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RUNX2 RUNX family transcription factor 2 [ Homo sapiens (human) ]

Gene ID: 860, updated on 17-Oct-2021

Summary

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Official Symbol
RUNX2provided by HGNC
Official Full Name
RUNX family transcription factor 2provided by HGNC
Primary source
HGNC:HGNC:10472
See related
Ensembl:ENSG00000124813 MIM:600211
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CCD; AML3; CCD1; CLCD; OSF2; CBFA1; OSF-2; PEA2aA; PEBP2aA; CBF-alpha-1
Summary
This gene is a member of the RUNX family of transcription factors and encodes a nuclear protein with an Runt DNA-binding domain. This protein is essential for osteoblastic differentiation and skeletal morphogenesis and acts as a scaffold for nucleic acids and regulatory factors involved in skeletal gene expression. The protein can bind DNA both as a monomer or, with more affinity, as a subunit of a heterodimeric complex. Two regions of potential trinucleotide repeat expansions are present in the N-terminal region of the encoded protein, and these and other mutations in this gene have been associated with the bone development disorder cleidocranial dysplasia (CCD). Transcript variants that encode different protein isoforms result from the use of alternate promoters as well as alternate splicing. [provided by RefSeq, Jul 2016]
Expression
Broad expression in bone marrow (RPKM 1.9), appendix (RPKM 1.3) and 23 other tissues See more
Orthologs
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Genomic context

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See RUNX2 in Genome Data Viewer
Location:
6p21.1
Exon count:
10
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 6 NC_000006.12 (45328330..45551082)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (45296067..45518819)

Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene SPT3 homolog, SAGA and STAGA complex component Neighboring gene poly(rC) binding protein 2 pseudogene Neighboring gene microRNA 586 Neighboring gene RUNX2 P1 promoter region Neighboring gene runt related transcription factor 2 polyalanine expansion region Neighboring gene Sharpr-MPRA regulatory region 695 Neighboring gene RUNX2 antisense RNA 1 Neighboring gene uncharacterized LOC107986519

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. The transcription factor RUNX2 fuels YAP1 signaling and gastric cancer tumorigenesis. Guo Z, et al. Cancer Sci, 2021 Sep. PMID 34160112, Free PMC Article
  2. RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia. Matthijssens F, et al. J Clin Invest, 2021 Mar 15. PMID 33555272, Free PMC Article
  3. Cancer-associated fibroblasts and the related Runt-related transcription factor 2 (RUNX2) promote bladder cancer progression. Liu B, et al. Gene, 2021 Apr 5. PMID 33482279
  4. Treatment of keloids through Runx2 siRNA‑induced inhibition of the PI3K/AKT signaling pathway. Lv W, et al. Mol Med Rep, 2021 Jan. PMID 33200804, Free PMC Article
  5. Non-coding RNAs repressive role in post-transcriptional processing of RUNX2 during the acquisition of the osteogenic phenotype of periodontal ligament mesenchymal stem cells. Assis RIF, et al. Dev Biol, 2021 Feb. PMID 33152274

