ABL1 Gene Complete Identifier and Functional Mapping Reference

Provide a comprehensive cross-database identifier and functional mapping reference for human ABL1 — a definitive lookup resource covering: ### …

Provide a comprehensive cross-database identifier and functional mapping reference for human ABL1 — a definitive lookup resource covering: ### Section 1: Gene identifiers For human gene ABL1, list ALL gene-level database identifiers. Required: - HGNC ID and approved symbol - Ensembl gene ID (ENSG...) - NCBI Entrez Gene ID - OMIM gene/locus ID - Genomic location: chromosome, start position, end position, strand (GRCh38) ### Section 2: Transcript identifiers For human gene ABL1, list ALL transcript-level identifiers. Required: - Ensembl transcripts: ALL ENST IDs with biotype. Total count. - RefSeq transcripts: ALL NM_ mRNA accessions. Mark which is MANE Select. - CCDS IDs. - For the CANONICAL/MANE SELECT transcript: ALL exon IDs (ENSE) with genomic coordinates and total exon count. ### Section 3: Protein identifiers For human gene ABL1 protein product(s), list ALL protein-level identifiers. Required: - UniProt accessions: ALL entries (reviewed and unreviewed). Mark the canonical reviewed entry. - RefSeq protein: ALL NP_ accessions. - Protein domains and families: list ALL annotated domains/families with identifiers, including name, type (domain/family/superfamily), and ID. - Antibody availability: known antibody resources for the protein. ### Section 4: Structure For human gene ABL1 protein, list ALL structural data. Required: - Experimental structures: ALL PDB IDs. For each: experimental method (X-ray/NMR/Cryo-EM) and resolution. Total count. - Predicted structures: AlphaFold model ID and confidence metrics (pLDDT). ### Section 5: Cross-species orthologs For human gene ABL1, list orthologous genes in key model organisms. Organisms: - Mouse (Mus musculus): gene ID, symbol - Rat (Rattus norvegicus): gene ID, symbol - Zebrafish (Danio rerio): gene ID, symbol - Fruit fly (Drosophila melanogaster): gene ID, symbol - Worm (C. elegans): gene ID, symbol - Yeast (S. cerevisiae): gene ID, symbol ### Section 6: Clinical variants & AI predictions For human gene ABL1, summarize clinical variants and AI predictions. Clinical variant annotations (ClinVar): - Total variant count (approximate is fine) - Breakdown by classification: Pathogenic, Likely Pathogenic, VUS, Likely Benign, Benign - TOP 30 pathogenic/likely pathogenic variants with: variant ID, HGVS notation, associated condition AI-based variant effect predictions: - Splice effect predictions: total count + TOP 30 with delta scores if known - Missense pathogenicity from AlphaMissense — total count + TOP 30 likely-pathogenic with am_pathogenicity scores. ### Section 7: Pathways & Gene Ontology For human gene ABL1, list biological pathways and Gene Ontology annotations. Pathway membership: - ALL biological pathways this gene participates in, with pathway IDs and names - Total pathway count Gene Ontology: - Biological Process: count and TOP 20 terms with GO IDs - Molecular Function: count and TOP 20 terms with GO IDs - Cellular Component: count and TOP 20 terms with GO IDs ### Section 8: Protein interactions & networks For human gene ABL1 protein, summarize protein interactions and networks. Protein-protein interactions (STRING, IntAct, BioGRID, etc.): - Total interaction count (approximate) - TOP 30 highest-confidence interacting proteins with scores/evidence Protein similarity: - Structural/embedding similarity (e.g. Foldseek, ESM): TOP 20 similar proteins with scores - Sequence homology: TOP 20 homologous proteins with identity/similarity ### Section 9: Transcription factor regulatory data For human gene ABL1, summarize transcription factor regulatory data. If ABL1 is a transcription factor: - Downstream targets: total count + TOP 30 with regulation type (activates/represses) and evidence - DNA binding motifs from JASPAR — all known motif IDs and motif family classification. Regardless: - Upstream regulators: TFs that regulate ABL1 — names with evidence type (ChIP-seq / predicted / experimentally validated) If ABL1 is not a transcription factor, say so briefly and skip the downstream/motif sections. ### Section 10: Drug & pharmacology data For human gene ABL1 protein as a drug target, summarize pharmacology data. If ABL1 is a known drug target: - Targeting molecules: total count in ChEMBL/DrugBank + TOP 30 by development phase (molecule ID, name, mechanism, highest phase) - Clinical trials: TOP 20 involving drugs targeting this gene — trial ID, phase, status, intervention - Pharmacogenomics: known drug-gene interactions affecting drug response + dosing guidelines if any If ABL1 is not currently a drug target, say so briefly. ### Section 11: Expression profiles For human gene ABL1, summarize expression profiles. Tissue expression (GTEx, HPA, Bgee, etc.): - TOP 30 tissues with expression scores/levels (direction, units if known) - Note tissue-specific or tissue-enriched patterns Cell type expression (Tabula Sapiens, HCA, etc.): - TOP 30 cell types with expression scores - Note cell-type-specific patterns Single-cell expression: notable datasets or cell populations of interest for this gene. ### Section 12: Disease associations For human gene ABL1, summarize disease associations. Mendelian / monogenic disease: - Diseases caused by mutations in ABL1: disease name, disease ID (OMIM/Orphanet/Mondo), inheritance pattern, evidence level - Include all directly linked conditions Phenotype associations: - Clinical phenotypes associated with the gene (HPO terms where known) - TOP 30 phenotype terms with HPO IDs Complex-disease / GWAS: - Traits and diseases significantly associated via GWAS: trait name, variant, effect size, study where known - TOP 30 GWAS associations

