LYN

Summary

LYN (LYN proto-oncogene, Src family tyrosine kinase, HGNC:6735) is a protein-coding gene on chromosome 8q12.1, encoding Tyrosine-protein kinase Lyn (P07948). Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA…. In precision oncology, LYN OVEREXPRESSION is associated with resistance to Bafetinib + Dasatinib in Chronic Myeloid Leukemia (CIViC Level D); 1 further curated variant–drug associations are listed below.

This gene encodes a tyrosine protein kinase, which maybe involved in the regulation of mast cell degranulation, and erythroid differentiation. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 4067 — RefSeq curated summary.

At a glance

• Gene–disease (curated): autoinflammatory disease, systemic, with vasculitis (Strong, GenCC)
• GWAS associations: 17
• Clinical variants (ClinVar): 319 total — 4 pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 83 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 2 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_002350

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6735
Approved symbol	LYN
Name	LYN proto-oncogene, Src family tyrosine kinase
Location	8q12.1
Locus type	gene with protein product
Status	Approved
Aliases	JTK8
Ensembl gene	ENSG00000254087
Ensembl biotype	protein_coding
OMIM	165120
Entrez	4067

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 10 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000420292, ENST00000519728, ENST00000520050, ENST00000520220, ENST00000862996, ENST00000862997, ENST00000862998, ENST00000862999, ENST00000967493, ENST00000967494, ENST00000967495

RefSeq mRNA: 2 — MANE Select: NM_002350 NM_001111097, NM_002350

CCDS: CCDS47859, CCDS6162

Canonical transcript exons

ENST00000519728 — 13 exons

Exon	Start	End
ENSE00002089756	56009908	56014169
ENSE00002120811	55879835	55880103
ENSE00002215964	55999418	55999549
ENSE00002225764	55950459	55950557
ENSE00002227592	55951966	55952115
ENSE00002235410	55950681	55950784
ENSE00002247695	55946448	55946493
ENSE00002289390	55941855	55941991
ENSE00002292125	55953832	55953984
ENSE00002292161	55947618	55947723
ENSE00002310886	55998346	55998499
ENSE00003505232	55969717	55969793
ENSE00003544022	55966715	55966897

Expression profiles

Bgee: expression breadth ubiquitous, 263 present calls, max score 98.64.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.0677 / max 3646.1187, expressed in 1704 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
88905	48.4511	1665
88904	4.2116	1194
88916	0.2852	118
88917	0.1197	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	98.64	gold quality
mononuclear cell	CL:0000842	98.59	gold quality
leukocyte	CL:0000738	98.47	gold quality
blood	UBERON:0000178	98.28	gold quality
palpebral conjunctiva	UBERON:0001812	97.26	gold quality
bone marrow	UBERON:0002371	96.38	gold quality
nasal cavity epithelium	UBERON:0005384	96.37	gold quality
bone marrow cell	CL:0002092	95.85	gold quality
vermiform appendix	UBERON:0001154	95.47	gold quality
periodontal ligament	UBERON:0008266	95.33	gold quality
granulocyte	CL:0000094	95.05	gold quality
trabecular bone tissue	UBERON:0002483	94.86	gold quality
epithelium of nasopharynx	UBERON:0001951	94.74	gold quality
pancreatic ductal cell	CL:0002079	93.98	gold quality
spleen	UBERON:0002106	92.99	gold quality
caecum	UBERON:0001153	91.70	gold quality
lower lobe of lung	UBERON:0008949	91.62	gold quality
lymph node	UBERON:0000029	91.50	gold quality
duodenum	UBERON:0002114	91.49	gold quality
epithelial cell of pancreas	CL:0000083	91.44	silver quality
tonsil	UBERON:0002372	91.05	gold quality
placenta	UBERON:0001987	90.46	gold quality
nasal cavity mucosa	UBERON:0001826	90.45	gold quality
gall bladder	UBERON:0002110	89.74	gold quality
epithelium of bronchus	UBERON:0002031	88.91	gold quality
bronchus	UBERON:0002185	88.76	gold quality
mucosa of paranasal sinus	UBERON:0005030	88.52	gold quality
choroid plexus epithelium	UBERON:0003911	88.48	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	88.42	gold quality
bronchial epithelial cell	CL:0002328	88.22	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 10.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	68.88
E-CURD-122	yes	41.35
E-MTAB-10553	yes	33.83
E-HCAD-35	yes	30.49
E-MTAB-9467	yes	24.73
E-MTAB-10287	yes	24.11
E-MTAB-9221	yes	23.81
E-HCAD-13	yes	23.75
E-CURD-119	yes	5.29
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ELF1, ELF2, MITF, NANOG, TP63

miRNA regulators (miRDB)

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

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-3671	99.90	73.04	3897
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-4496	99.88	68.89	2236
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-6857-5P	99.87	65.32	985

Literature-anchored findings (GeneRIF, showing 40)

