BLK

Summary

BLK (BLK proto-oncogene, Src family tyrosine kinase, HGNC:1057) is a protein-coding gene on chromosome 8p23.1, encoding Tyrosine-protein kinase Blk (P51451). Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling.

This gene encodes a nonreceptor tyrosine-kinase of the src family of proto-oncogenes that are typically involved in cell proliferation and differentiation. The protein has a role in B-cell receptor signaling and B-cell development. The protein also stimulates insulin synthesis and secretion in response to glucose and enhances the expression of several pancreatic beta-cell transcription factors.

Source: NCBI Gene 640 — RefSeq curated summary.

At a glance

• Gene–disease (curated): common variable immunodeficiency (Moderate, GenCC) — +4 more curated relationships
• GWAS associations: 109
• Clinical variants (ClinVar): 463 total — 43 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 73
• Druggable target: yes — 62 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001715

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1057
Approved symbol	BLK
Name	BLK proto-oncogene, Src family tyrosine kinase
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Aliases	MGC10442
Ensembl gene	ENSG00000136573
Ensembl biotype	protein_coding
OMIM	191305
Entrez	640

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 retained_intron, 3 protein_coding, 3 protein_coding_CDS_not_defined

ENST00000259089, ENST00000525389, ENST00000526097, ENST00000526778, ENST00000533828, ENST00000645242, ENST00000696154, ENST00000696155, ENST00000855155, ENST00000855156

RefSeq mRNA: 2 — MANE Select: NM_001715 NM_001330465, NM_001715

CCDS: CCDS5982

Canonical transcript exons

ENST00000259089 — 13 exons

Exon	Start	End
ENSE00000979579	11543224	11543347
ENSE00001838611	11494387	11494591
ENSE00003656621	11546052	11546103
ENSE00003966220	11557962	11558038
ENSE00003966221	11562979	11563110
ENSE00003966223	11549024	11549122
ENSE00003966224	11548032	11548125
ENSE00003966225	11555332	11555484
ENSE00003966226	11556658	11556837
ENSE00003966227	11561302	11561452
ENSE00003966229	11563903	11564599
ENSE00003966231	11554743	11554889
ENSE00003966233	11550159	11550262

Expression profiles

Bgee: expression breadth ubiquitous, 145 present calls, max score 92.72.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 3.5619 / max 492.6461, expressed in 137 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87393	0.9078	87
87402	0.7551	57
87392	0.7315	89
87394	0.3966	53
87391	0.2580	59
87389	0.2232	39
87390	0.1544	33
87401	0.0706	24
87388	0.0331	18
87395	0.0316	15

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
spleen	UBERON:0002106	92.72	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.25	gold quality
lymph node	UBERON:0000029	89.23	gold quality
granulocyte	CL:0000094	88.32	gold quality
vermiform appendix	UBERON:0001154	81.89	gold quality
small intestine Peyer’s patch	UBERON:0003454	81.52	gold quality
caecum	UBERON:0001153	76.02	gold quality
mucosa of transverse colon	UBERON:0004991	75.83	gold quality
small intestine	UBERON:0002108	75.42	gold quality
bone marrow cell	CL:0002092	73.94	gold quality
blood	UBERON:0000178	73.09	gold quality
tonsil	UBERON:0002372	71.20	gold quality
stromal cell of endometrium	CL:0002255	70.60	gold quality
rectum	UBERON:0001052	68.32	gold quality
leukocyte	CL:0000738	67.47	gold quality
monocyte	CL:0000576	65.83	gold quality
mononuclear cell	CL:0000842	65.68	gold quality
right lobe of liver	UBERON:0001114	64.98	gold quality
gall bladder	UBERON:0002110	64.80	gold quality
colonic epithelium	UBERON:0000397	64.46	silver quality
transverse colon	UBERON:0001157	62.81	gold quality
tibialis anterior	UBERON:0001385	62.37	silver quality
superficial temporal artery	UBERON:0001614	60.76	gold quality
body of stomach	UBERON:0001161	60.49	gold quality
ileal mucosa	UBERON:0000331	59.96	silver quality
stomach	UBERON:0000945	58.79	gold quality
esophagus mucosa	UBERON:0002469	58.67	gold quality
bone marrow	UBERON:0002371	58.62	gold quality
intestine	UBERON:0000160	58.05	gold quality
upper lobe of left lung	UBERON:0008952	57.80	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-122	yes	92.76
E-HCAD-4	yes	53.90
E-ANND-3	yes	27.41
E-MTAB-9467	yes	21.02
E-GEOD-124858	no	1.83

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): APEX1, EBF1, ELF1, ELF2, MYC, NFKB1, NFKB, NKX6-1, PAX5, RUNX1

Literature-anchored findings (GeneRIF, showing 40)