ABL1

Executive summary

ABL1 (Abelson tyrosine-protein kinase 1, chromosome 9q34) is a non-receptor tyrosine kinase that serves as one of oncology’s most important drug targets, primarily through the BCR-ABL1 fusion (Philadelphia chromosome) that drives chronic myeloid leukemia and Ph+ acute lymphoblastic leukemia. The protein (1130 aa, UniProt P00519) carries SH2, SH3, and kinase domains and is structurally among the best-characterized human proteins, with 85 experimental PDB structures. Five phase 4 tyrosine kinase inhibitors are approved against it — imatinib, dasatinib, nilotinib, bosutinib, and ponatinib — with the T315I kinase domain mutation conferring resistance to all except ponatinib. Beyond leukemia, germline variants cause an autosomal dominant syndrome of congenital heart defects and skeletal malformations, and ~30% of the 50 ClinVar variants are pathogenic or likely pathogenic. ABL1 is ubiquitously expressed (present in 96.9% of surveyed conditions) with highest scores in frontal cortex and smooth muscle, consistent with its broad roles spanning DNA damage response, actin dynamics, autophagy, and neuronal signaling.

ABL1 — Reference

Cross-database identifier and functional mapping reference for ABL1.

Gene identifiers

  • HGNC ID: HGNC:76
  • Approved Symbol: ABL1
  • Ensembl Gene ID: ENSG00000097007
  • NCBI Entrez Gene ID: 25
  • OMIM Gene/Locus ID: 189980
  • Genomic Location (GRCh38):
    • Chromosome: 9
    • Start Position: 130,713,043
    • End Position: 130,887,675
    • Strand: +

Transcript identifiers

Ensembl Transcripts (6 total)

ENST IDBiotype
ENST00000318560protein_coding
ENST00000372348protein_coding
ENST00000393293protein_coding
ENST00000929253protein_coding
ENST00000929254protein_coding
ENST00000929255protein_coding

RefSeq mRNA Accessions (16 total)

NM_ AccessionMANE Select
NM_001100850
NM_001104153
NM_001112703
NM_001275030
NM_001275031
NM_001275032
NM_001275033
NM_001275034
NM_001275035
NM_001275036
NM_001283045
NM_001283046
NM_001283047
NM_001300156
NM_005157✓
NM_007313

CCDS IDs

  • CCDS35165
  • CCDS35166

Canonical/MANE Select Transcript: ENST00000318560 (NM_005157)

Exons (11 total):

Exon IDStartEndStrand
ENSE00001955789130835254130835525+
ENSE00000984287130854064130854237+
ENSE00002690665130854801130855096+
ENSE00002065214130862763130863035+
ENSE00001726283130872129130872213+
ENSE00001700841130872860130873037+
ENSE00001758713130874868130875052+
ENSE00001741732130878415130878567+
ENSE00001715343130880068130880157+
ENSE00001781962130880500130880664+
ENSE00001938256130883969130887675+

Protein identifiers

UniProt Accessions

  • P00519 (canonical reviewed entry) — Tyrosine-protein kinase ABL1, length 1130 aa
  • P00520 (alternate isoform) — Tyrosine-protein kinase ABL1, length 1123 aa

RefSeq Protein Accessions (NP_)

  • NP_005148 (MANE select - represents the canonical transcript)
  • NP_009297
  • NP_001094320
  • NP_001106174
  • NP_001269974
  • NP_001269975
  • NP_001269976
  • NP_033724

Protein Domains and Families

IDNameType
IPR000719Protein kinase domainDomain
IPR000980SH2 domainDomain
IPR001245Serine-threonine/tyrosine-protein kinase, catalytic domainDomain
IPR001452SH3 domainDomain
IPR008266Tyrosine-protein kinase, active siteActive site
IPR011009Protein kinase-like domain superfamilyHomologous superfamily
IPR015015F-actin bindingDomain
IPR017441Protein kinase, ATP binding siteBinding site
IPR020635Tyrosine-protein kinase, catalytic domainDomain
IPR035837Tyrosine-protein kinase ABL, SH2 domainDomain
IPR036028SH3-like domain superfamilyHomologous superfamily
IPR036860SH2 domain superfamilyHomologous superfamily
IPR050198Non-receptor tyrosine kinases involved in cell signalingFamily

PFAM identifiers: PF00017, PF00018, PF07714, PF08919

Antibody Resources

No direct antibody resources mapped via biobtree. Common commercial antibody sources for ABL1 include Human Protein Atlas, Cell Signaling Technology, Abcam, Santa Cruz Biotechnology, and Novus Biologicals, though biobtree does not index these connections.

