RUNX1
Primary Author(s)*
Brian Davis, PhD
Synonyms
"Runt-related transcription factor 1"; "Acute Myeloid Leukemia 1 Protein"; AML1; ; "Core-Binding Factor Subunit Alpha-2"; CBF2 alpha; CBFA2; "Polyomavirus Enhancer-Binding Protein 2 Alpha B Subunit"; PEBP2aB; PEBP2 alpha; EVI-1; AML1-EVI-1; AMLCR1;
Genomic Location
Cytoband: 21q22.12
Genomic Coordinates:
chr21:36,160,098-37,376,965 [hg19]
chr21:34,787,801-36,004,667 [hg38]
Cancer Category/Type
Acute Myeloid Leukemia (AML); The most common chromosomal translocations is t(8;21)(q22;q22) in de novo AML (2) RUNX1-RUNX1T1. translocations confer a favorable prognosis in their respective diseases (2)
inv(16)(p13;q22) or t(16)(p13;q22), which disrupt CBFB the non-DNA-binding partner of RUNX1: also translocation confer a favorable prognosis in their respective diseases (2)
Mono- and biallelic mutations in RUNX1 include deletions, missense, splicing, frameshift, and nonsense mutations. These mutations are mechanistically distinct from the chromosomal translocations and confer a worse prognosis (2)
T-cell Acute Lymphocytic Leukemia (B-ALL)
B-cell Acute Lymphocytic Leukemia (B-ALL) most common chromosomal translocations is t(12;21)(p13;q22) in acute lymphocytic leukemia (B-ALL) (2) ETV6-RUNX1. translocation confer a favorable prognosis in their respective diseases(2)
Chromic Myeloid Leukemia (CML)
Myelodysplastic Syndrome (MDS)
CCUS or ICUS
RUNX1 mutations are more common in clonal cytopenia of undetermined significance (CCUS) (2)
Familial platelet disorder with predisposition to acute myeloid leukemia (FPD/AML)
Gene Overview
The protein encoded by RUNX1 can bind the protein encoded by CBFB to form "Core Binding Factor", a hetero-dimeric transcription factor, which can bind to DNA as a monomer and through the Runt domain within the Runx1 protein. Runx1 protein is essential for hemopoietic stem cell formation and is important for the differentiation of lymphoid, myeloid and megakaryocytic cell lineages (2). Chromosomal translocations involving this gene are well-documented and have been associated with several types of leukemia. Alterations of RUNX1 are considered "secondary driver mutations" (disease progression) in sporadic leukemias (2), but germline RUNX1 mutations contribute a lifetime risk of myeloid malignancy of about 44% (2). RUNX1 mutations (loss of function or decreased function) have been associated with decreased P53 activity and increased DNA repair defects (2).
Common Alteration Types
Fusions wiht RUNX1T1
ETV6
| Copy Number Loss | Copy Number Gain | LOH | Loss-of-Function Mutation | Gain-of-Function Mutation | Translocation/Fusion |
|---|---|---|---|---|---|
| X | X |
Internal Pages
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External Links
Put your text here - Include as applicable links to: 1) Atlas of Genetics and Cytogenetics in Oncology and Haematology, 2) COSMIC, 3) CIViC, 4) St. Jude ProteinPaint, 5) Precision Medicine Knnowledgebase (Weill Cornell), 6) Cancer Index, 7) OncoKB, 8) My Cancer Genome, 9) UniProt, 10) Pfam, 11) GeneCards, 12) GeneReviews, and 13) Any gene-specific databases.
EXAMPLES
RUNX1 by Atlas of Genetics and Cytogenetics in Oncology and Haematology - detailed gene information
RUNX1 by COSMIC - sequence information, expression, catalogue of mutations
RUNX1 by CIViC - general knowledge and evidence-based variant specific information
RUNX1 by St. Jude ProteinPaint mutational landscape and matched expression data.
RUNX1 by Precision Medicine Knowledgebase (Weill Cornell) - manually vetted interpretations of variants and CNVs
RUNX1 by Cancer Index - gene, pathway, publication information matched to cancer type
RUNX1 by OncoKB - mutational landscape, mutation effect, variant classification
RUNX1 by NCBI - brief gene overview
RUNX1 by My Cancer Genome - brief gene overview
RUNX1 by UniProt - protein and molecular structure and function
RUNX1 by Pfam - gene and protein structure and function information
RUNX1 by GeneCards - general gene information and summaries
"RUNX1" by VOVD(3) - Leiden Open Variation Database
References
1. Kamikubo, Y. (2018). Genetic compensation of RUNX family transcription factors in leukemia. Cancer Sci. (online version ahead of publication). PMID 29883054 doi.org/10.1111/cas.13664
2. Bellissimo, D.C. and Speck, N. A. (2017). RUNX1 Mutations in Inherited and Sporadic Leukemia. Front Cell Dev. Biol. 5: 111- PMID 29326930 10.3389/fcell.2017.00111
Notes
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