• The Lyn/CD22/SHP-1 pathway is important in autoimmunity. Naive and tolerant B-cells differ in their calcium signaling in response to antigenic stimulation. (PMID:11826756)
• Activation of Lyn kinase is necessary for proliferation of CD45+ myeloma cells by IL-6. (PMID:11877294)
• Association of Fyn and Lyn with the proline-rich domain of glycoprotein VI regulates intracellular signaling (PMID:11943772)
• CD45 tyrosine phosphatase inhibits erythroid differentiation of umbilical cord blood CD34+ cells associated with selective inactivation of Lyn. (PMID:12393728)
• role in transduction of the TPO proliferative signal in a megakaryocyte cell line (PMID:12495897)
• STI571 resistance is acquired through selection of BCR-ABL independent cells that overexpress src-related kinase LYN (PMID:12509383)
• Lyn tyrosine kinase inhibits nuclear export of the p53 tumor suppressor in breast neoplasms (PMID:12642697)
• SHIP-1 and Lyn have roles in the negative regulation of M-CSF-R-induced Akt activation (PMID:12882960)
• 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)
• SRC kinases LYN & HCK let engaged b2 integrins form focal-adhesion-like structures needed for stable shear-resistant PMN adhesion. SRC-dependent outside-in signalling is needed for integrin adhesiveness triggered by a classical chemoattractant like IL-8. (PMID:14969582)
• SHIP1 and Lyn have roles as negative regulators of integrin alpha(IIb)beta(3) adhesive and signaling function (PMID:15166241)
• The kinase domain of Lyn plays a role in Lyn trafficking besides catalysis of substrate phosphorylation. (PMID:15173188)
• LYN and FYN are downregulated by CBL in osteoblast differentiation induced by constitutive FGFR2 activation (PMID:15190072)
• LYN amplification is associated with malignant mixed tumor of salivary gland (PMID:15262430)
• role in the regulation of lipopolysaccharide priming in neutrophils (PMID:15501776)
• Kaposi sarcoma-associated herpesvirus K1 protein-mediated constitutive Lyn kinase activation in K1 lymphoma cells is crucial for the production of VEGF and NF-kappaB activation (PMID:15665117)
• The LYN is present in the majority of mediastinal B cell lymphomas. (PMID:15744341)
• HS1 Tyr phosphorylation catalyzed by Syk and Lyn plays a crucial role in the translocation of the protein to the membrane and is involved in the cytoskeleton rearrangement triggered by thrombin in human platelets (PMID:15795233)
• altered Lyn expression in B cells from a majority of patients with systemic lupus erythematosus (PMID:16320343)
• in hematopoietic cells stimulated via CXCR4, Lyn kinase is a positive regulator of cell movement while negatively regulating adhesion to stromal cells by inhibiting the ICAM-1-binding activity of beta(2) integrins (PMID:16467205)
• LYN can short-circuit conventional B cell receptor signaling in SLP65-deficient B cell lymphoma cells and thereby promote activation of survival and proliferation-related molecules (PMID:16568084)
• A key result is that the conformational transition involves a switch in an electrostatic network of six polar residues between the active and the down-regulated conformations. The exchange between interactions links the three main motions of the CD. (PMID:16597828)
• lysophosphatidic acid-induced IL-8 secretion is partly dependent on EGFR transactivation regulated by PKCdelta-dependent activation of Lyn kinase and MMPs and proHB-EGF (PMID:16687414)
• Activation of Lyn and its interaction with rafts and toll-like receptor 2 play an important role in the initial stages of Pseudomonas aeruginosa interaction with host lung cells. (PMID:16791881)
• FLT3/ITD (internal tandem duplication)specifically associates with Lyn, phosphorylating Lyn in vivo. FLT3/ITD receptors bind Lyn with a higher affinity than wild-type in vitro. This is relative to the intensity of tyrosyl phosphorylation of the receptor. (PMID:17230226)
• Hic-5 and paxillin function as negative feedback regulators of Src family kinases in aggregated platelets (PMID:17233630)
• Thus, these results suggest that endogenous c-Src, c-Yes, and Lyn are differentially activated through Cdc2 activation during M phase. (PMID:17692281)
• Lyn is weakly phosphorylated in normal B cells, but strongly phosphorylated in myeloma B cells. (PMID:17701175)
• role in control of proliferation and survival in most B-non-Hodgkin lymphomas (PMID:18070987)
• Thus the phosphorylation and dephosphorylation of caspase-8, mediated by Lyn and SHP-1, respectively, represents a novel, dynamic post-translational mechanism for the regulation of neutrophil apoptosis (PMID:18086677)
• Lyn activation is BCR-ABL independent, it is complexed with the Gab2 and c-Cbl adapter/scaffold proteins, and it mediates persistent Gab2 and BCR-ABL tyrosine phosphorylation in the presence or absence of imatinib. (PMID:18235045)
• A crystal of the mono-phosphorylated sample was diffracted to 3.2A (PMID:18272395)
• P-selectin-PSGL-1-induces TF and IL8 expression through Lyn phosphorylation, and part of the inhibitory effect of IL10 depends on reduced phosphorylation (PMID:18363812)
• These results suggest that Src-family tyrosine kinases, including c-Src and Lyn, are involved in formation of the cortical actin cap, which may serve as a platform of tyrosine phosphorylation signaling. (PMID:18457834)
• LYN activation was independent of BCR-ABL in cells from imatinib-resistant chronic myelogenous leukemia patients (CML); LYN kinase may be involved in imatinib resistance in CML patients with mutation-negative BCR-ABL (PMID:18577747)
• PLSCR1 is a novel amplifier of FcepsilonRI signaling that acts selectively on the Lyn-initiated LAT/phospholipase Cgamma1/calcium axis, resulting in potentiation of a selected set of mast cell responses (PMID:18579528)
• Geldanamycin-induced Lyn dissociation from aberrant Hsp90-stabilized cytosolic complex is an early event in apoptotic mechanisms in B-chronic lymphocytic leukemia. (PMID:18768392)
• Lyn is an important part of a regulatory network that couples SDF-1/CXCR4-induced monocyte chemotactic signals with down-regulation of beta2 integrin/LFA-1-dependent adhesion to activated brain microvascular endothelial cells. (PMID:18802065)
• These results suggest that Lyn being imported into and rapidly exported from the nucleus preferentially accumulates in the nucleus by inhibition of the kinase activity and lipid modification. (PMID:18817770)
• Lyn is downstream of Jak2, and Jak2 maintains activated Lyn kinase in CML through the SET-PP2A-Shp1 pathway. (PMID:19234487)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lyn	ENSDARG00000067916
mus_musculus	Lyn	ENSMUSG00000042228
rattus_norvegicus	Lyn	ENSRNOG00000008180

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122)

Protein

Protein identifiers

Tyrosine-protein kinase Lyn — P07948 (reviewed: P07948)

Alternative names: Lck/Yes-related novel protein tyrosine kinase, V-yes-1 Yamaguchi sarcoma viral related oncogene homolog, p53Lyn, p56Lyn

All UniProt accessions (2): E5RJ37, P07948

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that transmits signals from cell surface receptors and plays an important role in the regulation of innate and adaptive immune responses, hematopoiesis, responses to growth factors and cytokines, integrin signaling, but also responses to DNA damage and genotoxic agents. Functions primarily as negative regulator, but can also function as activator, depending on the context. Required for the initiation of the B-cell response, but also for its down-regulation and termination. Plays an important role in the regulation of B-cell differentiation, proliferation, survival and apoptosis, and is important for immune self-tolerance. Acts downstream of several immune receptors, including the B-cell receptor, CD79A, CD79B, CD5, CD19, CD22, FCER1, FCGR2, FCGR1A, TLR2 and TLR4. Plays a role in the inflammatory response to bacterial lipopolysaccharide. Mediates the responses to cytokines and growth factors in hematopoietic progenitors, platelets, erythrocytes, and in mature myeloid cells, such as dendritic cells, neutrophils and eosinophils. Acts downstream of EPOR, KIT, MPL, the chemokine receptor CXCR4, as well as the receptors for IL3, IL5 and CSF2. Plays an important role in integrin signaling. Regulates cell proliferation, survival, differentiation, migration, adhesion, degranulation, and cytokine release. Involved in the regulation of endothelial activation, neutrophil adhesion and transendothelial migration. Down-regulates signaling pathways by phosphorylation of immunoreceptor tyrosine-based inhibitory motifs (ITIM), that then serve as binding sites for phosphatases, such as PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1, that modulate signaling by dephosphorylation of kinases and their substrates. Phosphorylates LIME1 in response to CD22 activation. Phosphorylates BTK, CBL, CD5, CD19, CD72, CD79A, CD79B, CSF2RB, DOK1, HCLS1, LILRB3/PIR-B, MS4A2/FCER1B, SYK and TEC. Promotes phosphorylation of SIRPA, PTPN6/SHP-1, PTPN11/SHP-2 and INPP5D/SHIP-1. Mediates phosphorylation of the BCR-ABL fusion protein. Required for rapid phosphorylation of FER in response to FCER1 activation. Mediates KIT phosphorylation. Acts as an effector of EPOR (erythropoietin receptor) in controlling KIT expression and may play a role in erythroid differentiation during the switch between proliferation and maturation. Depending on the context, activates or inhibits several signaling cascades. Regulates phosphatidylinositol 3-kinase activity and AKT1 activation. Regulates activation of the MAP kinase signaling cascade, including activation of MAP2K1/MEK1, MAPK1/ERK2, MAPK3/ERK1, MAPK8/JNK1 and MAPK9/JNK2. Mediates activation of STAT5A and/or STAT5B. Phosphorylates LPXN on ‘Tyr-72’. Kinase activity facilitates TLR4-TLR6 heterodimerization and signal initiation. Phosphorylates SCIMP on ‘Tyr-107’; this enhances binding of SCIMP to TLR4, promoting the phosphorylation of TLR4, and a selective cytokine response to lipopolysaccharide in macrophages. Phosphorylates CLNK. Phosphorylates BCAR1/CAS and NEDD9/HEF1.

