ABL1

Chr 9ADSomatic

ABL proto-oncogene 1, non-receptor tyrosine kinase

Also known as: ABL, BCR-ABL, CHDSKM, JTK7, bcr/abl, c-ABL, c-ABL1, p150

NCBI Gene: 25 ENSG00000097007 UniProt: P00519

This gene is a protooncogene that encodes a protein tyrosine kinase involved in a variety of cellular processes, including cell division, adhesion, differentiation, and response to stress. The activity of the protein is negatively regulated by its SH3 domain, whereby deletion of the region encoding this domain results in an oncogene. The ubiquitously expressed protein has DNA-binding activity that is regulated by CDC2-mediated phosphorylation, suggesting a cell cycle function. This gene has been found fused to a variety of translocation partner genes in various leukemias, most notably the t(9;22) translocation that results in a fusion with the 5' end of the breakpoint cluster region gene (BCR; MIM:151410). Alternative splicing of this gene results in two transcript variants, which contain alternative first exons that are spliced to the remaining common exons. [provided by RefSeq, Aug 2014]

Primary Disease Associations & Inheritance

Congenital heart defects and skeletal malformations syndromeMIM #617602

Leukemia, Philadelphia chromosome-positive, resistant to imatinibMIM #608232

Somatic

UniProtLeukemia, chronic myeloid

Active trials

Pathogenic / LP

479

ClinVar variants

Pubs (1 yr)

2.6

Missense Z

0.18

LOEUF· LoF intolerant

Clinical Summary— ABL1

⚡

Population Constraint (gnomAD)

Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

📋

ClinVar Variants

10 Pathogenic / Likely Pathogenic· 201 VUS of 479 total submissions

💊

Clinical Trials

12 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

LoF intolerant — likely haploinsufficient

LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.

0.18LOEUF

pLI 1.000

Z-score 5.74

OE 0.07 (0.03–0.18)

Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.

2.56Z-score

OE missense 0.73 (0.68–0.79)

523 obs / 715.6 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.

LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.07 (0.03–0.18)

0≤0.351.4

Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.68–0.79)

0≤0.61.4

Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.03

0≤1.21.6

LoF obs/exp: 3 / 44.1Missense obs/exp: 523 / 715.6Syn Z: -0.47

0.4587th %ile

GOF

0.5563th %ile

LOF

0.73top 10%

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.

LOFprediction above median · LOEUF 0.18

GOF1 literature citation

Literature Evidence

GOFA gain-of-function mutation in germline ABL1 causes a syndrome including congenital heart defects.PMID:33075386

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

479 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic5

Likely Pathogenic5

VUS201

Likely Benign197

Benign45

Conflicting26

Pathogenic

Likely Pathogenic

201

VUS

197

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	0	1	4	0	5
Likely Pathogenic	0	5	0	0	5
VUS	8	169	24	0	201
Likely Benign	1	63	37	96	197
Benign	0	17	2	26	45
Conflicting	—				26
Total	9	255	67	122	479

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View 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.

Gene2Phenotype Curations

ABL1-related congenital heart defects and skeletal malformations

strong

ADGain Of FunctionAltered Gene Product Structure

Dev. DisordersSkin

G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

External Resources

Links to major genomics databases and tools

Franklin by Genoox

AI-powered variant curation and clinical analysis

DECIPHER

Genomic variants and phenotypes in rare disease patients

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

Chronic Myelogenous Leukemia

A Clinical Trial to Evaluate the Safety and Tolerability of TQB3911 Tablets in Patients With BCR::ABL Fusion Gene Positive Leukemia

NOT YET RECRUITING

NCT06672263Phase PHASE1Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.Started 2024-11

TQB3911 tablets

Chronic Myeloid Leukemia, Chronic PhaseAdult CMLLeukemia, Myeloid

Asciminib as Initial Therapy for Patients With Chronic Myeloid Leukemia in Chronic Phase