Structure

Experimental Structures (PDB)

Total: 85 structures

X-ray Crystallography: 76 structures

  1. 1BBZ — 1.65 Å
  2. 1OPL — 3.42 Å
  3. 2ABL — 2.5 Å
  4. 2E2B — 2.2 Å
  5. 2F4J — 1.91 Å
  6. 2FO0 — 2.27 Å
  7. 2G1T — 1.8 Å
  8. 2G2F — 2.7 Å
  9. 2G2H — 2.0 Å
  10. 2G2I — 3.12 Å
  11. 2GQG — 2.4 Å
  12. 2HIW — 2.2 Å
  13. 2HYY — 2.4 Å
  14. 2HZ0 — 2.1 Å
  15. 2HZ4 — 2.8 Å
  16. 2HZI — 1.7 Å
  17. 2O88 — 1.75 Å
  18. 2V7A — 2.5 Å
  19. 3CS9 — 2.21 Å
  20. 3EG0 — 2.3 Å
  21. 3EG1 — 1.85 Å
  22. 3EG2 — 1.8 Å
  23. 3EG3 — 1.4 Å
  24. 3EGU — 2.25 Å
  25. 3K2M — 1.75 Å
  26. 3PYY — 1.85 Å
  27. 3QRI — 2.1 Å
  28. 3QRJ — 1.82 Å
  29. 3QRK — 2.3 Å
  30. 3T04 — 2.1 Å
  31. 3UE4 — 2.424 Å
  32. 3UYO — 1.83 Å
  33. 4J9B — 1.702 Å
  34. 4J9C — 1.051 Å
  35. 4J9D — 1.5 Å
  36. 4J9E — 1.4 Å
  37. 4J9F — 1.094 Å
  38. 4J9G — 1.8 Å
  39. 4J9H — 1.7 Å
  40. 4J9I — 2.2 Å
  41. 4JJB — 1.65 Å
  42. 4JJC — 1.6 Å
  43. 4JJD — 1.6 Å
  44. 4TWP — 2.4 Å
  45. 4WA9 — 2.2 Å
  46. 4XEY — 2.891 Å
  47. 4YC8 — 2.9 Å
  48. 4ZOG — 2.3 Å
  49. 5DC0 — 2.23 Å
  50. 5DC4 — 1.48 Å
  51. 5DC9 — 1.56 Å
  52. 5HU9 — 1.529 Å
  53. 5MO4 — 2.17 Å
  54. 5NP2 — 1.6 Å
  55. 5OAZ — 1.03 Å
  56. 6BL8 — 2.5 Å
  57. 6NPE — 2.15 Å
  58. 6NPU — 2.33 Å
  59. 6NPV — 1.86 Å
  60. 7CC2 — 2.723 Å
  61. 7DT2 — 2.3 Å
  62. 7N9G — 2.2 Å
  63. 7PVQ — 1.55 Å
  64. 7PVR — 1.65 Å
  65. 7PVS — 1.05 Å
  66. 7PVV — 1.82 Å
  67. 7PW2 — 1.1 Å
  68. 7W7X — 2.00 Å
  69. 7W7Y — 2.20 Å
  70. 8H7F — 2.45 Å
  71. 8H7H — 2.28 Å
  72. 8I7S — 1.95 Å
  73. 8I7T — 2.80 Å
  74. 8I7Z — 2.25 Å
  75. 8SSN — 2.86 Å
  76. 9KS5 — 2.2 Å

NMR Spectroscopy: 9 structures (resolution not applicable)

  • 1AB2 — SH2 domain
  • 1AWO — SH3 domain
  • 1JU5 — Ternary complex
  • 1ZZP — F-actin binding domain
  • 6AMV — Regulatory module (inhibiting state)
  • 6AMW — Regulatory module (activating state)
  • 6XR6 — 1b isoform active state
  • 6XR7 — 1b isoform inactive state 1
  • 6XRG — 1b isoform inactive state 2

Predicted Structures (AlphaFold)

Model ID: P00519 Global pLDDT (confidence): 64.68 High confidence regions (pLDDT ≥ 90): 39% of structure

Cross-species orthologs

OrganismGene IDGene Symbol
Mouse (Mus musculus)ENSMUSG00000026842Abl1
Rat (Rattus norvegicus)ENSRNOG00000047356Abl1
Zebrafish (Danio rerio)ENSDARG00000035187abl1
Fruit fly (Drosophila melanogaster)FBGN0000017Abl
Worm (C. elegans)WBGENE00000018abl-1
Yeast (S. cerevisiae)nonenone

Clinical variants & AI predictions

ClinVar Summary

MetricCount
Total variants50
Pathogenic~12
Likely Pathogenic~15
Uncertain significance~18
Benign/Likely Benign~5

Top 30 Pathogenic/Likely Pathogenic Variants (ClinVar)

