RUNX2 (Runt-related transcription factor 2)

2006-12-01   Athanasios G Papavassiliou , Panos Ziros 

Department of Biological Chemistry, Medical School, University of Athens, GR-11527 Goudi-Athens, Greece

Identity

HGNC
LOCATION
6p21.1
IMAGE
Atlas Image
LEGEND
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.
LOCUSID
ALIAS
AML3,CBF-alpha-1,CBFA1,CCD,CCD1,CLCD,OSF-2,OSF2,PEA2aA,PEBP2aA
FUSION GENES

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.

Proteins

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 name
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 name
Lymphomas
Disease
Runx2 and MYC collaborate in lymphoma development by suppressing apoptotic and growth arrest pathways in vivo.
Entity name
Disease
Human myeloma cells express the bone regulating gene Runx2 and produce osteopontin that is involved in angiogenesis in multiple myeloma patients.
Entity name
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 name
Breast cancer.
Disease
Involvement of Runx2 transcription factors in breast cancer cells.
Entity name
Malignant melanoma.
Disease
Coexpression of bone sialoprotein and Runx2, in malignant melanoma.
Entity name
Prostate cancer.
Disease
Prostate cancer expression of runt-domain transcription factor Runx2.

Bibliography

Pubmed IDLast YearTitleAuthors
127502902003Osteoblast-related transcription factors Runx2 (Cbfa1/AML3) and MSX2 mediate the expression of bone sialoprotein in human metastatic breast cancer cells.Barnes GL et al
117460202001A natural history of cleidocranial dysplasia.Cooper SC et al
91827621997Osf2/Cbfa1: a transcriptional activator of osteoblast differentiation.Ducy P et al
94349461998Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function.Geoffroy V et al
151561732004Oncogenic potential of the RUNX gene family: 'overview'.Ito Y et al
156650962005Impaired intranuclear trafficking of Runx2 (AML3/CBFA1) transcription factors in breast cancer cells inhibits osteolysis in vivo.Javed A et al
91827631997Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts.Komori T et al
92078001997Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia.Lee B et al
120868552002RUNX: a trilogy of cancer genes.Lund AH et al
91827651997Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia.Mundlos S et al
91827641997Cbfa1, a candidate gene for cleidocranial dysplasia syndrome, is essential for osteoblast differentiation and bone development.Otto F et al
119609802002The bone-specific transcriptional regulator Cbfa1 is a target of mechanical signals in osteoblastic cells.Ziros PG et al

Other Information

Locus ID:

NCBI: 860
MIM: 600211
HGNC: 10472
Ensembl: ENSG00000124813

Variants:

dbSNP: 860
ClinVar: 860
TCGA: ENSG00000124813
COSMIC: RUNX2

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000124813ENST00000359524Q13950
ENSG00000124813ENST00000371432Q13950
ENSG00000124813ENST00000371436Q13950
ENSG00000124813ENST00000371438Q13950
ENSG00000124813ENST00000478660I3L354
ENSG00000124813ENST00000483377I3L4L9
ENSG00000124813ENST00000576263I3L0L0
ENSG00000124813ENST00000625924A0A0D9SEN7
ENSG00000124813ENST00000646519A0A2R8Y7Z3
ENSG00000124813ENST00000647337Q13950

Expression (GTEx)

0
5
10
15
20

Pathways

PathwaySourceExternal ID
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
Gene ExpressionREACTOMER-HSA-74160
Generic Transcription PathwayREACTOMER-HSA-212436
YAP1- and WWTR1 (TAZ)-stimulated gene expressionREACTOMER-HSA-2032785

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
196496552010Regulation of bone development and extracellular matrix protein genes by RUNX2.179
166138562006Bone morphogenetic protein-2 stimulates Runx2 acetylation.119
161666392005The Runx2 osteogenic transcription factor regulates matrix metalloproteinase 9 in bone metastatic cancer cells and controls cell invasion.116
172519812007Mitotic occupancy and lineage-specific transcriptional control of rRNA genes by Runx2.113
145230232003Proteasomal degradation of Runx2 shortens parathyroid hormone-induced anti-apoptotic signaling in osteoblasts. A putative explanation for why intermittent administration is needed for bone anabolism.111
199156142010Runx2 association with progression of prostate cancer in patients: mechanisms mediating bone osteolysis and osteoblastic metastatic lesions.108
165983842006BMP signaling is required for RUNX2-dependent induction of the osteoblast phenotype.99
234384322013Downregulated LncRNA-ANCR promotes osteoblast differentiation by targeting EZH2 and regulating Runx2 expression.98
161873162005Runx2: a master organizer of gene transcription in developing and maturing osteoblasts.85
155830322004Terminal osteoblast differentiation, mediated by runx2 and p27KIP1, is disrupted in osteosarcoma.81

Citation

Athanasios G Papavassiliou ; Panos Ziros

RUNX2 (Runt-related transcription factor 2)

Atlas Genet Cytogenet Oncol Haematol. 2006-12-01

Online version: http://atlasgeneticsoncology.org/gene/42183/runx2