RUNX2 runt related transcription factor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: RUNX2provided by HGNC
Official Full Name: runt related transcription factor 2provided by HGNC
Primary source: HGNC:HGNC:10472
See related: Ensembl:ENSG00000124813 MIM:600211; Vega:OTTHUMG00000014774
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: mouse all

Genomic context

Location:: 6p21.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	6	NC_000006.12 (45328317..45551082)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	6	NC_000006.11 (45296054..45518819)

Chromosome 6 - NC_000006.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Knockdown of RUNX2 significantly inhibited TE-1 and EC-109 cell viability, repressed TE-1 cell migration and invasion, and increased TE-1 cell apoptosis and were associated with the activation of the PI3K/AKT and ERK pathways.
Title: RUNX2 Plays An Oncogenic Role in Esophageal Carcinoma by Activating the PI3K/AKT and ERK Signaling Pathways.
Results show that RUNX2 gene silencing increased gemcitabine (GEM) sensitivity of p53mutated pancreatic cancer (PaCa) MiaPaCa2 spheres suggesting that RUNX2 is involved in PaCa-GEM resistance in presence of mutated p53.
Title: Impact of RUNX2 gene silencing on the gemcitabine sensitivity of p53‑mutated pancreatic cancer MiaPaCa‑2 spheres.
Runx2 overexpression effectively decreased TNF-alpha-induced Bax and cleaved caspase-3 expression levels
Title: Runt-related transcription factor 2 (RUNX2) inhibits apoptosis of intestinal epithelial cells in Crohn's disease.
RUNX2 is one of the promising molecular targets for the treatment of the patients with pancreatic cancer regardless of their p53 status[review]
Title: Impact of RUNX2 on drug-resistant human pancreatic cancer cells with p53 mutations.
we identified a novel missense mutation of RUNX2 in 2 patients by Whole exome sequencing and showed potential correlations between facial phenotypes and missense mutations in Runt domain through a mini-meta analysis.
Title: Identification of a novel mutation of RUNX2 in a family with supernumerary teeth and craniofacial dysplasia by whole-exome sequencing: A case report and literature review.
Mutant Runx2 regulates amelogenesis and osteogenesis through a miR-185-5p-Dlx2 axis.
Title: Mutant Runx2 regulates amelogenesis and osteogenesis through a miR-185-5p-Dlx2 axis.
Results show that RUNX2 is highly expressed in bladder cancer tissues and are negatively correlated with miR-154 levels. This is likely through miR-154 binding the 3'-UTR of RUNX2 mRNA, promoting its degradation.
Title: MicroRNA-154 as a prognostic factor in bladder cancer inhibits cellular malignancy by targeting RSF1 and RUNX2.
Results identified a novel mutation besides the previously known in one patient with cleidocranial dysplasia (CCD). G462X mutation in exon 8 is located in the C-terminus of proline/serine/threonine-rich (PST) domain. It might reduce the Runx2 transacting activity, lower the protein stability, downgrade the expression of bone marker genes, and eventually diminish osteoblast differentiation in CCD patients.
Title: A novel RUNX2 mutation in exon 8, G462X, in a patient with Cleidocranial Dysplasia.
Findings reveal a novel mechanism that Runx2 is transcriptionally regulated by HSP90 via the AKT/GSK-3beta/beta-catenin signaling pathway, and by which leads to apoptosis of osteosarcoma cells.
Title: Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK-3β/β-catenin signaling.
Increased baseline gene expressions of RUNX2, p21 and caspase 3 in the peripheral blood might predict better responses to methotrexate therapy.
Title: Increased baseline RUNX2, caspase 3 and p21 gene expressions in the peripheral blood of disease-modifying anti-rheumatic drug-naïve rheumatoid arthritis patients are associated with improved clinical response to methotrexate therapy.

