ABL2

Summary

ABL2 (ABL proto-oncogene 2, non-receptor tyrosine kinase, HGNC:77) is a protein-coding gene on chromosome 1q25.2, encoding Tyrosine-protein kinase ABL2 (P42684). Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. In precision oncology, ABL2 W469C confers sensitivity to Imatinib + Dasatinib in Lung Adenocarcinoma (CIViC Level D).

This gene encodes a member of the Abelson family of nonreceptor tyrosine protein kinases. The protein is highly similar to the c-abl oncogene 1 protein, including the tyrosine kinase, SH2 and SH3 domains, and it plays a role in cytoskeletal rearrangements through its C-terminal F-actin- and microtubule-binding sequences. This gene is expressed in both normal and tumor cells, and is involved in translocation with the ets variant 6 gene in leukemia. Multiple alternatively spliced transcript variants encoding different protein isoforms have been found for this gene.

Source: NCBI Gene 27 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 157 total — 14 pathogenic, 1 likely-pathogenic
• Druggable target: yes — 63 molecules with ChEMBL bioactivity
• Precision-oncology evidence (CIViC): 1 curated variant–drug association
• Cancer driver (intOGen): activating (oncogene-like) across 2 cancer types
• MANE Select transcript: NM_007314

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:77
Approved symbol	ABL2
Name	ABL proto-oncogene 2, non-receptor tyrosine kinase
Location	1q25.2
Locus type	gene with protein product
Status	Approved
Aliases	ARG
Ensembl gene	ENSG00000143322
Ensembl biotype	protein_coding
OMIM	164690
Entrez	27

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 7 protein_coding, 6 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000344730, ENST00000367623, ENST00000502732, ENST00000504324, ENST00000504405, ENST00000507173, ENST00000508127, ENST00000509520, ENST00000511413, ENST00000512653, ENST00000659126, ENST00000660584, ENST00000662960, ENST00000668691

RefSeq mRNA: 8 — MANE Select: NM_007314 NM_001136000, NM_001136001, NM_001168236, NM_001168237, NM_001168238, NM_001168239, NM_005158, NM_007314

CCDS: CCDS30947, CCDS41441, CCDS44282, CCDS53435, CCDS53436, CCDS53437, CCDS53438

Canonical transcript exons

ENST00000502732 — 12 exons

Exon	Start	End
ENSE00001445181	179099330	179109441
ENSE00001445182	179229241	179229677
ENSE00001578442	179112309	179112398
ENSE00001578655	179110282	179110455
ENSE00001586766	179114878	179115030
ENSE00002260002	179117332	179117516
ENSE00003459332	179120190	179120274
ENSE00003479196	179126377	179126672
ENSE00003484429	179118587	179118764
ENSE00003582099	179133312	179133374
ENSE00003676561	179121595	179121867
ENSE00003679673	179131311	179131481

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 94.37.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0211 / max 517.2459, expressed in 1758 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
16072	12.0687	1183
16078	4.5893	1535
16069	0.4597	147
16077	0.3755	173
16070	0.2872	125
16071	0.2406	75

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	94.37	gold quality
buccal mucosa cell	CL:0002336	89.62	gold quality
sural nerve	UBERON:0015488	89.49	gold quality
visceral pleura	UBERON:0002401	89.46	gold quality
parietal pleura	UBERON:0002400	88.34	gold quality
pleura	UBERON:0000977	87.51	gold quality
middle temporal gyrus	UBERON:0002771	87.24	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.10	gold quality
tendon	UBERON:0000043	85.96	gold quality
tibia	UBERON:0000979	85.94	gold quality
secondary oocyte	CL:0000655	85.73	gold quality
cerebellar vermis	UBERON:0004720	85.63	gold quality
colonic epithelium	UBERON:0000397	85.28	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.27	gold quality
medial globus pallidus	UBERON:0002477	84.99	gold quality
amniotic fluid	UBERON:0000173	84.11	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.09	gold quality
cartilage tissue	UBERON:0002418	83.54	gold quality
cortical plate	UBERON:0005343	83.52	gold quality
endothelial cell	CL:0000115	83.35	silver quality
stromal cell of endometrium	CL:0002255	82.99	gold quality
globus pallidus	UBERON:0001875	82.69	gold quality
calcaneal tendon	UBERON:0003701	82.14	gold quality
gall bladder	UBERON:0002110	81.51	gold quality
postcentral gyrus	UBERON:0002581	81.09	gold quality
oocyte	CL:0000023	80.81	gold quality
synovial joint	UBERON:0002217	80.44	gold quality
ganglionic eminence	UBERON:0004023	80.41	gold quality
superficial temporal artery	UBERON:0001614	80.17	gold quality
entorhinal cortex	UBERON:0002728	80.10	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	541.63
E-GEOD-135922	yes	20.10
E-MTAB-8142	yes	12.83
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BTF3, NFKB, NKX3-1, NR1H3, TP53

miRNA regulators (miRDB)

315 targeting ABL2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595

Literature-anchored findings (GeneRIF, showing 40)