RECRUITING

NCT05143840Phase PHASE2Augusta UniversityStarted 2022-04-22

Single Agent AsciminibLow TKIElective Free Treatment

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveAcute Biphenotypic LeukemiaAcute Lymphoblastic Leukemia

Personalized NK Cell Therapy in CBT

RECRUITING

NCT02727803Phase PHASE2M.D. Anderson Cancer CenterStarted 2016-05-19

Allogeneic Natural Killer Cell Line NK-92Anti-Thymocyte GlobulinBusulfan

Chronic Myeloid Leukemia in Chronic Phase

Real-world Study of Scemblix in the Treatment of Chronic Myeloid Leukemia in China

NOT YET RECRUITING

NCT07375355Novartis PharmaceuticalsStarted 2026-02-27

B Acute Lymphoblastic LeukemiaB Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1B Acute Lymphoblastic Leukemia, BCR-ABL1-Like

Studying the Effect of Levocarnitine in Protecting the Liver From Chemotherapy for Leukemia or Lymphoma

RECRUITING

NCT05602194Phase PHASE3Children's Oncology GroupStarted 2023-08-24

Biospecimen CollectionCalaspargase PegolLevocarnitine

Chronic Myeloid Leukemia

Efficacy and Safety of Generic Imatinib (Carcemia®) Compared to Glivec® in Real-Life Management of Chronic Phase of Chronic Myeloid Leukemia

RECRUITING

NCT05282108Hikma Pharmaceuticals LLCStarted 2022-07-20

CarcemiaGlivec

Myeloid Leukemia, Philadelphia Positive

Study to Determine the Dose and Safety of Asciminib in Pediatric Patients With Chronic Myeloid Leukemia

RECRUITING

NCT04925479Phase PHASE1, PHASE2Novartis PharmaceuticalsStarted 2021-12-27

Asciminib Pediatric formulation groupAsciminib Adult formulation group

Chronic Myeloid Leukemia (CML)

Improving Treatment Outcomes in Chronic Myeloid Leukaemia Patients Using Imatinib and Artesunate Combination Therapy

ACTIVE NOT RECRUITING

NCT07022743Phase PHASE2Obafemi Awolowo UniversityStarted 2025-07-01

ImatinibArtesunate

Acute Lymphoblastic Leukemia

Adding 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 RECRUITING

NCT02494882Phase PHASE1Memorial Sloan Kettering Cancer CenterStarted 2015-06-29

RuxolitinibDasatinibDexamethasone

Acute Lymphoblastic LeukemiaPhiladelphia ChromosomePhiladelphia-Positive ALL

A Single-arm, Open-label Study of Olverembatinib, CD3/CD19 Bispecific T-cell Engager, and Chidamide in Patients With Newly Diagnosed Ph+ALL

RECRUITING

NCT06220487Phase PHASE2Nanfang Hospital, Southern Medical UniversityStarted 2024-02-01

Prednisone, Olverembatinib, Blinatumomab, Chidamide

Chronic Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveMinimal Residual Disease

Pembrolizumab and Dasatinib, Imatinib Mesylate, or Nilotinib in Treating Patients With Chronic Myeloid Leukemia and Persistently Detectable Minimal Residual Disease

ACTIVE NOT RECRUITING

NCT03516279Phase PHASE2ECOG-ACRIN Cancer Research GroupStarted 2019-06-26

DasatinibImatinib MesylateLaboratory Biomarker Analysis

Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 PositiveAcute Lymphoblastic LeukemiaAcute Myeloid Leukemia

Triplex Vaccine in Preventing CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplantation

ACTIVE NOT RECRUITING

NCT04060277Phase PHASE2City of Hope Medical CenterStarted 2019-11-27

LetermovirMulti-peptide CMV-Modified Vaccinia Ankara VaccinePlacebo Administration

Clinical Literature

Landmark / reviewRecent case evidence

Full-Text Mentions

NLP-detected gene mentions in article bodies · via PubTator3