RUNX1 Gene: Structure, Function, and Clinical Significance
A master hematopoietic transcription factor implicated in leukemia and inherited platelet disorders
Gene Information Card
| Symbol | RUNX1 |
|---|---|
| Full Name | RUNX1 (runt-related transcription factor 1) |
| Gene Type | Protein-coding |
| Chromosomal Location | 21q22.12 |
| NCBI Gene ID | 861 ncbi.nlm.nih.gov/gene/861 |
| Ensembl ID | ENSG00000159216 |
| UniProt ID | Q01196 |
| OMIM ID | 153618 |
| HGNC ID | 10471 |
| Aliases | AML1, CBFA2, PEBP2aB, AML1-EVI-1 |
Description
The RUNX1 gene encodes the alpha subunit of the core binding factor (CBF) transcription factor complex. It is essential for definitive hematopoiesis, regulating the differentiation of hematopoietic stem cells into mature blood cells. RUNX1 functions as a sequence-specific DNA-binding protein that recruits co-activators or co-repressors to control gene expression. Chromosomal translocations involving RUNX1, such as t(8;21) and t(12;21), are common in acute leukemias. Germline mutations cause familial platelet disorder with associated myeloid malignancy (FPD/AML), and somatic mutations are frequent in various myeloid neoplasms.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute Myeloid Leukemia (AML) | Chromosomal translocations (e.g., t(8;21)) create fusion proteins (RUNX1-RUNX1T1) that act as aberrant transcriptional repressors, blocking hematopoietic differentiation. Somatic mutations can also disrupt RUNX1 function. | COSMIC, ClinVar, PMID: 15659725 |
| Familial Platelet Disorder with Associated Myeloid Malignancy (FPD/AML) | Germline loss-of-function mutations in RUNX1 cause haploinsufficiency or dominant-negative effects, leading to thrombocytopenia, platelet dysfunction, and increased risk of AML/MDS. | OMIM #601399, ClinVar |
| Myelodysplastic Syndromes (MDS) | Somatic mutations or deletions of RUNX1 are found in MDS, contributing to dysplastic hematopoiesis and progression to AML. | COSMIC, PMID: 21467544 |
| Acute Lymphoblastic Leukemia (ALL) | The t(12;21) translocation (ETV6-RUNX1) is the most common genetic alteration in pediatric ALL, leading to a pre-leukemic clone. | COSMIC, PMID: 10655503 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | High | High |
| Spleen | Medium | Medium |
| Thymus | Medium | Medium |
| Lymph Node | Medium | Medium |
| Blood | Medium | Medium |
| Other tissues | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K-562 (CML) | High | Leukemia cell line |
| HL-60 (PML) | Medium | Promyelocytic leukemia |
| MOLT-4 (ALL) | Medium | T-cell leukemia |
| A549 (Lung) | Low | Non-hematopoietic |
| HeLa (Cervical) | Low | Non-hematopoietic |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| Missense | ~20% | Loss of DNA binding or transactivation | |
| Nonsense | ~15% | Truncated protein, loss of function | |
| Frameshift | ~30% | Premature stop, loss of function | |
| Chromosomal translocation | Common in AML/ALL | Fusion proteins (e.g., RUNX1-RUNX1T1, ETV6-RUNX1) | |
| Deletion | ~10% | Haploinsufficiency |
Mutation functional classification
Loss of Function (LOF)
Most RUNX1 mutations result in loss of function, either through haploinsufficiency or dominant-negative effects, impairing hematopoietic differentiation.
Gain of Function (GOF)
Rare; some missense mutations may alter DNA-binding specificity or protein interactions, but gain-of-function is not typical.
Dominant Negative (DN)
Certain missense mutations in the RUNT domain produce proteins that bind DNA but fail to transactivate, interfering with wild-type RUNX1 function.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II cis-regulatory region sequence-specific DNA binding |
| • Protein heterodimerization activity | • Regulation of transcription by RNA polymerase II |
| • Hematopoietic stem cell differentiation | • Cell differentiation |
| • Negative regulation of cell population proliferation |
Pathways
• Hematopoietic stem cell differentiation
• RUNX1 regulation of megakaryocyte development
• Core binding factor (CBF) complex signaling
• Notch signaling (cross-talk)
• TGF-beta signaling (cross-talk)
Protein Summary
The RUNX1 protein (also known as AML1) is a 480-amino acid transcription factor containing a conserved RUNT domain responsible for DNA binding and heterodimerization with CBFB. It regulates the expression of genes critical for hematopoiesis, including cytokines, growth factors, and cell cycle regulators. Post-translational modifications such as phosphorylation and acetylation modulate its activity. RUNX1 is essential for the emergence of definitive hematopoietic stem cells and for the maturation of megakaryocytes and lymphocytes. Dysregulation of RUNX1 is a hallmark of several leukemias.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| RUNX1 Knockout HEK293 Cell Line | EDJ-KQ2234 | Human | 861 | Details Get a Quote |
| RUNX1T1 Knockout HEK293 Cell Line | EDJ-KQ3204 | Human | 862 | Details Get a Quote |
| RUNX1 Knockout A-549 Cell Line | EDJ-KQ23891 | Human | 861 | Details Get a Quote |
| RUNX1 Knockout HCT 116 Cell Line | EDJ-KQ23893 | Human | 861 | Details Get a Quote |
| RUNX1 Knockout HeLa Cell Line | EDJ-KQ23894 | Human | 861 | Details Get a Quote |
| RUNX1T1 Knockout HeLa Cell Line | EDJ-KQ52794 | Human | 862 | Details Get a Quote |
| RUNX1T1 Knockout A-549 Cell Line | EDJ-KQ61265 | Human | 862 | Details Get a Quote |
| RUNX1T1 Knockout HCT 116 Cell Line | EDJ-KQ69760 | Human | 862 | Details Get a Quote |
| RUNX1 Knockout 786-O Cell Line | EDC90779 | Human | 861 | Details Get a Quote |
| RUNX1 Knockout 769-P Cell Line | EDC90780 | Human | 861 | Details Get a Quote |
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