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

Summary

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: mouse all
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Genomic context

Location:: 6p21.1

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	6	NC_000006.12 (45328330..45551082)
RS_2024_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_000006.12 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: 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

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.
Title: Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.
Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.
Title: Exploring the transcriptional cooperation between RUNX2 and its associated elncRNA RAIN.
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.
FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
Title: FOXO1 regulates RUNX2 ubiquitination through SMURF2 in calcific aortic valve disease.
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.
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.
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.
Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.
Title: Keratocystoma: A Distinctive Salivary Gland Neoplasm Characterized by RUNX2 Rearrangements.
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.
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 (539)

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-maxillary hypoplasia-brachydacty syndrome MedGen: C3549874 OMIM: 156510 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

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

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

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

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
acts_upstream_of_or_within T cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of bone mineralization	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within cell maturation	IEA Inferred from Electronic Annotation more info
acts_upstream_of 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
acts_upstream_of_or_within chondrocyte development	IEA Inferred from Electronic Annotation more info
involved_in chondrocyte differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic cranial skeleton morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within embryonic forelimb morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within endochondral ossification	IEA Inferred from Electronic Annotation more info
acts_upstream_of epithelial cell proliferation	IEA Inferred from Electronic Annotation 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
acts_upstream_of_or_within negative regulation of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
involved_in ossification	IBA Inferred from Biological aspect of Ancestor more info
involved_in ossification	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within osteoblast development	IEA Inferred from Electronic Annotation more info
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
acts_upstream_of_or_within osteoblast fate commitment	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of cell population proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of chondrocyte differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within positive regulation of osteoblast differentiation	IEA Inferred from Electronic Annotation more info
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
acts_upstream_of_or_within positive regulation of stem cell proliferation	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within 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	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
acts_upstream_of_or_within regulation of fibroblast growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of gene expression	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of ossification	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of osteoblast differentiation	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
involved_in response to sodium phosphate	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within skeletal system development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within skeletal system morphogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of smoothened signaling pathway	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within stem cell differentiation	IEA Inferred from Electronic Annotation more info
acts_upstream_of stem cell proliferation	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
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

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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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_008020.2 RefSeqGene

Range

5014..227766

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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)
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)
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
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

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
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