Written | 2006-12 | Athanasios G Papavassiliou, Panos Ziros |
Department of Biological Chemistry, Medical School, University of Athens, GR-11527 Goudi-Athens, Greece |
Identity |
Alias (NCBI) | PEBP2-ALPHA-A | OSF2 | AML3 | CBFA1 |
HGNC (Hugo) | RUNX2 |
HGNC Alias symb | AML3 | PEBP2A1 | PEBP2aA1 |
HGNC Previous name | CCD | CBFA1 | CCD1 |
HGNC Previous name | runt-related transcription factor 2 | runt related transcription factor 2 |
LocusID (NCBI) | 860 |
Atlas_Id | 42183 |
Location | 6p21.1 [Link to chromosome band 6p21] |
Location_base_pair | Starts at 45422275 and ends at 45551082 bp from pter ( according to GRCh38/hg38-Dec_2013) [Mapping RUNX2.png] |
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RUNX2 (Runt-related transcription factor 2) Fluorescence in situ hybridization with SureFISH RUNX2 probe (Agilent Technologies, US) showing RUNX2 located on 6p21.1 (red signals) - Courtesy Adriana Zamecnikova. | |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
HS2ST1 (1p22.3) / RUNX2 (6p21.1) | MAX (14q23.3) / RUNX2 (6p21.1) | MDM2 (12q15) / RUNX2 (6p21.1) | |
RUNX2 (6p21.1) / IFT88 (13q12.11) | RUNX2 (6p21.1) / MAX (14q23.3) |
DNA/RNA |
Description | 124,63 kb, 8 Exon at least. |
Transcription | The transcription of the RUNX2 gene is regulated by two different promoters. The larger P1 transcript gives rise to a protein starting with the amino acid sequence MASNS (Runx2-type II or OSF2/CBFA1a, 521 amino acids), whereas the P2 gives rise to a protein starting with MRIPV (Runx2-type I or isoform c, 507 amino acids). Transcript variants of this protein have been reported as well due to alternative splicing. |
Protein |
Description | Runx2 is a transcription factor belonging to Runx family. This family is characterized by a highly conserved region of 128 amino acids, termed the Runt domain. The Runt domain is responsible for DNA binding and heterodimerization with CBFB (PEBP2b), which increases its DNA-binding affinity and also stabilizes RUNX proteins against proteolytic degradation. The C-terminal portion is rich in proline, serine and threonine (PST region) and contains functional domains acting to regulate transcription. |
Expression | Runx2 expression is largely restricted to osteoblasts and mesenchymal condensations forming bones, cartilages and teeth. |
Localisation | Nuclear |
Function | Runx2 is an osteoblast-specific transcription factor that plays a central role in osteoblast differentiation, chondrocyte maturation, bone formation and remodeling. Moreover, it is a key target of mechanical signals that affect bone biology. |
Homology | RUNX family. |
Mutations |
Note | Heterozygous mutations (frameshift, nonsense, missense, splicing mutations) of the Runx2 gene have been identified in patients with Cleidocranial dysplasia (CCD). |
Implicated in |
Note | |
Entity | Cleidocranial Dysplasia (CCD) |
Disease | CCD is a dominantly inherited autosomal skeletal disorder that is characterized by open sutures and delayed closure of sutures, hypoplastic or aplastic clavicles, short stature, large fontanelles, dental anomalies and delayed skeletal development. |
Prognosis | CCD does not affect life expectancy and most diagnosed persons enjoy good overall health. There is no specific treatment for CCD and the dental problems are the most significant complications. |
Entity | Lymphomas |
Disease | Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo. |
Entity | Multiple myeloma. |
Disease | Human myeloma cells express the bone regulating gene Runx2 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients. |
Entity | Metastatic properties of cancer cells. |