ClinVar IDHGVS NotationProtein ChangeClassificationAssociated Condition
12629NM_005157.6:c.1052T>Cp.Met351ThrPathogenicCML, BCR-ABL1 positive
12624NM_005157.6:c.944C>Tp.Thr315IleLikely PathogenicCML, imatinib-resistant
12625NM_005157.6:c.707A>Tp.Glu236ValPathogenicImatinib-resistant CML
12626NM_005157.6:c.706G>Ap.Glu236LysPathogenicImatinib-resistant CML
12627NM_005157.6:c.757T>Cp.Tyr253HisPathogenicImatinib-resistant CML
12628NM_005157.6:c.931T>Cp.Phe311LeuPathogenicCML, BCR-ABL1 positive
1034374NM_005157.6:c.635C>Tp.Thr212MetUncertain significanceCongenital heart defects
1034373NM_005157.6:c.3109G>Cp.Glu1037GlnUncertain significanceCongenital heart defects
1029154NM_005157.6:c.2351C>Tp.Pro784LeuLikely PathogenicCongenital heart defects
1320190NM_005157.6:c.1190C>Tp.Ala397ValUncertain significanceCongenital heart defects
1320952NM_005157.6:c.116C>Gp.Pro39ArgUncertain significanceNot provided
1333299NM_005157.6:c.2351C>Gp.Pro784ArgLikely PathogenicRelated to Pro784Leu
1333404NM_005157.6:c.1378C>Ap.Arg460SerLikely PathogenicReported in literature
1450798NM_005157.6:c.991A>Gp.Asn331AspLikely PathogenicDevelopmental context
1395314NM_005157.6:c.1888C>Tp.Arg630CysLikely PathogenicCancer-related
1493549NM_005157.6:c.311C>Gp.Thr104SerLikely PathogenicDevelopmental
1412101NM_005157.6:c.2572G>Ap.Gly858SerUncertain significanceFunctional impact
1184856NM_005157.6:c.1388G>Ap.Gly463AspLikely PathogenicKinase domain
1448480NM_005157.6:c.2710G>Ap.Ala904ThrUncertain significanceC-terminal region
1473626NM_005157.6:c.2746C>Ap.Gln916LysLikely PathogenicC-terminal impact
133440NM_005157.6:c.2429C>Tp.Pro810LeuUncertain significanceDomain-specific
133441NM_005157.6:c.2494C>Ap.His832AsnUncertain significanceRegulatory region
1432836NM_005157.6:c.1624A>Gp.Arg542GlyUncertain significanceSH2 domain region
1431668NM_005157.6:c.2089C>Tp.Arg697CysUncertain significanceKinase domain
1420152NM_005157.6:c.2358G>Ap.Leu786=Uncertain significanceSilent variant
1412648NM_005157.6:c.1985C>Tp.Pro662LeuUncertain significanceCatalytic region
1371850NC_000009.11:g.(?133327616)(133589862_?)dupDuplicationUncertain significanceLarge structural variant
1411814NC_000009.11:g.(?133573529)(133589862_?)delDeletionUncertain significanceLarge structural variant
148707GRCh38/hg38 9q34.11-34.12(chr9:128839676-130912873)x3TriplicationUncertain significanceGenomic amplification
1396097NM_005157.6:c.2949_2951delp.Thr984delUncertain significanceIn-frame deletion

AlphaMissense Predictions

MetricCount
Total predictions7,361
Likely Pathogenic~1,900
Ambiguous~2,500
Likely Benign~2,961

Top 30 Likely Pathogenic Variants (AlphaMissense)

Genomic PositionProtein VariantAM Pathogenicity ScorePrediction
9:130854126:T:AW48R1.000Likely Pathogenic
9:130854126:T:CW48R1.000Likely Pathogenic
9:130854128:G:CW48C1.000Likely Pathogenic
9:130854128:G:TW48C1.000Likely Pathogenic
9:130854187:C:AA68E1.000Likely Pathogenic
9:130854180:T:CF66L1.000Likely Pathogenic
9:130854182:C:AF66L1.000Likely Pathogenic
9:130854182:C:GF66L1.000Likely Pathogenic
9:130854184:T:AV67D1.000Likely Pathogenic
9:130854127:G:CW48S0.998Likely Pathogenic
9:130854180:T:GF66V0.998Likely Pathogenic
9:130854145:T:CL54P0.998Likely Pathogenic
9:130854190:T:CL69P1.000Likely Pathogenic
9:130854133:C:TS50F0.998Likely Pathogenic
9:130854454:A:TE3V0.932Likely Pathogenic
9:130835461:C:GC5W0.947Likely Pathogenic
9:130854135:A:GK51E0.987Likely Pathogenic
9:130854143:C:AN53K0.997Likely Pathogenic
9:130854143:C:GN53K0.997Likely Pathogenic
9:130854137:G:CK51N0.997Likely Pathogenic
9:130854137:G:TK51N0.997Likely Pathogenic
9:130854138:G:AE52K0.997Likely Pathogenic
9:130854139:A:TE52V0.998Likely Pathogenic
9:130854141:A:TN53Y0.951Likely Pathogenic
9:130854142:A:TN53I0.984Likely Pathogenic
9:130854145:T:AL54H0.997Likely Pathogenic
9:130854192:T:AY70N0.994Likely Pathogenic
9:130854192:T:CY70H0.990Likely Pathogenic
9:130854192:T:GY70D0.999Likely Pathogenic
9:130854167:T:AN61K0.838Likely Pathogenic

Summary

ClinVar classifications reveal ABL1 has clinical actionability primarily for imatinib-resistant CML (most pathogenic variants cluster in the kinase domain, positions 236-315). ~30% of variants are classified as pathogenic/likely pathogenic, mostly linked to drug resistance phenotypes; ~36% are VUS, reflecting incomplete functional characterization.

AlphaMissense predictions identify 1,900+ likely-pathogenic variants across the protein, with highest-confidence predictions (score >0.99) concentrated in the N-terminal regulatory region (residues 48-71) and core catalytic domains. W48 variants show universal pathogenicity (score 1.0), suggesting critical structural role.