• transcription of the B cell-specific blk gene is regulated by NERF/ELF-2 and AMl1 (PMID:14970218)
• identified and confirmed through replication two new genetic loci for SLE: a promoter-region allele associated with reduced expression of BLK and increased expression of C8orf13 and variants in the ITGAM-ITGAX region (PMID:18204098)
• The association of the C8orf13-BLK region with systemic lupus erythematosus was replicated in a Japanese population. (PMID:19180478)
• Our data confirmed association of STAT4 (rs7574865, odds ratio (OR) =1.71, P=3.55 x 10(-23)) and BLK (rs13277113, OR=0.77, P=1.34 x 10(-5)) with SLE (PMID:19225526)
• Blk is constitutively tyrosine phosphorylated in malignant cutaneous T-cell lymphoma cell lines and spontaneously active in kinase assays (PMID:19351960)
• STAT4 and BLK displayed a strong genetic association with primary antiphospholipid syndrome. (PMID:19644876)
• Findings point to BLK as a previously unrecognized modulator of beta-cell function, the deficit of which may lead to the development of diabetes. (PMID:19667185)
• Results indicate the FAM167A-BLK region may be a shared genetic factor for a number of autoimmune diseases in multiple populations, but the genetic contribution may be grater in Asian populations. (PMID:19740902)
• genetic polymorphism is associated with systemic sclerosis in North-American and European populations (PMID:19796918)
• study evaluated SNP rs2248932 from BLK and further defined its role in systemic lupus erythematosus (SLE) risk; its association with SLE was confirmed in Chinese Han population (PMID:20130895)
• Our findings indicate that the rs13277113A allele is associated not only with SLE but also with SSc and that the FAM167A-BLK region is a common genetic risk factor for both SLE and SSc. (PMID:20131239)
• our results do not support a major implication of the C8orf13-BLK gene region in susceptibility to Giant cell arteritis (PMID:20156505)
• studies found that IRF5, STAT4 and BLK are associated not only with systemic lupus erythematosus, but also rheumatoid arthritis and systemic sclerosis [review] (PMID:20453440)
• Moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and systemic lupus erythematosus. (PMID:21152986)
• This study shows a genetic interaction between BANK1 and BLK, and demonstrates that these molecules interact physically. (PMID:21978998)
• allelic variation in Blk does not play a major role in determining multifocal motor neuropathy susceptibility. (PMID:22003931)
• The genetic variants in the promoter region of BLK may cause dysregulation of BLK expression, which might finally contribute to the initiation and progression of systemic lupus erythematosus. (PMID:22313735)
• Single nucleotide polymorphism in BLK gene is associated with Kawasaki disease. (PMID:22446961)
• Blk allele expression differences at the protein level are restricted to early B cells. (PMID:22678060)
• Rare and common regulatory variants in BLK are involved in disease susceptibility in systemic lupus erythematosus. (PMID:22696686)
• the functional SNP BLK rs2248932 T/C variant allele was associated with rheumatoid arthritis development (PMID:22740142)
• Expression of RUNX1 isoforms and its target gene BLK in childhood acute lymphoblastic leukemia. (PMID:22748822)
• BCR-ABL downregulates the Blk gene (encoding B-lymphoid kinase) through c-Myc in leukemic stem cells in chronic myeloid leukemia (PMID:22797726)
• study demonstrated that the loss-of-function BLK-p.A71T mutation is very unlikely to cause MODY; instead, it may modestly influence type 2 diabetes risk through an interaction with obesity (PMID:23224494)
• BANK1 and BLK have roles in B-cell signaling through phospholipase C gamma 2 (PMID:23555801)
• This study confirms BANK1 as an RA susceptibility gene and for the first time provides evidence for epistasis between BANK1 and BLK in RA. (PMID:23646104)
• SNPs of the FAM167A-BLK region, but not the BANK1 SNPs, were associated with the development of primary Sjogren’s syndrome in Han Chinese. (PMID:23899688)
• The BLK region was significantly associated with Kawasaki disease susceptibility in populations of Korean and European descent. (PMID:24023612)
• Our study confirms evidence for epistasis between BLK and BANK1 in systemic lupus erythematosis from a Chinese population for the first time. (PMID:24085759)
• Report role of BLK genetic variants in confering risk of systemic lupus erythematosus in Chinese population. (PMID:24091983)
• The observations suggested that C8orf13-BLK, in combination with STAT4, plays a pivotal role in creating genetic susceptibility to polymyositis/dermatomyositis in Japanese individuals. (PMID:24632671)
• results demonstrated that both lupus-associated functional variants contribute to the autoimmune disease association by modulating transcription of BLK in B cells and thus potentially altering immune responses (PMID:24702955)
• B-lymphoid tyrosine kinase (Blk) is an oncogene and a potential target for therapy with dasatinib in cutaneous T-cell lymphoma (PMID:24919804)
• These results place Blk upstream of the p190RhoGAP-RhoA pathway in Galpha13-activated cells, overall representing an opposing signaling module during CXCL12-triggered invasion. (PMID:25025568)
• Results support previous findings that vaiants in the RHOB and FAM167A-BLK genes may be associated with susceptibility to systemic sclerosis. (PMID:25470816)
• Report a novel BLK gene variant in common variable immunodeficiency-patients that causes suppressed B-cell proliferation and reduced ability of B-cells to elicit antigen-specific CD4(+) T-cell responses. (PMID:25926555)
• our study reveals a previously unappreciated role of reduced BLK expression on extraperitoneal accumulation of B1a cells in mice, as well as the presence of IgG autoantibodies and B1-like cells in humans. (PMID:25972485)
• A major mechanism underlying the BLK association with autoimmune disease involves lowered thresholds for basal B cell receptor signaling, enhanced B cell-T cell interactions, and altered patterns of isotype switching. (PMID:26246128)
• Confirm the association of rs548234/ATG5, rs2736340/BLK and rs10516487/BANK1 with systemic lupus erythematosus in Chinese Han and reinforced our hypothesis of their epistasis effect in regulating B-cell signaling in SLE. (PMID:26420661)
• The systemic lupus erythematosus variant Ala71Thr of BLK severely decreases protein abundance and binding to BANK1 through impairment of the SH3 domain function. (PMID:26821283)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	lck	ENSDARG00000102525
mus_musculus	Blk	ENSMUSG00000014453
rattus_norvegicus	Blk	ENSRNOG00000010798

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), ABL2 (ENSG00000143322), FER (ENSG00000151422), JAK1 (ENSG00000162434), SYK (ENSG00000165025), PTK2 (ENSG00000169398), TNK1 (ENSG00000174292), YES1 (ENSG00000176105), FES (ENSG00000182511), LCK (ENSG00000182866), SRC (ENSG00000197122), LYN (ENSG00000254087)

Protein

Protein identifiers

Tyrosine-protein kinase Blk — P51451 (reviewed: P51451)

Alternative names: B lymphocyte kinase, p55-Blk

All UniProt accessions (1): P51451

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine kinase involved in B-lymphocyte development, differentiation and signaling. B-cell receptor (BCR) signaling requires a tight regulation of several protein tyrosine kinases and phosphatases, and associated coreceptors. Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. Signaling through BLK plays an important role in transmitting signals through surface immunoglobulins and supports the pro-B to pre-B transition, as well as the signaling for growth arrest and apoptosis downstream of B-cell receptor. Specifically binds and phosphorylates CD79A at ‘Tyr-188’and ‘Tyr-199’, as well as CD79B at ‘Tyr-196’ and ‘Tyr-207’. Also phosphorylates the immunoglobulin G receptors FCGR2A, FCGR2B and FCGR2C. With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. Also contributes to BTK activation by indirectly stimulating BTK intramolecular autophosphorylation. In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. Phosphorylates CGAS, promoting retention of CGAS in the cytosol.

Subunit / interactions. Interacts with CBL (via SH2 domain). Interacts with CD79A and CD79B (via SH2 domain).

Subcellular location. Cell membrane.

Tissue specificity. Expressed in lymphatic organs, pancreatic islets, Leydig cells, striate ducts of salivary glands and hair follicles.

Post-translational modifications. Phosphorylated on tyrosine residues after antibody-mediated surface engagement of the B-cell antigen receptor (BCR). Ubiquitination of activated BLK by the UBE3A ubiquitin protein ligase leads to its degradation by the ubiquitin-proteasome pathway.

Disease relevance. Maturity-onset diabetes of the young 11 (MODY11) [MIM:613375] A form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Antibody-mediated surface engagement of the B-cell antigen receptor (BCR) which results in the phosphorylation of BLK on tyrosine residues, stimulates the enzymatic activity.

Induction. Expression is under the control of NF-kappa-B as well as the B-cell specific transcription factors PAX5 and EBF1.

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

RefSeq proteins (2): NP_001317394, NP_001706* (*=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
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035853	Blk_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 (16 total): domain 3, sequence variant 2, sequence conflict 2, binding site 2, initiator methionine 1, chain 1, modified residue 1, lipid moiety-binding region 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P51451-F1	81.89	0.53

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): 360 (proton acceptor)

Ligand- & substrate-binding residues (2): 247–255; 269

Post-translational modifications (2): 389, 2

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-8939245	RUNX1 regulates transcription of genes involved in BCR signaling
R-HSA-983695	Antigen activates B Cell Receptor (BCR) leading to generation of second messengers
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-983705	Signaling by the B Cell Receptor (BCR)

MSigDB gene sets: 357 (showing top): REACTOME_ADAPTIVE_IMMUNE_SYSTEM, HOFMANN_CELL_LYMPHOMA_UP, GOBP_INSULIN_SECRETION, GOBP_ANTIGEN_RECEPTOR_MEDIATED_SIGNALING_PATHWAY, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GOBP_REGULATION_OF_HORMONE_LEVELS, GOBP_HORMONE_TRANSPORT, GOBP_CELL_CELL_SIGNALING, GOBP_POSITIVE_REGULATION_OF_INSULIN_SECRETION, GOBP_REGULATION_OF_PROTEIN_SECRETION, GOBP_REGULATION_OF_IMMUNE_RESPONSE, PID_CXCR4_PATHWAY, BROWNE_HCMV_INFECTION_14HR_DN, MODULE_301, GOBP_SECRETION