Subunit / interactions. Interacts with TEC. Interacts (via SH2 domain) with FLT3 (tyrosine phosphorylated). Interacts with LIME1 and with CD79A upon activation of the B-cell antigen receptor. Interacts with the B-cell receptor complex. Interacts with phosphorylated THEMIS2. Interacts with EPOR. Interacts with MS4A2/FCER1B. Interaction (via the SH2 and SH3 domains) with MUC1 is stimulated by IL7 and the subsequent phosphorylation increases the binding between MUC1 and CTNNB1/beta-catenin. Interacts with ADAM15. Interacts with NDFIP2 and more weakly with NDFIP1. Interacts with FASLG. Interacts with KIT. Interacts with HCLS1. Interacts with FCGR2B. Interacts with FCGR1A; the interaction may be indirect. Interacts with CD19, CD22, CD79A and CD79B. Interacts (via SH3 domain) with CBLC, PPP1R15A and PDE4A. Interacts with TGFB1I1. Interacts (via SH3 domain) with PIK3R1, the regulatory subunit of phosphatidylinositol 3-kinase; this interaction enhances phosphatidylinositol 3-kinase activity. Interacts with CSF2RB, the common subunit of the IL3, IL5 and CSF2 receptors. Interacts with PAG1; identified in a complex with PAG1 and STAT3. Interacts with ABL1. Interacts with PTPN6/SHP-1. Interacts (via SH3 domain) with SCIMP (via proline-rich region). This interaction facilitates the phosphorylation of SCIMP on ‘Tyr-107’, which enhances binding of SCIMP to TLR4, and consequently the phosphorylation of TLR4 in response to stimulation by lipopolysaccharide in macrophages. Interacts with LPXN (via LD motif 3) and the interaction is induced upon B-cell antigen receptor (BCR) activation. Interacts (via SH3-domain) with ANKRD54 (via ankyrin repeat region) in an activation-independent status of LYN. Forms a multiprotein complex with ANKRD54 and HCLS1. Interacts (via SH2 and SH3 domains) with UNC119; leading to LYN activation. Interacts with CD36. Interacts with LYN. Interacts with SKAP1 and FYB1; this interaction promotes the phosphorylation of CLNK. Interacts with BCAR1/CAS and NEDD9/HEF1. (Microbial infection) Interacts with Epstein-Barr virus LMP2A. (Microbial infection) Interacts with Herpes virus saimiri tyrosine kinase interacting protein (Tip).

Subcellular location. Cell membrane. Nucleus. Cytoplasm. Perinuclear region. Golgi apparatus. Membrane.

Tissue specificity. Detected in monocytes (at protein level). Detected in placenta, and in fetal brain, lung, liver and kidney. Widely expressed in a variety of organs, tissues, and cell types such as epidermoid, hematopoietic, and neuronal cells. Expressed in primary neuroblastoma tumors.

Post-translational modifications. Ubiquitinated by CBL, leading to its degradation. Ubiquitination is SH3-dependent. Autophosphorylated. Phosphorylated on tyrosine residues in response to KIT signaling. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylation at Tyr-508 inhibits kinase activity. Phosphorylated at Tyr-508 by CSK. Dephosphorylated by PTPRC/CD45. Becomes rapidly phosphorylated upon activation of the B-cell receptor and the immunoglobulin receptor FCGR1A. Phosphorylated in response to ITGB1 in B-cells.

Disease relevance. Autoinflammatory disease, systemic, with vasculitis (SAIDV) [MIM:620376] An autosomal dominant disorder characterized by systemic autoinflammation manifesting in the first hours of life with diffuse purpuric skin lesions, fever, hepatosplenomegaly, and increased C-reactive protein. Additional clinical features include periorbital edema, conjunctivitis, urticaria, atopic dermatitis, abdominal pain, and arthralgia. Laboratory studies may show leukocytosis, thrombocytopenia, and autoantibodies. The disease is caused by variants affecting the gene represented in this entry. Constitutively phosphorylated and activated in cells from a number of chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML) patients. Mediates phosphorylation of the BCR-ABL fusion protein. Abnormally elevated expression levels or activation of LYN signaling may play a role in survival and proliferation of some types of cancer cells.

Activity regulation. Subject to autoinhibition, mediated by intramolecular interactions between the SH2 domain and the C-terminal phosphotyrosine. Phosphorylation at Tyr-397 is required for optimal activity. Phosphorylated by CSK at Tyr-508; phosphorylation at Tyr-508 inhibits kinase activity. Kinase activity is modulated by dephosphorylation by PTPRC/CD45. Inhibited by Dasatinib, PP2, and SU6656.

Domain organisation. The protein kinase domain plays an important role in its localization in the cell membrane.

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

Isoforms (2)

UniProt ID	Names	Canonical?
P07948-1	1, LYN A, p56lyn	yes
P07948-2	2, LYN B, p53lyn

RefSeq proteins (2): NP_001104567, NP_002341* (*=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
IPR035748	Lyn_SH3	Domain
IPR035852	Lyn_SH2	Domain
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036860	SH2_dom_sf	Homologous_superfamily
IPR050198	Non-receptor_tyrosine_kinases	Family

Pfam: PF00017, PF00018, PF07714

Enzyme classification (BRENDA):

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

Substrate kinetics (BRENDA)

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

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

Catalyzed reactions (Rhea), 1 shown:

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

UniProt features (66 total): strand 14, helix 14, modified residue 10, mutagenesis site 9, sequence variant 5, domain 3, lipid moiety-binding region 2, turn 2, binding site 2, initiator methionine 1, chain 1, splice variant 1, region of interest 1, active site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
6NMW	X-RAY DIFFRACTION	1.2
8WFF	X-RAY DIFFRACTION	1.3
5XY1	X-RAY DIFFRACTION	2.7
3A4O	X-RAY DIFFRACTION	3
1W1F	SOLUTION NMR
1WA7	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P07948-F1	83.44	0.63

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): 367 (proton acceptor)

Ligand- & substrate-binding residues (2): 253–261; 275

Post-translational modifications (12): 13, 193, 228, 306, 316, 397, 460, 473, 508, 2, 3, 11

Mutagenesis-validated functional residues (9):

Position	Phenotype
2	loss of localization to the cell membrane; when associated with a-3.
3	loss of localization to the cell membrane; when associated with a-2.
275	loss of activity and no effect on localization to the cell membrane. abundant localization in the nucleus; when associat
275	loss of kinase activity.
346	impedes the trafficking from the golgi apparatus toward the cell membrane; when associated with a-353; a-498 and a-499.
353	impedes the trafficking from the golgi apparatus toward the cell membrane; when associated with a-346; a-498 and a-499.
397	strongly reduced kinase activity.
498	impedes the trafficking from the golgi apparatus toward the cell membrane; when associated with a-346; a-353 and a-499.
499	impedes the trafficking from the golgi apparatus toward the cell membrane; when associated with a-346; a-353 and a-498.

Function

Pathways and Gene Ontology

Reactome pathways

68 pathways

ID	Pathway
R-HSA-114604	GPVI-mediated activation cascade
R-HSA-1433557	Signaling by SCF-KIT
R-HSA-1433559	Regulation of KIT signaling
R-HSA-202733	Cell surface interactions at the vascular wall
R-HSA-2029481	FCGR activation
R-HSA-210990	PECAM1 interactions
R-HSA-2454202	Fc epsilon receptor (FCERI) signaling
R-HSA-2682334	EPH-Ephrin signaling
R-HSA-2730905	Role of LAT2/NTAL/LAB on calcium mobilization
R-HSA-2871796	FCERI mediated MAPK activation
R-HSA-2871809	FCERI mediated Ca+2 mobilization
R-HSA-2871837	FCERI mediated NF-kB activation
R-HSA-389356	Co-stimulation by CD28
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-3928662	EPHB-mediated forward signaling
R-HSA-3928663	EPHA-mediated growth cone collapse
R-HSA-3928665	EPH-ephrin mediated repulsion of cells
R-HSA-5621480	Dectin-2 family
R-HSA-5621575	CD209 (DC-SIGN) signaling
R-HSA-5690714	CD22 mediated BCR regulation
R-HSA-69231	Cyclin D associated events in G1
R-HSA-75892	Platelet Adhesion to exposed collagen
R-HSA-9006335	Signaling by Erythropoietin
R-HSA-9027276	Erythropoietin activates Phosphoinositide-3-kinase (PI3K)
R-HSA-9027277	Erythropoietin activates Phospholipase C gamma (PLCG)
R-HSA-9027283	Erythropoietin activates STAT5
R-HSA-9027284	Erythropoietin activates RAS
R-HSA-912631	Regulation of signaling by CBL
R-HSA-9664323	FCGR3A-mediated IL10 synthesis
R-HSA-9664422	FCGR3A-mediated phagocytosis