See all (571) citations in PubMed

See citations in PubMed for homologs of this gene provided by HomoloGene

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Vascular calcification in skin and subcutaneous tissue in patients with chronic and end-stage kidney disease.
    Title: Vascular calcification in skin and subcutaneous tissue in patients with chronic and end-stage kidney disease.
  2. Molecular Genetics of Cleidocranial Dysplasia.
    Title: Molecular Genetics of Cleidocranial Dysplasia.
  3. Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues.
    Title: Integrated expression analysis revealed RUNX2 upregulation in lung squamous cell carcinoma tissues.
  4. RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia.
    Title: RUNX2 regulates leukemic cell metabolism and chemotaxis in high-risk T cell acute lymphoblastic leukemia.
  5. Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.
    Title: Mechanical strain-mediated reduction in RANKL expression is associated with RUNX2 and BRD2.
  6. HIF-1alpha repairs degenerative chondrocyte glycolytic metabolism by the transcriptional regulation of Runx2.
    Title: HIF-1α repairs degenerative chondrocyte glycolytic metabolism by the transcriptional regulation of Runx2.
  7. Physiologic Mechanical Stress Directly Induces Bone Formation by Activating Glucose Transporter 1 (Glut 1) in Osteoblasts, Inducing Signaling via NAD+-Dependent Deacetylase (Sirtuin 1) and Runt-Related Transcription Factor 2 (Runx2).
    Title: Physiologic Mechanical Stress Directly Induces Bone Formation by Activating Glucose Transporter 1 (Glut 1) in Osteoblasts, Inducing Signaling via NAD+-Dependent Deacetylase (Sirtuin 1) and Runt-Related Transcription Factor 2 (Runx2).
  8. The transcription factor RUNX2 fuels YAP1 signaling and gastric cancer tumorigenesis.
    Title: The transcription factor RUNX2 fuels YAP1 signaling and gastric cancer tumorigenesis.
  9. MicroRNA-466 regulates the proliferation, migration and invasion of the human lung cancer cells by targeting transcription factor RUNX2.
    Title: MicroRNA-466 regulates the proliferation, migration and invasion of the human lung cancer cells by targeting transcription factor RUNX2.
  10. The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability.
    Title: The RNA demethylase ALKBH5 promotes osteoblast differentiation by modulating Runx2 mRNA stability.
Submit: New GeneRIF Correction See all GeneRIFs (479)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description Tests
Cleidocranial dysostosis
MedGen: C0008928 OMIM: 119600 GeneReviews: Cleidocranial Dysplasia Spectrum Disorder
Compare labs
Genome-wide association study of periodontal pathogen colonization.
GeneReviews: Not available
Many sequence variants affecting diversity of adult human height.
GeneReviews: Not available
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
GeneReviews: Not available
Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly
MedGen: C3549874 OMIM: 156510 GeneReviews: Not available
Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env In human osteoblast (hOB) cell lines, HIV-1 Gag and gp120 reduce RUNX-2 and PPAR-gamma mRNA expression and activity PubMed
Nef nef HIV-1 Nef downregulates the expression of RUNX2 protein in human mesenchymal stem cells PubMed
Pr55(Gag) gag In human osteoblast (hOB) cell lines, HIV-1 Gag and gp120 reduce RUNX-2 and PPAR-gamma mRNA expression and activity PubMed
Tat tat HIV-1 Tat downregulates the expression of RUNX2 protein in human mesenchymal stem cells PubMed
Vif vif The binding of HIV-1 Vif to CBF-beta is mutually exclusive of endogenous RUNX transcriptional factors in cells. Vif inhibits transcription of a RUNX1 reporter gene by competition with CBF-beta PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Clone Names

  • MGC120022, MGC120023

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription activator activity, RNA polymerase II-specific IEA
Inferred from Electronic Annotation
more info
  
enables DNA-binding transcription factor activity NAS
Non-traceable Author Statement
more info
 PubMed 
enables DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
enables bHLH transcription factor binding IEA
Inferred from Electronic Annotation
more info
  
enables chromatin binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein domain specific binding IEA
Inferred from Electronic Annotation
more info
  
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in T cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell maturation IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to BMP stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in chondrocyte development IEA
Inferred from Electronic Annotation
more info
  
involved_in chondrocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in embryonic cranial skeleton morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in embryonic forelimb morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in endochondral ossification IEA
Inferred from Electronic Annotation
more info
  
involved_in hemopoiesis IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in negative regulation of smoothened signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in odontogenesis of dentin-containing tooth IEA
Inferred from Electronic Annotation
more info
  
involved_in ossification IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in ossification TAS
Traceable Author Statement
more info
 PubMed 
involved_in osteoblast development IEA
Inferred from Electronic Annotation
more info
  
involved_in osteoblast differentiation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in osteoblast differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in osteoblast fate commitment IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of chondrocyte differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of gene expression IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of osteoblast differentiation IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in regulation of cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in regulation of fibroblast growth factor receptor signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of odontogenesis of dentin-containing tooth IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of ossification IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
 PubMed 
involved_in stem cell differentiation IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in chromatin ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
part_of transcription regulator complex IEA
Inferred from Electronic Annotation
more info
  

