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RUNX2 (Runt-related transcription factor 2)

Identity

Other namesPEBP2-ALPHA-A
OSF2
AML3
CBFA1
HGNC (Hugo) RUNX2
LocusID (NCBI) 860
Location 6p21.1
Location_base_pair Starts at 45296054 and ends at 45518819 bp from pter ( according to hg19-Feb_2009)  [Mapping]

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

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.
  

Other Leukemias implicated (Data extracted from papers in the Atlas)

Leukemias t0817q24q22ID1494

External links

Nomenclature
HGNC (Hugo)RUNX2   10472
Cards
AtlasRUNX2ID42183ch6p21
Entrez_Gene (NCBI)RUNX2  860  runt-related transcription factor 2
GeneCards (Weizmann)RUNX2
Ensembl (Hinxton)ENSG00000124813 [Gene_View]  chr6:45296054-45518819 [Contig_View]  RUNX2 [Vega]
ICGC DataPortalENSG00000124813
cBioPortalRUNX2
AceView (NCBI)RUNX2
Genatlas (Paris)RUNX2
WikiGenes860
SOURCE (Princeton)NM_001015051 NM_001024630 NM_001278478 NM_004348
Genomic and cartography
GoldenPath (UCSC)RUNX2  -  6p21.1   chr6:45296054-45518819 +  6p21   [Description]    (hg19-Feb_2009)
EnsemblRUNX2 - 6p21 [CytoView]
Mapping of homologs : NCBIRUNX2 [Mapview]
OMIM119600   156510   600211   
Gene and transcription
Genbank (Entrez)AF053952 AF087960 AL353944 AW469546 BC108919
RefSeq transcript (Entrez)NM_001015051 NM_001024630 NM_001278478 NM_004348
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_008020 NT_007592 NW_001838981 NW_004929326
Consensus coding sequences : CCDS (NCBI)RUNX2
Cluster EST : UnigeneHs.535845 [ NCBI ]
CGAP (NCI)Hs.535845
Alternative Splicing : Fast-db (Paris)GSHG0025774
Alternative Splicing GalleryENSG00000124813
Gene ExpressionRUNX2 [ NCBI-GEO ]     RUNX2 [ SEEK ]   RUNX2 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ13950 (Uniprot)
NextProtQ13950  [Medical]
With graphics : InterProQ13950
Splice isoforms : SwissVarQ13950 (Swissvar)
Domaine pattern : Prosite (Expaxy)RUNT (PS51062)   
Domains : Interpro (EBI)AML1_Runt [organisation]   p53-like_TF_DNA-bd [organisation]   p53/RUNT-type_TF_DNA-bd [organisation]   Runt_dom [organisation]   Runx_central_dom [organisation]   RunxI_C_dom [organisation]   TF_Runt-rel_RUNX [organisation]  
Related proteins : CluSTrQ13950
Domain families : Pfam (Sanger)Runt (PF00853)    RunxI (PF08504)   
Domain families : Pfam (NCBI)pfam00853    pfam08504   
DMDM Disease mutations860
Blocks (Seattle)Q13950
Human Protein AtlasENSG00000124813 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasQ13950
HPRD02566
IPIIPI01015485   IPI00604427   IPI00946868   IPI00216243   IPI00640084   IPI00930295   
Protein Interaction databases
DIP (DOE-UCLA)Q13950
IntAct (EBI)Q13950
FunCoupENSG00000124813
BioGRIDRUNX2
InParanoidQ13950
Interologous Interaction database Q13950
IntegromeDBRUNX2
STRING (EMBL)RUNX2
Ontologies - Pathways
Ontology : AmiGOnuclear chromatin  ossification  osteoblast differentiation  osteoblast differentiation  endochondral ossification  osteoblast fate commitment  chondrocyte development  osteoblast development  chromatin binding  sequence-specific DNA binding transcription factor activity  protein binding  ATP binding  nucleus  transcription factor complex  nucleolus  cytoplasm  transcription initiation from RNA polymerase II promoter  positive regulation of cell proliferation  gene expression  protein domain specific binding  T cell differentiation  BMP signaling pathway  positive regulation of chondrocyte differentiation  embryonic forelimb morphogenesis  regulation of fibroblast growth factor receptor signaling pathway  odontogenesis of dentin-containing tooth  regulation of odontogenesis of dentin-containing tooth  bHLH transcription factor binding  transcription regulatory region DNA binding  positive regulation of osteoblast differentiation  negative regulation of smoothened signaling pathway  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  cell maturation  embryonic cranial skeleton morphogenesis  stem cell differentiation  repressing transcription factor binding  cellular response to BMP stimulus  positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus  
