BCR

Summary

BCR (BCR activator of RhoGEF and GTPase, HGNC:1014) is a protein-coding gene on chromosome 22q11.23, encoding Breakpoint cluster region protein (P11274). Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

A reciprocal translocation between chromosomes 22 and 9 produces the Philadelphia chromosome, which is often found in patients with chronic myelogenous leukemia. The chromosome 22 breakpoint for this translocation is located within the BCR gene. The translocation produces a fusion protein which is encoded by sequence from both BCR and ABL, the gene at the chromosome 9 breakpoint. Although the BCR-ABL fusion protein has been extensively studied, the function of the normal BCR gene product is not clear. The unregulated tyrosine kinase activity of BCR-ABL1 contributes to the immortality of leukaemic cells. The BCR protein has serine/threonine kinase activity and is a GTPase-activating protein for p21rac and other kinases. Two transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 613 — RefSeq curated summary.

At a glance

• GWAS associations: 7
• Clinical variants (ClinVar): 399 total — 37 pathogenic, 4 likely-pathogenic (top 8% of genes corpus-wide)
• Regional missense constraint (gnomAD): 1 of 4 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 47 tissues, sQTL in 35 (q < 0.05)
• Phenotypes (HPO): 77
• Drug target: yes — 9 via a complex or family; 64 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs acting on a complex or family including it: 6 — Asciminib Hydrochloride, Bosutinib Monohydrate, Dasatinib, +3 more (Bcr/Abl fusion protein)
• Cancer driver (intOGen): activating (oncogene-like) across 6 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.61 (unconstrained)
• MANE Select transcript: NM_004327
• Interaction hub: 3,296 STRING partners (top 2% of genes corpus-wide)
• Notable: 399 clinical variants but no curated precision-oncology (CIViC) evidence yet

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1014
Approved symbol	BCR
Name	BCR activator of RhoGEF and GTPase
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	D22S662, CML, PHL, ALL
Ensembl gene	ENSG00000186716
Ensembl biotype	protein_coding
OMIM	151410
Entrez	613

Gene structure

Transcript identifiers

Ensembl transcripts: 35 — 17 protein_coding, 10 protein_coding_CDS_not_defined, 6 nonsense_mediated_decay, 2 retained_intron

MANE Select: ENST00000305877

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

ENST00000305877, ENST00000359540, ENST00000419722, ENST00000427791, ENST00000436990, ENST00000458056, ENST00000463770, ENST00000466076, ENST00000471452, ENST00000475025, ENST00000478978, ENST00000479188, ENST00000480973, ENST00000487679, ENST00000487968, ENST00000928586, ENST00000928587, ENST00000928588, ENST00000958107, ENST00000958108, ENST00000958109, ENST00001049284, ENST00001049285, ENST00001049286, ENST00001049287, ENST00001049288, ENST00001081958, ENST00001081959, ENST00001113226, ENST00001113227, ENST00001127897, ENST00001127898, ENST00001127899, ENST00001127900, ENST00001132929

RefSeq mRNA: 2 — MANE Select: NM_004327 NM_004327, NM_021574

CCDS: CCDS13806, CCDS13807

Canonical transcript exons

ENST00000305877 — 23 exons

Exon	Start	End
ENSE00001154392	23268408	23268515
ENSE00001616269	23283977	23284098
ENSE00001654687	23289517	23289621
ENSE00001658624	23261355	23261540
ENSE00001689593	23273081	23273133
ENSE00001753733	23315433	23318037
ENSE00001755753	23273634	23273774
ENSE00001781765	23290339	23290413
ENSE00001801315	23271532	23271592
ENSE00001897802	23180509	23182239
ENSE00003484066	23287159	23287278
ENSE00003495342	23285033	23285201
ENSE00003496602	23295024	23295155
ENSE00003500461	23314552	23314714
ENSE00003517761	23260950	23261054
ENSE00003524316	23292541	23292638
ENSE00003540236	23311697	23311836
ENSE00003561884	23253799	23253980
ENSE00003562142	23312887	23313021
ENSE00003599139	23310324	23310433
ENSE00003610811	23288097	23288172
ENSE00003648666	23309424	23309483
ENSE00003668832	23313968	23314073

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 14.4534 / max 316.2628, expressed in 1768 samples.

Highest expression (Bgee): nucleus accumbens, caudate nucleus, putamen, adenohypophysis, cortical plate.

Genetic regulation across tissues (GTEx eQTL / sQTL)

BCR is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 47 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 82 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Artery Tibial	sqtl	5.7e-75	+0.99	22:23289452:T:C
Adipose Visceral Omentum	sqtl	6.1e-42	-0.77	22:23307055:T:G
Brain Putamen basal ganglia	eqtl	1.2e-36	+0.56	22:23320470:A:ATT
Colon Transverse	eqtl	1.6e-36	-0.46	22:23307055:T:G
Brain Cortex	eqtl	3.7e-36	+0.61	22:23319613:A:G
Brain Caudate basal ganglia	eqtl	6.5e-36	+0.44	22:23318141:G:A
Artery Tibial	eqtl	1.9e-35	-0.32	22:23315779:G:A
Thyroid	sqtl	7.7e-34	-0.67	22:23307055:T:G
Brain Frontal Cortex BA9	eqtl	9.9e-34	-0.54	22:23313032:G:A
Spleen	eqtl	1.0e-33	-0.77	22:23307055:T:G
Testis	eqtl	1.9e-33	+0.37	22:23318141:G:A
Skin Not Sun Exposed Suprapubic	eqtl	4.8e-33	-0.27	22:23315793:G:A
Thyroid	eqtl	8.4e-33	+0.36	22:23321661:T:G
Colon Sigmoid	eqtl	2.5e-29	-0.52	22:23315793:G:A
Nerve Tibial	eqtl	4.7e-29	-0.28	22:23315793:G:A
Skin Sun Exposed Lower leg	eqtl	8.4e-29	-0.28	22:23187981:T:G
Adipose Subcutaneous	sqtl	1.1e-28	+0.76	22:23307182:A:G
Brain Cerebellar Hemisphere	eqtl	1.3e-28	+0.67	22:23319613:A:G
Brain Hypothalamus	eqtl	2.8e-28	-0.60	22:23315308:C:G
Brain Nucleus accumbens basal ganglia	eqtl	8.0e-28	+0.44	22:23321585:G:C

FANTOM5 promoters

5 alternative TSS:

Promoter ID	TPM avg	Samples expressed
191304	11.1144	1756
191305	2.8133	1064
191306	0.3487	183
191311	0.1525	74
191307	0.0245	8

