ABL1 Gene: Structure, Function, and Clinical Significance in Cancer
A comprehensive overview of the ABL1 proto-oncogene, its role in leukemia and solid tumors, and its implications for targeted therapy.
Gene Information Card
| Symbol | ABL1 |
|---|---|
| Full Name | ABL proto-oncogene 1, non-receptor tyrosine kinase |
| Gene Type | Protein coding |
| Chromosomal Location | 9q34.12 |
| NCBI Gene ID | 25 ncbi.nlm.nih.gov/gene/25 |
| Ensembl ID | ENSG00000097007 |
| UniProt ID | P00519 |
| OMIM ID | 189980 |
| HGNC ID | 76 |
| Aliases | ABL, JTK7, p150, c-ABL, v-abl |
Description
The ABL1 gene encodes a non-receptor tyrosine kinase that plays a critical role in cell division, differentiation, adhesion, and stress response. It is ubiquitously expressed and localizes to the cytoplasm and nucleus. ABL1 is most famous for its involvement in the Philadelphia chromosome translocation t(9;22), which creates the BCR-ABL1 fusion protein, a constitutively active kinase that drives chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL). Beyond its oncogenic role, ABL1 also functions in normal cellular processes, including DNA damage response and apoptosis. Mutations and overexpression of ABL1 have been implicated in various solid tumors, making it a key target for tyrosine kinase inhibitors (TKIs) such as imatinib.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Chronic Myeloid Leukemia (CML) | BCR-ABL1 fusion protein with constitutive kinase activity drives uncontrolled proliferation | Philadelphia chromosome t(9;22) present in >90% of CML cases (NCBI, OMIM) |
| Acute Lymphoblastic Leukemia (ALL) | BCR-ABL1 fusion in B-cell ALL; activates signaling pathways promoting survival | Present in ~25% of adult ALL and ~5% of pediatric ALL (NCBI, OMIM) |
| Acute Myeloid Leukemia (AML) | Rare ABL1 mutations or fusions (e.g., ETV6-ABL1) can contribute to leukemogenesis | Case reports and small studies (COSMIC, ClinVar) |
| Solid Tumors | ABL1 overexpression or activation may promote invasion and metastasis | Observed in breast, lung, and colorectal cancers (COSMIC, literature) |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Spleen | High | High |
| Lymph Node | High | High |
| Thymus | High | High |
| Brain | Low | Low |
| Heart | Low | Low |
| Liver | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (CML) | High | BCR-ABL1 fusion positive |
| HL-60 (AML) | Medium | Endogenous ABL1 expression |
| MCF7 (Breast cancer) | Medium | Overexpression in some studies |
| HeLa (Cervical cancer) | Medium | Normal expression |
| A549 (Lung cancer) | Medium | Normal expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| T315I | Point mutation | ~15-20% of resistant CML cases | Confer resistance to imatinib and most TKIs by altering drug binding |
| Y253H | Point mutation | ~5% of resistant CML cases | Disrupts imatinib binding; sensitive to dasatinib |
| E255K | Point mutation | ~5% of resistant CML cases | Reduces imatinib sensitivity; partial response to nilotinib |
| G250E | Point mutation | ~3% of resistant CML cases | Imatinib resistance; sensitive to bosutinib |
| F317L | Point mutation | ~2% of resistant CML cases | Resistance to dasatinib; sensitive to nilotinib |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in ABL1 are rare and not well characterized; they may impair DNA damage response and apoptosis, potentially contributing to genomic instability.
Gain of Function (GOF)
Gain-of-function mutations, particularly the BCR-ABL1 fusion, result in constitutive kinase activity, driving uncontrolled cell proliferation and survival. Point mutations in the kinase domain (e.g., T315I) also enhance kinase activity or alter drug binding.
Dominant Negative (DN)
Dominant-negative effects are not commonly described for ABL1 mutations; however, some mutations may interfere with normal ABL1 function in a dominant-negative manner, though evidence is limited.
View complete mutation data：
Gene Ontology (GO)
| • protein tyrosine kinase activity | • ATP binding |
| • signal transduction | • cell proliferation |
| • apoptotic process | • DNA damage response |
| • cell adhesion | • actin cytoskeleton organization |
| • nucleus | • cytoplasm |
Pathways
• BCR-ABL1 signaling in CML
• ErbB signaling pathway
• PI3K-Akt signaling pathway
• Ras signaling pathway
• JAK-STAT signaling pathway
• MAPK signaling pathway
• Apoptosis regulation
• DNA damage response
Protein Summary
The ABL1 protein is a 1130-amino acid non-receptor tyrosine kinase with multiple domains: an SH3 domain (regulatory), SH2 domain (phosphotyrosine binding), a catalytic kinase domain, and C-terminal actin-binding and DNA-binding domains. It shuttles between the nucleus and cytoplasm, participating in signal transduction, cell cycle regulation, and DNA repair. In the BCR-ABL1 fusion, the N-terminal portion of BCR replaces the SH3 domain, leading to constitutive kinase activity. The protein is a key therapeutic target; TKIs like imatinib bind to the ATP-binding pocket and inhibit its activity. Post-translational modifications, such as phosphorylation, regulate its function.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ABL1 Knockout HEK293 Cell Line | EDJ-KQ17798 | Human | 25 | Details Get a Quote |
| ABL1 Knockout A-549 Cell Line | EDJ-KQ20674 | Human | 25 | Details Get a Quote |
| ABL1 Knockout HCT 116 Cell Line | EDJ-KQ20675 | Human | 25 | Details Get a Quote |
| ABL1 Knockout HeLa Cell Line | EDJ-KQ20676 | Human | 25 | Details Get a Quote |
| ABL1 (p.P1108=) Point Mutation in HAP1 Cell Line | EDC03395 | Human | 25 | Details Get a Quote |
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