MSigDB gene sets: 0 (showing top):

GO Biological Process (96): DNA damage checkpoint signaling (GO:0000077), cell morphogenesis (GO:0000902), B cell homeostasis (GO:0001782), regulation of cytokine production (GO:0001817), regulation of protein phosphorylation (GO:0001932), negative regulation of protein phosphorylation (GO:0001933), stimulatory C-type lectin receptor signaling pathway (GO:0002223), hematopoietic progenitor cell differentiation (GO:0002244), adaptive immune response (GO:0002250), Fc receptor mediated stimulatory signaling pathway (GO:0002431), tolerance induction to self antigen (GO:0002513), histamine secretion by mast cell (GO:0002553), platelet degranulation (GO:0002576), negative regulation of myeloid leukocyte differentiation (GO:0002762), immune response-regulating cell surface receptor signaling pathway (GO:0002768), Fc receptor mediated inhibitory signaling pathway (GO:0002774), negative regulation of inflammatory response to antigenic stimulus (GO:0002862), regulation of B cell apoptotic process (GO:0002902), protein phosphorylation (GO:0006468), autophagy (GO:0006914), inflammatory response (GO:0006954), DNA damage response (GO:0006974), response to sterol depletion (GO:0006991), signal transduction (GO:0007165), cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), positive regulation of cell population proliferation (GO:0008284), negative regulation of cell population proliferation (GO:0008285), response to xenobiotic stimulus (GO:0009410), response to toxic substance (GO:0009636), response to hormone (GO:0009725), response to carbohydrate (GO:0009743), positive regulation of neuron projection development (GO:0010976), oligodendrocyte development (GO:0014003), fatty acid transport (GO:0015908), peptidyl-tyrosine phosphorylation (GO:0018108), erythrocyte differentiation (GO:0030218), eosinophil differentiation (GO:0030222), positive regulation of cell migration (GO:0030335), negative regulation of B cell proliferation (GO:0030889), neuron projection development (GO:0031175)

GO Molecular Function (24): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), platelet-derived growth factor receptor binding (GO:0005161), integrin binding (GO:0005178), ATP binding (GO:0005524), kinase activity (GO:0016301), SH3 domain binding (GO:0017124), enzyme binding (GO:0019899), signaling receptor activator activity (GO:0030546), ubiquitin protein ligase binding (GO:0031625), gamma-tubulin binding (GO:0043015), glycosphingolipid binding (GO:0043208), transmembrane transporter binding (GO:0044325), ephrin receptor binding (GO:0046875), phosphoprotein binding (GO:0051219), scaffold protein binding (GO:0097110), phosphorylation-dependent protein binding (GO:0140031), phosphatidylinositol 3-kinase activator activity (GO:0141038), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), transferase activity (GO:0016740), protein-containing complex binding (GO:0044877)

GO Cellular Component (20): nucleus (GO:0005634), cytoplasm (GO:0005737), lysosomal membrane (GO:0005765), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), adherens junction (GO:0005912), cytoplasmic side of plasma membrane (GO:0009898), mitochondrial crista (GO:0030061), endocytic vesicle membrane (GO:0030666), integrin alpha2-beta1 complex (GO:0034666), membrane raft (GO:0045121), perinuclear region of cytoplasm (GO:0048471), extracellular exosome (GO:0070062), glutamatergic synapse (GO:0098978), postsynaptic specialization, intracellular component (GO:0099091), lysosome (GO:0005764), membrane (GO:0016020), mitochondrial membrane (GO:0031966), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Fc epsilon receptor (FCERI) signaling	4
EPH-Ephrin signaling	3
Regulation of T cell activation by CD28 family	2
C-type lectin receptors (CLRs)	2
Platelet activation, signaling and aggregation	1
Signaling by Receptor Tyrosine Kinases	1
Signaling by SCF-KIT	1
Hemostasis	1
Fcgamma receptor (FCGR) dependent phagocytosis	1
Cell surface interactions at the vascular wall	1
Innate Immune System	1
Axon guidance	1
Signaling by the B Cell Receptor (BCR)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	5
cellular anatomical structure	5
cytoplasm	3
protein phosphorylation	2
establishment of localization in cell	2
signaling receptor binding	2
intracellular membrane-bounded organelle	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
anatomical structure morphogenesis	1
lymphocyte homeostasis	1
cytokine production	1
regulation of gene expression	1
regulation of multicellular organismal process	1
regulation of protein modification process	1
regulation of phosphorylation	1
regulation of protein phosphorylation	1
negative regulation of protein modification process	1
negative regulation of phosphorylation	1
innate immune response activating cell surface receptor signaling pathway	1
cellular response to lectin	1
hemopoiesis	1
cell differentiation	1
immune response	1
immune response-activating cell surface receptor signaling pathway	1
tolerance induction	1
histamine secretion involved in inflammatory response	1
mast cell degranulation	1
exocytic process	1
regulated exocytosis	1
myeloid leukocyte differentiation	1
regulation of myeloid leukocyte differentiation	1
negative regulation of myeloid cell differentiation	1
negative regulation of leukocyte differentiation	1
immune response-regulating signaling pathway	1
cell surface receptor signaling pathway	1
immune response-inhibiting cell surface receptor signaling pathway	1
inflammatory response to antigenic stimulus	1
regulation of inflammatory response to antigenic stimulus	1
negative regulation of inflammatory response	1

Protein interactions and networks

STRING

4558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LYN	CD79A	P11912	992
LYN	CD19	P15391	987
LYN	VAV1	P15498	987
LYN	BLNK	Q8WV28	986
LYN	SYK	P43405	986
LYN	CD79B	P40259	975
LYN	SCARB1	Q8WTV0	973
LYN	SCARB2	Q14108	973
LYN	CD36	P16671	973
LYN	FYN	P06241	965
LYN	BTK	Q06187	961
LYN	GP6	Q9HCN6	903
LYN	LCP2	Q13094	892
LYN	HCLS1	P14317	890
LYN	PAG1	Q9NWQ8	874

IntAct

290 interactions, top by confidence:

A	B	Type	Score
EGFR	LYN	psi-mi:“MI:0915”(physical association)	0.820
EGFR	GAPDH	psi-mi:“MI:0914”(association)	0.790
SRC	LYN	psi-mi:“MI:0914”(association)	0.670
PAG1	LYN	psi-mi:“MI:0915”(physical association)	0.640
PAG1	LYN	psi-mi:“MI:0914”(association)	0.640
GP6	LYN	psi-mi:“MI:0915”(physical association)	0.640
SLC17A5	LGALS8	psi-mi:“MI:0914”(association)	0.640
ADAM15	LYN	psi-mi:“MI:0407”(direct interaction)	0.610
LYN	KHDRBS1	psi-mi:“MI:0915”(physical association)	0.610
LYN	BANK1	psi-mi:“MI:0915”(physical association)	0.590
BANK1	LYN	psi-mi:“MI:0915”(physical association)	0.590
PTK2	LYN	psi-mi:“MI:0915”(physical association)	0.570
GP6	FYN	psi-mi:“MI:0914”(association)	0.560
ADAM12	LYN	psi-mi:“MI:0407”(direct interaction)	0.560
LYN	A2M	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (862): LYN (Affinity Capture-MS), LYN (Two-hybrid), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), LYN (Two-hybrid), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), PTK2 (Two-hybrid), LYN (Proximity Label-MS), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS), LYN (Affinity Capture-MS)

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

Diamond homologs: A0JNB0, A1A5H8, A1Y2K1, F1LM93, F1RDG9, G5EE56, O45539, P00519, P00520, P00521, P00522, P00523, P00524, P00525, P00526, P00527, P00528, P00544, P03949, P05480, P06239, P06240, P06241, P07947, P07948, P08103, P08630, P08631, P09324, P09769, P10447, P10936, P12931, P13115, P13116, P13406, P14084, P14085, P14234, P15054

SIGNOR signaling

94 interactions.