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
nucleus accumbens	UBERON:0001882	96.77	gold quality
caudate nucleus	UBERON:0001873	96.73	gold quality
putamen	UBERON:0001874	96.52	gold quality
adenohypophysis	UBERON:0002196	96.24	gold quality
cortical plate	UBERON:0005343	95.37	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	95.28	gold quality
sural nerve	UBERON:0015488	95.04	gold quality
lower esophagus mucosa	UBERON:0035834	94.90	gold quality
pituitary gland	UBERON:0000007	94.88	gold quality
right frontal lobe	UBERON:0002810	94.35	gold quality
prefrontal cortex	UBERON:0000451	94.31	gold quality
amygdala	UBERON:0001876	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	93.93	gold quality
cingulate cortex	UBERON:0003027	93.92	gold quality
anterior cingulate cortex	UBERON:0009835	93.84	gold quality
ganglionic eminence	UBERON:0004023	93.34	gold quality
peripheral nervous system	UBERON:0000010	93.20	gold quality
tibial nerve	UBERON:0001323	93.20	gold quality
stromal cell of endometrium	CL:0002255	92.81	gold quality
left lobe of thyroid gland	UBERON:0001120	92.78	gold quality
esophagus mucosa	UBERON:0002469	92.72	gold quality
mucosa of stomach	UBERON:0001199	92.64	gold quality
lateral globus pallidus	UBERON:0002476	92.62	gold quality
skin of leg	UBERON:0001511	92.47	gold quality
frontal cortex	UBERON:0001870	92.45	gold quality
neocortex	UBERON:0001950	92.44	gold quality
telencephalon	UBERON:0001893	92.33	gold quality
forebrain	UBERON:0001890	92.26	gold quality
metanephros cortex	UBERON:0010533	92.22	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	92.08	gold quality
popliteal artery	UBERON:0002250	92.04	gold quality
right lung	UBERON:0002167	92.03	gold quality
tibial artery	UBERON:0007610	92.03	gold quality
upper lobe of left lung	UBERON:0008952	91.93	gold quality
thyroid gland	UBERON:0002046	91.90	gold quality
aorta	UBERON:0000947	91.85	gold quality
ascending aorta	UBERON:0001496	91.84	gold quality
Brodmann (1909) area 9	UBERON:0013540	91.84	gold quality
thoracic aorta	UBERON:0001515	91.78	gold quality
Ammon’s horn	UBERON:0001954	91.62	gold quality
adult mammalian kidney	UBERON:0000082	91.61	gold quality
ventricular zone	UBERON:0003053	91.58	gold quality
descending thoracic aorta	UBERON:0002345	91.56	gold quality
left coronary artery	UBERON:0001626	91.55	gold quality
cerebral cortex	UBERON:0000956	91.42	gold quality
upper lobe of lung	UBERON:0008948	91.42	gold quality
brain	UBERON:0000955	91.31	gold quality
central nervous system	UBERON:0001017	91.20	gold quality
omental fat pad	UBERON:0010414	91.20	gold quality
skin of abdomen	UBERON:0001416	91.18	gold quality
left uterine tube	UBERON:0001303	91.14	gold quality
peritoneum	UBERON:0002358	91.14	gold quality
temporal lobe	UBERON:0001871	91.05	gold quality
body of stomach	UBERON:0001161	90.94	gold quality
right hemisphere of cerebellum	UBERON:0014890	90.86	gold quality
esophagus	UBERON:0001043	90.84	gold quality
granulocyte	CL:0000094	90.69	gold quality
hypothalamus	UBERON:0001898	90.66	gold quality
coronary artery	UBERON:0001621	90.59	gold quality
adipose tissue of abdominal region	UBERON:0007808	90.58	gold quality
minor salivary gland	UBERON:0001830	90.23	gold quality
apex of heart	UBERON:0002098	89.97	gold quality
bone marrow cell	CL:0002092	89.83	gold quality
zone of skin	UBERON:0000014	89.82	gold quality
cerebellar hemisphere	UBERON:0002245	89.78	gold quality
stomach	UBERON:0000945	89.73	gold quality
cerebellar cortex	UBERON:0002129	89.73	gold quality
mouth mucosa	UBERON:0003729	89.67	gold quality
left testis	UBERON:0004533	89.59	gold quality
right testis	UBERON:0004534	89.47	gold quality
subcutaneous adipose tissue	UBERON:0002190	89.42	gold quality
islet of Langerhans	UBERON:0000006	89.38	gold quality
nasal cavity mucosa	UBERON:0001826	89.36	gold quality
substantia nigra	UBERON:0002038	89.28	gold quality
ectocervix	UBERON:0012249	89.20	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.19	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	89.05	gold quality
substantia nigra pars reticulata	UBERON:0001966	88.85	gold quality
lower esophagus	UBERON:0013473	88.84	gold quality
lower esophagus muscularis layer	UBERON:0035833	88.83	gold quality
right adrenal gland cortex	UBERON:0035827	88.82	gold quality
endocervix	UBERON:0000458	88.71	gold quality
mucosa of transverse colon	UBERON:0004991	88.54	gold quality
right lobe of liver	UBERON:0001114	88.52	gold quality
nasal cavity epithelium	UBERON:0005384	88.51	gold quality
adipose tissue	UBERON:0001013	88.43	gold quality
saliva-secreting gland	UBERON:0001044	88.43	gold quality
left adrenal gland cortex	UBERON:0035825	88.42	gold quality
left adrenal gland	UBERON:0001234	88.39	gold quality
right adrenal gland	UBERON:0001233	88.36	gold quality
right coronary artery	UBERON:0001625	88.29	gold quality
cerebellum	UBERON:0002037	88.27	gold quality
spleen	UBERON:0002106	88.09	gold quality
colonic epithelium	UBERON:0000397	87.99	gold quality
blood	UBERON:0000178	87.97	gold quality
midbrain	UBERON:0001891	87.94	gold quality
spinal cord	UBERON:0002240	87.94	gold quality
connective tissue	UBERON:0002384	87.94	gold quality
muscle layer of sigmoid colon	UBERON:0035805	87.75	gold quality
adrenal gland	UBERON:0002369	87.69	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	138.9
Nucleus accumbens	tissue	136.4
Hippocampus	tissue	113.5	medium
Basal ganglia	tissue	84.5	medium
Locus coeruleus	tissue	72.6
Putamen	tissue	71.8
Postcentral gyrus	tissue	70.4
Ventral forebrain	tissue	61.0
Cerebellum	tissue	57.0	high
Choroid plexus	tissue	56.9
Prefrontal cortex	tissue	55.0
Cerebral cortex	tissue	55.0	medium
Insular cortex	tissue	53.8
Somatosensory cortex	tissue	53.5
Hippocampal formation	tissue	53.4
Entorhinal cortex	tissue	53.4
Motor cortex	tissue	52.6
Temporal cortex	tissue	49.9
Occipital cortex	tissue	49.7
Amygdala	tissue	49.0
Septum	tissue	48.3
Retrosplenial and cingulate cortex	tissue	46.8
Retrosplenial cortex	tissue	45.9
Thalamus	tissue	43.3
Frontal cortex	tissue	42.5
Midbrain	tissue	40.4
Superior colliculi	tissue	39.1
Hypothalamus	tissue	38.7
Pons	tissue	37.5
Spinal cord	tissue	35.4
Medulla oblongata	tissue	34.7
Substantia nigra	tissue	33.5
Bone marrow	tissue	32.7	low
Olfactory bulb	tissue	31.5
Periaqueductal gray	tissue	30.6
Pituitary gland	tissue	23.9
Corpus callosum	tissue	23.5
Esophagus	tissue	20.1	high
Parathyroid gland	tissue	19.3	medium
Thyroid gland	tissue	17.4	high
Salivary gland	tissue	17.3	medium
Kidney	tissue	16.6	medium
Adipose tissue	tissue	16.0	low
Epididymis	tissue	15.4	medium
Stomach 1	tissue	15.0	medium
Urinary bladder	tissue	14.2	high
Vagina	tissue	13.8	medium
Skin 1	tissue	13.7	medium
Pancreas	tissue	13.7	medium
Thymus	tissue	13.7
Cervix	tissue	13.6	medium
Lymph node	tissue	12.8	low
Lung	tissue	12.4	medium
Fallopian tube	tissue	11.0	medium
Testis	tissue	10.8	medium
Colon	tissue	10.6	medium
Appendix	tissue	10.4	medium
Spleen	tissue	10.3	not detected
Tonsil	tissue	10.2	medium
Placenta	tissue	9.7	high

Brain sub-regions (HPA Brain Atlas): detected in 191; highest nTPM — Caudate nucleus (152.1), Hippocampus, CA3 (127.8), Nucleus basalis of Meynert (121.1), Hippocampus, CA1 (115.4), Dentate gyrus (111.6).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BCL6, EBF1, EGR1, HHEX, HIF1A, IRF8, JUN, MYC, NFKB, PAX1, PAX5, RELA, RUNX1, STAT1, STAT5A, TCF3, TXK

miRNA regulators (miRDB)

Targeting BCR by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 106 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-96-5P	99.95	72.80	2140
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-12133	99.92	71.82	2006
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-3119	99.92	71.34	2390
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-1271-5P	99.91	71.99	1972
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-5582-3P	99.86	72.48	4221

Functional genomics

gnomAD constraint: pLI 6.29e-06, LOEUF 0.608, missense Z -0.178 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000305877 splits into 4 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
22:23,180,961–23,253,817	806 / 635.0	1.27	no
22:23,253,818–23,310,327	590 / 762.4	0.77	no
22:23,310,328–23,311,809	26 / 103.5	0.25	yes (p 2.6e-14)
22:23,311,810–23,315,519	177 / 226.4	0.78	no
ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• In the fusion of the BCR and FGFR1 genes in myeloproliferative disorder, it is likely that the dimerization properties of BCR lead to aberrant FGFR1 signaling and neoplastic transformation. (PMID:11746971)
• p38 MAPK-mediated activation of NF-kappaB by the RhoGEF domain of Bcr (PMID:12096337)
• 2 cases of e19a2-positive CML with a new in-frame BCR exon e16 deletion are reported. (PMID:12145699)
• expression of bcr/abl hybridized gene in chronic myeloid leukemia (CML), acute lymphatic leukemia (ALL) and polycythemia vera (PV), and its clinical significance (PMID:12408765)
• constitutively activated Bcr-Abl kinase pathways in primitive CML progenitors cooperate with growth factors producing a growth response and disrupt the normally required synergistic interactions between kit ligand and other cytokines to achieve activation (PMID:12556557)
• concluded that the IRS-1 protein is involved in the signalling pathway of the BCR-ABL tyrosine kinase (PMID:12560071)
• analyzed the clinical significance of bcr/abl mRNA levels in patients with chronic myeloid leukemia undergoing prolonged treatment with imatinib mesylate (PMID:12734675)
• BCR-ABL is inhibited by lyp tyrosine phosphatase (PMID:12764153)
• BCR/ABL amplification may play a role as a novel mechanism in the progression to an aggressive blast transformation in some cases of Philadelphia chromosome-positive chronic myelocytic leukemia (PMID:12781448)
• Bcr kinase downregulates Ras signaling by phosphorylating AF-6 and binding to its PDZ domain (PMID:12808105)
• BCR-ABL has a role in differentiation of embryonic stem cells (PMID:12821944)
• Expression of BCR/ABL and BCL-2 in myeloid progenitors leads to myeloid leukemias. (PMID:12890867)
• BCR fuses with ABL to form a fusion protein. (PMID:14534537)
• down-regulation of Bcr-Abl mRNA might be one of the mechanisms implicated in the apicidin-mediated apoptosis in the K562 cells (PMID:14581377)
• Endoplasmic reticulum stress resulting from inhibition of p210 bcr-abl triggers apoptosis in CML; leading to Bcl-2 dowmodulation and inactivation, release of caspase 12 from the ER membranes in its active form, and Ca(2+)release from the ER pool (PMID:14654084)
• ICSBP antagonizes BCR/ABL by down-regulation of bcl-2, implicating a central role for ICSBP in the pathogenesis of chronic myelogenous leukemia (PMID:14656881)
• identified a BCR/ABL-dependent increase in expression of multiple genes involved in pre-mRNA splicing; generic changes in pre-mRNA splicing as a result of p210BCR/ABL kinase activity may contribute to CML pathogenesis (PMID:14961028)
• bcr-abl transcript can be detected in the PBLs of Philadelphia chromosome (Ph)-negative essential thrombocythemia but the level of expression is markedly less than that in CML (PMID:14966468)
• BCR-ABL1 kinase activity is linked to defective pre-B cell receptor signaling (PMID:14993251)
• identified 61 genes up-regulated by BCR/ABL1, including genes encoding transcription factors, kinases, and signal transduction molecules, as well as genes regulating cell growth, differentiation, apoptosis, and cell adhesion (PMID:15145216)
• FISH analysis of the abl and bcr genes showed the signal for bcr/abl fusion on the der(22) chromosome but not on the der(9) chromosome in Philadelpha-Negative chronic myeloid leukemia. (PMID:15481444)
• We have examined the ability of Bcr to interact with other epithelial PDZ proteins and found specific binding to both the apical PDZK1 protein and the Golgi-localized Mint3. (PMID:15494376)
• Bcr-Abl mediates protection from apoptosis downstream of mitochondrial cytochrome c release (PMID:15542838)
• MCL-1 is a BCR/ABL-dependent survival factor and interesting target in chronic myeloid leukemia. (PMID:15626746)
• Results report the solution structure of AF-6 PDZ domain and its interaction with the C-terminal peptides from Neurexin and Bcr. (PMID:15684424)
• the incidence of deletions from the der(9) in childhood acute lymphoblastic leukemia is at least as high as that reported for chronic myeloid leukemia. (PMID:15716990)
• Along with ABL, deleted in leukemia, myeloid, philadelphia-positive. (PMID:15723338)
• Bcr-Abl-induced abnormalities in glucose transport regulation have roles in chronic myeloid leukaemia (PMID:15735728)
• ability of Bcr-Abl to stimulate the expression of osteopontin (PMID:15857938)
• Sequence deletoin detected in chronic myeloid leukemia. (PMID:16079118)
• Achievement of molecular remission in BCR-ABL-positive ALL occurs also in standard chemotherapy but molecular remissions begin 2-4 months later than clinicohematological ones. (PMID:16116902)
• detected the new mutation of BCR/ABL, resulting in premature termination and loss of BCR/ABL fusion protein expression (PMID:16264277)
• Identification of the CEBPB gene as a target of translational regulation in myeloid precursor cells transformed by the BCR/ABL oncogene. (PMID:16418324)
• Expressed Bcr is able to bind the transcription factor Tcf1 to disrupt the Tcf1/beta-catenin complex. Phosphorylation of Bcr by the tyrosine kinase pp60(src) can lead to dissociation of the transcriptionally inactive Bcr/Tcf1 complex (PMID:16442529)
• Enriched CD34+ cells from patients with BCR-ABL-positve chronic myelocytic leukemia in chronic phase or blast crisis do not associate blast crisis with mutation. (PMID:16442619)
• Pattern of BCR-ABL transcript levels after allograft is variable after stem cell transplantation for chronic myeloid leukemia. (PMID:16449534)
• The ability to negate calcium-dependent apoptotic signaling is a major prosurvival mechanism in Bcr-Abl-expressing cells. (PMID:16469868)
• Adaphostin+/-bortezomib circumvent imatinib resistance due to Bcr/Abl point mutations most likely through reactive oxygen species generation. (PMID:16481037)
• The minor BCR-ABL fusion gene involving a secondary Philadelphia chromosome superimposed on inversion(3) and monosomy 7 has not previously been reported in acute myelocytic leukemia. (PMID:16490599)
• The rate of glycolysis is significantly increased in Bcr-Abl expressing cells in a PI3K-dependent manner. (PMID:16494625)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	si:dkey-91m11.5	ENSDARG00000042329
danio_rerio	bcr	ENSDARG00000079286
mus_musculus	Bcr	ENSMUSG00000009681
rattus_norvegicus	Bcr	ENSRNOG00000001304
drosophila_melanogaster	RhoGAP1A	FBGN0025836