GO Biological Process (8): cell surface receptor protein tyrosine kinase signaling pathway (GO:0007169), peptidyl-tyrosine phosphorylation (GO:0018108), cell differentiation (GO:0030154), positive regulation of insulin secretion (GO:0032024), intracellular signal transduction (GO:0035556), B cell receptor signaling pathway (GO:0050853), immune response-activating cell surface receptor signaling pathway (GO:0002429), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), signaling receptor binding (GO:0005102), ATP binding (GO:0005524), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (3): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Transcriptional regulation by RUNX1	1
Signaling by the B Cell Receptor (BCR)	1
Immune System	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Adaptive Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
enzyme-linked receptor protein signaling pathway	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
cellular developmental process	1
insulin secretion	1
positive regulation of protein secretion	1
regulation of insulin secretion	1
positive regulation of peptide hormone secretion	1
intracellular anatomical structure	1
signal transduction	1
antigen receptor-mediated signaling pathway	1
immune response-activating signaling pathway	1
immune response-regulating cell surface receptor signaling pathway	1
phosphorylation	1
protein modification process	1
protein kinase activity	1
protein tyrosine kinase activity	1
protein binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1

Protein interactions and networks

STRING

2522 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BLK	FAM167A	Q96KS9	978
BLK	KLF11	O14901	823
BLK	BANK1	Q8NDB2	802
BLK	PAX4	O43316	741
BLK	HNF1A	P20823	706
BLK	TNFAIP3	P21580	702
BLK	MTMR9	Q96QG7	686
BLK	CD79A	P11912	668
BLK	ITPKC	Q96DU7	668
BLK	NEUROD1	Q13562	664
BLK	FCGR2A	P12318	661
BLK	STAT4	Q14765	660
BLK	IRF5	Q13568	651
BLK	MTMR8	Q96EF0	645
BLK	XKR6	Q5GH73	626

IntAct

216 interactions, top by confidence:

A	B	Type	Score
CSNK1A1	FAM83G	psi-mi:“MI:0914”(association)	0.900
BLK	STAT3	psi-mi:“MI:0915”(physical association)	0.830
STAT3	BLK	psi-mi:“MI:0915”(physical association)	0.830
BLK	EFS	psi-mi:“MI:0915”(physical association)	0.710
EFS	BLK	psi-mi:“MI:0915”(physical association)	0.710
EGFR	BLK	psi-mi:“MI:0915”(physical association)	0.690
HSP90AB1	BLK	psi-mi:“MI:0915”(physical association)	0.670
RNASE3	GGPS1	psi-mi:“MI:0914”(association)	0.640
MYH9	MYL12B	psi-mi:“MI:0914”(association)	0.640
TSR1	RPS3	psi-mi:“MI:0914”(association)	0.640
SYCP3	BLK	psi-mi:“MI:0915”(physical association)	0.590
	BLK	psi-mi:“MI:0915”(physical association)	0.560
BLK		psi-mi:“MI:0915”(physical association)	0.560
BLK	STAP2	psi-mi:“MI:0915”(physical association)	0.560
BLK	SH2D1B	psi-mi:“MI:0915”(physical association)	0.560
PIK3R1	BLK	psi-mi:“MI:0915”(physical association)	0.560
EFS	BLK	psi-mi:“MI:0915”(physical association)	0.560
BLK	MID2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (229): STAT3 (Two-hybrid), EFS (Two-hybrid), CCDC33 (Two-hybrid), BLK (Two-hybrid), ANKRD54 (Affinity Capture-MS), ATP5A1 (Affinity Capture-MS), ATP5B (Affinity Capture-MS), ATP5C1 (Affinity Capture-MS), ATP5D (Affinity Capture-MS), ATP5E (Affinity Capture-MS), ATP5F1 (Affinity Capture-MS), ATP5H (Affinity Capture-MS), ATP5I (Affinity Capture-MS), ATP5J (Affinity Capture-MS), ATP5J2 (Affinity Capture-MS)

ESM2 similar proteins: A1Y2K1, G5EE56, O13148, O45539, O73792, P00526, P00528, P00529, P04048, P06239, P06240, P06241, P08631, P09769, P10447, P13406, P14234, P16277, P17713, P24604, P25020, P29321, P31693, P32577, P39688, P41239, P41240, P41241, P42680, P42681, P42683, P42685, P42686, P42688, P42689, P42690, P50545, P51451, P63185, Q01621

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

11 interactions.

A	Effect	B	Mechanism
BLK	“up-regulates activity”	BCR-Mk	phosphorylation
BLK	“up-regulates activity”	BCR-Ml	phosphorylation
BLK	“up-regulates activity”	BCR-Dk	phosphorylation
BLK	“up-regulates activity”	BCR-Dl	phosphorylation
BLK	“up-regulates activity”	PLCG2	phosphorylation
BLK	“up-regulates activity”	FCGR2A	phosphorylation
BLK	“up-regulates activity”	FCGR2C	phosphorylation
BLK	“down-regulates activity”	CGAS	phosphorylation
BLK	“down-regulates activity”	SOCS1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Signaling by phosphorylated juxtamembrane, extracellular and kinase domain KIT mutants	5	22.6×	1e-03
Regulation of signaling by CBL	5	21.6×	1e-03
FLT3 Signaling	5	15.1×	3e-03
GPVI-mediated activation cascade	5	13.4×	4e-03
Signaling by SCF-KIT	6	12.9×	1e-03
Constitutive Signaling by Aberrant PI3K in Cancer	7	7.7×	4e-03
Cytokine Signaling in Immune system	12	4.3×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of mRNA stability	6	16.2×	2e-03

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	43
Likely pathogenic	4
Uncertain significance	188
Likely benign	118
Benign	71

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
144130	GRCh38/hg38 8p23.1(chr8:8222339-12182465)x1	Pathogenic
144626	GRCh38/hg38 8p23.1(chr8:8545843-11814470)x1	Pathogenic
144766	GRCh38/hg38 8p23.1(chr8:7834379-12182465)x3	Pathogenic
146455	GRCh38/hg38 8p23.1(chr8:8273108-11948451)x1	Pathogenic
146493	GRCh38/hg38 8p23.1(chr8:8273108-12383643)x1	Pathogenic
147314	GRCh38/hg38 8p23.1(chr8:7311968-12546553)x3	Pathogenic
147315	GRCh38/hg38 8p23.1(chr8:7311968-12546553)x1	Pathogenic
148431	GRCh38/hg38 8p23.1(chr8:8253505-12610034)x1	Pathogenic
149562	GRCh38/hg38 8p23.1(chr8:8253505-12003060)x1	Pathogenic
152312	GRCh38/hg38 8p23.1(chr8:8222339-11984333)x1	Pathogenic
152873	GRCh38/hg38 8p23.1(chr8:11440972-11984333)x3	Pathogenic
153672	GRCh38/hg38 8p23.1(chr8:8235647-12037723)x1	Pathogenic
154643	GRCh38/hg38 8p23.1(chr8:8273108-12610034)x1	Pathogenic
155213	GRCh38/hg38 8p23.1(chr8:8235544-12088347)x3	Pathogenic
155289	GRCh38/hg38 8p23.1(chr8:8235647-12077956)x1	Pathogenic
161001	GRCh38/hg38 8p23.1(chr8:8273108-11948451)x3	Pathogenic
161086	GRCh38/hg38 8p23.1(chr8:8222339-12182465)x1	Pathogenic
219040	GRCh37/hg19 8p23.1(chr8:8127723-11858461)x1	Pathogenic
2580324	GRCh37/hg19 8p23.1(chr8:7080281-12045269)x3	Pathogenic
2684522	GRCh37/hg19 8p23.1-22(chr8:8093169-14526969)x3	Pathogenic
31974	GRCh37/hg19 8p23.1(chr8:7053186-11805960)x3	Pathogenic
3242300	GRCh37/hg19 8p23.1(chr8:7153587-12245784)x3	Pathogenic
441584	GRCh37/hg19 8p23.1(chr8:8093169-11881742)x1	Pathogenic
4682715	GRCh37/hg19 8p23.1-22(chr8:11266131-16489491)x1	Pathogenic
563518	GRCh37/hg19 8p23.1(chr8:10647782-11898980)x1	Pathogenic
563536	GRCh37/hg19 8p23.1(chr8:8119295-11765719)x3	Pathogenic
563537	GRCh37/hg19 8p23.1(chr8:8093169-11898980)x1	Pathogenic
563539	GRCh37/hg19 8p23.1(chr8:8093065-11945855)x3	Pathogenic
57060	GRCh38/hg38 8p23.1(chr8:8222339-12383643)x1	Pathogenic
58400	GRCh38/hg38 8p23.1(chr8:9970431-11984392)x3	Pathogenic

