796_2062	Electrocardiogram morphology (amplitude at temporal datapoints)	2e-8
GCST002324_4	Anger	3e-8
GCST010049_6	Parkinson’s disease	3e-8
GCST010796_2059	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST010796_2060	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST010796_2063	Electrocardiogram morphology (amplitude at temporal datapoints)	3e-8
GCST008839_392	Height	4e-8
GCST004946_216	Schizophrenia	5e-8
GCST010991_36	Parkinson’s disease	2e-7
GCST009548_2	NASH resolution in nonalcoholic steatohepatitis	9e-7
GCST002337_36	Amyotrophic lateral sclerosis (sporadic)	3e-6
GCST008103_88	Bipolar disorder	3e-6

EFO canonical traits (from GWAS)

5 canonical traits:

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

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

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the FYN protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

1 curated-mechanism drugs:

Drug	Modality	Max phase
JNJ-26483327	Small molecule	1

Drugs acting on a complex or family that includes this protein

Curated ChEMBL mechanism-of-action drugs whose target is a protein complex or family of ≤10 members that includes FYN — the drug acts on the assembly or class, not necessarily on this subunit alone.

5 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
DASATINIB ANHYDROUS	SRC	10	4
ENMD-981693	SRC	10	2
ILORASERTIB	SRC	10	2
TG100-801	SRC	10	2
XL-228	SRC	10	1

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 4,619,625 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 120 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL539	ACETIC ACID	4	3,642,061
CHEMBL633	AMIODARONE	4	30,023
CHEMBL296419	ASTEMIZOLE	4	21,684
CHEMBL1366	AURANOFIN	4
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL3545311	BRIGATINIB	4	5,988
CHEMBL1200748	CARBIDOPA	4	358
CHEMBL71	CHLORPROMAZINE	4	46,206
CHEMBL1200528	CHROMIC CHLORIDE	4
CHEMBL11359	CISPLATIN	4
CHEMBL104	CLOTRIMAZOLE	4	56,839
CHEMBL6067481	COLISTIN	4
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL2028663	DABRAFENIB	4	13,060
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL411	DIETHYLSTILBESTROL	4	373,838
CHEMBL926	DOBUTAMINE	4	17,217
CHEMBL53463	DOXORUBICIN	4	317,622
CHEMBL305660	EBASTINE	4	10,106
CHEMBL808	ECONAZOLE	4
CHEMBL1983268	ENTRECTINIB	4
CHEMBL417	EPIRUBICIN	4
CHEMBL442	ERGOTAMINE	4
CHEMBL1287853	FEDRATINIB	4
CHEMBL726	FLUPHENAZINE	4
CHEMBL64894	GENTIAN VIOLET	4
CHEMBL1201469	GRAMICIDIN	4
CHEMBL496	HEXACHLOROPHENE	4
CHEMBL1873475	IBRUTINIB	4
CHEMBL941	IMATINIB	4
CHEMBL1852688	INFIGRATINIB	4
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4
CHEMBL64391	ITRACONAZOLE	4
CHEMBL1009	LEVODOPA	4
CHEMBL459	METHYLDOPA	4
CHEMBL91	MICONAZOLE	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL1276308	MIFEPRISTONE	4
CHEMBL58	MITOXANTRONE	4
CHEMBL787	MONTELUKAST	4
CHEMBL584	NELFINAVIR	4
CHEMBL180022	NERATINIB	4
CHEMBL255863	NILOTINIB	4
CHEMBL502835	NINTEDANIB	4
CHEMBL428647	PACLITAXEL	4
CHEMBL477772	PAZOPANIB	4
CHEMBL75880	PERHEXILINE	4
CHEMBL1171837	PONATINIB	4
CHEMBL728	PROCHLORPERAZINE	4
CHEMBL81	RALOXIFENE	4
CHEMBL1336	SORAFENIB	4
CHEMBL1221	SULCONAZOLE	4
CHEMBL404849	SULOCTIDIL	4
CHEMBL535	SUNITINIB	4
CHEMBL83	TAMOXIFEN	4
CHEMBL506247	TANNIC ACID	4
CHEMBL1714574	TERCONAZOLE	4
CHEMBL17157	TERFENADINE	4
CHEMBL479	THIORIDAZINE	4

