ABL1
Chr 9ADSomaticABL proto-oncogene 1, non-receptor tyrosine kinase
The ABL1 protein is a non-receptor tyrosine kinase that regulates cytoskeleton remodeling, cell motility, DNA damage response, and apoptosis through phosphorylation of multiple substrate proteins. Germline mutations cause congenital heart defects and skeletal malformations syndrome with autosomal dominant inheritance, while somatic mutations lead to Philadelphia chromosome-positive leukemia resistant to imatinib. ABL1 is highly constrained against loss-of-function variants (pLI = 1.0, LOEUF = 0.18), reflecting its essential cellular functions.
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Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and gain-of-function). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.
Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
ABL1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Canadian Profiling and Targeted Agent Utilization Trial (CAPTUR)
RECRUITINGAsciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase
RECRUITINGAnti-CD19/20/22 Chimeric Antigen Receptor T Cells (TriCAR19.20.22 T Cells) for the Treatment of Relapsed or Refractory Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, and Chronic Lymphocytic Leukemia
RECRUITINGPembrolizumab and Dasatinib, Imatinib Mesylate, or Nilotinib in Treating Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease
ACTIVE NOT RECRUITINGA Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Ph+ALL
RECRUITINGEvaluation of CD47, "Do Not Eat Me" Signal Expression in Chronic Myeloid Leukemia
NOT YET RECRUITINGAdapting Treatment to the Tumor Molecular Alterations for Patients With Advanced Solid Tumors: MyOwnSpecificTreatment
RECRUITINGHA-1 T TCR T Cell Immunotherapy for the Treatment of Patients With Relapsed or Refractory Acute Leukemia After Donor Stem Cell Transplant
RECRUITINGAdding Ruxolitinib to a Combination of Dasatinib Plus Dexamethasone in Remission Induction Therapy in Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia Patients Aged 40 Years or Older
ACTIVE NOT RECRUITINGA Study to Investigate Tolerability and Efficacy of Asciminib (Oral) Versus Nilotinib (Oral) in Adult Participants (≥18 Years of Age) With Newly Diagnosed Philadelphia Chromosome Positive Chronic Myelogenous Leukemia in Chronic Phase (Ph+ CML-CP)
ACTIVE NOT RECRUITINGA Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia
NOT YET RECRUITINGOpen-label Study of Asciminib for CML-CP or CML-AP Patients With T315I Mutation Who Are Resistant, Intolerant or Ineligible to Ponatinib.
RECRUITINGExternal Resources
Links to major genomics databases and tools