Submit: New GeneRIF Correction See all GeneRIFs (381)

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
Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly MedGen: C1834969 OMIM: 156510 GeneReviews: Not available	Compare labs

NHGRI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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 BioSystems

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Androgen receptor signaling pathway, organism-specific biosystem (from WikiPathways)
Androgen receptor signaling pathway, organism-specific biosystemAndrogens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biolo...
Bone Morphogenic Protein (BMP) Signalling and Regulation, organism-specific biosystem (from WikiPathways)
Bone Morphogenic Protein (BMP) Signalling and Regulation, organism-specific biosystem"BMP signals are mediated by type I and II BMP receptors and their downstream molecules Smad1, 5 and 8. Phosphorylated Smad1, 5 and 8 proteins form a complex with Smad4 and then are translocated into...
Development of pulmonary dendritic cells and macrophage subsets, organism-specific biosystem (from WikiPathways)
Development of pulmonary dendritic cells and macrophage subsets, organism-specific biosystemDevelopment of pulmonary DC and macrophage subsets. This model of pulmonary DC and macrophage subset differentiation in mice summarizes recent findings suggesting early lineage commitment of cDCs in ...
Endochondral Ossification, organism-specific biosystem (from WikiPathways)
Endochondral Ossification, organism-specific biosystemEndochondral ossification is the process by which the embryonic cartilaginous model of most bones contributes to longitudinal growth and is gradually replaced by bone. During endochondral ossificatio...
FGF signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
FGF signaling pathway, organism-specific biosystem
FGF signaling pathway
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
Hypothesized Pathways in Pathogenesis of Cardiovascular Disease, organism-specific biosystem (from WikiPathways)
Hypothesized Pathways in Pathogenesis of Cardiovascular Disease, organism-specific biosystemThe pathways hypothesized to be involved in cardiovascular diseases begin with LTBPs and Fibrillins activating a TGFBR complex. The complex can begin the canonical TGFB pathway involving SMAD protei...
Interleukin-11 Signaling Pathway, organism-specific biosystem (from WikiPathways)
Interleukin-11 Signaling Pathway, organism-specific biosystemIL-11 is a multifunctional cytokine that belongs to the gp130 family. It was first isolated from a primate bone marrow derived cell line, PU-34 for its ability to stimulate the proliferation of a pla...
Notch-mediated HES/HEY network, organism-specific biosystem (from Pathway Interaction Database)
Notch-mediated HES/HEY network, organism-specific biosystem
Notch-mediated HES/HEY network
Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
Regulation of nuclear SMAD2/3 signaling
Regulation of retinoblastoma protein, organism-specific biosystem (from Pathway Interaction Database)
Regulation of retinoblastoma protein, organism-specific biosystem
Regulation of retinoblastoma protein
TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition, organism-specific biosystem (from WikiPathways)
TGF-B Signaling in Thyroid Cells for Epithelial-Mesenchymal Transition, organism-specific biosystemThis pathway is based on the Figure 7 of "Cadherin 6 Is a New RUNX2 Target in TGF-? Signalling Pathway" (see bibliography). TGF-B is a target gene in thyroid cells in the causation of cancer. When TG...
TGF-beta Receptor Signaling, organism-specific biosystem (from WikiPathways)
TGF-beta Receptor Signaling, organism-specific biosystemThe Transforming growth factor beta (TGFβ) signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiat...
TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...
Transcriptional misregulation in cancer, organism-specific biosystem (from KEGG)
Transcriptional misregulation in cancer, organism-specific biosystem
Transcriptional misregulation in cancer
Transcriptional misregulation in cancer, conserved biosystem (from KEGG)
Transcriptional misregulation in cancer, conserved biosystem
Transcriptional misregulation in cancer
YAP1- and WWTR1 (TAZ)-stimulated gene expression, organism-specific biosystem (from REACTOME)
YAP1- and WWTR1 (TAZ)-stimulated gene expression, organism-specific biosystemYAP1 and WWTR1 (TAZ) are transcriptional co-activators, both homologues of the Drosophila Yorkie protein. They both interact with members of the TEAD family of transcription factors, and WWTR1 intera...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC150810P1 (e-PCR)
- UniSTS:271104