Paralogs (1): ABR (ENSG00000159842)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:88141) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 19 distinct phenotype terms.

Mouse phenotype (MP)	Records
increased leukocyte cell number	1
increased neutrophil cell number	1
weight loss	1
abnormal definitive hematopoiesis	1
abnormal neutrophil physiology	1
abnormal ileum morphology	1
increased circulating alanine transaminase level	1
intestinal edema	1
renal necrosis	1
abnormal proximal convoluted tubule morphology	1
decreased hematopoietic stem cell number	1
sepsis	1
abnormal renal glomerulus morphology	1
increased circulating aspartate transaminase level	1
increased blood urea nitrogen level	1
increased susceptibility to endotoxin shock	1
abnormal liver parenchyma morphology	1
abnormal bone marrow cell physiology	1
increased circulating lactate dehydrogenase level	1

Additional cross-species homologs

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

Organism	UniProt	Identity	Method
Pongo pygmaeus	Q7YQL5	100.0%	Diamond
Pan troglodytes	Q7YQL6	100.0%	Diamond
Bos taurus	A6QNS3	98.8%	Diamond
Canis lupus familiaris	P83509	98.7%	Diamond
Macaca fascicularis	Q9BE31	98.3%	Diamond
Xenopus tropicalis	A4II46	97.6%	Diamond
Xenopus laevis	Q8AVG0	97.6%	Diamond
Pongo abelii	Q5RB40	94.3%	Diamond
Caenorhabditis briggsae	A8WRJ2	89.0%	Diamond
Caenorhabditis elegans	Q20498	89.0%	Diamond
Gallus gallus	Q5ZMW5	84.5%	Diamond

Genomic neighbors (locus context)

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

Symbol	Type	Entrez
LINC02556	ncRNA	102724679
RSPH14	protein-coding	27156
RAB36	protein-coding	9609
GNAZ	protein-coding	2781
IGL	protein-coding	3535

Protein

Protein identifiers

Breakpoint cluster region protein — P11274 (reviewed: P11274)

Alternative names: Renal carcinoma antigen NY-REN-26

All UniProt accessions (2): H0Y554, P11274

UniProt curated annotations — full annotation on UniProt →

Function. Protein with a unique structure having two opposing regulatory activities toward small GTP-binding proteins. The C-terminus is a GTPase-activating protein (GAP) domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. Accelerates the intrinsic rate of GTP hydrolysis of RAC1 or CDC42, leading to down-regulation of the active GTP-bound form. The central Dbl homology (DH) domain functions as guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The amino terminus contains an intrinsic kinase activity. Functions as an important negative regulator of neuronal RAC1 activity. Regulates macrophage functions such as CSF1-directed motility and phagocytosis through the modulation of RAC1 activity. Plays a major role as a RHOA GEF in keratinocytes being involved in focal adhesion formation and keratinocyte differentiation.

Subunit / interactions. Homotetramer. Interacts with PDZK1. May interact with CCPG1. Interacts with FES/FPS, ABL1, PIK3R1 and GRB2. Interacts with HCK. Interacts with SH2D5. Interacts with DLG4.

Subcellular location. Postsynaptic density. Cell projection. Dendritic spine. Axon. Synapse.

Post-translational modifications. Autophosphorylated. Phosphorylated by FES/FPS on tyrosine residues, leading to down-regulation of the BCR kinase activity. Phosphorylation at Tyr-177 by HCK is important for interaction with GRB2.

Disease relevance. Leukemia, chronic myeloid (CML) [MIM:608232] A clonal myeloproliferative disorder of a pluripotent stem cell with a specific cytogenetic abnormality, the Philadelphia chromosome (Ph), involving myeloid, erythroid, megakaryocytic, B-lymphoid, and sometimes T-lymphoid cells, but not marrow fibroblasts. The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving BCR has been found in patients with chronic myeloid leukemia. Translocation t(9;22)(q34;q11) with ABL1. The translocation produces a BCR-ABL found also in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL).

Domain organisation. The region involved in binding to ABL1 SH2-domain is rich in serine residues and needs to be Ser/Thr phosphorylated prior to SH2 binding. This region is essential for the activation of the ABL1 tyrosine kinase and transforming potential of the chimeric BCR-ABL oncogene. The DH domain is involved in interaction with CCPG1. The amino terminus contains an intrinsic kinase activity. The central Dbl homology (DH) domain functions as a guanine nucleotide exchange factor (GEF) that modulates the GTPases CDC42, RHOA and RAC1. Promotes the conversion of CDC42, RHOA and RAC1 from the GDP-bound to the GTP-bound form. The C-terminus is a Rho-GAP domain which stimulates GTP hydrolysis by RAC1, RAC2 and CDC42. The protein has a unique structure having two opposing regulatory activities toward small GTP-binding proteins.

Isoforms (2)

UniProt ID	Names	Canonical?
P11274-1	1	yes
P11274-2	2

RefSeq proteins (2): NP_004318, NP_067585 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000008	C2_dom	Domain
IPR000198	RhoGAP_dom	Domain
IPR000219	DH_dom	Domain
IPR001331	GDS_CDC24_CS	Conserved_site
IPR001849	PH_domain	Domain
IPR008936	Rho_GTPase_activation_prot	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR015123	Bcr-Abl_oncoprot_oligo	Domain
IPR035892	C2_domain_sf	Homologous_superfamily
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036481	Bcr-Abl_oncoprot_oligo_sf	Homologous_superfamily
IPR037769	Abr/Bcr	Family

Pfam: PF00168, PF00620, PF00621, PF09036, PF19057

Catalyzed reactions (Rhea)

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (104 total): modified residue 24, sequence variant 19, helix 16, strand 10, compositionally biased region 7, region of interest 6, mutagenesis site 6, sequence conflict 6, domain 4, site 2, chain 1, coiled-coil region 1, splice variant 1, turn 1

Structure

Experimental structures (PDB)

5 structures by resolution:

PDB	Title	Method	Resolution (Å)
5N7E	Crystal structure of the Dbl-homology domain of Bcr-Abl in complex with monobody …	X-RAY DIFFRACTION	1.65
5OC7	Crystal structure of the pleckstrin-homology domain of Bcr-Abl in complex with monobody …	X-RAY DIFFRACTION	1.65
1K1F	Structure of the Bcr-Abl Oncoprotein Oligomerization domain	X-RAY DIFFRACTION	2.2
2AIN	Solution structure of the AF-6 PDZ domain complexed with the C-terminal peptide from the …	SOLUTION NMR
5N6R	Solution structure of the Dbl-homology domain of Bcr-Abl	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P11274-F1	65.61	0.23

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Transferases, Predicted intracellular proteins, Cancer-related genes, Disease related genes, FDA approved drug targets, Small molecule drugs, Human disease related genes