A	Effect	B	Mechanism
LYN	up-regulates	PPP1R15A	phosphorylation
LYN	unknown	SLAMF1	phosphorylation
CSK	down-regulates	LYN	phosphorylation
LYN	down-regulates	CDKN1B	phosphorylation
Bafetinib	down-regulates	LYN	“chemical inhibition”
LYN	“up-regulates activity”	HCLS1	phosphorylation
LYN	“up-regulates activity”	PTPN6	phosphorylation
ponatinib	“down-regulates activity”	LYN	“chemical inhibition”
LYN	“up-regulates activity”	LPXN	phosphorylation
LYN	“up-regulates activity”	BCR-Mk	phosphorylation
LYN	“up-regulates activity”	BCR-Ml	phosphorylation
LYN	“up-regulates activity”	BCR-Dk	phosphorylation
LYN	“up-regulates activity”	BCR-Dl	phosphorylation
LYN	“down-regulates activity”	CD22	phosphorylation
LYN	“up-regulates activity”	DOK3	phosphorylation
NEDD4	“down-regulates quantity by destabilization”	LYN	polyubiquitination
LYN	“up-regulates activity”	WAS	phosphorylation
LYN	“up-regulates activity”	ACLY	phosphorylation
CSNK1G3	“up-regulates quantity by stabilization”	LYN	phosphorylation
CSNK1G1	“up-regulates quantity by stabilization”	LYN	phosphorylation
CSNK1G2	“up-regulates quantity by stabilization”	LYN	phosphorylation
LYN	“down-regulates activity”	IKBKG	phosphorylation
LYN	“up-regulates activity”	KCND3	phosphorylation
LYN	“down-regulates activity”	YY1	phosphorylation
PTPRO	“down-regulates activity”	LYN	dephosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 160 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	9	42.9×	2e-10
Constitutive Signaling by EGFRvIII	5	32.7×	2e-05
Signaling by ERBB2 ECD mutants	5	30.8×	2e-05
Regulation of KIT signaling	5	27.6×	3e-05
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	5	26.2×	4e-05
Downstream signal transduction	7	24.4×	1e-06
Signaling by SCF-KIT	9	20.5×	2e-07
DAP12 signaling	6	20.3×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
leukocyte migration	6	25.8×	7e-05
Fc-gamma receptor signaling pathway involved in phagocytosis	5	24.2×	6e-04
T cell costimulation	7	18.1×	7e-05
response to interleukin-1	5	17.6×	2e-03
peptidyl-tyrosine phosphorylation	5	14.5×	4e-03
ephrin receptor signaling pathway	5	11.9×	6e-03
platelet aggregation	5	11.6×	6e-03
receptor internalization	5	11.2×	7e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 2 cancer types — CLLSLL, DLBCLNOS.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	0
Uncertain significance	126
Likely benign	159
Benign	11

Top pathogenic / likely-pathogenic (4)

Variant ID	HGVS	Classification
1895415	NM_002350.4(LYN):c.1519C>T (p.Gln507Ter)	Pathogenic
1895416	NM_002350.4(LYN):c.1523A>T (p.Tyr508Phe)	Pathogenic
1895417	NM_002350.4(LYN):c.1524C>G (p.Tyr508Ter)	Pathogenic
2502324	NM_002350.4(LYN):c.1522T>C (p.Tyr508His)	Pathogenic

SpliceAI

2789 predictions. Top by Δscore:

Variant	Effect	Δscore
8:55880100:GCGG:G	donor_gain	1.0000
8:55880102:GG:G	donor_gain	1.0000
8:55880103:GG:G	donor_gain	1.0000
8:55941992:G:GG	donor_gain	1.0000
8:55947610:A:AG	acceptor_gain	1.0000
8:55947611:T:G	acceptor_gain	1.0000
8:55947613:TTTA:T	acceptor_loss	1.0000
8:55947614:TTA:T	acceptor_loss	1.0000
8:55947616:A:AG	acceptor_gain	1.0000
8:55947617:G:GA	acceptor_gain	1.0000
8:55947617:GA:G	acceptor_gain	1.0000
8:55947617:GAT:G	acceptor_gain	1.0000
8:55947617:GATC:G	acceptor_gain	1.0000
8:55947617:GATCC:G	acceptor_gain	1.0000
8:55947719:GAGGA:G	donor_gain	1.0000
8:55947720:AGGA:A	donor_gain	1.0000
8:55947720:AGGAG:A	donor_loss	1.0000
8:55947721:GGA:G	donor_gain	1.0000
8:55947721:GGAG:G	donor_gain	1.0000
8:55947721:GGAGT:G	donor_loss	1.0000
8:55947722:GA:G	donor_gain	1.0000
8:55947722:GAG:G	donor_gain	1.0000
8:55947723:AGT:A	donor_loss	1.0000
8:55947724:G:GG	donor_gain	1.0000
8:55947724:GTAAG:G	donor_loss	1.0000
8:55947725:T:A	donor_loss	1.0000
8:55947765:GCCAC:G	donor_gain	1.0000
8:55950454:TCTAG:T	acceptor_loss	1.0000
8:55950455:CTA:C	acceptor_loss	1.0000
8:55950456:TAG:T	acceptor_loss	1.0000

AlphaMissense

3401 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:55950469:T:A	W99R	1.000
8:55950469:T:C	W99R	1.000
8:55950682:T:A	W129R	1.000
8:55950682:T:C	W129R	1.000
8:55950704:G:C	R136T	1.000
8:55950704:G:T	R136M	1.000
8:55950705:G:C	R136S	1.000
8:55950705:G:T	R136S	1.000
8:55950712:G:C	A139P	1.000
8:55950725:T:A	L143H	1.000
8:55950725:T:C	L143P	1.000
8:55950758:T:C	L154P	1.000
8:55950763:A:G	R156G	1.000
8:55950764:G:C	R156T	1.000
8:55950764:G:T	R156I	1.000
8:55950765:A:C	R156S	1.000
8:55950765:A:T	R156S	1.000
8:55951978:T:C	L167P	1.000
8:55951980:T:C	S168P	1.000
8:55951981:C:A	S168Y	1.000
8:55951981:C:T	S168F	1.000
8:55952022:C:G	H182D	1.000
8:55952023:A:G	H182R	1.000
8:55952024:C:A	H182Q	1.000
8:55952024:C:G	H182Q	1.000
8:55952025:T:G	Y183D	1.000
8:55953912:T:A	W240R	1.000
8:55953912:T:C	W240R	1.000
8:55953960:G:A	G256R	1.000
8:55953960:G:C	G256R	1.000

dbSNP variants (sampled 300 via entrez): RS1000009575 (8:55996118 T>G), RS1000031811 (8:55904488 C>A,T), RS1000053078 (8:55920944 G>A,C,T), RS1000054242 (8:55898146 T>TC), RS1000055701 (8:55962050 G>A), RS1000069733 (8:56005127 T>C), RS1000119340 (8:55946762 C>G), RS1000121718 (8:56005398 C>A,G), RS1000146441 (8:55947202 T>C), RS1000185469 (8:55881698 A>G), RS1000185972 (8:55913784 C>T), RS1000221347 (8:55929676 G>A), RS1000230780 (8:55956025 G>A), RS1000233094 (8:55998163 G>A), RS1000261843 (8:55956345 T>A,C)

Disease associations

OMIM: gene MIM:165120 | disease phenotypes: MIM:620376

GenCC curated gene-disease

Disease	Classification	Inheritance
autoinflammatory disease, systemic, with vasculitis	Strong	Autosomal dominant

Mondo (1): autoinflammatory disease, systemic, with vasculitis (MONDO:0957271)

Orphanet (0):