• Data show that overexpression of either heat-shock proteins 26 or 27 extended the mean lifespan by 30%, and the flies also displayed increased stress resistance. (PMID:15308776)
• The data suggest that the Drosophila HSP27 protein acts as a chaperone to provide cellular stress resistance, although its function may be limited to a subset of the stress response such as the starvation resistance. (PMID:18229455)
• study identifies two distinct sets of sequences respectively mediating the nuclear import of Hsp27 and its association to nuclear speckles. (PMID:18339325)
• The functional similarities and differences of neuronal expression of hsp26 and hsp27 in adult Drosophila were demonstrated. (PMID:18796296)
• We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila. (PMID:22621211)
• The study evidenced the neuroprotective efficacy of hsp27 overexpression against prolonged dichlorvos exposure. (PMID:26033218)
• Altogether, the results characterize wild-type Hsp27 and its alpha-crystallin domain (ACD) arginine mutants and may give insight into protection mechanism of small heat shock proteins. (PMID:27933579)
• We show that while Hsp70 or Hsp83 expression under normal or stress conditions was not affected by AR feeding, Hsp27 levels were elevated in AR-fed wild-type control as well as heat-shocked larvae (PMID:27966490)
• Hsp27, a potential EcR target, protects nonylphenol-induced cellular and organismal toxicity in Drosophila melanogaster. (PMID:34774861)
• Hsp27 over expression protect against cadmium induced nephrotoxicity in Drosophila melanogaster. (PMID:37586579)
• The highest Arg transcript and protein levels are in the mature B cells. (PMID:12220663)
• Review. ABL protein tyrosine kinases regulate cell proliferation, survival, adhesion, migration, stress responses, and cytoskeletal dynamics. (PMID:12374288)
• c-Abl and Arg regulate catalase and that this signaling pathway is of importance to apoptosis in the oxidative stress response (PMID:12777400)
• findings indicate that, in addition to stimulating catalase activity, c-Abl and Arg promote catalase degradation in the oxidative stress response (PMID:12950161)
• High Arg expression is correlated with thymoma stage (PMID:15679048)
• several critical domains within TEL/ARG necessary for function (PMID:15729383)
• The present study demonstrates that c-Abl and Arg (abl-related gene) tyrosine kinases associate with and phosphorylate the proteasome PSMA7 (alpha4) subunit at Tyr-153. (PMID:16678104)
• ABL2/ARG is a novel mediator of SEMA3F-induced RhoA inactivation and collapsing activity. (PMID:18660502)
• Abl kinases not only are activated by PDGFR and promote PDGFR-mediated proliferation and migration, but also act in an intricate negative feedback loop to turn-off PDGFR-mediated chemotaxis. (PMID:19275932)
• Results describe the NMR structure of human Arg F-actin-binding domain. (PMID:20077570)
• The Arg tyrosine kinase regulated lysosomal degradation of antiapoptotic Gal3 may provide one of the important arms in Arg tyrosine kinase dependent antiapoptotic pathways. (PMID:20150913)
• A 35-bp insertion in the BCR-ABL2 gene is associated with resistance to tyrosine kinase inhibitors, but sensitivity to omacetaxine in chronic myelogenous leukemia. (PMID:20448119)
• Our findings suggest a novel mechanism by which an EGFR-Src-Arg-cortactin pathway mediates functional maturation of invadopodia and breast cancer cell invasion (PMID:21257711)
• Knockout mutation of p27-p55 operon in Mycobacterium bovis severely decreased the virulence of the bacteria when assessed in a progressive model of pulmonary tuberculosis in Balb/c mice. (PMID:21543883)
• c-Abl and Arg not only promote in vitro processes important for melanoma progression, but also promote metastasis in vivo (PMID:21892207)
• Arg acts as a switch in metastatic cancer cells that governs the decision to ‘grow or go’ (divide or invade). (PMID:22777352)
• Beta1 integrin regulates Arg to promote invadopodial maturation and matrix degradation. (PMID:23552693)
• data provide evidence that Aurora A, AMPK, ABL and CDKs are functionally integrated into human cytomegalovirus (HCMV) replication; inhibition of AMPK and ABL kinases exerted a negative effect, inhibition of Aurora A kinase a slightly positive effect on HCMV replication (PMID:23648710)
• Data shows that c-Abl and Arg induce NM23-H1 degradation by increasing expression and activation of cathepsin L and B, which directly cleave NM23-H1 in the lysosome. (PMID:24096484)
• Knockdown of ABL2 promoted cell invasion and migration and we identified miR-20a-induced cell invasion and migration can be rescued by ABL2. (PMID:24464651)
• the ETV6/ARG oncoprotein contributes to autonomous cell growth by compensating for the requirement of growth factor through activating STAT5 signaling, which leads to the up-regulation of c-Myc. (PMID:25373509)
• Two distinct interfaces mediate direct binding of integrin beta1 with Arg in vitro and in cells and promote Arg kinase activation. (PMID:25694433)
• Q112H mutation hinders the ability of the protein to interact with Abl kinase, leading to defective tyrosine phosphorylation and a resultant defect in respiration (PMID:27913209)
• c-Abl/Arg are oncogenic kinases that regulate differential gene expression (PMID:28555614)
• High expression of ABL2 suppresses apoptosis in gastric cancer cell lines (PMID:29767389)
• Arg kinase mediates CXCL12/CXCR4-induced invadopodia formation and invasion of glioma cells. (PMID:32035133)
• Epidermal Growth Factor Receptor and Abl2 Kinase Regulate Distinct Steps of Human Papillomavirus 16 Endocytosis. (PMID:32188731)
• miR-143 inhibits renal cell carcinoma cells metastatic potential by suppressing ABL2. (PMID:32196963)
• Combating acquired resistance to MAPK inhibitors in melanoma by targeting Abl1/2-mediated reactivation of MEK/ERK/MYC signaling. (PMID:33122628)
• The ABL2 kinase regulates an HSF1-dependent transcriptional program required for lung adenocarcinoma brain metastasis. (PMID:33318173)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	abl2	ENSDARG00000013841
mus_musculus	Abl2	ENSMUSG00000026596
rattus_norvegicus	Abl2	ENSRNOG00000004305

Paralogs (32): FGR (ENSG00000000938), MATK (ENSG00000007264), BTK (ENSG00000010671), FYN (ENSG00000010810), STYK1 (ENSG00000060140), TNK2 (ENSG00000061938), TXK (ENSG00000074966), JAK2 (ENSG00000096968), ABL1 (ENSG00000097007), PTK6 (ENSG00000101213), HCK (ENSG00000101336), BMX (ENSG00000102010), CSK (ENSG00000103653), TYK2 (ENSG00000105397), JAK3 (ENSG00000105639), FRK (ENSG00000111816), ITK (ENSG00000113263), ZAP70 (ENSG00000115085), PTK2B (ENSG00000120899), SRMS (ENSG00000125508), TEC (ENSG00000135605), BLK (ENSG00000136573), 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 ABL2 — P42684 (reviewed: P42684)

Alternative names: Abelson murine leukemia viral oncogene homolog 2, Abelson tyrosine-protein kinase 2, Abelson-related gene protein, Tyrosine-protein kinase ARG

All UniProt accessions (1): P42684

UniProt curated annotations — full annotation on UniProt →

Function. Non-receptor tyrosine-protein kinase that plays an ABL1-overlapping role in key processes linked to cell growth and survival such as cytoskeleton remodeling in response to extracellular stimuli, cell motility and adhesion and receptor endocytosis. Coordinates actin remodeling through tyrosine phosphorylation of proteins controlling cytoskeleton dynamics like MYH10 (involved in movement); CTTN (involved in signaling); or TUBA1 and TUBB (microtubule subunits). Binds directly F-actin and regulates actin cytoskeletal structure through its F-actin-bundling activity. Involved in the regulation of cell adhesion and motility through phosphorylation of key regulators of these processes such as CRK, CRKL, DOK1 or ARHGAP35. Adhesion-dependent phosphorylation of ARHGAP35 promotes its association with RASA1, resulting in recruitment of ARHGAP35 to the cell periphery where it inhibits RHO. Phosphorylates multiple receptor tyrosine kinases like PDGFRB and other substrates which are involved in endocytosis regulation such as RIN1. In brain, may regulate neurotransmission by phosphorylating proteins at the synapse. ABL2 also acts as a regulator of multiple pathological signaling cascades during infection. Pathogens can highjack ABL2 kinase signaling to reorganize the host actin cytoskeleton for multiple purposes, like facilitating intracellular movement and host cell exit. Finally, functions as its own regulator through autocatalytic activity as well as through phosphorylation of its inhibitor, ABI1. Positively regulates chemokine-mediated T-cell migration, polarization, and homing to lymph nodes and immune-challenged tissues, potentially via activation of NEDD9/HEF1 and RAP1.

