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

Gene ID: 860, updated on 3-Mar-2026
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; AllianceGenome:HGNC:10472
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
all
Try the new Gene page
Try the new Transcripts and proteins table
See RUNX2 in Genome Data Viewer
Location:
6p21.1
Exon count:
10
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (45328330..45551082)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (45163134..45385899)
RS_2024_09 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 MPRA-validated peak5821 silencer Neighboring gene microRNA 586 Neighboring gene MPRA-validated peak5822 silencer Neighboring gene RUNX2 P1 promoter region Neighboring gene MPRA-validated peak5825 silencer Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:45345603-45346146 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17265 Neighboring gene uncharacterized LOC124901324 Neighboring gene runt related transcription factor 2 polyalanine expansion region Neighboring gene NANOG hESC enhancer GRCh37_chr6:45413685-45414186 Neighboring gene Sharpr-MPRA regulatory region 695 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr6:45487956-45488510 Neighboring gene Sharpr-MPRA regulatory region 12811 Neighboring gene RUNX2 antisense RNA 1 Neighboring gene U6 spliceosomal RNA

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. Novel RUNX2 frameshift mutations in Chinese patients with cleidocranial dysplasia. Huang Y, et al. Eur J Oral Sci, 2013 Jun. PMID 23659235
  2. Runx-2 gene expression is associated with age-related changes of bone mineral density in the healthy young-adult population. Zanatta M, et al. J Bone Miner Metab, 2012 Nov. PMID 22903460
  3. The cancer-related transcription factor Runx2 modulates cell proliferation in human osteosarcoma cell lines. Lucero CM, et al. J Cell Physiol, 2013 Apr. PMID 22949168, Free PMC Article
  4. Lipopolysaccharide extracted from Porphyromonas gingivalis induces DNA hypermethylation of runt-related transcription factor 2 in human periodontal fibroblasts. Uehara O, et al. J Microbiol Immunol Infect, 2014 Jun. PMID 23010540
  5. Overexpression of runt-related transcription factor-2 is associated with advanced tumor progression and poor prognosis in epithelial ovarian cancer. Li W, et al. J Biomed Biotechnol, 2012. PMID 23093845, Free PMC Article

See all (641) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.
    Title: Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.
  2. Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.
    Title: Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.
  3. Hypomethylation of the RUNX2 Gene Is a New Potential Biomarker of Primary Osteoporosis in Men and Women.
    Title: Hypomethylation of the RUNX2 Gene Is a New Potential Biomarker of Primary Osteoporosis in Men and Women.
  4. FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
    Title: FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
  5. Polymorphisms in the Runx2 and osteocalcin genes affect BMD in postmenopausal women: a systematic review and meta-analysis.
    Title: Polymorphisms in the Runx2 and osteocalcin genes affect BMD in postmenopausal women: a systematic review and meta-analysis.
  6. METTL3 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells through IGF2BP1-Mediated Regulation of Runx2 Stability.
    Title: METTL3 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells through IGF2BP1-Mediated Regulation of Runx2 Stability.
  7. A synthetic, closed-looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis.
    Title: A synthetic, closed-looped gene circuit for the autonomous regulation of RUNX2 activity during chondrogenesis.
  8. Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.
    Title: Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.
  9. Scopolamine regulates the osteogenic differentiation of human periodontal ligament stem cells through lactylation modification of RUNX2 protein.
    Title: Scopolamine regulates the osteogenic differentiation of human periodontal ligament stem cells through lactylation modification of RUNX2 protein.
  10. RUNX2 prompts triple negative breast cancer drug resistance through TGF-beta pathway regulating breast cancer stem cells.
    Title: RUNX2 prompts triple negative breast cancer drug resistance through TGF-β pathway regulating breast cancer stem cells.
Submit: New GeneRIF Correction See all GeneRIFs (536)

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of periodontal pathogen colonization.
EBI GWAS Catalog
Many sequence variants affecting diversity of adult human height.
EBI GWAS Catalog
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

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

Products Interactant Other Gene Complex Source Pubs Description

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 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 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
  
enables DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
  
enables DNA-binding transcription factor binding IEA
Inferred from Electronic Annotation
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables bHLH transcription factor binding IEA
Inferred from Electronic Annotation
more info
  
enables chromatin DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables chromatin binding IEA
Inferred from Electronic Annotation
more info
  
enables cis-regulatory region sequence-specific DNA 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 
enables sequence-specific double-stranded DNA binding IEA
Inferred from Electronic Annotation
more info
  
enables transcription cis-regulatory region binding IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in BMP signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in BMP signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in SMAD protein signal transduction IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in cell differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell population proliferation IEA
Inferred from Electronic Annotation
more info
  
involved_in cell surface receptor protein serine/threonine kinase signaling pathway IEA
Inferred from Electronic Annotation
more info
  
involved_in chondrocyte differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in gene expression IEA
Inferred from Electronic Annotation
more info
  
involved_in hemopoiesis IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ligamentous ossification IEA
Inferred from Electronic Annotation
more info
  
involved_in negative regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in negative regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in neuron differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ossification IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in ossification TAS
Traceable Author Statement
more info
 PubMed 
involved_in osteoblast differentiation IEA
Inferred from Electronic Annotation
more info
  
involved_in osteoblast differentiation IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in osteoblast differentiation IGI
Inferred from Genetic Interaction
more info
 PubMed 
involved_in osteoblast differentiation TAS
Traceable Author Statement
more info
 PubMed 
involved_in positive regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of osteoblast differentiation 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 IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
  
involved_in regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of transcription by RNA polymerase II IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in response to sodium phosphate IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
located_in chromatin IEA
Inferred from Electronic Annotation
more info
  
located_in chromatin ISA
Inferred from Sequence Alignment
more info
  
located_in chromatin ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in cytoplasm ISS
Inferred from Sequence or Structural Similarity
more info
  
located_in cytosol IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm TAS
Traceable Author Statement
more info
  
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleus IDA
Inferred from Direct Assay
more info
 PubMed 
located_in nucleus IEA
Inferred from Electronic Annotation
more info
  
part_of transcription regulator complex IEA
Inferred from Electronic Annotation
more info
  
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

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
    O14614, O14615, O95181, 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
    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
    Consensus CDS
    CCDS4913.1
    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: GCF_000001405.40-RS_2025_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000006.12 Reference GRCh38.p14 Primary Assembly

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

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060930.1 Alternate T2T-CHM13v2.0

    Range
    45163134..45385899
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q13950.2 GenPept UniProtKB/Swiss-Prot:Q13950

Gene LinkOut

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