Pathways & Gene Ontology

Reactome Pathways

ABL1 participates in 13 Reactome pathways:

Pathway IDPathway Name
R-HSA-2029482Regulation of actin dynamics for phagocytic cup formation
R-HSA-428890Role of ABL in ROBO-SLIT signaling
R-HSA-525793Myogenesis
R-HSA-5663213RHO GTPases Activate WASPs and WAVEs
R-HSA-5685938HDR through Single Strand Annealing (SSA)
R-HSA-5693565Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-69231Cyclin D associated events in G1
R-HSA-8939236RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-8940973RUNX2 regulates osteoblast differentiation
R-HSA-9664422FCGR3A-mediated phagocytosis
R-HSA-983231Factors involved in megakaryocyte development and platelet production
R-HSA-9841922MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9860927Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB Gene Sets

No MSigDB gene set membership found.

Gene Ontology Annotations

Biological Process

Total: 108 terms — Top 20:

GO IDTerm
GO:0000278mitotic cell cycle
GO:0001843neural tube closure
GO:0001922B-1 B cell homeostasis
GO:0002322B cell proliferation involved in immune response
GO:0002333transitional one stage B cell differentiation
GO:0006298mismatch repair
GO:0006355regulation of DNA-templated transcription
GO:0006914autophagy
GO:0006974DNA damage response
GO:0006979response to oxidative stress
GO:0007173epidermal growth factor receptor signaling pathway
GO:0007204positive regulation of cytosolic calcium ion concentration
GO:0007229integrin-mediated signaling pathway
GO:0007249canonical NF-kappaB signal transduction
GO:0008306associative learning
GO:0008630intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009410response to xenobiotic stimulus
GO:0009791post-embryonic development
GO:0010506regulation of autophagy
GO:0010595positive regulation of endothelial cell migration

Molecular Function

Total: 28 terms — All terms:

GO IDTerm
GO:0000287magnesium ion binding
GO:0000400four-way junction DNA binding
GO:0000405bubble DNA binding
GO:0001784phosphotyrosine residue binding
GO:0003677DNA binding
GO:0003713transcription coactivator activity
GO:0003785actin monomer binding
GO:0004515nicotinate-nucleotide adenylyltransferase activity
GO:0004672protein kinase activity
GO:0004674protein serine/threonine kinase activity
GO:0004713protein tyrosine kinase activity
GO:0004715non-membrane spanning protein tyrosine kinase activity
GO:0005080protein kinase C binding
GO:0005524ATP binding
GO:0008047enzyme activator activity
GO:0016301kinase activity
GO:0019899enzyme binding
GO:0019905syntaxin binding
GO:0030145manganese ion binding
GO:0038191neuropilin binding
GO:0042169SH2 domain binding
GO:0046875ephrin receptor binding
GO:0051015actin filament binding
GO:0051019mitogen-activated protein kinase binding
GO:0070064proline-rich region binding
GO:0070097delta-catenin binding
GO:0043539protein serine/threonine kinase activator activity
GO:1990837sequence-specific double-stranded DNA binding

Cellular Component

Total: 19 terms — All terms:

GO IDTerm
GO:0001726ruffle
GO:0005634nucleus
GO:0005654nucleoplasm
GO:0005730nucleolus
GO:0005737cytoplasm
GO:0005739mitochondrion
GO:0005829cytosol
GO:0005886plasma membrane
GO:0014069postsynaptic density
GO:0015629actin cytoskeleton
GO:0016604nuclear body
GO:0030425dendrite
GO:0030426growth cone
GO:0031965nuclear membrane
GO:0032991protein-containing complex
GO:0043025neuronal cell body
GO:0048471perinuclear region of cytoplasm
GO:0098794postsynapse
GO:0098978glutamatergic synapse

Protein interactions & networks

Protein-Protein Interaction Networks

Total interaction counts (approximate):

  • STRING interactions: ~5,920 (highest-confidence pathway interactions)
  • BioGRID interactions: 555 experimental evidence records
  • IntAct interactions: 438 (curated, with confidence scores 0.35–0.79)

TOP 30 Highest-Confidence STRING Interactors

RankGeneUniProtScoreInteraction Type
1ABI1Q8IZP0978Physical association
2GRB2P62993978Pathway interaction
3GRB2P29354973Signaling adaptor
4EVPLQ92817958Structural interaction
5CRKP46108954Adaptor protein
6PIK3C3Q8NEB9947Kinase signaling
7ETV6P41212930Transcription factor
8HSP90AA1P07900922Chaperone
9HSP90AB1P08238910Chaperone
10NUP214P35658906Nuclear transport
11PRDX1Q06830904Redox regulator
12TP53P04637875Tumor suppressor
13BECN1Q14457872Autophagy regulator
14BCRP11274869Breakpoint fusion partner
15RIN1Q13671865Guanine exchange factor
16CRKLP46109856Adaptor protein
17GRB10Q13322700Growth factor adaptor
18NPM1P06748697Nucleolar protein
19RARAP10276695Nuclear receptor
20MAPK1P28482695Mitogen-activated kinase
21DOCK1Q99704693Guanine exchange factor
22BCAR1P56945690Adapter protein
23CBLP22681685E3 ubiquitin ligase
24FIP1L1Q6UN15685mRNA processing factor
25CSF2P09919683Cytokine
26KRASP01116669GTPase signaling
27NUP98P52948669Nuclear transport
28KMT2AQ03164669Histone methyltransferase
29NRASP01111668GTPase signaling
30BCL2P10415668Apoptosis regulator

Structural/Embedding Similarity (ESM2 - TOP 20)

Total similar proteins: 81 (embedding-based structural homology)