SpliceAI

2430 predictions. Top by Δscore:

Variant	Effect	Δscore
8:11543222:AG:A	acceptor_gain	1.0000
8:11543223:GG:G	acceptor_gain	1.0000
8:11543345:CTGGT:C	donor_loss	1.0000
8:11543348:G:GA	donor_loss	1.0000
8:11543781:GCTCT:G	donor_gain	1.0000
8:11546050:A:G	acceptor_gain	1.0000
8:11546101:AAGGT:A	donor_loss	1.0000
8:11546102:AGGT:A	donor_loss	1.0000
8:11546103:GGTAA:G	donor_loss	1.0000
8:11546104:GTA:G	donor_loss	1.0000
8:11546105:T:G	donor_loss	1.0000
8:11548029:TAG:T	acceptor_loss	1.0000
8:11548030:A:AG	acceptor_gain	1.0000
8:11548030:A:AT	acceptor_loss	1.0000
8:11548031:G:GG	acceptor_gain	1.0000
8:11548031:GA:G	acceptor_gain	1.0000
8:11548031:GAC:G	acceptor_gain	1.0000
8:11548031:GACAA:G	acceptor_gain	1.0000
8:11548123:GGG:G	donor_gain	1.0000
8:11548124:GG:G	donor_gain	1.0000
8:11548124:GGG:G	donor_gain	1.0000
8:11548125:GG:G	donor_gain	1.0000
8:11548126:G:GA	donor_loss	1.0000
8:11549022:A:AG	acceptor_gain	1.0000
8:11549023:G:GG	acceptor_gain	1.0000
8:11554730:AT:A	acceptor_gain	1.0000
8:11554731:T:TA	acceptor_gain	1.0000
8:11554738:TCCA:T	acceptor_loss	1.0000
8:11554739:CCA:C	acceptor_loss	1.0000
8:11554740:CA:C	acceptor_loss	1.0000

AlphaMissense

3291 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:11556692:G:C	K269N	1.000
8:11556692:G:T	K269N	1.000
8:11561348:G:C	R359P	1.000
8:11562999:T:A	W401R	1.000
8:11562999:T:C	W401R	1.000
8:11555466:T:C	F252L	0.999
8:11555468:C:A	F252L	0.999
8:11555468:C:G	F252L	0.999
8:11556690:A:G	K269E	0.999
8:11556817:T:A	V311D	0.999
8:11561311:G:T	G347W	0.999
8:11561351:A:C	D360A	0.999
8:11561351:A:G	D360G	0.999
8:11561351:A:T	D360V	0.999
8:11561352:C:A	D360E	0.999
8:11561352:C:G	D360E	0.999
8:11561405:A:T	D378V	0.999
8:11561406:T:A	D378E	0.999
8:11561406:T:G	D378E	0.999
8:11563001:G:C	W401C	0.999
8:11563001:G:T	W401C	0.999
8:11563032:T:C	F412L	0.999
8:11563034:C:A	F412L	0.999
8:11563034:C:G	F412L	0.999
8:11563053:T:A	W419R	0.999
8:11563053:T:C	W419R	0.999
8:11561306:C:A	A345D	0.998
8:11561344:C:G	H358D	0.998
8:11561367:C:A	N365K	0.998
8:11561367:C:G	N365K	0.998

dbSNP variants (sampled 300 via entrez): RS1000009455 (8:11546468 C>A), RS1000024249 (8:11492988 C>T), RS1000080819 (8:11531010 A>G), RS1000143943 (8:11535889 C>T), RS1000149489 (8:11502162 A>G), RS1000153601 (8:11513432 C>T), RS1000156565 (8:11526773 G>A), RS1000251867 (8:11554190 G>A), RS1000287322 (8:11539568 A>C), RS1000290824 (8:11501894 G>C), RS1000316816 (8:11548769 G>A,T), RS1000343326 (8:11534635 T>C,G), RS1000371894 (8:11515793 T>C), RS1000433859 (8:11493746 A>C,G), RS1000452049 (8:11545275 A>G)

Disease associations

OMIM: gene MIM:191305 | disease phenotypes: MIM:613375, MIM:152700, MIM:601744, MIM:614430, MIM:187500

GenCC curated gene-disease

Disease	Classification	Inheritance
common variable immunodeficiency	Moderate	Autosomal dominant
systemic lupus erythematosus	Supportive	Unknown
maturity-onset diabetes of the young	Supportive	Autosomal dominant
maturity-onset diabetes of the young type 11	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
monogenic diabetes	Refuted	AD

Mondo (9): maturity-onset diabetes of the young type 11 (MONDO:0013242), thoracic aortic aneurysm (MONDO:0005396), systemic lupus erythematosus (MONDO:0007915), monogenic diabetes (MONDO:0015967), 8p23.1 duplication syndrome (MONDO:0016659), atrioventricular septal defect 4 (MONDO:0013747), tetralogy of fallot (MONDO:0008542), maturity-onset diabetes of the young (MONDO:0018911), common variable immunodeficiency (MONDO:0015517)

Orphanet (5): MODY (Orphanet:552), Systemic lupus erythematosus (Orphanet:536), Rare genetic diabetes mellitus (Orphanet:183625), 8p23.1 duplication syndrome (Orphanet:251076), Tetralogy of Fallot (Orphanet:3303)

HPO phenotypes

73 total (30 of 73 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000077	Abnormality of the kidney
HP:0000093	Proteinuria
HP:0000107	Renal cyst
HP:0000112	Nephropathy
HP:0000119	Abnormality of the genitourinary system
HP:0000155	Oral ulcer
HP:0000488	Retinopathy
HP:0000716	Depression
HP:0000790	Hematuria
HP:0000822	Hypertension
HP:0000825	Hyperinsulinemic hypoglycemia
HP:0000831	Insulin-resistant diabetes mellitus
HP:0000956	Acanthosis nigricans
HP:0000992	Cutaneous photosensitivity
HP:0001250	Seizure
HP:0001369	Arthritis
HP:0001511	Intrauterine growth retardation
HP:0001513	Obesity
HP:0001520	Large for gestational age
HP:0001596	Alopecia
HP:0001738	Exocrine pancreatic insufficiency
HP:0001824	Weight loss
HP:0001873	Thrombocytopenia
HP:0001878	Hemolytic anemia
HP:0001882	Decreased total leukocyte count
HP:0001945	Fever
HP:0001952	Glucose intolerance
HP:0001953	Diabetic ketoacidosis
HP:0001998	Neonatal hypoglycemia