PharmGKB: 1 entry (CPIC guideline: no)

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)

934 measured of 1263 human assays (1308 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
AP-26113	IC50	0.37 nM
1-[(2R)-2-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	IC50	0.8 nM	US-20240317756: INHIBITORS OF BRUTON’S TYROSINE KINASE
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	IC50	1 nM	US-8530652: Pyrrolopyrazoles, potent kinase inhibitors
Jak Inhibitor 1	EC50	1 nM
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
K02288a	IC50	1.1 nM
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9181263: Inhibitors of bruton’s tyrosine kinase
rac-2-(6-hydroxy-6-methylheptan-2-ylamino)-4-methyl-6-(5-methyl-1H-pyrazol-3-ylamino)nicotinonitrile hydrochloride	KI	1.2 nM
Staurosporine	KD	1.7 nM
CHEMBL404367	IC50	2 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
CHEMBL5285357	IC50	2.2 nM
(2,4-Dichloro-5-methoxy-phenyl)-[7-methoxy-8-(2-methoxy-ethoxy)-4a,5,10,10a-tetrahydro-pyrimido[4,5-b]quinolin-4-yl]-amine	IC50	2.3 nM
CHEMBL3335371	IC50	3 nM
CHEMBL255955	IC50	3 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
2-{6-Methyl-2-[(tetrahydro-furan-2-ylmethyl)-amino]-pyrimidin-4-ylamino}-benzothiazole-6-carboxylic acid (2-chloro-6-methyl-phenyl)-amide	KI	3.2 nM
CEP-701	KD	3.4 nM
CHEMBL3893914	KI	4 nM
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
6-amino-9-[(3R)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one	IC50	4.3 nM	US-9199997: Purinone derivative hydrochloride
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
4-[4-[(5-tert-butyl-2-quinolin-6-ylpyrazol-3-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	IC50	5.5 nM
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	IC50	5.6 nM	US-8822500: Tyrosine kinase inhibitors
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	IC50	5.6 nM	US-9481682: Substituted benzamides and substituted pyridinecarboxamides as Btk inhibitors
N-[3-[6-amino-5-(3,4,5-trimethoxyphenyl)-3-pyridinyl]phenyl]methanesulfonamide	IC50	6 nM	US-10688093: Methods, compositions, and uses of novel Fyn kinase inhibitors
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
Staurosporine, 8	IC50	6.5 nM
benzyl 21-methoxy-5,7,19-trioxa-2,13,24,26-tetrazapentacyclo[18.6.2.03,11.04,8.023,27]octacosa-1(26),3(11),4(8),9,20,22,24,27-octaene-13-carboxylate	IC50	6.69 nM	US-10688093: Methods, compositions, and uses of novel Fyn kinase inhibitors
CHEMBL3923175	IC50	7 nM
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
9-methoxy-N-{3- methoxy-4-[3- (pyrrolidin-1-yl)propyl] phenyl}-6,6-dimethyl- 5H,6H-benzo[h] quinazolin-2-amine	IC50	8 nM	US-10688093: Methods, compositions, and uses of novel Fyn kinase inhibitors
N-{4-[2-(dimethyl- amino)ethoxy]- 3,5-dimethyl phenyl}-9-methoxy- 5H,6H-benzo[h] quinazolin-2-amine	IC50	8 nM	US-10688093: Methods, compositions, and uses of novel Fyn kinase inhibitors
Momelotinib	IC50	8 nM	US-9469613: (N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide
CHEMBL4465866	KD	8 nM
CHEMBL4576489	KD	8 nM
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
2-(2-cyanopropan-2-yl)-N-[4-methyl-3-[2-[2-(pyrazin-2-ylamino)-1,3-thiazol-5-yl]ethyl]phenyl]pyridine-4-carboxamide	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
4-({2-[(3-tert-butylphenyl)(methyl)amino]-1H-1,3-benzodiazol-5-yl}oxy)-N-methylpyridine-2-carboxamide	IC50	10 nM
2-[2-(2-Hydroxy-ethylamino)-6-methyl-pyrimidin-4-ylamino]-benzothiazole-6-carboxylic acid (2-chloro-6-methyl-phenyl)-amide	IC50	10 nM