Subunit / interactions. Interacts with PSMA7. Interacts with CTTN. Found in a complex with ABL1, ABL2, CRK and UNC119; leading to the inhibition of CRK phosphorylation by ABL kinases.

Subcellular location. Cytoplasm. Cytoskeleton.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated at Tyr-261 by ABL1 in response to oxidative stress. Phosphorylated by PDGFRB. Polyubiquitinated. Polyubiquitination of ABL2 leads to degradation.

Activity regulation. Stabilized in the inactive form by an association between the SH3 domain and the SH2-TK linker region, interactions of the N-terminal cap, and contributions from an N-terminal myristoyl group and phospholipids. Activated by autophosphorylation as well as by SRC-family kinase-mediated phosphorylation. Activated by RIN1 binding to the SH2 and SH3 domains. Inhibited by imatinib mesylate (Gleevec) which is used for the treatment of chronic myeloid leukemia (CML). Phosphatidylinositol 4,5-bisphosphate (PIP2), a highly abundant phosphoinositide known to regulate cytoskeletal and membrane proteins, inhibits the tyrosine kinase activity.

Domain organisation. Contains two distinct classes of F-actin-binding domains. Although both can bind F-actin, the 2 are required to bundle actin filaments.

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

Isoforms (9)

UniProt ID	Names	Canonical?
P42684-1	1, IB, 1BLCTL	yes
P42684-2	2, IA, 1ASCTL
P42684-3	3, IC, 1ALCTL
P42684-4	4, 1ASCTS
P42684-5	5, 1BLCTS
P42684-6	6, 1BSCTL
P42684-7	7, 1BSCTS
P42684-10	10, 1ALCTS
P42684-8	8

RefSeq proteins (8): NP_001129472, NP_001129473, NP_001161708, NP_001161709, NP_001161710, NP_001161711, NP_005149, NP_009298* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR000980	SH2	Domain
IPR001245	Ser-Thr/Tyr_kinase_cat_dom	Domain
IPR001452	SH3_domain	Domain
IPR008266	Tyr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR015015	F-actin-binding	Domain
IPR017441	Protein_kinase_ATP_BS	Binding_site
IPR020635	Tyr_kinase_cat_dom	Domain
IPR035837	ABL_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, PF08919

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 (135 total): modified residue 35, helix 27, strand 25, region of interest 10, sequence variant 10, splice variant 6, compositionally biased region 5, domain 3, binding site 3, sequence conflict 3, turn 2, short sequence motif 2, initiator methionine 1, chain 1, active site 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4EIH	X-RAY DIFFRACTION	1.2
5NP5	X-RAY DIFFRACTION	1.4
3HMI	X-RAY DIFFRACTION	1.65
3ULR	X-RAY DIFFRACTION	1.65
5NP3	X-RAY DIFFRACTION	2
3GVU	X-RAY DIFFRACTION	2.05
2XYN	X-RAY DIFFRACTION	2.81
2ECD	SOLUTION NMR
2KK1	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P42684-F1	60.19	0.29

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): 409 (proton acceptor)

Ligand- & substrate-binding residues (3): 294–302; 317; 362–368

Post-translational modifications (36): 647, 683, 662, 668, 97, 116, 161, 174, 185, 218, 231, 261, 272, 275, 299, 303, 439, 459, 568, 620 …

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-428890	Role of ABL in ROBO-SLIT signaling
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle
R-HSA-9706369	Negative regulation of FLT3
R-HSA-1266738	Developmental Biology
R-HSA-1280215	Cytokine Signaling in Immune system
R-HSA-162582	Signal Transduction
R-HSA-168256	Immune System
R-HSA-194315	Signaling by Rho GTPases
R-HSA-376176	Signaling by ROBO receptors
R-HSA-422475	Axon guidance
R-HSA-9012999	RHO GTPase cycle
R-HSA-9607240	FLT3 Signaling
R-HSA-9675108	Nervous system development
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 0 (showing top):

GO Biological Process (20): cell adhesion (GO:0007155), signal transduction (GO:0007165), epidermal growth factor receptor signaling pathway (GO:0007173), phospholipase C-activating G protein-coupled receptor signaling pathway (GO:0007200), positive regulation of cytosolic calcium ion concentration (GO:0007204), regulation of autophagy (GO:0010506), positive regulation of neuron projection development (GO:0010976), peptidyl-tyrosine phosphorylation (GO:0018108), regulation of endocytosis (GO:0030100), regulation of cell adhesion (GO:0030155), regulation of actin cytoskeleton organization (GO:0032956), cellular response to oxidative stress (GO:0034599), negative regulation of Rho protein signal transduction (GO:0035024), exploration behavior (GO:0035640), protein modification process (GO:0036211), cellular response to retinoic acid (GO:0071300), positive regulation of establishment of T cell polarity (GO:1903905), regulation of cell motility (GO:2000145), positive regulation of T cell migration (GO:2000406), protein phosphorylation (GO:0006468)