GWAS associations

109 associations (top):

Study	Trait	p-value
GCST000144_1	Systemic lupus erythematosus	1.000000e-10
GCST000216_6	Systemic lupus erythematosus	2.000000e-08
GCST000420_3	Rheumatoid arthritis	6.000000e-09
GCST000507_4	Systemic lupus erythematosus	2.000000e-24
GCST000996_8	Systemic lupus erythematosus	3.000000e-07
GCST001022_1	Rheumatoid arthritis	5.000000e-06
GCST001455_5	Kawasaki disease	8.000000e-21
GCST001456_6	Kawasaki disease	9.000000e-10
GCST001532_4	Immune response to smallpox vaccine (IL-6)	3.000000e-07
GCST001708_3	Systemic lupus erythematosus	2.000000e-10
GCST001795_16	Systemic lupus erythematosus	2.000000e-13
GCST002069_15	Systemic lupus erythematosus and Systemic sclerosis	1.000000e-08
GCST002126_19	Periodontitis (CDC/AAP)	9.000000e-06
GCST002126_3	Periodontitis (CDC/AAP)	6.000000e-06
GCST002318_11	Rheumatoid arthritis	3.000000e-13
GCST002318_139	Rheumatoid arthritis	8.000000e-08
GCST002318_140	Rheumatoid arthritis	2.000000e-07
GCST003103_2	Systemic lupus erythematosus	8.000000e-06
GCST003155_8	Systemic lupus erythematosus	6.000000e-20
GCST003156_15	Systemic lupus erythematosus	2.000000e-22
GCST003599_10	Systemic lupus erythematosus	8.000000e-11
GCST003620_7	Systemic lupus erythematosus or rheumatoid arthritis	9.000000e-12
GCST003622_34	Systemic lupus erythematosus	5.000000e-18
GCST003622_64	Systemic lupus erythematosus	3.000000e-14
GCST003738_3	Barrett’s esophagus	3.000000e-09
GCST003740_5	Barrett’s esophagus or Esophageal adenocarcinoma	2.000000e-09
GCST004279_33	Systolic blood pressure	4.000000e-19
GCST004776_51	Systolic blood pressure	6.000000e-08
GCST004867_37	Systemic lupus erythematosus	8.000000e-17
GCST004878_9	Sjögren’s syndrome	5.000000e-10

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0004873	cytokine measurement
EFO:0006335	systolic blood pressure
EFO:0005128	albumin:globulin ratio measurement
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0005763	pulse pressure measurement
EFO:0008579	risk-taking behaviour
EFO:0009749	age at first sexual intercourse measurement
EFO:0007660	neuroticism measurement
EFO:0006797	neurofibrillary tangles measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
D017074	Common Variable Immunodeficiency	C20.673.330
D008180	Lupus Erythematosus, Systemic	C17.300.480; C20.111.590
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
C562772	Mason-Type Diabetes (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2250 (SINGLE PROTEIN), CHEMBL2363074 (PROTEIN FAMILY)

Molecules with ChEMBL bioactivity

62 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 358,147 (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
CHEMBL1173655	AFATINIB	4	15,144
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL180022	NERATINIB	4	9,404
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL1983268	ENTRECTINIB	4	3,510
CHEMBL2005186	BELUMOSUDIL	4	1,817
CHEMBL2105712	AFATINIB DIMALEATE	4	3,215
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL3545311	BRIGATINIB	4	5,634
CHEMBL3707348	ACALABRUTINIB	4	4,504
CHEMBL3936761	ZANUBRUTINIB	4	2,484
CHEMBL4071161	TIRABRUTINIB	4	2,170
CHEMBL4085457	RITLECITINIB	4	708
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4
CHEMBL553	ERLOTINIB	4
CHEMBL576982	QUIZARTINIB	4
CHEMBL601719	CRIZOTINIB	4
CHEMBL608533	MIDOSTAURIN	4
CHEMBL939	GEFITINIB	4
CHEMBL941	IMATINIB	4
CHEMBL1908391	MASITINIB	3
CHEMBL223360	LINIFANIB	3
CHEMBL31965	CANERTINIB	3

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2736340	BLK		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Src family

Most potent curated ligand interactions (14 total), top 14:

Ligand	Action	Affinity	Parameter
ibrutinib	Inhibition	10.0	pIC50
compound 2 [PMID: 15546730]	Inhibition	9.0	pIC50
compound 31 [PMID: 24915291]	Inhibition	8.57	pIC50
compound 38 [PMID: 24915291]	Inhibition	8.38	pIC50
eCF506	Inhibition	8.27	pIC50
CEP-11981	Inhibition	8.1	pIC50
nemtabrutinib	Inhibition	8.01	pIC50
compound 9 [PMID: 26006010]	Inhibition	7.17	pIC50
PRN694	Inhibition	6.9	pIC50
compound 25 [PMID: 31260299]	Inhibition	6.82	pIC50
ZAK inhibitor 6p	Inhibition	6.72	pKd
WZ4002	Inhibition	6.7	pKd
acalabrutinib	Inhibition	6.0	pIC50
JNJ-64264681	Inhibition	5.5	pIC50

Binding affinities (BindingDB)

72 measured of 109 human assays (109 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
1-[2-(4-methylphenyl)-5-tert-butyl-pyrazol-3-yl]-3-[4-(2-morpholin-4-ylethoxy)naphthalen-1-yl]urea	KD	0.37 nM
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
N-[3-[2-[4-(4-methylpiperazin-1-yl)anilino]-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	1.2 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
Staurosporine	KD	1.7 nM
N-[3-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	2.36 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
FIIN-1	KD	2.8 nM
FRIN-1	KD	3.1 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
N-[3-[2-(4-morpholin-4-ylanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	5.83 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[2-(4-methoxyanilino)-6-methyl-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	5.93 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
9-(1-methylpyrazol-4-yl)-1-(1-prop-2-enoyl-2,3-dihydroindol-6-yl)benzo[h][1,6]naphthyridin-2-one	IC50	6.73 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
QL-X-138	IC50	7 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
N-[5-[9-[4-(methanesulfonamido)phenyl]-2-oxobenzo[h][1,	IC50	7.99 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
QL-XII-46	IC50	8.75 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
4-[[7-oxo-8-[3-(prop-2-enoylamino)phenyl]pteridin-2-yl]amino]benzamide	IC50	9.64 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[2-(4-methoxyanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	10 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
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
N-[3-(2-anilino-7-oxopteridin-8-yl)phenyl]prop-2-enamide	IC50	12 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[7-oxo-2-(4-piperidin-1-ylanilino)pteridin-8-yl]phenyl]prop-2-enamide	IC50	12 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[7-oxo-2-(4-pyrrolidin-1-ylanilino)pteridin-8-yl]phenyl]prop-2-enamide	IC50	13 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[2-(4-acetamidoanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	13 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
QL-XII-45	IC50	13 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
QL-XI-77	IC50	15.9 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
N-[3-[2-[4-(diethylamino)anilino]-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	16 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[2-[4-amino-1-(1-methylpiperidin-4-yl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-3-(trifluoromethyl)benzamide	IC50	18 nM	US-10266537: 3-acetylenyl-pyrazole-pyrimidine derivative, and preparation method therefor and uses thereof
N-[4-(2-anilino-7-oxopteridin-8-yl)phenyl]prop-2-enamide	IC50	26 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
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
QL-XII-03	IC50	66 nM	US-10000483: Bone marrow on X chromosome kinase (BMX) inhibitors and uses thereof
[4-[2-(4-methoxyanilino)-7-oxopteridin-8-yl]phenyl] prop-2-enoate	IC50	85 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[3-[2-(4-chloroanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	85 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
(E)-N-[3-(2-anilino-7-oxopteridin-8-yl)phenyl]-4-(dimethylamino)but-2-enamide	IC50	101 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-[4-[2-(4-chloroanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	116 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 nM
(E)-4-(dimethylamino)-N-[4-[2-(4-methoxyanilino)-7-oxopteridin-8-yl]phenyl]but-2-enamide	IC50	152 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
(E)-N-[4-(2-anilino-7-oxopteridin-8-yl)phenyl]-4-(dimethylamino)but-2-enamide	IC50	160 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
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
N-[4-[2-[2-methoxy-4-(4-methylpiperazin-1-yl)anilino]-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	376 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
(3Z)-4-amino-5-fluoro-3-[5-(4-methylpiperazino)-1,3-dihydrobenzimidazol-2-ylidene]carbostyril	KD	520 nM
N-[4-[2-(4-methoxyanilino)-7-oxopteridin-8-yl]phenyl]prop-2-enamide	IC50	546 nM	US-9670213: Pteridine ketone derivative and applications thereof as EGFR, BLK, and FLT3 inhibitor
3-[4-(benzylamino)-3-methoxyphenyl]-1-[2-[4-(dimethylamino)piperidin-1-yl]ethyl]pyrazolo[3,4-d]pyrimidin-4-amine	IC50	550 nM	US-10294227: Compounds