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000031	Epididymitis
HP:0000155	Oral ulcer
HP:0000316	Hypertelorism
HP:0000509	Conjunctivitis
HP:0000952	Jaundice
HP:0000979	Purpura
HP:0001025	Urticaria
HP:0001047	Atopic dermatitis
HP:0001369	Arthritis
HP:0001395	Hepatic fibrosis
HP:0001396	Cholestasis
HP:0001433	Hepatosplenomegaly
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth
HP:0001640	Cardiomegaly
HP:0001744	Splenomegaly
HP:0001789	Hydrops fetalis
HP:0001873	Thrombocytopenia
HP:0001903	Anemia
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002007	Frontal bossing
HP:0002014	Diarrhea
HP:0002027	Abdominal pain
HP:0002099	Asthma
HP:0002240	Hepatomegaly
HP:0002315	Headache
HP:0002583	Colitis
HP:0002720	Decreased circulating IgA concentration

GWAS associations

17 associations (top):

Study	Trait	p-value
GCST000175_46	Height	7.000000e-08
GCST002458_1	Serum thyroid-stimulating hormone levels	2.000000e-10
GCST004610_164	White blood cell count	8.000000e-10
GCST004613_118	Sum neutrophil eosinophil counts	3.000000e-10
GCST004614_47	Granulocyte count	3.000000e-10
GCST004620_15	Sum basophil neutrophil counts	4.000000e-10
GCST004626_61	Myeloid white cell count	2.000000e-10
GCST004629_124	Neutrophil count	4.000000e-10
GCST005752_119	Systemic lupus erythematosus	4.000000e-08
GCST005973_34	White blood cell count	4.000000e-08
GCST010002_300	Refractive error	1.000000e-19
GCST90002394_278	Monocyte percentage of white cells	7.000000e-14
GCST90002396_429	Mean reticulocyte volume	2.000000e-11
GCST90002397_340	Mean spheric corpuscular volume	1.000000e-10
GCST90002398_402	Neutrophil count	1.000000e-22
GCST90002402_46	Platelet count	2.000000e-14
GCST90002407_505	White blood cell count	2.000000e-22

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004833	neutrophil count
EFO:0004842	eosinophil count
EFO:0007987	granulocyte count
EFO:0005090	basophil count
EFO:0007989	monocyte percentage of leukocytes
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2363074 (PROTEIN FAMILY), CHEMBL3905 (SINGLE PROTEIN), CHEMBL6066565 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

83 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 357,339 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1448	NICLOSAMIDE	4	14,322
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1834657	INFIGRATINIB PHOSPHATE	4	285
CHEMBL1852688	INFIGRATINIB	4	2,209
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL2403108	CERITINIB	4	8,551
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4
CHEMBL535	SUNITINIB	4
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL571546	TIRBANIBULIN	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL939	GEFITINIB	4
CHEMBL941	IMATINIB	4

Clinical evidence (CIViC)

Drug × variant × indication: 2 predictive associations from 2 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
LYN OVEREXPRESSION	Bafetinib + Dasatinib	Chronic Myeloid Leukemia	Resistance	CIViC D	EID7874
LYN OVEREXPRESSION	Nilotinib	Chronic Myeloid Leukemia	Resistance	CIViC D	EID7875

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs1546519	LYN		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (12 total), top 12:

Ligand	Action	Affinity	Parameter
eCF506	Inhibition	9.1	pIC50
compound 23 [PMID: 17600705]	Inhibition	9.0	pIC50
bosutinib	Inhibition	8.1	pIC50
bafetinib	Inhibition	7.96	pIC50
NG-25	Inhibition	7.89	pIC50
ibrutinib	Inhibition	7.7	pIC50
pexmetinib	Inhibition	7.6	pIC50
tolimidone	Activation	7.2	pEC50
SU6656	Inhibition	6.89	pIC50
xiliertinib	Inhibition	6.3	pIC50
compound 36 [PMID: 21958547]	Inhibition	6.2	pIC50
acalabrutinib	Inhibition	6.0	pEC50

Binding affinities (BindingDB)

110 measured of 359 human assays (359 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
A-419259	IC50	0.3 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
1-[3-[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-9975882: Heteroaromatic compounds as BTK inhibitors
IBRUTINIB	IC50	0.8 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
N-[4-[4-amino-3-(4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]cyclohexyl]prop-2-enamide	IC50	1.1 nM	US-9278100: Inhibitors of bruton’s tyrosine kinase for the treatment of solid tumors
Staurosporine	KD	1.7 nM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
(3R,4R)-3-methoxy-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	3.93 nM	US-10189849: CDK inhibitors
3-[[2-[3-(morpholin-4-ylmethyl)phenyl]thieno[3,2-b]pyridin-7-yl]amino]phenol	IC50	5.1 nM	US-9062066: Anti-inflammatory compound having inhibitory activity against multiple tyrosine kinases and pharmaceutical composition containing same
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	IC50	10 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
BIIB-057	IC50	10.5 nM
BMS-354825	KD	27 nM
4-methyl-N-[3-(4-methyl-1H-imidazol-1-yl)-5-(trifluoromethyl)phenyl]-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	IC50	33 nM
3-(4-phenoxyphenyl)-1-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]imidazo[4,5-c]pyridin-2-one	IC50	55 nM	US-10358446: Bruton’s tyrosine kinase inhibitors
3-[3-chloro-4-(3-methylphenoxy)phenyl]-1-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]imidazo[4,5-c]pyridin-2-one	IC50	55 nM	US-10358446: Bruton’s tyrosine kinase inhibitors
3-[4-(2-chloro-3-fluorophenoxy)phenyl]-1-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]imidazo[4,5-c]pyridin-2-one	IC50	55 nM	US-10358446: Bruton’s tyrosine kinase inhibitors
N-[3-[3-[4-(3,5-difluorophenoxy)phenyl]-2-oxoimidazo[4,5-c]pyridin-1-yl]phenyl]prop-2-enamide	IC50	55 nM	US-10358446: Bruton’s tyrosine kinase inhibitors
3-[4-(3-fluoro-2-methoxyphenoxy)phenyl]-1-[(3R)-1-prop-2-enoylpyrrolidin-3-yl]imidazo[4,5-c]pyridin-2-one	IC50	55 nM	US-10358446: Bruton’s tyrosine kinase inhibitors
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
PKC-412	KD	190 nM
AMG 706	KD	300 nM
4-[[7-[2,6-bis(fluoranyl)phenyl]-9-chloranyl-5H-pyrimido[5,4-d][2]benzazepin-2-yl]amino]benzoic acid	KD	300 nM
CHEMBL2018022	IC50	352 nM
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-1-ethyl-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-7-[[5-(morpholine-4-carbonyl)-2-pyridinyl]amino]-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-phenyl-7-(pyridin-2-ylamino)-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-phenyl-3,4,4a,5,6,7,8,8a-octahydro-1H-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-1-(oxolan-3-yl)-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-1-phenyl-3-propan-2-yl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-7-[(5-methyl-2-pyridinyl)amino]-3-prop-1-ynyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-phenyl-1-propan-2-yl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-cyclopentyl-7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-cyclopropyl-7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
3-cyclopropyl-1-ethyl-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
3-cyclopentyl-1-ethyl-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-(2-fluorophenyl)-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-cyclopropyl-7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-propan-2-yl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
3-(3,3-dimethylbut-1-ynyl)-1-ethyl-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-(4-methylphenyl)-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-7-[(5-morpholin-4-yl-2-pyridinyl)amino]-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-(2-methylphenyl)-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-cyclopentyl-7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-3-propan-2-yl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
US9714247, 49	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-1-ethyl-3-propan-2-yl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-7-[(5-methoxy-2-pyridinyl)amino]-3-phenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-(3-hydroxyprop-1-ynyl)-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
1-ethyl-3-(3-hydroxy-3-methylbut-1-ynyl)-7-[(5-methyl-2-pyridinyl)amino]-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors
7-[[5-[2-(diethylamino)ethoxy]-2-pyridinyl]amino]-1,3-diphenyl-1,6-naphthyridin-2-one	IC50	550 nM	US-9714247: Multiple kinase pathway inhibitors