WI-17995 (e-PCR)
- UniSTS:72450

PMC156282P1 (e-PCR)
- UniSTS:271389

SHGC-106818 (e-PCR)
- UniSTS:170058

RH37568 (e-PCR)
- UniSTS:45390

RH16435 (e-PCR)
- UniSTS:48722

RH77889 (e-PCR)
- UniSTS:74326

Runx2 (e-PCR), detects polymorphism
- UniSTS:280406

D6S1460 (e-PCR)
- UniSTS:27991

NoName (e-PCR)
- UniSTS:480861

AF029259 (e-PCR)
- UniSTS:32376

stbA90G6T7 (e-PCR)
- UniSTS:181386

SHGC-56693 (e-PCR)
- UniSTS:23471

SHGC-56456 (e-PCR)
- UniSTS:80071

RH120734 (e-PCR)
- UniSTS:132816

SHGC-146198 (e-PCR)
- UniSTS:175074

SHGC-106694 (e-PCR)
- UniSTS:169980

Homology

Homologs of the RUNX2 gene: The RUNX2 gene is conserved in chimpanzee, Rhesus monkey, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 212 organisms have orthologs with human gene RUNX2
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IEA Inferred from Electronic Annotation more info
DNA-binding transcription factor activity	NAS Non-traceable Author Statement more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	ISA Inferred from Sequence Alignment more info
DNA-binding transcription factor activity, RNA polymerase II-specific	ISM Inferred from Sequence Model more info	PubMed
DNA-binding transcription factor activity, RNA polymerase II-specific	NAS Non-traceable Author Statement more info	PubMed
RNA polymerase II proximal promoter sequence-specific DNA binding	IEA Inferred from Electronic Annotation more info
bHLH transcription factor binding	IEA Inferred from Electronic Annotation more info
chromatin binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IEA Inferred from Electronic Annotation more info
proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific	IEA Inferred from Electronic Annotation more info
repressing transcription factor binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
BMP signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
T cell differentiation	IEA Inferred from Electronic Annotation more info
cell maturation	IEA Inferred from Electronic Annotation more info
cellular response to BMP stimulus	ISS Inferred from Sequence or Structural Similarity more info
chondrocyte development	IEA Inferred from Electronic Annotation more info
embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic forelimb morphogenesis	IEA Inferred from Electronic Annotation more info
endochondral ossification	IEA Inferred from Electronic Annotation more info
hemopoiesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
negative regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
negative regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
ossification	TAS Traceable Author Statement more info	PubMed
osteoblast development	IEA Inferred from Electronic Annotation more info
osteoblast differentiation	IEP Inferred from Expression Pattern more info	PubMed
osteoblast differentiation	TAS Traceable Author Statement more info	PubMed
osteoblast fate commitment	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
positive regulation of osteoblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
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
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
regulation of fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
regulation of odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
stem cell differentiation	IEA Inferred from Electronic Annotation more info
transcription initiation from RNA polymerase II promoter	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info
nuclear chromatin	ISS Inferred from Sequence or Structural Similarity more info
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
transcription factor 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

NCBI Reference Sequences (RefSeq)

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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

NG_008020.1 RefSeqGene

Range

5001..227766

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001015051.3 → 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)
NM_001024630.3 → 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) represents the longest transcript and 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, OTTHUMP00000016533, ENST00000647337.1, OTTHUMT00000040754

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)
NM_001278478.1 → 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)

AL161907, BC108919, DR005078

Consensus CDS

CCDS64443.1

UniProtKB/TrEMBL

A0A0D9SEN7, Q32MY8

Related

ENSP00000485863.1, OTTHUMP00000279213, ENST00000625924.1, OTTHUMT00000484119

Conserved Domains (3) summary

pfam00853
Location:95 → 216

Runt; Runt domain

pfam08504
Location:394 → 485

RunxI; Runx inhibition domain

cl25496
Location:252 → 445

Herpes_BLLF1; Herpes virus major outer envelope glycoprotein (BLLF1)

RNA

NR_103532.1 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, AW469546, BX108677

Related

ENST00000483243.5
NR_103533.1 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 Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000006.12 Reference GRCh38.p12 Primary Assembly

Range

45328317..45551082

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

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.