The RUNX1 gene provides instructions for making a protein called runt-related transcription factor 1 (RUNX1). Like other transcription factors, the RUNX1 protein attaches (binds) to specific regions of DNA and helps control the activity of particular genes. This protein interacts with another protein called core binding factor beta or CBFβ (produced from the CBFB gene), which helps RUNX1 bind to DNA and prevents it from being broken down. Together, these proteins form one version of a complex known as core binding factor (CBF). The RUNX1 protein turns on (activates) genes that help control the development of blood cells (hematopoiesis). In particular, it plays an important role in development of hematopoietic stem cells, early blood cells that have the potential to develop into all types of mature blood cells such as white blood cells, red blood cells, and platelets.
Health Conditions Related to Genetic Changes
Core binding factor acute myeloid leukemia
A rearrangement (translocation) of genetic material involving the RUNX1 gene is found in approximately 7 percent of individuals with a form of blood cancer known as acute myeloid leukemia (AML). The translocation, written as t(8;21), combines genetic information from chromosome 21 and chromosome 8, fusing the RUNX1 gene on chromosome 21 with a gene on chromosome 8 called RUNX1T1 (also known as ETO). Because this genetic change affects CBF, the condition is classified as core binding factor AML (CBF-AML).
The resulting fusion protein, RUNX1-ETO, is able to form CBF and attach to DNA, like the normal RUNX1 protein; however, instead of turning genes on, it turns them off. This change in gene activity blocks the maturation (differentiation) of blood cells and leads to the production of abnormal, immature white blood cells called myeloid blasts. While t(8;21) is important for leukemia development, a mutation in one or more additional genes is typically needed for the myeloid blasts to develop into cancerous leukemia cells.More About This Health Condition
Cytogenetically normal acute myeloid leukemia
MedlinePlus Genetics provides information about Cytogenetically normal acute myeloid leukemiaMore About This Health Condition
Juvenile idiopathic arthritis
MedlinePlus Genetics provides information about Juvenile idiopathic arthritisMore About This Health Condition
MedlinePlus Genetics provides information about Rheumatoid arthritisMore About This Health Condition
MedlinePlus Genetics provides information about Systemic mastocytosisMore About This Health Condition
Translocations and other types of mutations involving the RUNX1 gene have been associated with different types of leukemia and related blood disorders, including acute lymphoblastic leukemia (ALL), chronic myelomonocytic leukemia (CMML), familial platelet disorder with predisposition to acute myeloid leukemia, and myelodysplastic syndromes (MDS). Depending on the type of mutation, these conditions can be related to impaired regulation of gene activity or loss of normal gene function. The RUNX1 gene mutations associated with these diseases are somatic mutations and are not inherited. They are found only in certain cells of the body.
Other Names for This Gene
- acute myeloid leukemia 1 protein
- core-binding factor, runt domain, alpha subunit 2
- oncogene AML-1
- PEA2-alpha B
- PEBP2-alpha B
- polyomavirus enhancer-binding protein 2 alpha B subunit
- runt-related transcription factor 1
- SL3-3 enhancer factor 1 alpha B subunit
- SL3/AKV core-binding factor alpha B subunit
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Goyama S, Mulloy JC. Molecular pathogenesis of core binding factor leukemia: current knowledge and future prospects. Int J Hematol. 2011 Aug;94(2):126-133. doi: 10.1007/s12185-011-0858-z. Epub 2011 May 3. Citation on PubMed
- Goyama S, Schibler J, Cunningham L, Zhang Y, Rao Y, Nishimoto N, Nakagawa M, Olsson A, Wunderlich M, Link KA, Mizukawa B, Grimes HL, Kurokawa M, Liu PP, Huang G, Mulloy JC. Transcription factor RUNX1 promotes survival of acute myeloid leukemia cells. J Clin Invest. 2013 Sep;123(9):3876-88. doi: 10.1172/JCI68557. Epub 2013 Aug 27. Erratum In: J Clin Invest. 2013 Nov 1;123(11):4979. Citation on PubMed or Free article on PubMed Central
- Huang G, Shigesada K, Ito K, Wee HJ, Yokomizo T, Ito Y. Dimerization with PEBP2beta protects RUNX1/AML1 from ubiquitin-proteasome-mediated degradation. EMBO J. 2001 Feb 15;20(4):723-33. doi: 10.1093/emboj/20.4.723. Citation on PubMed or Free article on PubMed Central
- Lam K, Zhang DE. RUNX1 and RUNX1-ETO: roles in hematopoiesis and leukemogenesis. Front Biosci (Landmark Ed). 2012 Jan 1;17(3):1120-39. doi: 10.2741/3977. Citation on PubMed or Free article on PubMed Central
- Ran D, Shia WJ, Lo MC, Fan JB, Knorr DA, Ferrell PI, Ye Z, Yan M, Cheng L, Kaufman DS, Zhang DE. RUNX1a enhances hematopoietic lineage commitment from human embryonic stem cells and inducible pluripotent stem cells. Blood. 2013 Apr 11;121(15):2882-90. doi: 10.1182/blood-2012-08-451641. Epub 2013 Jan 31. Citation on PubMed or Free article on PubMed Central
The information on this site should not be used as a substitute for professional medical care or advice. Contact a health care provider if you have questions about your health.