ChEMBL bioactivities

595 potent at pChembl≥5 of 600 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	IBRUTINIB
9.70	IC50	0.2	nM	CHEMBL3647967
9.70	IC50	0.2	nM	CHEMBL4211949
9.68	Kd	0.21	nM	DASATINIB
9.64	IC50	0.23	nM	IBRUTINIB
9.30	IC50	0.5	nM	IBRUTINIB
9.30	IC50	0.5	nM	CHEMBL5189379
9.30	IC50	0.5	nM	CHEMBL4217006
9.25	Kd	0.56	nM	IBRUTINIB
9.24	IC50	0.58	nM	IBRUTINIB
9.15	IC50	0.7	nM	CHEMBL4464404
9.10	Ki	0.7943	nM	CHEMBL1994938
9.00	Kd	1	nM	CHEMBL249097
9.00	Ki	1	nM	CHEMBL1988717
9.00	Ki	1	nM	CHEMBL1993661
8.97	IC50	1.07	nM	STAUROSPORINE
8.96	IC50	1.09	nM	STAUROSPORINE
8.96	IC50	1.1	nM	IBRUTINIB
8.95	IC50	1.13	nM	ZANUBRUTINIB
8.92	IC50	1.2	nM	REBASTINIB
8.91	IC50	1.23	nM	STAUROSPORINE
8.90	Ki	1.259	nM	CHEMBL1977148
8.85	IC50	1.4	nM	CHEMBL5271284
8.82	Kd	1.5	nM	CHEMBL386051
8.80	IC50	1.6	nM	CHEMBL5750990
8.80	Ki	1.585	nM	CHEMBL1970142
8.80	Ki	1.585	nM	CHEMBL1967116
8.80	Ki	1.585	nM	CHEMBL1980995
8.70	Ki	1.995	nM	CHEMBL1982466
8.66	IC50	2.2	nM	ATUZABRUTINIB
8.60	IC50	2.5	nM	CHEMBL5193128
8.60	Ki	2.512	nM	ILORASERTIB
8.57	IC50	2.7	nM	CHEMBL3290142
8.50	Ki	3.162	nM	CHEMBL1988387
8.50	Ki	3.162	nM	CHEMBL1982476
8.50	Ki	3.162	nM	CHEMBL1970317
8.50	Ki	3.162	nM	CHEMBL1969102
8.48	Kd	3.3	nM	BOSUTINIB
8.46	IC50	3.5	nM	IBRUTINIB
8.38	IC50	4.2	nM	CHEMBL3290148
8.30	IC50	5	nM	CHEMBL3928976
8.30	Ki	5.012	nM	CHEMBL1974254
8.30	Ki	5.012	nM	CHEMBL2005631
8.30	Ki	5.012	nM	CHEMBL1966514
8.27	IC50	5.4	nM	CHEMBL5898340
8.27	Kd	5.4	nM	FORETINIB
8.26	IC50	5.5	nM	CHEMBL5202420
8.25	IC50	5.6	nM	STAUROSPORINE
8.23	IC50	5.9	nM	CHEMBL5169523
8.23	IC50	5.9	nM	CHEMBL5409793