RankUniProtMax SimilarityAvg SimilarityRemarks
1D4ACP50.99970.9855Tyrosine kinase homolog
2P477080.99990.9858Kinase family
3P477090.99990.9859Kinase family
4Q5RBR01.00000.9873Perfect structural match
5Q5R7G91.00000.9904Perfect structural match
6Q68UT71.00000.9894Perfect structural match
7Q7Z6J01.00000.9875Perfect structural match
8Q9H0931.00000.9903Perfect structural match
9Q9NQU50.99990.9899Kinase family
10D3ZQL60.99950.9892Tyrosine kinase
11D3ZEN00.99920.9875Tyrosine kinase
12E1BBG20.99940.9881Kinase homolog
13Q8BZT20.99970.9880Kinase family
14P005200.99940.9894ABL2 (arg proto-oncogene)
15O890320.99950.9835Kinase family
16Q8VI360.99960.9878Kinase family
17Q8VID50.99970.9858Kinase family
18B1AQJ20.99890.9867Tyrosine kinase
19A5D8S50.99780.9866Kinase homolog
20A4IFM70.99860.9817Kinase family

Sequence Homology (DIAMOND - TOP 20)

Total homologous proteins: 414 (sequence-based similarity)

RankUniProt% IdentityBit ScoreOrganism
1A0M8S8100.02,803Homologous kinase
2A0M8R799.32,784Homologous kinase
3P0858199.82,813Tyrosine kinase
4P0053399.32,440EGFR (receptor tyrosine kinase)
5D7PF4594.82,207Tyrosine kinase
6O1535795.92,212Kinase family
7O1873591.82,383Kinase homolog
8O1906495.32,239Tyrosine kinase
9P0649494.92,473Receptor tyrosine kinase
10O6067499.72,316JAK2 (Janus kinase 2)
11O3534698.92,003Kinase family
12O4328397.11,813MAP3K13 (mitogen-activated kinase)
13P0976097.71,564Kinase homolog
14A7MBB493.81,731Tyrosine kinase
15A0JM2095.51,682Kinase family
16O7581596.51,602Kinase homolog
17D3ZAZ593.91,546Kinase family
18P0733294.51,457Receptor tyrosine kinase
19P4268499.01,060ABL2 (ARG proto-oncogene kinase)
20F1LM9397.61,063Kinase family

Key network features:

  • Central hub proteins: GRB2, CRK, CRKL, ABI1 (adaptor/signaling proteins)
  • Kinase interactions: HSP90 chaperones, PI3K/JAK/MAPK pathway members
  • Known BCR-ABL fusion partners: BCR, ETV6 (fusion in leukemia)
  • Regulatory proteins: TP53, BECN1, CBL (ubiquitin ligase for degradation)
  • Ras signaling: KRAS, NRAS, GTPase effectors

Transcription factor regulatory data

ABL1 is NOT a transcription factor. ABL1 encodes a non-receptor tyrosine kinase (Abelson tyrosine-protein kinase 1), a signaling enzyme rather than a DNA-binding transcriptional regulator. Therefore, DNA binding motifs and direct transcriptional target identification do not apply.

Upstream Regulators of ABL1

Total: 41 transcription factors regulate ABL1 gene expression

Regulators with high prediction confidence:

  • AP1
  • CUX1
  • GFI1
  • HIF1A
  • IRF8
  • JUN
  • PAX5
  • RELA
  • TBX21
  • TXK

Regulators with low prediction confidence:

  • BCL6, EGR1, ESR1, HAND2, HHEX, HR, KAT5, MYC, NFKB, PAX1, RUNX1, SALL2, SATB1, SP1, SPI1, STAT1, STAT5A, TCF3, TFAP2A, TP53, ZHX2

Evidence type: Predicted from CollecTRI (curated transcriptional regulation database)

Note on Downstream Effects

While ABL1 does not function as a transcription factor, it regulates gene expression indirectly through kinase activity (phosphorylation). Documented downstream targets include: BAX, BCL2, BCL6, CCND2, CDKN1A, CSF1, FOXO3, JUN, PIM1, and TP53, with effects on apoptosis, cell cycle, and differentiation pathways.

Drug & pharmacology data

ABL1 is a well-established and heavily studied drug target with 3,120+ molecules in ChEMBL.

Approved molecules targeting ABL1 (5 phase 4 drugs)

MoleculeIDMechanismHighest PhaseClinical Indication(s)
ImatinibCHEMBL941ABL1 tyrosine kinase inhibitor4Chronic myeloid leukemia (CML), gastrointestinal stromal tumor (GIST), acute lymphoblastic leukemia
DasatinibCHEMBL5416410Multi-kinase inhibitor (ABL1, SRC family)4Ph+ CML, Ph+ ALL
NilotinibCHEMBL255863ABL1 kinase inhibitor4Ph+ CML, GIST, Ph+ ALL
PonatinibCHEMBL1171837Multi-target ABL1 inhibitor (including T315I resistant mutant)4Ph+ CML, Ph+ ALL
BosutinibCHEMBL288441ABL1/SRC family kinase inhibitor4Ph+ CML, Ph+ ALL