Ontology : EGO-EBInuclear chromatin  ossification  osteoblast differentiation  osteoblast differentiation  endochondral ossification  osteoblast fate commitment  chondrocyte development  osteoblast development  chromatin binding  sequence-specific DNA binding transcription factor activity  protein binding  ATP binding  nucleus  transcription factor complex  nucleolus  cytoplasm  transcription initiation from RNA polymerase II promoter  positive regulation of cell proliferation  gene expression  protein domain specific binding  T cell differentiation  BMP signaling pathway  positive regulation of chondrocyte differentiation  embryonic forelimb morphogenesis  regulation of fibroblast growth factor receptor signaling pathway  odontogenesis of dentin-containing tooth  regulation of odontogenesis of dentin-containing tooth  bHLH transcription factor binding  transcription regulatory region DNA binding  positive regulation of osteoblast differentiation  negative regulation of smoothened signaling pathway  negative regulation of transcription, DNA-dependent  positive regulation of transcription, DNA-dependent  cell maturation  embryonic cranial skeleton morphogenesis  stem cell differentiation  repressing transcription factor binding  cellular response to BMP stimulus  positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus  
Pathways : KEGGTranscriptional misregulation in cancer   
Protein Interaction DatabaseRUNX2
Wikipedia pathwaysRUNX2
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)RUNX2
snp3D : Map Gene to Disease860
SNP (GeneSNP Utah)RUNX2
SNP : HGBaseRUNX2
Genetic variants : HAPMAPRUNX2
Exome VariantRUNX2
1000_GenomesRUNX2 
ICGC programENSG00000124813 
Somatic Mutations in Cancer : COSMICRUNX2 
CONAN: Copy Number AnalysisRUNX2 
Mutations and Diseases : HGMDRUNX2
Genomic VariantsRUNX2  RUNX2 [DGVbeta]
dbVarRUNX2
ClinVarRUNX2
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM119600    156510    600211   
MedgenRUNX2
GENETestsRUNX2
Disease Genetic AssociationRUNX2
Huge Navigator RUNX2 [HugePedia]  RUNX2 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneRUNX2
Homology/Alignments : Family Browser (UCSC)RUNX2
Phylogenetic Trees/Animal Genes : TreeFamRUNX2
Chemical/Protein Interactions : CTD860
Chemical/Pharm GKB GenePA34885
Clinical trialRUNX2
Cancer Resource (Charite)ENSG00000124813
Other databases
Other databasehttp://www.nlm.nih.gov/medlineplus/ency/article/001589.htm
Other databasehttp://www.rarediseases.org/search/rdbdetail_abstract.html?disname=Cleidocranial+Dysplasia
Other databasehttp://www.gfmer.ch/genetic_diseases_v2/gendis_detail_list.php?cat3=66
Probes
Litterature
PubMed299 Pubmed reference(s) in Entrez
CoreMineRUNX2
iHOPRUNX2

Bibliography

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
 
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
 
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
 
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
 
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
 
RUNX: a trilogy of cancer genes.
Lund AH, van Lohuizen M
Cancer cell. 2002 ; 1 (3) : 213-215.
PMID 12086855
 
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
 
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
 
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
 
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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Contributor(s)

Written12-2006Athanasios G Papavassiliou, Panos Ziros

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 online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/RUNX2ID42183ch6p21.html

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indexed on : Fri Jul 11 17:25:48 CEST 2014

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