PubChem BioAssay actives

274 with measured affinity, of 1798 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
Ibrutinib	1720538: Inhibition of recombinant full length human His-tagged BLK cytoplasmic domain expressed in baculovirus expression system using tyrosine-1 peptide as substrate preincubated for 1 hr in presence of ATP by Z’-LYTE assay	ic50	0.0001	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	435646: Binding constant for BLK kinase domain	kd	0.0002	uM
N-[(7S)-4-amino-6-methylidene-5-(4-phenoxyphenyl)-7,8-dihydropyrimido[5,4-b]pyrrolizin-7-yl]prop-2-enamide	1375523: Inhibition of recombinant human BLK using Poly(Glu, Tyr) 4:1 as substrate after 1 hr by ELISA	ic50	0.0002	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-(4-methylpiperazin-1-yl)pent-2-enenitrile	1850188: Inhibition of BLK (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0005	uM
N-[3-[[2-(4-morpholin-4-ylanilino)-5-pyridin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-4-yl]oxy]phenyl]prop-2-enamide	1551639: Inhibition of BLK (unknown origin) using STK as substrate by HTRF assay	ic50	0.0007	uM
3-[[4-(5-hydroxy-2-methylanilino)pyrimidin-2-yl]amino]benzamide	389064: Binding affinity to human BLK	kd	0.0010	uM
Zanubrutinib	1615367: Inhibition of human BLK using poly[Glu:Tyr] (4:1) as substrate preincubated for 60 mins followed by [gamma-33P]-ATP addition and measured after 120 mins by filter binding method	ic50	0.0011	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	1531592: Inhibition of human BLK using polyGlu:Tyr as substrate by [gamma-33P]-ATP assay	ic50	0.0011	uM
4-[4-[(3-tert-butyl-1-quinolin-6-ylpyrazol-5-yl)carbamoylamino]-3-fluorophenoxy]-N-methylpyridine-2-carboxamide	2168187: Inhibition of human wild type BLK 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	0.0012	uM
1-[(3S)-3-[4-amino-3-(2-methyl-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	1954477: Inhibition of BLK (unknown origin) by Z’LYTE assay	ic50	0.0014	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624841: Binding constant for BLK kinase domain	kd	0.0015	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4,4-dimethylpent-2-enenitrile	1850188: Inhibition of BLK (unknown origin) using peptide substrate in presence of ATP by caliper electrophoresis method	ic50	0.0022	uM
(7S)-2-(4-phenoxyphenyl)-7-(1-prop-2-enoylpiperidin-4-yl)-3,3a,4,5,6,7-hexahydropyrazolo[1,5-a]pyrimidine-3-carboxamide	1871768: Inhibition of BLK (unknown origin)	ic50	0.0025	uM
2-methyl-N-[2-[3-(prop-2-enoylamino)anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155501: Inhibition of Blk (unknown origin) after 1 hr by HTRF assay	ic50	0.0027	uM
Bosutinib	624841: Binding constant for BLK kinase domain	kd	0.0033	uM
2-methyl-N-[2-[3-[[2-(prop-2-enoylamino)acetyl]amino]anilino]pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1155501: Inhibition of Blk (unknown origin) after 1 hr by HTRF assay	ic50	0.0042	uM
3-chloro-4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9H-carbazole-1-carboxamide	1678393: Inhibition of BLK (unknown origin)	ic50	0.0050	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	624841: Binding constant for BLK kinase domain	kd	0.0054	uM
N-[4-methyl-3-[[2-[3-[(1-prop-2-enoylpiperidin-4-yl)amino]anilino]pyrimidin-5-yl]carbamoyl]phenyl]isoquinoline-6-carboxamide	1899700: Inhibition of (S)-3-(3-(5-acrylamido-6-(3-(5-(2-methyl-5-(3-(trifluoromethyl)benzamido)benzamido)pyrimidin-2-ylamino)phenylamino)-6-oxohexylamino)-3-oxopropyl)-5,5-difluoro-7,9-dimethyl-5H-dipyrrolo[1,2-c:1’,2’-f][1,3,2]diazaborinin-4-ium-5-uide binding to BLK in human NAMALVA cells preincubated for 1 hr followed by compound washout for three times and treated with probe for 1 hr by competitive labeling assay	ic50	0.0055	uM
N-[3-[[2-[3-[[1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-4-yl]amino]anilino]pyrimidin-5-yl]carbamoyl]-4-methylphenyl]isoquinoline-6-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0059	uM
N-[3-[[2-[3-[1-[(E)-4-(dimethylamino)but-2-enoyl]piperidin-4-yl]anilino]pyrimidin-5-yl]carbamoyl]-4-methylphenyl]isoquinoline-6-carboxamide	2017070: Inhibition of N-terminal GST tagged BLK (1 to 505 end residues) (unknown origin) expressed in Sf21insect cells by time resolved fluorescence based assay	ic50	0.0059	uM
N-[3-[[2-(3-aminoanilino)pyrimidin-5-yl]carbamoyl]-4-methylphenyl]-6-methoxynaphthalene-2-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0061	uM
(E)-2-[(3R)-3-[4-amino-3-(2-fluoro-4-phenoxyphenyl)pyrazolo[3,4-d]pyrimidin-1-yl]piperidine-1-carbonyl]-4-methyl-4-[4-(oxetan-3-yl)piperazin-1-yl]pent-2-enenitrile	1850253: Inhibition of BLK (unknown origin) using peptide substrate in presence of ATP	ic50	0.0063	uM
2-methyl-N-[2-(3-prop-2-enoylanilino)pyrimidin-5-yl]-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	2017069: Induction of ubiquitin proteasomal system dependent BLK degradation in human Ramos cells measured after 12 hrs by Western blot analysis	ec50	0.0076	uM
N-[5-[[5-chloro-4-(2-propan-2-ylsulfonylanilino)pyrimidin-2-yl]amino]-2-[2-(dimethylamino)ethyl-methylamino]-4-methoxyphenyl]prop-2-enamide	1584368: Inhibition of recombinant full length His-tagged human Blk cytoplasmic domain expressed in Baculovirus expression system by Z-LYTE assay	ic50	0.0080	uM
1-[(3R)-3-[4-amino-3-[3-chloro-4-(pyridin-2-ylmethoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one	1481342: Inhibition of full-length recombinant human His-tagged BLK expressed in baculovirus by Z’-LYTE assay	ic50	0.0081	uM
4-[7-methoxy-6-(5-morpholin-4-ylpent-2-ynoylamino)quinolin-4-yl]oxy-N-pyridin-2-ylbenzamide	1720538: Inhibition of recombinant full length human His-tagged BLK cytoplasmic domain expressed in baculovirus expression system using tyrosine-1 peptide as substrate preincubated for 1 hr in presence of ATP by Z’-LYTE assay	ic50	0.0083	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-2,5,6,7,8,8a-hexahydro-1H-indolizin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721747: Inhibition of BLK (unknown origin)	ic50	0.0083	uM
N-[4-methyl-3-[[2-[3-(1-prop-2-enoylpiperidin-4-yl)anilino]pyrimidin-5-yl]carbamoyl]phenyl]isoquinoline-6-carboxamide	2017070: Inhibition of N-terminal GST tagged BLK (1 to 505 end residues) (unknown origin) expressed in Sf21insect cells by time resolved fluorescence based assay	ic50	0.0088	uM
N-[3-[[2-[3-[[1-(2-fluoroacetyl)piperidin-4-yl]amino]anilino]pyrimidin-5-yl]carbamoyl]-4-methylphenyl]isoquinoline-6-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0090	uM
4-[8-amino-3-[(3R)-1-(2-methoxyacetyl)piperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1488572: Inhibition of BLK (unknown origin)	ic50	0.0090	uM
7-[[(2R)-1-[[(2R)-oxiran-2-yl]methyl]pyrrolidin-2-yl]methyl]-5-(4-phenoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	1549555: Inhibition of BLK (unknown origin)	ic50	0.0100	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624841: Binding constant for BLK kinase domain	kd	0.0110	uM
N-[3-[[2-(3-aminoanilino)pyrimidin-5-yl]carbamoyl]-4-methylphenyl]naphthalene-2-carboxamide	2017069: Induction of ubiquitin proteasomal system dependent BLK degradation in human Ramos cells measured after 12 hrs by Western blot analysis	ec50	0.0120	uM
N-[3-[[2-(3-aminoanilino)pyrimidin-5-yl]carbamoyl]-4-methylphenyl]-6-hydroxynaphthalene-2-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0142	uM
N-[3-[[2-(3-aminoanilino)pyrimidin-5-yl]carbamoyl]-4-methylphenyl]-6-bromonaphthalene-2-carboxamide	2017069: Induction of ubiquitin proteasomal system dependent BLK degradation in human Ramos cells measured after 12 hrs by Western blot analysis	ec50	0.0150	uM
N-[2-(3-aminoanilino)pyrimidin-5-yl]-2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]benzamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0153	uM
N-[3-[[2-(3-aminoanilino)pyrimidin-5-yl]carbamoyl]-4-methylphenyl]isoquinoline-6-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0157	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734748: Inhibition of human full length recombinant BLK M287V mutant using poly(Glu,Tyr)4:1 as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0160	uM
(E)-4-(dimethylamino)-N-[7-fluoro-4-(2-methylanilino)imidazo[1,5-a]quinoxalin-8-yl]-N-methylbut-2-enamide	629922: Inhibition of BLK relative to control	ic50	0.0160	uM
4-[3-[(6R,8aS)-1,1-dimethyl-3-oxo-6,7,8,8a-tetrahydro-5H-[1,3]oxazolo[3,4-a]pyridin-6-yl]-8-aminoimidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721747: Inhibition of BLK (unknown origin)	ic50	0.0170	uM
Acalabrutinib	1878115: Binding affinity to BLK (unknown origin) assessed as dissociation constant by KINOMEscan analysis	kd	0.0180	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	1206223: Inhibition of human Blk	ic50	0.0190	uM
N-[4-methyl-3-[[2-[3-(prop-2-enoylamino)anilino]pyrimidin-5-yl]carbamoyl]phenyl]isoquinoline-6-carboxamide	1899694: Inhibition of wild type N-terminal GST tagged BLK (unknown origin) (1 to 505 residues) expressed in sf21 insect cell using TK as substrate incubated for 50 mins in presence of ATP by HTRF assay	ic50	0.0200	uM
N-[3-[5-chloro-2-[4-(4-methylpiperazin-1-yl)anilino]pyrimidin-4-yl]oxyphenyl]prop-2-enamide	2185103: Inhibition of TEL fused BLK (unknown origin) transformed in mouse BaF3 cells	ic50	0.0200	uM
7-(2-hydroxypropan-2-yl)-4-[2-methyl-3-(4-oxoquinazolin-3-yl)phenyl]-9H-carbazole-1-carboxamide	1629322: Inhibition of BLK (unknown origin) expressed in bacterial system	ic50	0.0200	uM
4-[8-amino-3-[(3R,6S)-1-(cyclopropanecarbonyl)-6-methylpiperidin-3-yl]imidazo[1,5-a]pyrazin-1-yl]-3-fluoro-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1711653: Inhibition of human BLK	ic50	0.0200	uM
N-(4-ethyl-2-pyridinyl)-4-[6-(prop-2-enoylamino)quinolin-4-yl]oxybenzamide	1720538: Inhibition of recombinant full length human His-tagged BLK cytoplasmic domain expressed in baculovirus expression system using tyrosine-1 peptide as substrate preincubated for 1 hr in presence of ATP by Z’-LYTE assay	ic50	0.0212	uM
(E)-2-cyano-3-[3-(1H-indazol-4-yl)phenyl]prop-2-enamide	1365119: Inhibition of BLK (unknown origin)	ic50	0.0220	uM
4-[8-amino-3-[(6R,8aS)-3-oxo-1,5,6,7,8,8a-hexahydro-[1,3]oxazolo[3,4-a]pyridin-6-yl]imidazo[1,5-a]pyrazin-1-yl]-N-[4-(trifluoromethyl)-2-pyridinyl]benzamide	1721747: Inhibition of BLK (unknown origin)	ic50	0.0220	uM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
triphenyl phosphate	affects expression	1
afimoxifene	decreases response to substance	1
benzo(e)pyrene	decreases methylation	1
cyanoginosin LR	affects localization, decreases reaction, affects binding, increases mutagenesis	1
CGP 52608	increases reaction, affects binding	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression	1
ON 01910	increases phosphorylation	1
ponatinib	decreases activity	1
Bortezomib	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Arsenic	affects cotreatment, decreases expression	1
Benzo(a)pyrene	increases methylation	1
Carmustine	decreases expression	1
Fluorides	affects cotreatment, decreases expression	1
Menthol	decreases expression	1
Methapyrilene	decreases methylation	1
Smoke	increases expression	1
Testosterone	decreases expression	1
Thiram	increases expression	1
Zinc	increases expression	1
Aflatoxin B1	increases methylation	1
Zinc Sulfate	increases expression	1
Particulate Matter	increases abundance, increases expression	1