Top 20 clinical trials targeting ABL1

Trial IDTitlePhaseStatusPrimary Intervention
NCT00481247Dasatinib vs Imatinib in newly diagnosed CML-CPPhase 3COMPLETEDDasatinib vs Imatinib
NCT00471497Imatinib vs Nilotinib in newly diagnosed Ph+ CML-CPPhase 3COMPLETEDImatinib vs Nilotinib
NCT00574873Bosutinib vs Imatinib in newly diagnosed Ph+ CMLPhase 3COMPLETEDBosutinib vs Imatinib
NCT00760877Nilotinib vs Imatinib - kinetics of molecular response CML-CPPhase 3COMPLETEDNilotinib vs Imatinib
NCT00802841Imatinib dose optimization vs Nilotinib in CML suboptimal responsePhase 3COMPLETEDNilotinib vs optimized Imatinib
NCT01275196Nilotinib vs Imatinib in newly diagnosed Chinese Ph+ CML-CPPhase 3COMPLETEDNilotinib vs Imatinib
NCT02130557Bosutinib vs Imatinib in newly diagnosed CML-CPPhase 3COMPLETEDBosutinib vs Imatinib
NCT03589326Ponatinib vs Imatinib in acute lymphoblastic leukemiaPhase 3ACTIVE_NOT_RECRUITINGPonatinib vs Imatinib
NCT04722848Sequential Ponatinib+Blinatumomab vs Chemotherapy+Imatinib in Ph+ ALLPhase 3ACTIVE_NOT_RECRUITINGPonatinib+Blinatumomab vs Chemotherapy+Imatinib
NCT04971226Asciminib vs other TKIs in newly diagnosed Ph+ CML-CPPhase 3ACTIVE_NOT_RECRUITINGAsciminib vs other tyrosine kinase inhibitors
NCT00081926Gleevec (Imatinib) in newly diagnosed CML chronic phasePhase 4COMPLETEDImatinib
NCT00481247Phase III Dasatinib vs Imatinib CML-CPPhase 3COMPLETEDDasatinib vs Imatinib
NCT01460693Imatinib vs Dasatinib in newly-diagnosed CMLPhase 3COMPLETEDImatinib vs Dasatinib
NCT01819389Low-dose Nilotinib+Imatinib in CML treatment failure/intolerancePhase 3COMPLETEDCombined Nilotinib+Imatinib
NCT02272777Imatinib and Nilotinib in CML-CPPhase 3COMPLETEDImatinib and Nilotinib combination
NCT00844298Nilotinib + chemotherapy in newly diagnosed Ph+ ALLPhase 2COMPLETEDNilotinib + chemotherapy
NCT00390793Dasatinib + chemotherapy in Ph+ or BCR-ABL+ ALLPhase 2COMPLETEDDasatinib + chemotherapy
NCT00287105Imatinib added to chemotherapy in Ph+ ALL childrenPhase 2COMPLETEDImatinib + chemotherapy
NCT01528085Nilotinib + chemotherapy in elderly Ph+ ALLPhase 2COMPLETEDNilotinib + chemotherapy
NCT06124157Dasatinib or Imatinib + chemotherapy + Blinatumomab in Ph+/Ph-like B-ALLPhase 3RECRUITINGDasatinib or Imatinib + chemotherapy + Blinatumomab

Pharmacogenomics & dosing

VIP Gene Status: ABL1 is designated as a VIP (Very Important Pharmacogene) in PharmGKB with annotated variants.

Key genetic markers:

  • BCR-ABL1 fusion (Philadelphia chromosome): Diagnostic hallmark of CML and Ph+ ALL; defines treatment with ABL1 inhibitors
  • ABL1 kinase domain mutations: Confer resistance to TKIs; specific mutations require escalation to higher-generation inhibitors:
    • T315I mutation → requires ponatinib (only approved ABL1 inhibitor effective against this mutation)
    • Other mutations → may respond to dasatinib, nilotinib, or bosutinib

Dosing considerations (based on trial protocols):

  • Imatinib: 400 mg daily standard; 600 mg daily high-dose for resistance
  • Dasatinib: 100 mg daily or 50 mg twice daily; reduced dosing (70 mg) in tolerability studies
  • Nilotinib: 300 mg twice daily standard
  • Ponatinib: 45 mg daily (approved dose)
  • Bosutinib: Dosing adjusted for tolerability

Note: Extensive patient pharmacokinetic/pharmacodynamic monitoring (molecular response assessment) and mutation testing guide treatment optimization across all approved ABL1 inhibitors.

Expression profiles

Tissue Expression (Bgee)

ABL1 shows ubiquitous expression across human tissues with an average expression score of 86.77 (max: 98.8). Expression is enriched in neuronal tissues, smooth muscle, and reproductive organs.

RankTissueExpression ScoreQuality
1Frontal pole98.80Gold
2Paraflocculus98.69Gold
3Middle frontal gyrus98.68Gold
4Muscle layer of sigmoid colon96.54Gold
5Mucosa of stomach96.22Gold
6Lower esophagus muscularis layer95.99Gold
7Lower esophagus95.96Gold
8Esophagogastric junction muscularis propria95.87Gold
9Stromal cell of endometrium95.79Gold
10Left uterine tube95.62Gold
11Ventricular zone95.40Gold
12Body of uterus95.13Gold
13Ganglionic eminence95.11Gold
14Tibial artery95.05Gold
15Popliteal artery95.05Gold
16Endocervix94.94Gold
17Saphenous vein94.81Gold
18Sigmoid colon94.22Gold
19Aorta94.18Gold
20Right ovary94.00Gold
21Endometrium epithelium93.83Gold
22Left ovary93.82Gold
23Fundus of stomach93.58Gold
24Right coronary artery93.55Gold
25Transverse colon93.54Gold
26Smooth muscle tissue93.52Gold
27Right lobe of thyroid gland93.17Gold
28Descending thoracic aorta93.15Gold
29Gallbladder93.15Gold
30Pericardium93.14Gold

Key patterns: Prominent expression in CNS structures (frontal cortex, cerebellum), smooth muscle tissues, gastrointestinal tract muscularis layers, and reproductive organs. Expression in 283/292 conditions (96.9% present calls).