GO Molecular Function (16): magnesium ion binding (GO:0000287), phosphotyrosine residue binding (GO:0001784), actin monomer binding (GO:0003785), protein kinase activity (GO:0004672), protein tyrosine kinase activity (GO:0004713), non-membrane spanning protein tyrosine kinase activity (GO:0004715), ATP binding (GO:0005524), enzyme activator activity (GO:0008047), enzyme binding (GO:0019899), manganese ion binding (GO:0030145), actin filament binding (GO:0051015), nucleotide binding (GO:0000166), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (5): cytosol (GO:0005829), plasma membrane (GO:0005886), actin cytoskeleton (GO:0015629), cytoplasm (GO:0005737), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
RHO GTPase cycle	2
Signaling by ROBO receptors	1
FLT3 Signaling	1
Immune System	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Axon guidance	1
Nervous system development	1
Signaling by Rho GTPases	1
Cytokine Signaling in Immune system	1
Developmental Biology	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of cellular process	3
cellular process	2
actin binding	2
catalytic activity	2
cellular anatomical structure	2
cell communication	1
signaling	1
cellular response to stimulus	1
ERBB signaling pathway	1
G protein-coupled receptor signaling pathway	1
phospholipase C activator activity	1
regulation of biological quality	1
autophagy	1
regulation of catabolic process	1
regulation of neuron projection development	1
neuron projection development	1
positive regulation of cell projection organization	1
protein phosphorylation	1
peptidyl-tyrosine modification	1
endocytosis	1
regulation of cellular component organization	1
regulation of vesicle-mediated transport	1
cell adhesion	1
actin cytoskeleton organization	1
regulation of actin filament-based process	1
regulation of cytoskeleton organization	1
response to oxidative stress	1
cellular response to chemical stress	1
Rho protein signal transduction	1
regulation of Rho protein signal transduction	1
negative regulation of small GTPase mediated signal transduction	1
behavior	1
protein metabolic process	1
macromolecule modification	1
response to retinoic acid	1
cellular response to lipid	1
cellular response to oxygen-containing compound	1
establishment of T cell polarity	1
positive regulation of T cell activation	1
regulation of establishment of T cell polarity	1

Protein interactions and networks

STRING

2361 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ABL2	ETV6	P41212	858
ABL2	AGRN	O00468	686
ABL2	CTTN	Q14247	654
ABL2	ABL1	P00519	627
ABL2	HCLS1	P14317	623
ABL2	RIN1	Q13671	611
ABL2	CRLF2	Q9HC73	598
ABL2	NUP214	P35658	597
ABL2	ACSL6	Q9UKU0	587
ABL2	CRK	P46108	583
ABL2	CRKL	P46109	576
ABL2	SEMA3F	Q13275	559
ABL2	ACSL5	Q9ULC5	558
ABL2	DOK7	Q18PE1	546
ABL2	PTPN12	Q05209	545

IntAct

166 interactions, top by confidence:

A	B	Type	Score
RIN1	NRAS	psi-mi:“MI:0914”(association)	0.840
RIN1	ABL2	psi-mi:“MI:0915”(physical association)	0.800
ABL2	RIN1	psi-mi:“MI:0915”(physical association)	0.800
RIN1	ABL1	psi-mi:“MI:0914”(association)	0.790
CRK	ABL2	psi-mi:“MI:0217”(phosphorylation reaction)	0.770
ABL2	CRK	psi-mi:“MI:0915”(physical association)	0.770
HSPA8	GAK	psi-mi:“MI:0914”(association)	0.760
BAG5	HSPA8	psi-mi:“MI:0914”(association)	0.740
ABL2	NCK1	psi-mi:“MI:0915”(physical association)	0.730
NCK1	ABL2	psi-mi:“MI:2364”(proximity)	0.730
EGFR	ABL2	psi-mi:“MI:0915”(physical association)	0.690
ABL2	EGFR	psi-mi:“MI:0407”(direct interaction)	0.690
NCK2	SH3PXD2B	psi-mi:“MI:0914”(association)	0.640
YWHAG	BLTP3B	psi-mi:“MI:2364”(proximity)	0.640
ABL2	PLCG1	psi-mi:“MI:0915”(physical association)	0.600

BioGRID (170): TRIP10 (Two-hybrid), ABL2 (Reconstituted Complex), ABL2 (Biochemical Activity), CRK (Reconstituted Complex), GRB2 (Reconstituted Complex), CRK (Biochemical Activity), RIN1 (Affinity Capture-Western), ABL2 (Affinity Capture-Western), ABL2 (Biochemical Activity), CRK (Biochemical Activity), CRK (Biochemical Activity), ABL2 (Affinity Capture-Western), HRAS (Affinity Capture-Western), ABL2 (Two-hybrid), ABL2 (Affinity Capture-MS)

ESM2 similar proteins: A4IFM7, A8C984, B6D5P1, B6D5P6, E9PT87, O08815, O54988, O55092, O70551, O88831, P00519, P00520, P00521, P07313, P0C865, P13234, P20689, P42684, P46087, Q13164, Q14028, Q16566, Q2KI23, Q32MK0, Q3SYS4, Q3UH66, Q3UIZ8, Q3ULB5, Q4JIM5, Q4KMM3, Q4V8B0, Q5R8Z4, Q5RDG7, Q5TGJ6, Q63553, Q6AYH9, Q6PDI6, Q80XI3, Q8BHL3, Q8BWQ5

Diamond homologs: A0A0K3AV08, A7J1T0, A7J1T2, A7MBB4, A8X775, D3ZG83, G5EE56, H2KZW3, O01700, O19064, O22558, O43283, O54967, O60674, P00529, P00533, P00534, P00535, P03949, P04412, P06239, P06240, P08069, P08922, P08941, P09760, P09769, P11273, P11362, P13388, P14234, P14616, P14617, P16092, P16591, P18461, P21802, P21803, P21804, P22607

SIGNOR signaling

33 interactions.

A	Effect	B	Mechanism
ABL2	“up-regulates activity”	CAT	phosphorylation
ABL2	“up-regulates activity”	GPX1	phosphorylation
ABL2	up-regulates	SIVA1	phosphorylation
ABL1	up-regulates	ABL2	phosphorylation
ABL2	up-regulates	ABL2	phosphorylation
ABL2	down-regulates	CRK	phosphorylation
RIN1	up-regulates	ABL2	phosphorylation
ABL2	down-regulates	PSMA7	phosphorylation
ABL2	up-regulates	LGALS3	phosphorylation
ABL2	up-regulates	CEBPB	phosphorylation
BTF3	“up-regulates quantity by expression”	ABL2	“transcriptional regulation”
ABL2	“up-regulates activity”	IRF3	phosphorylation
PDGFRB	“up-regulates activity”	ABL2	phosphorylation
ABL2	“up-regulates activity”	RIN1	phosphorylation
ABL2	up-regulates	CAT	phosphorylation
DIP2A	“up-regulates activity”	ABL2	binding
ABL2	up-regulates	Actin_cytoskeleton_reorganization
ABL2	“down-regulates quantity by destabilization”	ABL2	phosphorylation
ABL2	“up-regulates quantity by stabilization”	ABL2	phosphorylation
ABL2	“up-regulates activity”	PDGFRB	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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 ERBB2 ECD mutants	9	66.4×	3e-13
Constitutive Signaling by EGFRvIII	8	62.8×	1e-11
Activation of BAD and translocation to mitochondria	7	58.6×	4e-10
Signaling by ERBB2 TMD/JMD mutants	10	52.3×	2e-13
Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex	7	51.7×	1e-09
SARS-CoV-1 targets host intracellular signalling and regulatory pathways	7	51.7×	1e-09
Signaling by ERBB2 KD Mutants	11	51.1×	4e-14
Constitutive Signaling by Ligand-Responsive EGFR Cancer Variants	8	50.2×	8e-11