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 1919 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	decreases expression, increases abundance, increases expression, increases phosphorylation, increases reaction	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	increases reaction, increases phosphorylation, decreases reaction, increases activity, increases expression	2
Acetaminophen	increases expression, decreases 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
Particulate Matter	increases abundance, increases expression, affects 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	decreases expression, increases reaction	1
tobacco tar	decreases expression	1
potassium chromate(VI)	affects cotreatment, decreases expression	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)

Via MONDO — disease-level, not drug-specific.

showing 60 of 75 trials:

NCT	Phase	Status	Title
NCT00417066	Phase 4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	Phase 4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	Phase 4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	Phase 4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	Phase 4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	Phase 4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	Phase 3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	Phase 2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	Phase 2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	Phase 2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	Phase 2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	Phase 2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	Phase 2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	Phase 1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	Phase 1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	Phase 1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	Phase 1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	Phase 1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	Phase 2/3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	Phase 2/3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	Phase 1/2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	Phase 1/2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	Phase 1/2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	Phase 1/2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	Phase 1/2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	Phase 1/2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	Phase 1/2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	Phase 1/2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	Phase 1/2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	Phase 1/2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	Phase 1/2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	Phase 1/2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	Phase 1/2	COMPLETED	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	Early Phase 1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	Early Phase 1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	Early Phase 1	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
NCT00295087	Not specified	COMPLETED	X-Chromosome Inactivation Status and Premature Ovarian Failure
NCT00417157	Not specified	COMPLETED	Modified Natural Cycle Offers a Chance of Pregnancy in Patients With Poor Response and High Basal FSH
NCT00619333	Not specified	UNKNOWN	Inactive FSH in Galactosemia
NCT00780897	Not specified	UNKNOWN	Premature Ovarian Failure (Genetic and Physiopathologic Analysis)
NCT01187524	Not specified	TERMINATED	The Natural History of Reproductive and Overall Health in Girls and Women With a Pre-Mutation in the FMR1 Gene; Creation of a Patient Registry
NCT01411644	Not specified	UNKNOWN	Pheno- & Genotyping POF (WHO III)
NCT02086318	Not specified	UNKNOWN	A New Algorithm to Predict Ovarian Age
NCT02467231	Not specified	ACTIVE_NOT_RECRUITING	Ovarian Reserve After Cancer: Longitudinal Effects
NCT02696889	Not specified	COMPLETED	Rejuvenation of Premature Ovarian Failure With Stem Cells
NCT02779374	Not specified	TERMINATED	Autologous Bone Marrow Transplantation for Premature Ovarian Insufficiency
NCT03207412	Not specified	UNKNOWN	Human Amniotic Epithelial Cells Treatment for Ovarian Insufficiency
NCT03381300	Not specified	ACTIVE_NOT_RECRUITING	Preservation of Ovarian Cortex Tissue in Girls With Turner Syndrome
NCT03412487	Not specified	UNKNOWN	Ovarian Histopathology and Laparoscopic Assessment of Premature Ovarian Failure
NCT03474120	Not specified	UNKNOWN	Prospective Genetic Study in Patients With Ovarian Insufficiency
NCT03480412	Not specified	UNKNOWN	Second Step Protocol in Poor Ovarian Responder (POR)
NCT03840824	Not specified	COMPLETED	Blood Spot Self-administered Test and Assay
NCT03861715	Not specified	UNKNOWN	Single Follicular Dexarelix for LH Suppression During Ovarian Stimulation in Oocyte Donors.
NCT03924648	Not specified	COMPLETED	Endocan Levels in Women With Premature Ovarian Insufficiency
NCT04149028	Not specified	COMPLETED	Platelet Rich Plasma Injection Into Ovary of Patients With Premature Ovarian Insufficiency
NCT04189406	Not specified	UNKNOWN	Turner Syndrome Minipuberty Study

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for FYN across ~30M SureChEMBL compounds — explore on Sugi Predict.