Protein evidence: Evidence at protein level

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

Antibody reliability (HPA): IH approved · IF approved

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 (2)

Position	Role
426–427	breakpoint for translocation to form bcr-abl oncogene
1090	arginine finger; crucial for gtp hydrolysis by stabilizing the transition state

Post-translational modifications (24)

Type	Positions
N-acetylmethionine	1
Phosphoserine	122, 139, 202, 215, 222, 236, 356, 377, 382, 459, 463, 473, 488, 894, 1264
Phosphotyrosine	177, 246, 554, 644
Phosphothreonine	385, 641, 693
Omega-n-methylarginine	471

Mutagenesis-validated functional residues (6)

Position	Phenotype
177	abolishes interaction with fes and grb2.
689–690	loss of rhoa gef activity.
1090	loss of gap activity. loss of gap activity; when associated with a-1202.
1202	loss of gap activity; when associated with a-1090.
1269–1271	abolishes interaction with pdzk1.
1271	reduces interaction with pdzk1. abolishes interaction with dlg4. no effect on synaptic localization.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 17; 6 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-5655302	Signaling by FGFR1 in disease ⚕	curated
R-HSA-1839117	Signaling by cytosolic FGFR1 fusion mutants ⚕	curated
R-HSA-9013148	CDC42 GTPase cycle	curated
R-HSA-9013149	RAC1 GTPase cycle	curated
R-HSA-9013404	RAC2 GTPase cycle	curated
R-HSA-9013423	RAC3 GTPase cycle	curated
R-HSA-8980692	RHOA GTPase cycle	curated
R-HSA-9013026	RHOB GTPase cycle	curated
R-HSA-9013106	RHOC GTPase cycle	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-1839124	FGFR1 mutant receptor activation ⚕	—
R-HSA-1226099	Signaling by FGFR in disease ⚕	—
R-HSA-9012999	RHO GTPase cycle	—
R-HSA-162582	Signal Transduction	—
R-HSA-194315	Signaling by Rho GTPases	—
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3	—

MSigDB gene sets: 570 (showing top): GOBP_REGULATION_OF_RESPIRATORY_BURST, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, MODULE_255, GOBP_INFLAMMATORY_RESPONSE, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_CELLULAR_RESPONSE_TO_BIOTIC_STIMULUS, GOBP_NEGATIVE_REGULATION_OF_LEUKOCYTE_MEDIATED_IMMUNITY, GOBP_NEGATIVE_REGULATION_OF_REACTIVE_OXYGEN_SPECIES_METABOLIC_PROCESS, GOBP_ACTIVATION_OF_GTPASE_ACTIVITY, GOBP_FOCAL_ADHESION_ASSEMBLY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP

GO Biological Process (14): negative regulation of cellular extravasation (GO:0002692), protein phosphorylation (GO:0006468), signal transduction (GO:0007165), small GTPase-mediated signal transduction (GO:0007264), keratinocyte differentiation (GO:0030216), regulation of Rho protein signal transduction (GO:0035023), regulation of vascular permeability (GO:0043114), focal adhesion assembly (GO:0048041), modulation of chemical synaptic transmission (GO:0050804), regulation of small GTPase mediated signal transduction (GO:0051056), negative regulation of blood vessel remodeling (GO:0060313), activation of GTPase activity (GO:0090630), intracellular signal transduction (GO:0035556), positive regulation of GTPase activity (GO:0043547)

GO Molecular Function (10): protein serine/threonine kinase activity (GO:0004674), protein tyrosine kinase activity (GO:0004713), guanyl-nucleotide exchange factor activity (GO:0005085), GTPase activator activity (GO:0005096), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (11): cytosol (GO:0005829), plasma membrane (GO:0005886), postsynaptic density (GO:0014069), membrane (GO:0016020), axon (GO:0030424), protein-containing complex (GO:0032991), dendritic spine (GO:0043197), extracellular exosome (GO:0070062), Schaffer collateral - CA1 synapse (GO:0098685), glutamatergic synapse (GO:0098978), synapse (GO:0045202)

Reactome top-level categories

9 top-level categories:

Category	Pathways
RHO GTPase cycle	7
FGFR1 mutant receptor activation	1
Signaling by FGFR in disease	1
Diseases of signal transduction by growth factor receptors and second messengers	1
Signaling by FGFR1 in disease	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Disease	1
Signaling by Rho GTPases	1
Signal Transduction	1

GO top-level categories

showing 60 of 61 GO namespaces:

Category	Terms
protein kinase activity	3
GTPase activity	2
GTPase regulator activity	2
cellular anatomical structure	2
synapse	2
negative regulation of leukocyte migration	1
regulation of cellular extravasation	1
cellular extravasation	1
phosphorylation	1
protein modification process	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
intracellular signaling cassette	1
epidermal cell differentiation	1
skin development	1
Rho protein signal transduction	1
regulation of small GTPase mediated signal transduction	1
vascular process in circulatory system	1
blood circulation	1
regulation of biological quality	1
cell-substrate junction assembly	1
cell-matrix adhesion	1
chemical synaptic transmission	1
regulation of trans-synaptic signaling	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
blood vessel remodeling	1
negative regulation of tissue remodeling	1
negative regulation of developmental process	1
regulation of blood vessel remodeling	1
positive regulation of GTPase activity	1
intracellular anatomical structure	1
signal transduction	1
regulation of GTPase activity	1
positive regulation of hydrolase activity	1
GTP binding	1
GDP binding	1
enzyme activator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
anion binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
cytoplasm	1
membrane	1
cell periphery	1
asymmetric synapse	1
postsynaptic specialization	1
neuron projection	1
cellular_component	1
dendrite	1
neuron spine	1
postsynapse	1
extracellular vesicle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 10 of 35 annotations. The rest are phylogenetic / computational / electronic (IEA).

10 experimentally-supported GO terms:

GO term	NS	Evidence
activation of GTPase activity	BP	direct assay
focal adhesion assembly	BP	mutant phenotype
keratinocyte differentiation	BP	mutant phenotype
regulation of Rho protein signal transduction	BP	mutant phenotype
small GTPase-mediated signal transduction	BP	mutant phenotype
extracellular exosome	CC	high-throughput assay
membrane	CC	high-throughput assay
protein-containing complex	CC	direct assay
GTPase activator activity	MF	direct assay
guanyl-nucleotide exchange factor activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,296 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BCR	ABL1	P00519	974
BCR	EVPL	Q92817	856
BCR	IKZF1	Q13422	842
BCR	LYN	P07948	841
BCR	BTK	Q06187	822
BCR	CD79B	P40259	817
BCR	CD22	P20273	809
BCR	CD79A	P11912	792
BCR	AFF1	P51825	778
BCR	CD19	P15391	777
BCR	IGHV4-38-2	P0DP08	771
BCR	KIT	P10721	764
BCR	SRC	P12931	757
BCR	ETV6	P41212	755
BCR	SYK	P43405	741

IntAct

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

showing 30 of 106 partners by confidence:

Partner	Interaction type	MIscore	Records
GRB2	association	0.930	9
PDZK1	direct interaction	0.740	8
APBA3	direct interaction	0.720	6
TNKS2	direct interaction	0.590	2
CFTR	colocalization	0.590	1
ERCC3	association	0.530	1
TP53	proximity	0.520	2
EZR	association	0.480	2
PATJ	direct interaction	0.440	7
GRIP1	direct interaction	0.440	5
MAGI2	direct interaction	0.440	4
DLG1	direct interaction	0.440	3
FRMPD2	direct interaction	0.440	3
GRIP2	direct interaction	0.440	3
SCRIB	direct interaction	0.440	3
WHRN	direct interaction	0.440	3
APBA1	direct interaction	0.440	2
APBA2	direct interaction	0.440	2
DLG2	direct interaction	0.440	2
DLG3	direct interaction	0.440	2
DLG4	direct interaction	0.440	2
GRID2IP	direct interaction	0.440	2
LNX2	direct interaction	0.440	2
MAGI1	direct interaction	0.440	2
MPDZ	direct interaction	0.440	2
NHERF4	direct interaction	0.440	2
AHNAK	direct interaction	0.440	1
ARHGAP21	direct interaction	0.440	1
ARHGEF11	direct interaction	0.440	1
ARHGEF12	direct interaction	0.440	1

BioGRID (348 interactions; top human partners by supporting records): GRB2 (Affinity Capture-MS; 15 records), ERCC3 (Reconstituted Complex; 7 records), AP2M1 (Affinity Capture-MS; 6 records), ABL1 (Reconstituted Complex; 5 records), CRKL (Affinity Capture-Western; 5 records), CSNK2A2 (Affinity Capture-MS; 5 records), MLLT4 (Affinity Capture-Western; 5 records), CBL (Biochemical Activity; 4 records), FES (Affinity Capture-Western; 4 records), YWHAH (Affinity Capture-MS; 4 records), CCDC183 (Affinity Capture-MS; 3 records), CSNK2A1 (Affinity Capture-MS; 3 records), DOK1 (Affinity Capture-Western; 3 records), ERBB2IP (Protein-peptide; 3 records), EZR (Proximity Label-MS; 3 records)

SIGNOR signaling

showing 11 of 18 signaling interactions:

A	Effect	B	Mechanism
FES	“down-regulates activity”	BCR	phosphorylation
BCR	“down-regulates activity”	RAC1	“gtpase-activating protein”
BCR-ABL	“down-regulates activity”	BCR	phosphorylation
MYC	“up-regulates quantity by expression”	BCR	“transcriptional regulation”
LNX1	“down-regulates quantity by destabilization”	BCR	ubiquitination
BCR	“down-regulates activity”	PPARG	phosphorylation
BCR-ABL	down-regulates	BCR	phosphorylation
FES	down-regulates	BCR	phosphorylation
PTPN1	down-regulates	BCR	dephosphorylation
BCR	unknown	YWHAQ	phosphorylation
BCR	unknown	YWHAZ	phosphorylation

Protein complexes (CORUM) (6)

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

6 complexes by size:

Complex	Subunits	Members
★ ABL1-BCR-(BCR-ABL fusion kinase)-MAP2K1-MAP2K2 complex	5	ABL1, BCR, BCR/ABL fusion, MAP2K1, MAP2K2
★ ABL1-BCR-MAP2K1-MAP2K2 complex	4	BCR, MAP2K1, MAP2K2, ABL1
★ BCR-ABL1(fusion kinase)-SHC1 complex	3	ABL1, BCR, SHC1
★ BCR-ABL1(fusion kinase)-GRB2 complex	3	ABL1, BCR, GRB2
★ BCR-ABL1(fusion kinase)-CBL complex	3	ABL1, BCR, CBL
★ BCR-FES complex	2	BCR, FES

Ligand–receptor pairs (CellPhoneDB) (1)

Curated ligand–receptor partners (cell-cell communication), distinct from the protein–protein interactions above.