GO biological processes:

GO term	Partners	Fold	FDR
peptidyl-tyrosine phosphorylation	10	40.5×	5e-11
ephrin receptor signaling pathway	10	33.1×	2e-10
epidermal growth factor receptor signaling pathway	10	23.8×	5e-09
protein targeting	6	21.1×	5e-05
positive regulation of actin filament polymerization	6	19.1×	8e-05
neuron projection morphogenesis	7	18.6×	1e-05
protein autophosphorylation	11	15.4×	4e-08
cell surface receptor protein tyrosine kinase signaling pathway	9	15.0×	2e-06

Disease & clinical

Cancer significance

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

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	14
Likely pathogenic	1
Uncertain significance	116
Likely benign	2
Benign	2

Top pathogenic / likely-pathogenic (15)

Variant ID	HGVS	Classification
1341276	GRCh37/hg19 1q25.2-31.1(chr1:178522021-190322133)x1	Pathogenic
144717	GRCh38/hg38 1q25.2-31.3(chr1:176595962-196301688)x1	Pathogenic
1527381	GRCh37/hg19 1q24.2-25.3(chr1:169873155-181823980)	Pathogenic
1527404	GRCh37/hg19 1q24.3-31.3(chr1:171990029-195086758)	Pathogenic
1527437	GRCh37/hg19 1q25.2-32.1(chr1:179073386-200192265)	Pathogenic
155448	GRCh38/hg38 1q21.2-25.2(chr1:149854269-180267197)x3	Pathogenic
253471	GRCh37/hg19 1q24.3-25.3(chr1:172742952-181814496)x1	Pathogenic
3062777	GRCh37/hg19 1q25.1-25.3(chr1:173162501-182702252)x3	Pathogenic
3063521	GRCh37/hg19 1q24.2-31.1(chr1:167994071-187711459)x1	Pathogenic
395654	GRCh37/hg19 1q23.3-25.3(chr1:161676893-184071723)x1	Pathogenic
442042	GRCh37/hg19 1q25.2-32.1(chr1:179011314-199022759)x1	Pathogenic
57510	GRCh38/hg38 1q25.1-31.1(chr1:175035040-186042595)x1	Pathogenic
60076	GRCh38/hg38 1q25.2-32.1(chr1:179032905-199724897)x1	Pathogenic
814145	GRCh37/hg19 1q25.2-32.1(chr1:177551193-199599056)x1	Pathogenic
443359	GRCh37/hg19 1q25.1-25.3(chr1:173138799-185129406)x3	Likely pathogenic

SpliceAI

2690 predictions. Top by Δscore:

Variant	Effect	Δscore
1:179110456:C:CC	acceptor_gain	1.0000
1:179112307:A:AC	donor_gain	1.0000
1:179112308:C:CC	donor_gain	1.0000
1:179112308:C:CT	donor_loss	1.0000
1:179112308:CCTT:C	donor_gain	1.0000
1:179112394:CCAGC:C	acceptor_gain	1.0000
1:179112395:CAGC:C	acceptor_gain	1.0000
1:179112395:CAGCC:C	acceptor_gain	1.0000
1:179112397:GC:G	acceptor_gain	1.0000
1:179112397:GCCT:G	acceptor_loss	1.0000
1:179112398:CC:C	acceptor_gain	1.0000
1:179112399:C:CC	acceptor_gain	1.0000
1:179112401:A:AC	acceptor_gain	1.0000
1:179112401:A:C	acceptor_gain	1.0000
1:179112403:G:C	acceptor_gain	1.0000
1:179112403:G:GC	acceptor_gain	1.0000
1:179114869:AATAC:A	donor_loss	1.0000
1:179114870:ATACT:A	donor_loss	1.0000
1:179114871:TACT:T	donor_loss	1.0000
1:179114872:AC:A	donor_loss	1.0000
1:179114873:C:CG	donor_loss	1.0000
1:179114874:TCAC:T	donor_loss	1.0000
1:179114875:CAC:C	donor_loss	1.0000
1:179114876:A:AC	donor_gain	1.0000
1:179114876:AC:A	donor_loss	1.0000
1:179114876:ACATG:A	donor_gain	1.0000
1:179114877:C:CC	donor_gain	1.0000
1:179114877:C:CT	donor_loss	1.0000
1:179114877:CA:C	donor_gain	1.0000
1:179114877:CATG:C	donor_gain	1.0000

AlphaMissense

7686 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:179107839:A:G	L1143P	1.000
1:179107860:A:G	F1136S	1.000
1:179107920:A:G	L1116P	1.000
1:179112373:C:A	R529S	1.000
1:179112373:C:G	R529S	1.000
1:179112374:C:A	R529M	1.000
1:179112374:C:G	R529T	1.000
1:179112390:A:G	W524R	1.000
1:179112390:A:T	W524R	1.000
1:179112394:C:A	W522C	1.000
1:179112394:C:G	W522C	1.000
1:179112396:A:G	W522R	1.000
1:179112396:A:T	W522R	1.000
1:179112397:G:C	C521W	1.000
1:179114878:A:G	C521R	1.000
1:179114889:A:G	L517P	1.000
1:179114909:G:C	C510W	1.000
1:179114910:C:T	C510Y	1.000
1:179114911:A:G	C510R	1.000
1:179114919:G:T	P507H	1.000
1:179114928:A:G	M504T	1.000
1:179114946:A:G	L498P	1.000
1:179114946:A:T	L498Q	1.000
1:179114949:A:G	L497P	1.000
1:179114958:A:T	V494D	1.000
1:179114983:A:C	Y486D	1.000
1:179114983:A:G	Y486H	1.000
1:179114983:A:T	Y486N	1.000
1:179114985:G:C	P485R	1.000
1:179114985:G:T	P485Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000031860 (1:179207589 A>C,G), RS1000032422 (1:179182236 C>A,G,T), RS1000039426 (1:179190106 C>A,T), RS1000047585 (1:179165947 T>A), RS1000124965 (1:179145126 G>A), RS1000128412 (1:179101465 C>T), RS1000160396 (1:179172354 G>C), RS1000200607 (1:179214244 T>C), RS1000201317 (1:179118842 G>A,C,T), RS1000226690 (1:179129783 C>T), RS1000319448 (1:179214882 G>A,C), RS1000322193 (1:179138954 C>A,T), RS1000330259 (1:179117114 C>G,T), RS1000361758 (1:179132075 G>A,C), RS1000379872 (1:179177635 C>G)