Disease | Runx2 control multiple genes that contribute to the metastatic properties of cancer cells and their activity in the bone microenvironment. |
Entity | Breast cancer. |
Disease | Involvement of Runx2 transcription factors in breast cancer cells. |
Entity | Malignant melanoma. |
Disease | Coexpression of bone sialoprotein and Runx2, in malignant melanoma. |
Entity | Prostate cancer. |
Disease | Prostate cancer expression of runt-domain transcription factor Runx2. |
Bibliography |
Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells. |
Barnes GL, Javed A, Waller SM, Kamal MH, Hebert KE, Hassan MQ, Bellahcene A, Van Wijnen AJ, Young MF, Lian JB, Stein GS, Gerstenfeld LC |
Cancer research. 2003 ; 63 (10) : 2631-2637. |
PMID 12750290 |
A natural history of cleidocranial dysplasia. |
Cooper SC, Flaitz CM, Johnston DA, Lee B, Hecht JT |
American journal of medical genetics. 2001 ; 104 (1) : 1-6. |
PMID 11746020 |
Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation. |
Ducy P, Zhang R, Geoffroy V, Ridall AL, Karsenty G |
Cell. 1997 ; 89 (5) : 747-754. |
PMID 9182762 |
Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function. |
Geoffroy V, Corral DA, Zhou L, Lee B, Karsenty G |
Mammalian genome : official journal of the International Mammalian Genome Society. 1998 ; 9 (1) : 54-57. |
PMID 9434946 |
Oncogenic potential of the RUNX gene family: 'overview'. |
Ito Y |
Oncogene. 2004 ; 23 (24) : 4198-4208. |
PMID 15156173 |
Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo. |
Javed A, Barnes GL, Pratap J, Antkowiak T, Gerstenfeld LC, van Wijnen AJ, Stein JL, Lian JB, Stein GS |
Proceedings of the National Academy of Sciences of the United States of America. 2005 ; 102 (5) : 1454-1459. |
PMID 15665096 |
Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. |
Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K, Shimizu Y, Bronson RT, Gao YH, Inada M, Sato M, Okamoto R, Kitamura Y, Yoshiki S, Kishimoto T |
Cell. 1997 ; 89 (5) : 755-764. |
PMID 9182763 |
Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. |
Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G |
Nature genetics. 1997 ; 16 (3) : 307-310. |
PMID 9207800 |
RUNX: a trilogy of cancer genes. |
Lund AH, van Lohuizen M |
Cancer cell. 2002 ; 1 (3) : 213-215. |
PMID 12086855 |
Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. |
Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR |
Cell. 1997 ; 89 (5) : 773-779. |
PMID 9182765 |
Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development. |
Otto F, Thornell AP, Crompton T, Denzel A, Gilmour KC, Rosewell IR, Stamp GW, Beddington RS, Mundlos S, Olsen BR, Selby PB, Owen MJ |
Cell. 1997 ; 89 (5) : 765-771. |
PMID 9182764 |
The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells. |
Ziros PG, Gil AP, Georgakopoulos T, Habeos I, Kletsas D, Basdra EK, Papavassiliou AG |
The Journal of biological chemistry. 2002 ; 277 (26) : 23934-23941. |
PMID 11960980 |
Citation |
This paper should be referenced as such : |
Ziros, P ; Papavassiliou, AG |
RUNX 2 (runt-related transcription factor 2) |
Atlas Genet Cytogenet Oncol Haematol. 2007;11(2):109-110. |
Free journal version : [ pdf ] [ DOI ] |
Other Leukemias implicated (Data extracted from papers in the Atlas) [ 2 ] |
dic(9;18)(p13;q11) PAX5/ZNF521
TAL1 (1p32) deletion in lymphoid malignancies |
Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 6 ] |
Bone: Osteosarcoma
t(6;12)(p21;q15) MDM2/RUNX2 t(6;13)(p21;q12) RUNX2/IFT88 t(6;14)(p21;q23) MAX/RUNX2 t(6;14)(p21;q23) RUNX2/MAX t(6;17)(p21;p13) RUNX2/USP6 |
External links |
REVIEW articles | automatic search in PubMed |
Last year publications | automatic search in PubMed |
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