1 ligand–receptor pairs:

Partner	This gene’s role	Signaling class
BCR;PTPRC;CD22		Signaling by Galectin

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 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
Assembly and cell surface presentation of NMDA receptors	7	24.0×	3e-06
Neurexins and neuroligins	9	23.9×	5e-08
Protein-protein interactions at synapses	5	17.9×	7e-04
RHOQ GTPase cycle	5	12.2×	2e-03
Sensory processing of sound by inner hair cells of the cochlea	5	11.0×	3e-03
RHOB GTPase cycle	5	10.4×	4e-03
RHOC GTPase cycle	5	9.9×	4e-03
RHOA GTPase cycle	6	6.0×	9e-03

GO biological processes:

GO term	Partners	Fold	FDR
establishment or maintenance of epithelial cell apical/basal polarity	10	56.4×	7e-13
protein localization to synapse	6	44.6×	9e-07
receptor clustering	6	36.4×	2e-06
regulation of postsynaptic membrane neurotransmitter receptor levels	7	33.7×	5e-07
establishment of cell polarity	5	18.6×	4e-04
bicellular tight junction assembly	5	16.0×	7e-04
protein-containing complex assembly	9	9.9×	3e-05
cell-cell adhesion	9	8.9×	7e-05

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 6 cancer types — BL, CLLSLL, DLBCLNOS, LUSC, NHL, WDTC.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for BCR: 399 ClinVar records (41 pathogenic / likely pathogenic); 7 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	37
Likely pathogenic	4
Uncertain significance	227
Likely benign	68
Benign	15

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 41 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
59252	GRCh38/hg38 22q11.21-11.23(chr22:21443815-24235645)x1	Pathogenic	criteria provided, single submitter	1
59253	GRCh38/hg38 22q11.21-11.23(chr22:21443815-23397298)x1	Pathogenic	criteria provided, single submitter	1
59264	GRCh38/hg38 22q11.21-11.23(chr22:21457690-24220231)x1	Pathogenic	criteria provided, single submitter	1
59267	GRCh38/hg38 22q11.21-11.23(chr22:21562911-24307688)x1	Pathogenic	criteria provided, single submitter	1
59283	GRCh38/hg38 22q11.21-11.23(chr22:21623411-23315617)x1	Pathogenic	criteria provided, single submitter	1
59284	GRCh38/hg38 22q11.22-11.23(chr22:22651209-23299955)x1	Pathogenic	criteria provided, single submitter	1
59285	GRCh38/hg38 22q11.22-11.23(chr22:22660238-23305976)x1	Pathogenic	criteria provided, single submitter	1
59286	GRCh38/hg38 22q11.22-11.23(chr22:22686122-23315617)x1	Pathogenic	criteria provided, single submitter	1
59287	GRCh38/hg38 22q11.22-11.23(chr22:22703701-23285204)x1	Pathogenic	criteria provided, single submitter	1
59326	GRCh38/hg38 22q11.21-11.23(chr22:21386914-23305976)x3	Pathogenic	criteria provided, single submitter	1
253433	GRCh37/hg19 22q11.21-11.23(chr22:21400683-23654222)x3	Pathogenic	criteria provided, single submitter	1
253499	GRCh37/hg19 22q11.22-11.23(chr22:22988879-24276233)x3	Pathogenic	criteria provided, single submitter	1
816559	GRCh37/hg19 22q11.21-11.23(chr22:21465661-23666232)x3	Pathogenic	criteria provided, single submitter	1
2506549	GRCh37/hg19 22q11.22-11.23(chr22:22893189-24177119)	Pathogenic	criteria provided, single submitter	1
2684931	GRCh37/hg19 22q11.21-11.23(chr22:21798907-23652586)x3	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 2,323):

Position(s)	Effect	Δscore	Sites
22:23182240	donor_loss	1.0000	2
22:23253792	acceptor_gain	1.0000
22:23253796	acceptor_gain	1.0000
22:23253797–23253798	acceptor_loss	1.0000	3
22:23261353–23261354	acceptor_loss	1.0000	6
22:23261541–23261542	donor_loss	1.0000	5
22:23268406–23268407	acceptor_loss	1.0000	6
22:23271530–23271531	acceptor_loss	1.0000	6
22:23271590	donor_gain	1.0000
22:23271593	donor_loss	1.0000

AlphaMissense

3,439 missense substitutions predicted likely pathogenic (of 8,366 scored), across 811 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M1198	9	0.996	1.000
M498	9	0.981	0.997
M56	9	0.950	0.997
M1240	9	0.859	0.979
D659	8	0.998	0.999
F581	8	0.995	1.000
D670	8	0.994	0.998
H557	8	0.993	0.999
F615	8	0.993	1.000
D1120	8	0.993	0.999
H1185	8	0.993	0.997
F1207	8	0.992	0.999
F684	8	0.990	1.000
F54	8	0.989	1.000
N1196	8	0.989	0.999
F547	8	0.984	0.998
D712	8	0.982	0.995
F1052	8	0.982	0.999
H727	8	0.981	0.998
D936	8	0.981	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

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

2 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	5.86e-10
Kidney Renal Clear Cell Carcinoma (validation)	favorable	0.000146

Disease associations

OMIM: gene MIM:151410 | disease phenotypes: MIM:613523

GenCC curated gene-disease

Mondo (1): myeloid neoplasm associated with FGFR1 rearrangement (MONDO:0013296)

Orphanet (1): Myeloid/lymphoid neoplasm associated with FGFR1 rearrangement (Orphanet:168953)

HPO phenotypes

showing 60 of 77 phenotypes (HPO-id order):

HPO	Term
HP:0000010	Recurrent urinary tract infections
HP:0000023	Inguinal hernia
HP:0000160	Narrow mouth
HP:0000175	Cleft palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000272	Malar flattening
HP:0000276	Long face
HP:0000307	Pointed chin
HP:0000319	Smooth philtrum
HP:0000324	Facial asymmetry
HP:0000363	Abnormal earlobe morphology
HP:0000407	Sensorineural hearing impairment
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000453	Choanal atresia
HP:0000490	Deeply set eye
HP:0000581	Blepharophimosis
HP:0000657	Oculomotor apraxia
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0001166	Arachnodactyly
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001382	Joint hypermobility
HP:0001442	Typified by somatic mosaicism
HP:0001510	Growth delay
HP:0001511	Intrauterine growth retardation
HP:0001622	Premature birth
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001659	Aortic regurgitation
HP:0001660	Truncus arteriosus
HP:0001744	Splenomegaly
HP:0001763	Pes planus
HP:0001770	Toe syndactyly
HP:0001802	Absent toenail
HP:0001817	Absent fingernail
HP:0001852	Sandal gap
HP:0001871	Abnormality of blood and blood-forming tissues
HP:0001873	Thrombocytopenia
HP:0001894	Thrombocytosis
HP:0001911	Abnormal granulocyte morphology
HP:0001912	Abnormal basophil morphology
HP:0001945	Fever
HP:0001974	Increased total leukocyte count
HP:0002021	Pyloric stenosis
HP:0002205	Recurrent respiratory infections
HP:0002463	Language impairment
HP:0002553	Highly arched eyebrow
HP:0002607	Bowel incontinence
HP:0002664	Neoplasm
HP:0002673	Coxa valga
HP:0002705	High, narrow palate
HP:0002721	Immunodeficiency
HP:0003307	Hyperlordosis
HP:0004209	Clinodactyly of the 5th finger
HP:0004279	Short palm
HP:0004322	Short stature

GWAS associations

7 associations:

Study	Trait	p-value
GCST009599_11	Kidney stones	3e-12
GCST009598_10	Kidney stones	4e-12
GCST90013421_3	Left-handedness	2e-8
GCST003831_44	Asthma	4e-7
GCST003523_25	Coenzyme Q10 levels	2e-6
GCST000175_47	Height	6e-6
GCST001491_12	Immune response to smallpox vaccine (IL-6)	8e-6

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004645	response to vaccine
EFO:0007836	coenzyme Q10 measurement
EFO:0009902	handedness

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (8): CHEMBL2096618 (CHIMERIC PROTEIN), CHEMBL4296119 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296120 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296137 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523751 (PROTEIN-PROTEIN INTERACTION), CHEMBL5146 (SINGLE PROTEIN), CHEMBL6193840 (PROTEIN-PROTEIN INTERACTION), CHEMBL6193843 (PROTEIN-PROTEIN INTERACTION)

Drugs acting on a complex or family that includes this protein

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

9 drugs via a complex or family:

Drug	Target (ChEMBL)	Members	Max phase
ASCIMINIB HYDROCHLORIDE	Bcr/Abl fusion protein	2	4
BOSUTINIB MONOHYDRATE	Bcr/Abl fusion protein	2	4
DASATINIB	Bcr/Abl fusion protein	2	4
IMATINIB MESYLATE	Bcr/Abl fusion protein	2	4
NILOTINIB HYDROCHLORIDE MONOHYDRATE	Bcr/Abl fusion protein	2	4
PONATINIB HYDROCHLORIDE	Bcr/Abl fusion protein	2	4
OLVEREMBATINIB	Bcr/Abl fusion protein	2	3
RADOTINIB	Bcr/Abl fusion protein	2	3
VODOBATINIB	Bcr/Abl fusion protein	2	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 508,462 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

showing 60 of 64 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4208229	ASCIMINIB	4	946
CHEMBL1289926	AXITINIB	4	16,510
CHEMBL288441	BOSUTINIB	4	12,869
CHEMBL2105717	CABOZANTINIB	4	11,799
CHEMBL601719	CRIZOTINIB	4	15,133
CHEMBL5416410	DASATINIB	4	674
CHEMBL1421	DASATINIB ANHYDROUS	4	55,947
CHEMBL553	ERLOTINIB	4	109,860
CHEMBL1287853	FEDRATINIB	4	3,770
CHEMBL1873475	IBRUTINIB	4	8,363
CHEMBL941	IMATINIB	4	113,105
CHEMBL1642	IMATINIB MESYLATE	4	70,926
CHEMBL1852688	INFIGRATINIB	4	2,298
CHEMBL1289601	LENVATINIB	4	9,224
CHEMBL255863	NILOTINIB	4	39,362
CHEMBL502835	NINTEDANIB	4	8,978
CHEMBL1171837	PONATINIB	4	9,435
CHEMBL1946170	REGORAFENIB	4	13,318
CHEMBL571546	TIRBANIBULIN	4	1,248
CHEMBL1289494	TIVOZANIB	4	4,697
CHEMBL3348923	TOVORAFENIB	4
CHEMBL24828	VANDETANIB	4
CHEMBL31965	CANERTINIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL3545413	FLUMATINIB	3
CHEMBL1908391	MASITINIB	3
CHEMBL4297524	RADOTINIB	3
CHEMBL165	RESVERATROL	3
CHEMBL217092	SARACATINIB	3
CHEMBL109480	TANESPIMYCIN	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL1976040	ADAVOSERTIB	2
CHEMBL587723	AEE-788	2
CHEMBL495727	AT-9283	2
CHEMBL206834	BAFETINIB	2
CHEMBL2029988	CEP-32496	2
CHEMBL402548	DANUSERTIB	2
CHEMBL1230609	FORETINIB	2
CHEMBL278315	GELDANAMYCIN	2
CHEMBL3989914	GLESATINIB	2
CHEMBL3039525	GOLVATINIB	2
CHEMBL564829	MILCICLIB	2
CHEMBL253969	OSI-632	2
CHEMBL607707	PELITINIB	2
CHEMBL3991932	PEXMETINIB	2
CHEMBL83527	PTEROSTILBENE	2
CHEMBL1738757	REBASTINIB	2
CHEMBL403989	TG100-801	2
CHEMBL572878	TOZASERTIB	2
CHEMBL4130229	VODOBATINIB	2
CHEMBL2140408	AMG-900	1
CHEMBL574738	AST-487	1
CHEMBL2041933	AZD-7762	1
CHEMBL482967	CYC-116	1
CHEMBL1908397	KW-2449	1
CHEMBL3600873	MK-5108	1
CHEMBL259084	MLN-8054	1
CHEMBL3128043	PF-03758309	1
CHEMBL4289017	PF-03814735	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — BCR family

Binding affinities (BindingDB)

634 measured of 795 human assays (800 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL3808884	EC50	0.04 nM
3-[2-(Imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide	EC50	0.05 nM
CHEMBL6159841	IC50	0.06 nM
ABL-001	EC50	0.13 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(4-piperidin-1-yl )propoxy]-3-quinolinecarbonitrile	IC50	0.14 nM
4-[(2-chloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.23 nM
CHEMBL6146115	IC50	0.231 nM
CHEMBL6114872	IC50	0.24 nM
CHEMBL6150452	IC50	0.27 nM
CHEMBL6134515	IC50	0.27 nM
CHEMBL6167998	IC50	0.3 nM
CHEMBL2178270	IC50	0.33 nM
CHEMBL6148910	IC50	0.33 nM
CHEMBL6101887	IC50	0.33 nM
CHEMBL6145061	IC50	0.33 nM
CHEMBL2178277	IC50	0.36 nM
CHEMBL2178271	IC50	0.41 nM
4-[(2,4-dichloro-5-methoxyphenyl)amino]-6-methoxy-7-[3-(morpholin-4-yl)propoxy]quinoline-3-carbonitrile	IC50	0.42 nM
CHEMBL2178276	IC50	0.42 nM
CHEMBL5423801	EC50	0.44 nM
CHEMBL2178268	IC50	0.45 nM
CHEMBL2177649	IC50	0.45 nM
CHEMBL5208315	IC50	0.49 nM
CHEMBL2178269	IC50	0.52 nM
CHEMBL2177648	IC50	0.52 nM
CHEMBL2177646	IC50	0.52 nM
CHEMBL2177632	IC50	0.52 nM
CHEMBL2375971	IC50	0.52 nM
CHEMBL2177634	IC50	0.54 nM
CHEMBL2177645	IC50	0.6 nM
CHEMBL5206449	IC50	0.6 nM
4-[(2-chloro-5-methoxyphenyl)amino]-6,7-dimethoxyquinoline-3-carbonitrile	IC50	0.64 nM
CHEMBL5182032	IC50	0.65 nM
CHEMBL2177642	IC50	0.69 nM
CHEMBL2178278	IC50	0.7 nM
CHEMBL2177647	IC50	0.72 nM
4-[(2,4-Dichloro-5-methoxyphenyl)amino]-6,7-dimethoxy-3-quinolinecarbonitrile	IC50	0.76 nM
CHEMBL2177633	IC50	0.78 nM
CHEMBL5435926	EC50	0.8 nM
CHEMBL6150612	IC50	0.8 nM
CHEMBL5200499	IC50	0.83 nM
CHEMBL6144120	IC50	0.87 nM
CHEMBL6160648	IC50	0.93 nM
CHEMBL5179613	IC50	0.94 nM
CHEMBL2178279	IC50	0.98 nM
CHEMBL3736320	EC50	1 nM
CHEMBL6167632	IC50	1 nM
CHEMBL2178275	IC50	1.01 nM
CHEMBL2177636	IC50	1.01 nM
CHEMBL2178273	IC50	1.03 nM

ChEMBL bioactivities

917 potent at pChembl≥5 of 1027 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.80	IC50	0.016	nM	DASATINIB
10.52	Ki	0.03	nM	DASATINIB
10.40	EC50	0.04	nM	CHEMBL3808884
10.40	EC50	0.04	nM	DASATINIB
10.30	EC50	0.05	nM	PONATINIB
10.22	IC50	0.06	nM	CHEMBL6159841
10.10	IC50	0.08	nM	BOSUTINIB
10.06	Kd	0.088	nM	CHEMBL4746371
9.96	Kd	0.11	nM	CHEMBL4748640
9.89	Kd	0.13	nM	CHEMBL4742867
9.89	EC50	0.13	nM	DASATINIB
9.89	EC50	0.13	nM	ASCIMINIB
9.85	IC50	0.14	nM	CHEMBL334364
9.68	Kd	0.21	nM	CHEMBL4761731
9.64	Kd	0.23	nM	CHEMBL4747034
9.64	IC50	0.231	nM	CHEMBL6146115
9.64	IC50	0.23	nM	CHEMBL128706
9.62	IC50	0.24	nM	CHEMBL6114872
9.59	Kd	0.26	nM	CHEMBL4747034
9.57	IC50	0.27	nM	CHEMBL6150452
9.57	IC50	0.27	nM	CHEMBL6134515
9.55	Kd	0.28	nM	CHEMBL4748640
9.55	Kd	0.28	nM	CHEMBL4746371
9.52	EC50	0.3	nM	PONATINIB
9.52	Kd	0.3	nM	CHEMBL4796635
9.52	IC50	0.3	nM	CHEMBL6167998
9.49	Kd	0.32	nM	CHEMBL4642168
9.48	IC50	0.33	nM	CHEMBL2178270
9.48	IC50	0.33	nM	NILOTINIB
9.48	IC50	0.33	nM	CHEMBL6148910
9.48	IC50	0.33	nM	CHEMBL6101887
9.48	IC50	0.33	nM	CHEMBL6145061
9.44	IC50	0.36	nM	CHEMBL2178277
9.44	Kd	0.36	nM	CHEMBL4761731
9.42	Kd	0.38	nM	CHEMBL4742867
9.39	IC50	0.41	nM	CHEMBL2178271
9.38	IC50	0.42	nM	CHEMBL2178276
9.38	IC50	0.42	nM	CHEMBL131725
9.36	EC50	0.44	nM	CHEMBL5423801
9.35	IC50	0.45	nM	CHEMBL2178268
9.35	IC50	0.45	nM	CHEMBL2177649
9.35	Kd	0.45	nM	ASCIMINIB
9.33	Kd	0.47	nM	CHEMBL4544893
9.31	IC50	0.49	nM	CHEMBL5208315
9.30	IC50	0.5	nM	PONATINIB
9.28	IC50	0.52	nM	CHEMBL2178269
9.28	IC50	0.52	nM	CHEMBL2177648
9.28	IC50	0.52	nM	CHEMBL2177646
9.28	IC50	0.52	nM	CHEMBL2177632
9.28	IC50	0.52	nM	CHEMBL2375971