ChEMBL bioactivities

782 potent at pChembl≥5 of 808 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.80	IC50	0.16	nM	PONATINIB
9.62	IC50	0.24	nM	PONATINIB
9.40	IC50	0.4	nM	CHEMBL475584
9.32	IC50	0.473	nM	STAUROSPORINE
9.31	IC50	0.49	nM	STAUROSPORINE
9.24	Kd	0.57	nM	DASATINIB
9.14	IC50	0.728	nM	STAUROSPORINE
9.09	IC50	0.805	nM	STAUROSPORINE
9.05	IC50	0.9	nM	CHEMBL272888
9.02	IC50	0.964	nM	STAUROSPORINE
9.00	IC50	1	nM	CHEMBL249317
8.92	IC50	1.2	nM	CHEMBL3647967
8.92	IC50	1.2	nM	DASATINIB
8.90	Ki	1.259	nM	CHEMBL508928
8.89	IC50	1.3	nM	STAUROSPORINE
8.86	IC50	1.39	nM	STAUROSPORINE
8.81	IC50	1.55	nM	CHEMBL1916879
8.80	Ki	1.585	nM	CHEMBL1977148
8.72	IC50	1.9	nM	PONATINIB
8.70	IC50	2	nM	CHEMBL281957
8.70	Ki	1.995	nM	CHEMBL1988717
8.70	Ki	1.995	nM	CHEMBL1981725
8.70	Ki	1.995	nM	CHEMBL1982466
8.70	Ki	1.995	nM	ILORASERTIB
8.68	IC50	2.1	nM	STAUROSPORINE
8.67	IC50	2.118	nM	CHEMBL4436086
8.66	Kd	2.2	nM	CHEMBL386051
8.64	IC50	2.3	nM	CHEMBL2336005
8.63	IC50	2.36	nM	STAUROSPORINE
8.60	IC50	2.5	nM	CHEMBL2057912
8.60	Ki	2.512	nM	CHEMBL1982476
8.60	Ki	2.512	nM	CHEMBL1967116
8.60	Ki	2.512	nM	CHEMBL1989708
8.57	IC50	2.68	nM	STAUROSPORINE
8.55	IC50	2.8	nM	DASATINIB ANHYDROUS
8.52	IC50	3	nM	CHEMBL249097
8.51	IC50	3.1	nM	CHEMBL383010
8.50	Ki	3.162	nM	CHEMBL1970142
8.47	IC50	3.4	nM	CHEMBL536073
8.40	IC50	4	nM	CHEMBL2347053
8.40	IC50	4	nM	CHEMBL364623
8.40	IC50	4	nM	CHEMBL4798527
8.40	Ki	3.981	nM	CHEMBL1972584
8.40	Ki	3.981	nM	CHEMBL1090360
8.40	Ki	3.981	nM	CHEMBL1969102
8.40	Ki	3.981	nM	CHEMBL2005631
8.38	Ki	4.19	nM	CHEMBL256101
8.38	Kd	4.2	nM	BOSUTINIB
8.37	IC50	4.3	nM	CHEMBL2336005
8.36	IC50	4.4	nM	DASATINIB ANHYDROUS