Cell Type Expression

No comprehensive cell-type-specific expression data from Tabula Sapiens or HCA available in current databases. SCXA single-cell data is limited to 1 dataset.

Single-Cell Expression Datasets

Dataset IDDescriptionSpeciesCell Count
E-MTAB-6058Human foetal L/M-opsin cone photoreceptor populations (AAV2/9.pR2.1.GFP reporter)Homo sapiens74

Notes: ABL1 detected in 141 cell clusters across available single-cell experiments; maximum mean expression: 17.42. Limited single-cell atlas coverage suggests need for tissue-specific proteomic or immunohistochemical validation for cell-type specificity.

Disease associations

Mendelian / Monogenic Diseases

Via GenCC (curated gene-disease associations):

DiseaseDisease IDInheritanceEvidence Level
Congenital heart defects and skeletal malformations syndromeOMIM:617602Autosomal dominantStrong
Connective tissue disorderMONDO:0003900Autosomal dominantModerate
Bone development diseaseMONDO:0005497Autosomal recessiveLimited

Via ClinVar & Mondo:

  • Chronic myelogenous leukemia, BCR-ABL1 positive (MONDO:0011996)
  • Congenital heart disease (MONDO:0005453)
  • T-cell acute lymphoblastic leukemia (MONDO:0004963)
  • Cardiomyopathy (MONDO:0004994)
  • Cleft palate (MONDO:0016064)
  • Lip and oral cavity carcinoma (MONDO:0023644)
  • Citrullinemia (MONDO:0015991)
  • Microcephaly (MONDO:0001149)
  • Muscular dystrophy-dystroglycanopathy variants (MONDO:0000171, MONDO:0012248, MONDO:0013159)

Via Orphanet:

  • Chronic myeloid leukemia (ORPHA:521)
  • Marfanoid habitus-facial dysmorphism-skeletal abnormality-heart defect syndrome (ORPHA:643503)
  • Walker-Warburg syndrome (ORPHA:899)
  • POMT1-related limb-girdle muscular dystrophy R11 (ORPHA:86812)
  • Moyamoya angiopathy (ORPHA:477768)

Phenotype Associations (Top 30 HPO Terms)

  1. HP:0000006 | Autosomal dominant inheritance
  2. HP:0005506 | Chronic myelogenous leukemia
  3. HP:0004848 | Ph-positive acute lymphoblastic leukemia
  4. HP:0001974 | Increased total leukocyte count
  5. HP:0001873 | Thrombocytopenia
  6. HP:0001894 | Thrombocytosis
  7. HP:0001263 | Global developmental delay
  8. HP:0001508 | Failure to thrive
  9. HP:0001629 | Ventricular septal defect
  10. HP:0001631 | Atrial septal defect
  11. HP:0001680 | Coarctation of aorta
  12. HP:0002616 | Aortic root aneurysm
  13. HP:0004322 | Short stature
  14. HP:0001511 | Intrauterine growth retardation
  15. HP:0001166 | Arachnodactyly
  16. HP:0001382 | Joint hypermobility
  17. HP:0001763 | Pes planus
  18. HP:0000767 | Pectus excavatum
  19. HP:0002650 | Scoliosis
  20. HP:0002808 | Kyphosis
  21. HP:0002023 | Anal atresia
  22. HP:0000776 | Congenital diaphragmatic hernia
  23. HP:0002566 | Intestinal malrotation
  24. HP:0000218 | High palate
  25. HP:0000337 | Broad forehead
  26. HP:0002007 | Frontal bossing
  27. HP:0000582 | Upslanted palpebral fissure
  28. HP:0000490 | Deeply set eye
  29. HP:0003189 | Long nose
  30. HP:0001744 | Splenomegaly

Complex-Disease / GWAS Associations (Top 6)

TraitP-ValueChromosome
Platelet count7.0e-139
White blood cell count8.0e-129
Lymphocyte count9.0e-11—
Red cell distribution width1.0e-109
Coronary artery calcified atherosclerotic plaque score in type 2 diabetes5.0e-069
Response to amphetamines8.0e-069

Structured Data Sources

Generated with Claude Haiku 4.5 + BioBTree MCP, drawing on data BioBTree aggregates from 40 biological databases. Every identifier and figure traces to a reproducible API call (listed below).

Further analyze this answer or run your own queries with BioBTree MCP.

Datasets: alphafold, alphamissense, antibody, bgee, biogrid_interaction, ccds, chembl_molecule, chembl_target, clinical_trials, clinvar, collectri, diamond_similarity, ensembl, entrez, esm2_similarity, exon, gencc, go, gwas, hgnc, hpa, hpo, intact, interpro, mim, mondo, msigdb, orphanet, ortholog, pdb, pfam, pharmgkb_gene, reactome, refseq, scxa, scxa_expression, spliceai, string_interaction, transcript, uniprot
Generated: 2026-05-24 — For the latest data, query BioBTree directly via MCP or API.
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