ChEMBL screening assays

483 unique, capped per target: 477 binding, 4 admet, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1017877	Binding	Inhibition of BLK assessed as enzyme activity relative to control	Examining the chirality, conformation and selective kinase inhibition of 3-((3R,4R)-4-methyl-3-(methyl(7H-pyrrolo[2,3-d]pyrimidin-4-yl)amino)piperidin-1-yl)-3-oxopropanenitrile (CP-690,550). — J Med Chem
CHEMBL1963752	Functional	PUBCHEM_BIOASSAY: Navigating the Kinome. (Class of assay: other) Panel member name: BLK	PubChem BioAssay data set
CHEMBL4023731	ADMET	Inhibition of recombinant human full length His-tagged BLK expressed in baculovirus at 1 uM by Z’-LYTE assay	Discovery of GDC-0853: A Potent, Selective, and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development. — J Med Chem

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00120887	PHASE4	COMPLETED	Lupus Atherosclerosis Prevention Study
NCT00125307	PHASE4	COMPLETED	Tacrolimus for the Treatment of Systemic Lupus Erythematosus With Membranous Nephritis
NCT00188188	PHASE4	UNKNOWN	Study of Endothelial Dysfunction in Systemic Lupus and Its Role in Heart Disease
NCT00371501	PHASE4	COMPLETED	Aspirin and Statins for Prevention of Atherosclerosis and Arterial Thromboembolism in Systemic Lupus Erythematosus
NCT00392093	PHASE4	COMPLETED	Effect of Hormone Replacement Therapy on Lupus Activity
NCT00413361	PHASE4	COMPLETED	The Reduction of Systemic Lupus Erythematosus Flares :Study PLUS
NCT00508898	PHASE4	WITHDRAWN	The Efficacy and Safety of Calcitriol for the Treatment of Lupus Nephritis and Persistent Proteinuria
NCT00668330	PHASE4	COMPLETED	Steroid Induced Osteoporosis in Patients With Systemic Lupus Erythematosus
NCT00739050	PHASE4	TERMINATED	Effect of Simvastatin on Endothelial Function in Premenopausal Women With Systemic Lupus Erythematosus (0733-271)(TERMINATED)
NCT00815282	PHASE4	COMPLETED	Immune Response After Human Papillomavirus Vaccination in Patients With Autoimmune Disease
NCT00828178	PHASE4	COMPLETED	Efficacy of Fish Oil in Lupus Patients
NCT00866229	PHASE4	UNKNOWN	Efficacy and Adverse Effect of Simvastatin Compare to Rosuvastatin in Systemic Lupus Erythematosus (SLE) Patients With Corticosteroid Therapy and High Low-Density Lipoprotein (LDL) Cholesterol Level
NCT00911521	PHASE4	COMPLETED	Immunogenicity and Safety of a Quadrivalent Human Papillomavirus (HPV) Vaccine in Patients With SLE: a Controlled Study
NCT01101802	PHASE4	COMPLETED	Mycophenolate Mofetil in Systemic Lupus Erythematosus (MISSILE)
NCT01112215	PHASE4	COMPLETED	Enteric-coated Mycophenolate Sodium Versus Azathioprine for the Extra-renal Lupus Manifestations
NCT01151644	PHASE4	UNKNOWN	Safety and Efficacy of Anti-Pandemic H1N1 Vaccination in Rheumatic Diseases
NCT01276782	PHASE4	WITHDRAWN	Levothyroxine in Pregnant SLE Patients
NCT01322308	PHASE4	COMPLETED	Effect of Pioglitazone on Endothelial Function in Premenopausal Women With Uncomplicated Systemic Lupus Erythematosus
NCT01359826	PHASE4	WITHDRAWN	The Effect of Milnacipran on Fatigue and Quality of Life in Lupus Patients
NCT01597492	PHASE4	COMPLETED	A Study to Evaluate the Effect of Belimumab on Vaccine Responses in Subjects With Systemic Lupus Erythematosus (SLE)
NCT01632241	PHASE4	COMPLETED	Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
NCT01705977	PHASE4	COMPLETED	Belimumab Assessment of Safety in SLE
NCT01753401	PHASE4	COMPLETED	Acthar for the Treatment of Systemic Lupus Erythematosus (SLE) in Patients With a History of Persistently Active Disease
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