PubChem BioAssay actives

948 with measured affinity, of 2485 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
N-(2-chloro-6-methylphenyl)-2-[[6-[4-(2-hydroxyethyl)piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide;hydrate	1301834: Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay	ec50	<0.0001	uM
methyl 5-[[2-methyl-5-[[3-(4-methylimidazol-1-yl)-5-(trifluoromethyl)benzoyl]amino]phenyl]methylamino]-1H-pyrrolo[2,3-b]pyridine-2-carboxylate	1301834: Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay	ec50	<0.0001	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0001	uM
2-[2-[2-[2-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]acetamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[2-[2-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0001	uM
Ponatinib	1301834: Inhibition of human wild type BCR-ABL expressed in mouse BAF3 cells assessed as inhibition of cell proliferation after 72 hrs by MTT assay	ec50	0.0001	uM
Bosutinib	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0001	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0001	uM
Asciminib	2020214: Inhibition of wild type human BCR-ABL1 using Tyr2 peptide as substrate incubated for 1 hrs in presence of dasatinib by FRET based Z-LYTE assay	ec50	0.0001	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[2-[2-[2-[2-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-2-oxoethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0002	uM
4-(2-amino-4-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0002	uM
4-(2-acetamido-4-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0002	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0002	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[6-[[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]amino]-6-oxohexoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0003	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0003	uM
N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]-4-[2-(methanesulfonamido)-4-pyridinyl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-(3-piperidin-1-ylpropoxy)quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0003	uM
N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]-4-[2-(methanesulfonamido)-4-pyridinyl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
3-(6-acetamido-3-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
3-(6-amino-3-pyridinyl)-N-[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]benzamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
5-[4-[[(2S)-1-[4-chloro-3-(trifluoromethyl)anilino]-3-hydroxy-1-oxopropan-2-yl]carbamoyl]phenyl]-N,N-diethylpyridine-3-carboxamide	2214253: Inhibition of wild type Bcr-Abl (unknown origin) using Abltide as substrate incubated for 1 hr by luminescence based ADP-glo assay	ic50	0.0003	uM
Nilotinib	744878: Inhibition of Bcr-Abl kinase (unknown origin) after 30 mins by HTRF assay	ic50	0.0003	uM
N-[4-[[4-(dimethylamino)piperidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0003	uM
2-[[6-[4-[3-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[2-[[1-[5-[[4-[chloro(difluoro)methoxy]phenyl]carbamoyl]-3-(1H-pyrazol-5-yl)-2-pyridinyl]piperidine-4-carbonyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-N-(2-chloro-6-methylphenyl)-1,3-thiazole-5-carboxamide	2020212: Inhibition of wild type human BCR-ABL1 using Tyr2 peptide as substrate incubated for 1 hrs by FRET based Z-LYTE assay	ec50	0.0004	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-(3-morpholin-4-ylpropoxy)quinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0004	uM
N-[4-[[(3R)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-chloro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-fluoro-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
4-methyl-N-[4-[(4-methyl-1,4-diazepan-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
N-[4-[[(3aR,6aS)-2-methyl-1,3,3a,4,6,6a-hexahydropyrrolo[3,4-c]pyrrol-5-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0004	uM
N-(2-chloro-6-methylphenyl)-2-[[6-[4-[6-[2-[2-[6-[[(2S)-1-[(2S,4R)-4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-6-oxohexoxy]ethoxy]ethoxy]hexyl]piperazin-1-yl]-2-methylpyrimidin-4-yl]amino]-1,3-thiazole-5-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0005	uM
(2S,4S)-N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[4-[6-(methanesulfonamido)-3-pyridinyl]triazol-1-yl]pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0005	uM
N-[4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-3-[4-[2-(methylamino)pyrimidin-5-yl]triazol-1-yl]-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(3-methyl-2H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
3-(4-imidazo[1,2-a]pyridin-3-yltriazol-1-yl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
4-methyl-N-[4-[[4-(4-methylpiperazin-1-yl)piperidin-1-yl]methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0005	uM
N-[4-[3-(dimethylamino)propoxy]phenyl]-4-methoxy-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]benzamide	744878: Inhibition of Bcr-Abl kinase (unknown origin) after 30 mins by HTRF assay	ic50	0.0005	uM
6-[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]ethoxy]-N-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]hexanamide	1678549: Protac binding affinity at CRBN/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0006	uM
(2S,4S)-N-[4-chloro-3-(trifluoromethyl)phenyl]-4-[4-[6-(cyclopropanecarbonylamino)-3-pyridinyl]triazol-1-yl]pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0006	uM
(2S,4S)-4-[4-[2-(cyclopropanecarbonylamino)-[1,3]thiazolo[5,4-b]pyridin-5-yl]triazol-1-yl]-N-(2,4-dichlorophenyl)pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0006	uM
4-(2-chloro-5-methoxyanilino)-6,7-dimethoxyquinoline-3-carbonitrile	2236715: Inhibition of wild-type Bcr-Abl (unknown origin) in presence of ATP	ic50	0.0006	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0006	uM
(2S,4R)-1-[(2S)-2-[[2-[2-[6-[4-[3-[3-cyano-4-(2,4-dichloro-5-methoxyanilino)-6-methoxyquinolin-7-yl]oxypropyl]piperazin-1-yl]hexoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1678553: Protac binding affinity at VHL/BCR-ABL (unknown origin) assessed as binding to phosphorylated c-ABL kinase domain by Kinomescan assay	kd	0.0007	uM
4-methyl-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]-N-[4-(pyrrolidin-1-ylmethyl)-3-(trifluoromethyl)phenyl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
4-bromo-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrazolo[3,4-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-(1H-pyrrolo[2,3-b]pyridin-5-yl)triazol-1-yl]benzamide	710018: Inhibition of wild type Bcr-Abl using Tyr2 peptide as substrate after 2 hrs by FRET-based Z’-Lyte assay	ic50	0.0007	uM
(2S,4S)-4-[4-[3-(cyclopropanecarbonylamino)-1H-indazol-6-yl]triazol-1-yl]-N-(2,4-dichlorophenyl)pyrrolidine-2-carboxamide	1860252: Inhibition of wild type Bcr-Abl (unknown origin) incubated for 1 hr in presence of ATP by ADP-Glo kinase assay	ic50	0.0008	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Imatinib Mesylate	affects cotreatment, affects binding, decreases phosphorylation, increases reaction, decreases reaction (+4 more)	8
Arsenic Trioxide	increases degradation, increases reaction, increases localization, decreases expression, affects binding (+1 more)	6
Dasatinib	affects cotreatment, decreases expression, decreases phosphorylation, decreases reaction, increases phosphorylation (+2 more)	5
Vorinostat	decreases expression, decreases phosphorylation, decreases activity, affects cotreatment	3
sodium arsenite	increases abundance, increases expression, affects cotreatment, decreases expression	2
nilotinib	increases expression, decreases phosphorylation, affects binding, decreases reaction, increases chemical synthesis	2
Benzo(a)pyrene	affects methylation, decreases expression, decreases methylation	2
Estradiol	affects expression, increases expression	2
Valproic Acid	increases expression	2
FR900359	affects phosphorylation	1
dicrotophos	increases expression	1
bisphenol A	increases methylation	1
trichostatin A	decreases expression	1
arsenite	affects binding, decreases reaction	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	increases abundance, affects methylation	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
coumarin	decreases phosphorylation	1
muconaldehyde	decreases expression	1
cyfluthrin	increases expression	1
arsenic disulfide	decreases activity, decreases expression	1
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one	affects binding, decreases reaction, increases chemical synthesis, increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
purmorphamine	decreases expression, decreases reaction, affects binding	1
clothianidin	decreases expression	1
tozasertib	affects cotreatment, decreases activity	1
abrine	decreases expression	1
NCX 4040	increases expression	1
ponatinib	decreases phosphorylation	1

ChEMBL screening assays

486 unique, capped per target: 478 binding, 6 functional, 2 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1022417	Binding	Inhibition of Bcr/Abl phosphorylation in human K562 cells at 10 uM after 1 to 3 hrs by Western blot	Design of chimeric histone deacetylase- and tyrosine kinase-inhibitors: a series of imatinib hybrides as potent inhibitors of wild-type and mutant BCR-ABL, PDGF-Rbeta, and histone deacetylases. — *J Med Chem*
CHEMBL5237472	Toxicity	Inhibition of BCR-ABL (unknown origin) expressed in mouse BaF3 cells assessed as cell growth inhibition incubated for 20 mins by TR-FRET assay	Imidazo[1,2-b]pyridazine as privileged scaffold in medicinal chemistry: An extensive review. — *Eur J Med Chem*
CHEMBL861701	Functional	Antiproliferative activity against human K562 cell line expressing Bcr-Abl	Identification of a terphenyl derivative that blocks the cell cycle in the G0-G1 phase and induces differentiation in leukemia cells. — *J Med Chem*

Cellosaurus cell lines

6,100 cell lines: 6,077 cancer cell line, 19 induced pluripotent stem cell, 3 transformed cell line, 1 spontaneously immortalized cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0004	K-562	Cancer cell line	Female
CVCL_0087	MC3	Cancer cell line	Female
CVCL_0091	NALM-1	Cancer cell line	Female
CVCL_0094	SD-1	Transformed cell line	Female
CVCL_0103	SUP-B15	Cancer cell line	Male
CVCL_0181	BV-173	Cancer cell line	Male
CVCL_0368	K562/A02	Cancer cell line	Female
CVCL_0369	K562YO	Cancer cell line	Female
CVCL_0373	KBM-5	Cancer cell line	Female
CVCL_0379	Ku812	Cancer cell line	Male

Clinical trials (associated diseases)

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

showing 60 of 300 trials:

NCT	Phase	Status	Title
NCT00081926	Phase 4	COMPLETED	Gleevec Trial in Patients With Newly Diagnosed Chronic Phase Chronic Myelogenous Leukemia
NCT00171899	Phase 4	COMPLETED	Study Comparing Standard Dose and High-dose Imatinib Mesylate in Patients With Chronic Phase Philadelphia Chromosome Positive (Ph+) Chronic Myelogenous Leukemia (CML)
NCT00390897	Phase 4	COMPLETED	Glivec® (Imatinib Mesylate, STI571) in Monotherapy Versus Glivec®-Interferon Alpha in the Treatment of Chronic-Phase Chronic Myeloid Leukaemia
NCT00461929	Phase 4	TERMINATED	Chromosome Abnormalities in Chronic Myeloid Leukemia (CML) on Imatinib. GIST Patients on Imatinib
NCT00786812	Phase 4	COMPLETED	Study of Treatment With Nilotinib in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase
NCT00845221	Phase 4	COMPLETED	Glivec in Pediatric Chronic Myeloid Leukemia (CML)
NCT00980018	Phase 4	COMPLETED	An Exploratory Trial to Assess the Improvement of Adverse Events in Chronic Myelogenous Leukemia Patients Treated With Imatinib When Switched to Nilotinib Treatment
NCT01131325	Phase 4	TERMINATED	Study of Nilotinib in Ph+ CML-CP Patients With Low Imatinib Trough Plasma Concentrations
NCT01206088	Phase 4	COMPLETED	Tasigna in Glivec-resistant or Intolerant Patients in CML
NCT01243489	Phase 4	COMPLETED	Compliance: Role Emerges for Success in Chronic Myelogenous Leukaemia (CML): Evaluation aND Optimisation
NCT01368523	Phase 4	COMPLETED	Study of Oral AMN107 (Nilotinib) in Adult Patients With Imatinib - Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase Previously Enrolled to CAMN107A2109 Trial
NCT01578213	Phase 4	COMPLETED	Validation of Digital-PCR Analysis Through Programmed Imatinib Interruption in PCR Negative CML Patients
NCT01605981	Phase 4	WITHDRAWN	Trial Evaluating Nilotinib as Treatment for Newly Diagnosed CML Patients in Accelerated Phase.
NCT01735955	Phase 4	COMPLETED	Study to Allow Access to Nilotinib for Patients Who Are on Nilotinib Treatment in a Novartis-sponsored Study
NCT01901666	Phase 4	UNKNOWN	Assessment Of Gh-Igf-1 Axis In Children With Chronic Myelogenous Leukemia (CML) In Remission
NCT02086487	Phase 4	TERMINATED	Efficacy and Safety Assessment of NIlotinib in CML Patients With Suboptimal Response on Imatinib Therapy
NCT02204722	Phase 4	TERMINATED	A Study to Evaluate Efficacy and Safety of Glinib in Newly Diagnosed CML Patients
NCT02317159	Phase 4	UNKNOWN	Efficacy and Safety of Imatinib Mesylate as First-line Treatment for the Patients With Chronic Phase of Chronic Myeloid Leukemia
NCT02546674	Phase 4	COMPLETED	Study Assessing Deep Molecular Response in Adult Patients With CML in Chronic Phase Treated With Nilotinib Firstline.
NCT03216070	Phase 4	UNKNOWN	Low-dose Dasatinib as First-line Treatment for Chronic Myeloid Leukemia
NCT04155411	Phase 4	UNKNOWN	Dose Reduced Dasatinib (70 mg Daily) as First-line Treatment for Newly Diagnosed CML-CP
NCT04877522	Phase 4	RECRUITING	Asciminib Roll-over Study
NCT07105319	Phase 4	COMPLETED	Ropeginterferon for Treatment Free Remission
NCT00152139	Phase 3	COMPLETED	Stem Cell Transplantation for Patients With Hematologic Malignancies
NCT00219739	Phase 3	COMPLETED	STI571 ProspectIve RandomIzed Trial: SPIRIT
NCT00327262	Phase 3	UNKNOWN	Comparing Imatinib Standard Dose With Imatinib High Dose Induction in Pretreated Chronic Myeloid Leukemia (CML) Patients in Chronic Phase
NCT00333840	Phase 3	COMPLETED	Safety and Efficacy of Imatinib Versus Interferon-α Plus Cytarabine in Patients With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
NCT00412360	Phase 3	COMPLETED	Single vs Double Umbilical Cord Blood Transplants in Children With High Risk Leukemia and Myelodysplasia (BMT CTN 0501)
NCT00481247	Phase 3	COMPLETED	A Phase III Study of Dasatinib vs Imatinib in Patients With Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia
NCT00514488	Phase 3	COMPLETED	Imatinib Standard Dose (400 mg/Day) Versus Imatinib High Dose (800 mg/Day)
NCT00574873	Phase 3	COMPLETED	Compare Bosutinib To Imatinib In Subjects With Newly Diagnosed Chronic Phase Philadelphia Chromosome Positive CML
NCT00760877	Phase 3	COMPLETED	Nilotinib Versus Standard Imatinib (400/600 mg Every Day (QD)) Comparing the Kinetics of Complete Molecular Response for Chronic Myelogenous Leukemia in Chronic Phase (CML-CP) Pts With Evidence of Persistent Leukemia by Real-time Quantitative Polymerase Chain Reaction (RQ-PCR)
NCT00799461	Phase 3	COMPLETED	Internet-Based Program With or Without Telephone-Based Problem-Solving Training in Helping Long-Term Survivors of Hematopoietic Stem Cell Transplant Cope With Late Complications
NCT00802841	Phase 3	COMPLETED	Randomized Phase Lll Study of Imatinib Dose Optimization vs Nilotinib in CML Patients With Suboptimal Response to Imatinib
NCT01020175	Phase 3	COMPLETED	Peripheral Blood (PB) Versus Bone Marrow (BM) in Allogeneic Stem Cell Transplantation
NCT01126892	Phase 3	COMPLETED	A Study of Nilotinib in Adult Patients With Imatinib Resistant or - Intolerant Chronic Myeloid Leukemia in Blast Crisis, Accelerated Phase or Chronic Phase
NCT01188798	Phase 3	COMPLETED	Methotrexate or Pentostatin for Graft-versus-host Disease Prophylaxis in Risk-adapted Allogeneic Bone Marrow Transplantation for Hematologic Malignancies
NCT01231412	Phase 3	COMPLETED	Graft-Versus-Host Disease Prophylaxis in Treating Patients With Hematologic Malignancies Undergoing Unrelated Donor Peripheral Blood Stem Cell Transplant
NCT01254188	Phase 3	COMPLETED	Safety and Efficacy of Nilotinib in Newly Diagnosed Chronic Myeloid Leukemia Patients
NCT01275196	Phase 3	COMPLETED	Safety and Efficacy of Nilotinib vs. Imatinib in the Treatment of Newly Diagnosed Chinese Ph+ CML-CP Patients
NCT01305200	Phase 3	COMPLETED	Supersaturated Calcium Phosphate Rinse in Preventing Oral Mucositis in Young Patients Undergoing Autologous or Donor Stem Cell Transplant
NCT01366612	Phase 3	TERMINATED	Fludarabine and Busulfan vs. Fludarabine, Busulfan and Total Body Irradiation
NCT01400074	Phase 3	UNKNOWN	Efficacy of Nilotinib Versus Imatinib in Ph+ CML in Early CP Who Have a Suboptimal Molecular Response to Imatinib
NCT01535391	Phase 3	COMPLETED	Nilotinib in PH+, BCR-, ABL+ CML Patients
NCT01596114	Phase 3	COMPLETED	European Stop Tyrosine Kinase Inhibitor Study
NCT01650805	Phase 3	TERMINATED	Ponatinib in Newly Diagnosed Chronic Myeloid Leukemia (CML) (EPIC)
NCT01657604	Phase 3	COMPLETED	TKI and Interferon Alpha Evaluation Initiated by the German Chronic Myeloid Leukemia Study Group - the TIGER Study
NCT01749111	Phase 3	TERMINATED	Comparison Between Cyclophosphamide and Combination of Methotrexate + Calcineurin Inhibitor for GVHD Prophylaxis
NCT01755325	Phase 3	SUSPENDED	Phase III Study of Compound Formula Realgar-Indigo Naturalis Plus Imatinib Versus Placebo Plus Imatinib in Adult CML-CP Patients With Ph+
NCT01951885	Phase 3	COMPLETED	Tac, Mini-MTX, MMF Versus Tac, MTX for GVHD Prevention
NCT02174445	Phase 3	TERMINATED	An Open-label, Randomised Multicenter Phase 3b Study to Determine the Confirmed Rate of Molecular Response ≥ 4 Log (MR4) at Two Years
NCT02201459	Phase 3	COMPLETED	Nilotinib ± Peg-IFN for First Line Chronic Phase CML Patients
NCT02566395	Phase 3	COMPLETED	Stem Cell Transplantation From HLA Partially-Matched Related Donors for Patients With Hematologic Malignancies
NCT02730299	Phase 3	COMPLETED	Stem Cell Transplantation With NiCord® (Omidubicel) vs Standard UCB in Patients With Leukemia, Lymphoma, and MDS
NCT02890784	Phase 3	COMPLETED	Dasatinib Holiday for Improved Tolerability
NCT03106779	Phase 3	COMPLETED	Study of Efficacy of CML-CP Patients Treated With ABL001 Versus Bosutinib, Previously Treated With 2 or More TKIs
NCT03480360	Phase 3	COMPLETED	Haploidentical Allogeneic Peripheral Blood Transplantation: Examining Checkpoint Immune Regulators’ Expression
NCT03746054	Phase 3	TERMINATED	Evaluation of a Cardiovascular Active Prevention in Chronic Myeloid Leukemia on the Cardiovascular Morbi-mortality
NCT03959241	Phase 3	COMPLETED	TAC/MTX vs. TAC/MMF/PTCY for Prevention of Graft-versus-Host Disease and Microbiome and Immune Reconstitution Study (BMT CTN 1703/1801)
NCT04948333	Phase 3	COMPLETED	Asciminib Treatment Optimization in ≥ 3rd Line CML-CP

Predicted chemistry — Sugi Predict

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