PubChem BioAssay actives

461 with measured affinity, of 2154 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
5-[2-[5-[[4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-3-(trifluoromethyl)phenyl]carbamoyl]-2-methylphenyl]ethynyl]-N,1-dimethylimidazole-2-carboxamide	601221: Inhibition of human LYN using poly[Glu:Tyr] by Hotspot assay	ic50	0.0001	uM
Ponatinib	1431279: Inhibition of recombinant human Lyn using peptide substrate poly[Glu:Tyr] (4:1) in presence of [33-P]ATP by kinase hotspot assay	ic50	0.0002	uM
7-[4-(4-methylpiperazin-1-yl)cyclohexyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-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	0.0003	uM
1-[2-[4-[4-amino-5-(3-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]phenyl]ethyl]piperidin-4-ol	1407823: Inhibition of Lyn (unknown origin) using Src-family kinase bisamide rhodamine 110 peptide substrate after 1 hr by fluorescence assay	ic50	0.0004	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	1350985: Inhibition of LYN (unknown origin)	ic50	0.0005	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	435804: Binding constant for LYN kinase domain	kd	0.0006	uM
2-methyl-N-[2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	326716: Inhibition of Lyn by HTRF assay	ic50	0.0009	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzenesulfonamide	308762: Inhibition of Lyn	ic50	0.0010	uM
N-[3-[[8-[[(E)-4-(dimethylamino)but-2-enoyl]-methylamino]imidazo[1,5-a]quinoxalin-4-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	631101: Inhibition of LYN-A expressed in Sf9 cells after 60 mins by TR-FRET Assay	ic50	0.0015	uM
2-(2,6-dichloroanilino)-7-[(E)-3-(diethylamino)prop-1-enyl]-1,6-dimethyl-8H-imidazo[4,5-h]isoquinolin-9-one	164694: Inhibition of Protein tyrosine kinase Lyn	ic50	0.0020	uM
3-[[2-[(E)-2-(6-bromo-1,3-benzodioxol-5-yl)ethenyl]quinazolin-4-yl]amino]phenol	1612824: Inhibition of Lyn B (unknown origin) preincubated for 10 mins followed by substrate addition and measured after 1 hr by ADP-Glo luminescence assay	ic50	0.0021	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624862: Binding constant for LYN kinase domain	kd	0.0022	uM
Dasatinib	2193618: Inhibition of GST tagged Lyn (unknown origin) assessed as inhibition of phosphorylation using PTK biotinylated peptide substrate 2 as substrate preincubated for 5 mins followed by [gamma-32P]ATP addition	ic50	0.0028	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	308762: Inhibition of Lyn	ic50	0.0030	uM
3-bromo-4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0031	uM
4-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide;hydrochloride	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0034	uM
N-(2-chloro-6-methylphenyl)-2-[(2,6-dimethylpyrimidin-4-yl)amino]-1,3-thiazole-5-carboxamide	271969: Inhibition of Lyn	ic50	0.0040	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734745: Inhibition of human full length recombinant LYN using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0040	uM
(3Z)-3-[[5-(2-nitrophenyl)-1H-pyrazol-4-yl]methylidene]-1H-indol-2-one	739583: Inhibition of LYNA (unknown origin) after 10 mins by mobility shift assay	ic50	0.0040	uM
7-(2,6-dichlorophenyl)-5-methyl-N-[4-[2-(1-oxidopyrrolidin-1-ium-1-yl)ethoxy]phenyl]-1,2,4-benzotriazin-3-amine	330571: Inhibition of Lyn by luminescence based kinase assay	ki	0.0042	uM
Bosutinib	624862: Binding constant for LYN kinase domain	kd	0.0042	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0048	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(1-methylpiperidin-4-yl)oxy-5-(trifluoromethyl)benzamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0050	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-5-tert-butylthiophene-2-carboxamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0050	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(4-methylpiperazin-1-yl)-5-(trifluoromethyl)benzamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0060	uM
6-amino-7-(4-phenoxyphenyl)-9-[(3S)-1-prop-2-enoylpiperidin-3-yl]purin-8-one	1425037: 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	0.0060	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-(2,4-dichlorophenyl)-4-methylbenzamide	1780012: Inhibition of human full length recombinant LYN by radiometric scintillation counting analysis	ic50	0.0070	uM
46179972	446591: Inhibition of Lyn A	ic50	0.0070	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-tert-butylpyridine-4-carboxamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0070	uM
[4-[[(3S)-3-[(dimethylamino)methyl]pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]anilino]methanol;hydrochloride	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0076	uM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0085	uM
[(2S,3R,4R,5R)-5-[4-amino-3-(4-methylphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]-3-methyl-4-prop-2-ynoxyoxolan-2-yl]methyl ethenesulfonate	1940021: Inhibition of LYN (unknown origin) at 1 uM by kinase-profiling analysis	ic50	0.0089	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(4-ethylpiperazin-1-yl)-5-(trifluoromethyl)benzamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0090	uM
3-[2-[2-amino-5-(1-methylpyrazol-4-yl)-3-pyridinyl]ethynyl]-N-[3,5-bis(trifluoromethyl)phenyl]-4-methylbenzamide	1780012: Inhibition of human full length recombinant LYN by radiometric scintillation counting analysis	ic50	0.0090	uM
1-N’-[3-fluoro-4-[6-methoxy-7-(3-morpholin-4-ylpropoxy)quinolin-4-yl]oxyphenyl]-1-N-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide	624862: Binding constant for LYN kinase domain	kd	0.0091	uM
4-[5-(1-ethylpyrazol-4-yl)benzimidazol-1-yl]-2,6-dimethoxybenzamide	1992755: Inhibition of human LynA using poly (Glu,Tyr) as substrate incubated for 45 to 60 mins in presence of ATP by [33P]-gammaATP based Topcount scintillation counting analysis	ic50	0.0095	uM
5-[5-(hydroxymethyl)-3-pyridinyl]-N-(oxan-4-ylmethyl)-1H-indazole-3-carboxamide	1655580: Inhibition of human LynB using His-tagged Rb truncated protein as substrate incubated for 30 mins in presence of ATP at Km concentration by HTRF assay	ic50	0.0100	uM
7-[[(2R)-1-[[(2R)-oxiran-2-yl]methyl]pyrrolidin-2-yl]methyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1549561: Inhibition of human recombinant LYN using biotinyl-beta amyloid beta amyloid beta AKVEKIGEGTYGVVYK as substrate measured after 120 mins in the presence of ATP by HTRF assay	ic50	0.0100	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-chloro-4-[(4-ethylpiperazin-1-yl)methyl]benzamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0100	uM
2,6-difluoro-N-[2-fluoro-5-[5-[2-[(6-morpholin-4-yl-3-pyridinyl)amino]pyrimidin-4-yl]-2-propan-2-yl-1,3-thiazol-4-yl]phenyl]benzenesulfonamide	609678: Inhibition of Lyn	ic50	0.0100	uM
N-[(1S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-1,2-dihydroinden-5-yl]-3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylbenzamide	1817095: Inhibition of human LYN using poly [Glu:Tyr] as substrate incubated for 30 mins followed by 33P-ATP addition and measured after 2 hrs by liquid scintillation counter method	ic50	0.0100	uM
3-[(E)-[2-(2-hydroxy-5-methoxy-1H-indol-3-yl)indol-3-ylidene]amino]oxypropane-1,2-diol	1895373: Inhibition of recombinant Lyn (unknown origin)	ic50	0.0107	uM
(E)-4-(dimethylamino)-N-[4-(5-hydroxy-2-methylanilino)imidazo[1,5-a]quinoxalin-8-yl]-N-methylbut-2-enamide	631101: Inhibition of LYN-A expressed in Sf9 cells after 60 mins by TR-FRET Assay	ic50	0.0109	uM
(E)-4-(dimethylamino)-N-[7-methoxy-4-(2-methylanilino)imidazo[1,5-a]quinoxalin-8-yl]but-2-enamide	631101: Inhibition of LYN-A expressed in Sf9 cells after 60 mins by TR-FRET Assay	ic50	0.0109	uM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	295288: Inhibition of human Lyn kinase expressed in Sf9 cells	ic50	0.0110	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573277: Binding affinity to LYN in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0110	uM
N-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-(1H-pyrrolo[2,3-b]pyridin-4-yloxy)benzamide	2180128: Inhibition of LYN (unknown origin) Lys1 labeling site by KiNativ Profiling analysis	ic50	0.0129	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168216: Inhibition of human LYNB preincubated for 2 hrs followed by ATP addition and measured every 2 mins for 2.5 hrs by spectrophotometric analysis	ic50	0.0130	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435804: Binding constant for LYN kinase domain	kd	0.0140	uM
N-[3-[[1-(6-aminopyrimidin-4-yl)benzimidazol-2-yl]amino]-4-methylphenyl]-3-(trifluoromethyl)benzamide	469074: Inhibition of Tel-fused LYN expressed in mouse BAF3 cells	ic50	0.0140	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases expression, affects expression, affects cotreatment	7
methylmercuric chloride	increases expression, affects cotreatment, decreases expression	4
Tretinoin	decreases expression, increases expression	4
trichostatin A	affects cotreatment, increases expression	3
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	3
AG 1879	decreases reaction, increases phosphorylation, decreases phosphorylation	3
Imatinib Mesylate	decreases phosphorylation, decreases response to substance, affects cotreatment	3
Dasatinib	affects binding, decreases phosphorylation, decreases activity	3
Tetrachlorodibenzodioxin	affects cotreatment, decreases expression, increases expression	3
manganese chloride	decreases methylation, affects cotreatment, increases abundance, increases expression	2
entinostat	increases expression, affects cotreatment	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	2
Vorinostat	affects cotreatment, increases expression	2
Panobinostat	affects cotreatment, increases expression	2
Arsenic	increases abundance, increases expression, affects cotreatment	2
Estradiol	affects cotreatment, decreases expression, increases expression	2
Nickel	increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Polycyclic Aromatic Hydrocarbons	affects cotreatment, increases abundance, increases expression, affects expression	2
Quercetin	decreases reaction, increases phosphorylation, decreases expression, increases expression, affects cotreatment (+1 more)	2
Tobacco Smoke Pollution	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases methylation	1
triphenyl phosphate	affects expression	1
honokiol	decreases reaction, increases phosphorylation	1
sodium arsenate	increases abundance, increases expression	1
afimoxifene	decreases response to substance	1
potassium chromate(VI)	increases expression	1

ChEMBL screening assays

820 unique, capped per target: 814 binding, 4 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5719121	Binding	Inhibition of Src family in human RPMI-8226 cells assessed as reduction of cell growth incubated for 72 hrs by CellTiter 96 aqueous one solution cell proliferation assay	Small molecule inhibitor screen identifies synergistic activity of the bromodomain inhibitor CPI203 and bortezomib in drug resistant myeloma. — Oncotarget
CHEMBL1963745	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: LYN	PubChem BioAssay data set
CHEMBL4414990	ADMET	Inhibition of human LYN at 1 uM using poly[Glu:Tyr] (4:1) as substrate preincubated for 15 to 20 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method relative to control	Discovery of Zanubrutinib (BGB-3111), a Novel, Potent, and Selective Covalent Inhibitor of Bruton’s Tyrosine Kinase. — J Med Chem

Cellosaurus cell lines

12 cell lines: 10 cancer cell line, 1 induced pluripotent stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8JW	Abcam HCT 116 LYN KO	Cancer cell line	Male
CVCL_B8YD	Abcam MCF-7 LYN KO	Cancer cell line	Female
CVCL_B9M5	Abcam A-549 LYN KO	Cancer cell line	Male
CVCL_C4RU	NIHTVBi028-A	Induced pluripotent stem cell	Male
CVCL_D7TW	Ubigene A-549 LYN KO	Cancer cell line	Male
CVCL_D8PK	Ubigene HCT 116 LYN KO	Cancer cell line	Male
CVCL_D9IX	Ubigene HEK293 LYN KO	Transformed cell line	Female
CVCL_E0GT	Ubigene HeLa LYN KO	Cancer cell line	Female
CVCL_E2UG	ILKM2 Lyn	Cancer cell line	Female
CVCL_E2UH	ILKM8 Lyn	Cancer cell line	Sex unspecified

Clinical trials (associated diseases)

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