Disease associations

OMIM: gene MIM:164690 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST001303_8	IgE grass sensitization	5.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL2111414 (PROTEIN FAMILY), CHEMBL4014 (SINGLE PROTEIN), CHEMBL4523736 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

63 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 637,380 (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
CHEMBL288441	BOSUTINIB	4	12,255
CHEMBL941	IMATINIB	4	111,611
CHEMBL1171837	PONATINIB	4	8,955
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1289494	TIVOZANIB	4	4,455
CHEMBL1289926	AXITINIB	4	15,732
CHEMBL1336	SORAFENIB	4	86,060
CHEMBL1421	DASATINIB ANHYDROUS	4	55,003
CHEMBL1873475	IBRUTINIB	4	7,994
CHEMBL2028663	DABRAFENIB	4	12,430
CHEMBL2105717	CABOZANTINIB	4	11,177
CHEMBL24828	VANDETANIB	4	42,230
CHEMBL255863	NILOTINIB	4	38,627
CHEMBL3348923	TOVORAFENIB	4	834
CHEMBL477772	PAZOPANIB	4	15,540
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL5416410	DASATINIB	4	655
CHEMBL553	ERLOTINIB	4	108,300
CHEMBL601719	CRIZOTINIB	4	14,403
CHEMBL939	GEFITINIB	4
CHEMBL1908391	MASITINIB	3
CHEMBL217092	SARACATINIB	3
CHEMBL31965	CANERTINIB	3
CHEMBL3544983	TESEVATINIB	3
CHEMBL377300	BRIVANIB	3
CHEMBL483158	ALISERTIB	3
CHEMBL491473	CEDIRANIB	3
CHEMBL522892	DOVITINIB	3
CHEMBL572881	MOTESANIB	3

Clinical evidence (CIViC)

Drug × variant × indication: 1 predictive associations from 1 curated evidence items.

Variant	Therapy	Indication	Effect	Level	CIViC
ABL2 W469C	Imatinib + Dasatinib	Lung Adenocarcinoma	Sensitivity/Response	CIViC D	EID10077

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Abl family

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 24 [PMID: 23441572]	Inhibition	9.0	pIC50
pexmetinib	Inhibition	8.0	pIC50
risvodetinib	Inhibition	7.11	pIC50

Binding affinities (BindingDB)

16 measured of 19 human assays (19 total across all organisms); most potent 16 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
Staurosporine	KD	1.7 nM
5-(2,6-dichlorophenyl)-2-(2,4-difluorophenyl)sulfanylpyrimido[1,6-b]pyridazin-6-one	KD	2.8 nM
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
BMS-354825	KD	27 nM
N-(4-bromo-2-fluorophenyl)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinazolin-4-amine	KD	150 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
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide	KD	370 nM
4-[(4-methylpiperazin-1-yl)methyl]-N-[4-methyl-3-[(4-pyridin-3-ylpyrimidin-2-yl)amino]phenyl]benzamide	KD	1000 nM
N-[4-({4-[(3-methyl-1H-pyrazol-5-yl)amino]-6-(4-methylpiperazin-1-yl)pyrimidin-2-yl}sulfanyl)phenyl]cyclopropanecarboxamide	KD	1100 nM
ERLOTINIB HYDROCHLORIDE	KD	1200 nM
1-[4-[(4-ethyl-1-piperazinyl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[[6-(methylamino)-4-pyrimidinyl]oxy]phenyl]urea	KD	1400 nM
CI-1033	KD	1700 nM
5-({4-[(2,3-dimethyl-2H-indazol-6-yl)(methyl)amino]pyrimidin-2-yl}amino)-2-methylbenzene-1-sulfonamide	KD	2900 nM
(E)-N-[4-(3-chloro-4-fluoro-anilino)-3-cyano-7-ethoxy-6-quinolyl]-4-(dimethylamino)but-2-enamide	KD	3500 nM
N-[2-(diethylamino)ethyl]-5-[(Z)-(5-fluoro-2-oxo-1,2-dihydro-3H-indol-3-ylidene)methyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	KD	3500 nM
1-methyl-5-[2-[5-(trifluoromethyl)-1H-imidazol-2-yl]pyridin-4-yl]oxy-N-[4-(trifluoromethyl)phenyl]benzimidazol-2-amine	KD	4500 nM

ChEMBL bioactivities

297 potent at pChembl≥5 of 316 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	Kd	0.17	nM	DASATINIB
9.30	IC50	0.5	nM	BOSUTINIB
9.16	Kd	0.69	nM	CHEMBL386051
9.11	IC50	0.78	nM	CHEMBL290921
9.00	IC50	1	nM	CHEMBL2324924
9.00	IC50	1	nM	BOSUTINIB
9.00	Kd	1	nM	CHEMBL400402
8.96	IC50	1.1	nM	BOSUTINIB
8.89	IC50	1.3	nM	CHEMBL373101
8.82	Kd	1.5	nM	BOSUTINIB
8.70	IC50	2	nM	CHEMBL2324924
8.64	IC50	2.3	nM	CHEMBL364955
8.54	IC50	2.9	nM	CHEMBL41465
8.54	IC50	2.9	nM	CHEMBL42136
8.52	IC50	3	nM	CHEMBL2324925
8.47	Kd	3.4	nM	AST-487
8.46	IC50	3.5	nM	CHEMBL290664
8.44	Kd	3.631	nM	DASATINIB ANHYDROUS
8.40	Kd	4	nM	DASATINIB
8.40	IC50	4	nM	CHEMBL4798527
8.40	Kd	4	nM	TOZASERTIB
8.40	Kd	4	nM	DASATINIB ANHYDROUS
8.34	IC50	4.6	nM	CHEMBL40557
8.30	IC50	5	nM	CHEMBL355330
8.22	IC50	6	nM	CHEMBL2324926
8.22	Kd	6	nM	IMATINIB
8.19	IC50	6.42	nM	STAUROSPORINE
8.10	IC50	8	nM	CHEMBL2324930
8.10	Kd	8	nM	XL-228
8.08	IC50	8.3	nM	CHEMBL290308
8.08	IC50	8.3	nM	CHEMBL41633
8.00	IC50	10	nM	CHEMBL2324925
8.00	Kd	10	nM	DANUSERTIB
8.00	Kd	10	nM	BAFETINIB
8.00	Kd	10	nM	IMATINIB
8.00	IC50	10.1	nM	STAUROSPORINE
8.00	IC50	10	nM	CHEMBL169390
7.96	IC50	11	nM	CHEMBL2324923
7.96	IC50	10.9	nM	CHEMBL5598020
7.92	IC50	12	nM	CHEMBL2324927
7.92	IC50	12	nM	CHEMBL440847
7.89	Kd	13	nM	IMATINIB
7.85	IC50	14	nM	CHEMBL2324928
7.82	IC50	15	nM	CHEMBL2324923
7.80	IC50	15.8	nM	STAUROSPORINE
7.80	Kd	16	nM	CHEMBL4462318
7.80	IC50	16	nM	CHEMBL43577
7.79	IC50	16.2	nM	STAUROSPORINE
7.75	IC50	18	nM	CHEMBL2324931
7.70	Kd	20	nM	PONATINIB