General protein information

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Preferred Names
runt-related transcription factor 2
Names
PEA2-alpha A
PEBP2-alpha A
SL3-3 enhancer factor 1 alpha A subunit
SL3/AKV core-binding factor alpha A subunit
acute myeloid leukemia 3 protein
core-binding factor, runt domain, alpha subunit 1
oncogene AML-3
osteoblast-specific transcription factor 2
polyomavirus enhancer-binding protein 2 alpha A subunit
runt related transcription factor 2

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_008020.2 RefSeqGene

    Range
    5014..227766
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001015051.4 → NP_001015051.3  runt-related transcription factor 2 isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an in-frame exon in the 3' coding region, compared to variant 1. The encoded isoform (b, also known as OSF2/CBF1b) is shorter, compared to isoform a.
    Source sequence(s)
    AL096865, AL161907, AL358135
    Consensus CDS
    CCDS43468.2
    UniProtKB/Swiss-Prot
    Q13950
    Related
    ENSP00000360486.4, ENST00000371432.7
    Conserved Domains (3) summary
    pfam00853
    Location:109 → 230
    Runt; Runt domain
    pfam08504
    Location:408 → 499
    RunxI; Runx inhibition domain
    cl25496
    Location:266 → 459
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

  2. NM_001024630.4 → NP_001019801.3  runt-related transcription factor 2 isoform a

    See identical proteins and their annotated locations for NP_001019801.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (a, also known as OSF2/CBFA1a).
    Source sequence(s)
    AL096865, AL161907, AL358135
    Consensus CDS
    CCDS43467.2
    UniProtKB/Swiss-Prot
    Q13950
    Related
    ENSP00000495497.1, ENST00000647337.2
    Conserved Domains (3) summary
    pfam00853
    Location:109 → 230
    Runt; Runt domain
    pfam08504
    Location:430 → 521
    RunxI; Runx inhibition domain
    cl25496
    Location:266 → 481
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

  3. NM_001278478.2 → NP_001265407.1  runt-related transcription factor 2 isoform d

    See identical proteins and their annotated locations for NP_001265407.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate 5'-most exon, lacks an in-frame exon in the 3' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (d) has a distinct and shorter N-terminus, compared to isoform a.
    Source sequence(s)
    AL096865, AL161907, AL358135
    Consensus CDS
    CCDS64443.1
    UniProtKB/TrEMBL
    A0A0D9SEN7, Q32MY8
    Related
    ENSP00000485863.1, ENST00000625924.1
    Conserved Domains (3) summary
    pfam05109
    Location:252 → 445
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00853
    Location:91 → 217
    Runt; Runt domain
    pfam08504
    Location:394 → 485
    RunxI; Runx inhibition domain

  4. NM_001369405.1 → NP_001356334.1  runt-related transcription factor 2 isoform e

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7) contains an alternate 5'-most exon and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (e) has a distinct and shorter N-terminus, compared to isoform a.
    Source sequence(s)
    AL096865, AL161907, AL358135
    Related
    ENSP00000352514.5, ENST00000359524.7
    Conserved Domains (3) summary
    pfam05109
    Location:252 → 467
    Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)
    pfam00853
    Location:91 → 217
    Runt; Runt domain
    pfam08504
    Location:416 → 507
    RunxI; Runx inhibition domain

RNA

  1. NR_103532.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) uses an alternate splice site in the 5'-terminal exon, lacks several exons, and contains an alternate 3'-terminal exon, compared to variant 1. This variant is represented as non-coding because it lacks a significant portion of the coding region and does not encode a supported protein.
    Source sequence(s)
    AL096865, BX108677
    Related
    ENST00000483243.5

  2. NR_103533.2 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) lacks several exons, and contains an alternate 3'-terminal exon, compared to variant 1. This variant is represented as non-coding because it lacks a significant portion of the coding region and does not encode a supported protein.
    Source sequence(s)
    AL096865, AW469546, BX108677

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p13 Primary Assembly

    Range
    45328330..45551082
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_004348.3: Suppressed sequence

    Description
    NM_004348.3: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript and the protein.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13950.2 GenPept UniProtKB/Swiss-Prot:Q13950

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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