PubChem BioAssay actives

250 with measured affinity, of 1236 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	435777: Binding constant for ABL2 kinase domain	kd	0.0002	uM
Bosutinib	507431: Inhibition of ABL2	ic50	0.0005	uM
6-(2,6-dichlorophenyl)-8-methyl-2-(3-methylsulfanylanilino)pyrido[2,3-d]pyrimidin-7-one	624993: Binding constant for ABL2 kinase domain	kd	0.0007	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[3-(1-methylpiperidin-4-yl)propoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0008	uM
4-chloro-3-[5-methyl-3-[4-(2-pyrrolidin-1-ylethoxy)anilino]-1,2,4-benzotriazin-7-yl]phenol	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0010	uM
3-(2-imidazo[1,2-a]pyrazin-5-ylethynyl)-4-methyl-N-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]benzamide	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0010	uM
7-(2,4-dichloro-5-methoxyanilino)-2-[5-[(4-methylpiperazin-1-yl)methyl]-2-pyridinyl]thieno[3,2-b]pyridine-6-carbonitrile	255763: Inhibitory activity against Abl kinase	ic50	0.0013	uM
7-(2,4-dichloro-5-methoxyanilino)-2-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]thieno[3,2-b]pyridine-6-carbonitrile	255763: Inhibitory activity against Abl kinase	ic50	0.0023	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0029	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[2-(1-methylpiperidin-4-yl)ethoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0029	uM
1-[5-(2-imidazo[1,2-a]pyrazin-3-ylethynyl)-1-methylpyrazol-3-yl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea	729371: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins by platform assay	ic50	0.0030	uM
1-[4-[(4-ethylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[4-[6-(methylamino)pyrimidin-4-yl]oxyphenyl]urea	435777: Binding constant for ABL2 kinase domain	kd	0.0034	uM
4-(2-chloro-5-methoxyanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0035	uM
Dasatinib	2147774: Binding affinity to human ABL2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0036	uM
N-[3-[2-[4-amino-1-(4-hydroxycyclohexyl)pyrazolo[3,4-d]pyrimidin-3-yl]ethynyl]-4-methylphenyl]-4-methyl-3-(trifluoromethyl)benzamide	1734753: Inhibition of human recombinant ARG (38 to end residues) using EAIYAAPFAKKK as substrate incubated for 40 mins in presence of [gamma33P-ATP] by radiometric scintillation counting analysis	ic50	0.0040	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	353662: Binding affinity to Abl2	kd	0.0040	uM
4-(2,4-dichloro-5-methoxyanilino)-6-methoxy-7-[(1-methylpiperidin-3-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0046	uM
3-(4-amino-7-cyclobutylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	228829: Inhibition of v-Abl tyrosine kinase activity	ic50	0.0050	uM
Imatinib	593557: Binding affinity to human active site of N-terminal hexahistidine-tagged ABL2 expressed in Trichoplusia ni infected Sf9 cells by isothermal titration calorimetric assay	kd	0.0060	uM
1-[5-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-1-methylpyrazol-3-yl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0060	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	2195241: Inhibition of ABL2 (unknown origin) incubated for 120 mins in presence of 33P-ATP by radiometric kinase assay	ic50	0.0064	uM
N-[3-(2-imidazo[1,2-b]pyridazin-3-ylethynyl)-4-methylphenyl]-4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)benzamide	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0080	uM
4-N-(5-cyclopropyl-1H-pyrazol-3-yl)-6-(4-methylpiperazin-1-yl)-2-N-[(3-propan-2-yl-1,2-oxazol-5-yl)methyl]pyrimidine-2,4-diamine	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0080	uM
6-methoxy-4-(5-methoxy-2-methylanilino)-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0083	uM
6-methoxy-4-(5-methoxy-2,4-dimethylanilino)-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0083	uM
4-[[(3S)-3-(dimethylamino)pyrrolidin-1-yl]methyl]-N-[4-methyl-3-[(4-pyrimidin-5-ylpyrimidin-2-yl)amino]phenyl]-3-(trifluoromethyl)benzamide	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0100	uM
N-[5-[(2R)-2-methoxy-2-phenylacetyl]-4,6-dihydro-1H-pyrrolo[3,4-d]pyrazol-3-yl]-4-(4-methylpiperazin-1-yl)benzamide	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0100	uM
3-(4-amino-7-cyclopentylpyrrolo[2,3-d]pyrimidin-5-yl)phenol	228829: Inhibition of v-Abl tyrosine kinase activity	ic50	0.0100	uM
2-amino-5-[2-[(3R)-3-aminopyrrolidin-1-yl]-6-fluoro-4-pyridinyl]-3-(3-hydroxy-2,6-dimethylphenyl)benzamide	2122450: Inhibition of Arg (unknown origin)	ic50	0.0109	uM
1-[5-(2-imidazo[1,2-a]pyrazin-5-ylethynyl)-1-methylpyrazol-3-yl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea	729371: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins by platform assay	ic50	0.0110	uM
6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]-4-(3,4,5-trimethoxyanilino)quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0120	uM
1-[5-(2-imidazo[1,2-a]pyridin-3-ylethynyl)-1-methylpyrazol-3-yl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0120	uM
1-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]-3-[1-methyl-5-(2-pyridin-3-ylethynyl)pyrazol-3-yl]urea	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0140	uM
4-(2,4-dichloroanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0160	uM
2,6-difluoro-N-[3-fluoro-4-[6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinolin-4-yl]oxyphenyl]benzenesulfonamide	1573284: Binding affinity to ABL2 in SILAC-labeled human MDA-MB-231 cells lysate by mass spectrometry based kinAffinity assay	kd	0.0160	uM
4-[[4-(2-hydroxyethyl)piperazin-1-yl]methyl]-N-[3-(2-imidazo[1,2-a]pyridin-3-ylethynyl)-4-methylphenyl]-3-(trifluoromethyl)benzamide	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0180	uM
Ponatinib	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0200	uM
5,7-diphenylpyrrolo[2,3-d]pyrimidin-4-amine	228643: Tested in vitro for inhibition of non-receptor tyrosine kinase v-Abl	ic50	0.0200	uM
2-amino-7-(3-aminopropylamino)-1-[4-[[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]carbamoylamino]phenyl]pyrrolo[3,2-b]quinoxaline-3-carboxamide	1695221: Inhibition of wild-type human ABL2 (A248 to G542 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0260	uM
Nilotinib	624993: Binding constant for ABL2 kinase domain	kd	0.0260	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	624993: Binding constant for ABL2 kinase domain	kd	0.0270	uM
1-[3-(6,7-dimethoxyquinazolin-4-yl)oxyphenyl]-3-[5-(1,1,1-trifluoro-2-methylpropan-2-yl)-1,2-oxazol-3-yl]urea	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0300	uM
2-amino-1-[4-[[3-tert-butyl-1-(4-methylphenyl)pyrazol-5-yl]carbamoylamino]phenyl]pyrrolo[3,2-b]quinoxaline-3-carboxamide	1695221: Inhibition of wild-type human ABL2 (A248 to G542 residues) expressed in bacterial expression system by Kinomescan method	kd	0.0310	uM
1-[5-[2-(6-amino-3-pyridinyl)ethynyl]-1-methylpyrazol-3-yl]-3-[4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl]urea	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0360	uM
4-(2,4-dimethylanilino)-6-methoxy-7-[(1-methylpiperidin-4-yl)methoxy]quinoline-3-carbonitrile	32559: Inhibition of Abl kinase	ic50	0.0380	uM
(3R,4R)-4-amino-1-[[4-(3-methoxyanilino)pyrrolo[2,1-f][1,2,4]triazin-5-yl]methyl]piperidin-3-ol	1424891: Kinobeads (epsilon), multiple immobilized ATP-competitive broad spectrum kinase inhibitors, used to assess residual binding of ~300 proteins simultaneously from cell lysate in the presence of a compound. Quantitative readout performed by mass spectrometry.	kd	0.0400	uM
[3-[4-amino-5-(3-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-7-yl]cyclobutyl]methanol	228829: Inhibition of v-Abl tyrosine kinase activity	ic50	0.0400	uM
3-(4-amino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)cyclopentan-1-ol	228829: Inhibition of v-Abl tyrosine kinase activity	ic50	0.0400	uM
4-(imidazol-1-ylmethyl)-N-[4-methyl-3-(2-pyrimidin-5-ylethynyl)phenyl]-3-(trifluoromethyl)benzamide	729369: Inhibition of Abl2 kinase (unknown origin) using Tyr 6 peptide as substrate assessed as residual enzyme activity after every 10 secs measured for 10 mins	ic50	0.0400	uM
7-cyclobutyl-5-(3-methoxyphenyl)pyrrolo[2,3-d]pyrimidin-4-amine	228829: Inhibition of v-Abl tyrosine kinase activity	ic50	0.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	3
Asbestos, Crocidolite	affects expression, increases expression	3
Particulate Matter	affects expression, increases abundance, increases expression	3
cadmium sulfate	increases expression	2
Dasatinib	affects binding	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Estradiol	affects cotreatment, increases expression	2
Nickel	increases expression	2
Silicon Dioxide	increases expression	2
Tetrachlorodibenzodioxin	affects expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	decreases expression, increases abundance, affects cotreatment	1
sodium arsenate	increases abundance, increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
arsenite	affects binding, decreases reaction	1
boron nitride	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
potassium chromate(VI)	affects cotreatment, increases expression	1
coumarin	affects phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases abundance	1
epigallocatechin gallate	affects cotreatment, increases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1

ChEMBL screening assays

358 unique, capped per target: 356 binding, 1 functional, 1 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1176909	Binding	Inhibition of human ABL F255K mutant after 2 hrs by TR-FRET assay	Discovery of 3-[2-(imidazo[1,2-b]pyridazin-3-yl)ethynyl]-4-methyl-N-{4-[(4-methylpiperazin-1-yl)methyl]-3-(trifluoromethyl)phenyl}benzamide (AP24534), a potent, orally active pan-inhibitor of breakpoint cluster region-abelson (BCR-ABL) kinase including the T315I gatekeeper mutant. — J Med Chem
CHEMBL883697	Functional	Inhibitory activity against Abl kinase	Inhibition of Src kinase activity by 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-heteroaryl-thieno[3,2-b]pyridine-6-carbonitriles. — Bioorg Med Chem Lett
CHEMBL4313107	ADMET	Inhibition of recombinant human ARG (38 to end residues) at 100 nM using EAIYAAPFAKKK as substrate measured after 40 mins in presence of [gamma33P]ATP by scintillation counting method	Discovery and Development of a Series of Pyrazolo[3,4-d]pyridazinone Compounds as the Novel Covalent Fibroblast Growth Factor Receptor Inhibitors by the Rational Drug Design. — J Med Chem

Cellosaurus cell lines

9 cell lines: 9 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8AR	Abcam HCT 116 ABL2 KO	Cancer cell line	Male
CVCL_B8S2	Abcam MCF-7 ABL2 KO	Cancer cell line	Female
CVCL_B9CT	Abcam A-549 ABL2 KO	Cancer cell line	Male
CVCL_D8H1	Ubigene HCT 116 ABL2 KO	Cancer cell line	Male
CVCL_D9X4	Ubigene HeLa ABL2 KO	Cancer cell line	Female
CVCL_E331	HT93A	Cancer cell line	Male
CVCL_SB10	HAP1 ABL2 (-) 1	Cancer cell line	Male
CVCL_SB11	HAP1 ABL2 (-) 2	Cancer cell line	Male
CVCL_SB12	HAP1 ABL2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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