Nkx2-5 NK2 homeobox 5 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Nkx2-5provided by MGI
Official Full Name: NK2 homeobox 5provided by MGI
Primary source: MGI:MGI:97350
See related: Ensembl:ENSMUSG00000015579 AllianceGenome:MGI:97350
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Csx; Nkx2.5; tinman; Nkx-2.5
Summary: Enables several functions, including DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II cis-regulatory region sequence-specific DNA binding activity; and protein homodimerization activity. Involved in several processes, including cardiac muscle tissue development; positive regulation of transcription by RNA polymerase II; and regulation of heart contraction. Acts upstream of or within several processes, including circulatory system development; hematopoietic or lymphoid organ development; and regulation of transcription by RNA polymerase II. Located in cytoplasm and nucleus. Part of transcription regulator complex. Is expressed in several structures, including alimentary system; brain; branchial arch; heart; and hemolymphoid system. Used to study atrial heart septal defect 7; congenital heart disease; hypoplastic left heart syndrome; and tetralogy of Fallot. Human ortholog(s) of this gene implicated in aortic valve disease 2; atrioventricular block; congenital heart disease (multiple); and congenital nongoitrous hypothyroidism 5. Orthologous to human NKX2-5 (NK2 homeobox 5). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Biased expression in heart adult (RPKM 27.8), spleen adult (RPKM 10.5) and 1 other tissue See more
Orthologs: human all
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Genomic context

Location:: 17 A3.3; 17 13.6 cM

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	17	NC_000083.7 (27057638..27063962, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	17	NC_000083.6 (26838664..26844988, complement)

Chromosome 17 - NC_000083.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

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Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation.
Title: Smad4 regulates the nuclear translocation of Nkx2-5 in cardiac differentiation.
Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf.
Title: Second heart field-specific expression of Nkx2-5 requires promoter proximal interaction with Srf.
Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.
Title: Conjugated activation of myocardial-specific transcription of Gja5 by a pair of Nkx2-5-Shox2 co-responsive elements.
Nkx2-5 defines distinct scaffold and recruitment phases during formation of the murine cardiac Purkinje fiber network.
Title: Nkx2-5 defines distinct scaffold and recruitment phases during formation of the murine cardiac Purkinje fiber network.
Nkx2-5 defines a population of pacemaker cells in the transitional zone. Despite Nkx2-5 being dispensable for Sinoatrial node morphogenesis during embryogenesis, its deletion hampers atrial activation by the pacemaker.
Title: Nkx2-5 defines a subpopulation of pacemaker cells and is essential for the physiological function of the sinoatrial node in mice.
Analysis of murine hearts and human induced pluripotent stem cell-derived cardiomyocytes provided histologic and molecular evidence for the NKX2-5 variant's contribution as a genetic modifier.
Title: Oligogenic inheritance of a human heart disease involving a genetic modifier.
Study shows that Nkx2-5 directly represses cardiac Furin expression. Furthermore, Furin is required for the maturation of the cardiac progenitor cells and for the correct formation of the atrioventricular junction where it is expressed. Finally, study shows that this function is, at least in part, mediated by modulation of the BMP pathway.
Title: Furin, a transcriptional target of NKX2-5, has an essential role in heart development and function.
confirms that our models are the first murine genetic models to our knowledge to present all spectra of clinically relevant adult congenital heart disease phenotypes generated by NKX2-5 mutations in patients
Title: Point mutations in murine Nkx2-5 phenocopy human congenital heart disease and induce pathogenic Wnt signaling.
Postnatal cardiac injury reactivates a cardiac-specific Nkx2.5 enhancer element known to specifically mark myocardial progenitor cells during embryonic development.
Title: Reactivation of the Nkx2.5 cardiac enhancer after myocardial infarction does not presage myogenesis.
To determine the lineage contribution of the Nkx2.5+ cardiomyoblasts, we generated a doxycycline suppressible Cre transgenic mouse under the regulation of the Nkx2.5 enhancer and showed that neonatal Nkx2.5+ cardiomyoblasts mature into cardiomyocytes in vivo.
Title: Nkx2.5+ Cardiomyoblasts Contribute to Cardiomyogenesis in the Neonatal Heart.

Submit: New GeneRIF Correction See all GeneRIFs (103)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (26) 1 citation
Endonuclease-mediated (5) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

UniSTS:472868 (e-PCR)
- UniSTS:472868

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:472868

UniSTS:463422 (e-PCR)
- UniSTS:463422

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:463422

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:238143

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:527451

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:516486

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:531346

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:144024

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:144025

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:144026

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:144027

Nkx2-5 (e-PCR), detects polymorphism
- UniSTS:496056

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables DNA binding	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription activator activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	IDA Inferred from Direct Assay more info	PubMed
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
contributes_to DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity	ISO Inferred from Sequence Orthology more info
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	IDA Inferred from Direct Assay more info	PubMed
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	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables RNA polymerase II-specific DNA-binding transcription factor binding	ISO Inferred from Sequence Orthology more info
enables chromatin binding	IDA Inferred from Direct Assay more info	PubMed
enables chromatin binding	ISO Inferred from Sequence Orthology more info
enables histone deacetylase binding	ISO Inferred from Sequence Orthology more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IDA Inferred from Direct Assay more info	PubMed
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info
enables transcription cis-regulatory region binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within Purkinje myocyte differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within adult heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in adult heart development	ISO Inferred from Sequence Orthology more info
acts_upstream_of apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within apoptotic process involved in heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in atrial cardiac muscle cell development	TAS Traceable Author Statement more info	PubMed
involved_in atrial cardiac muscle tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in atrial septum morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within atrioventricular node cell development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within atrioventricular node cell fate commitment	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in atrioventricular node development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within bundle of His development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cardiac conduction system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cardiac conduction system development	ISO Inferred from Sequence Orthology more info
involved_in cardiac muscle cell development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle cell differentiation	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within cardiac muscle cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cardiac muscle cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac muscle tissue development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle tissue morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle tissue morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in cardiac septum morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within cardiac ventricle formation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within cardiac ventricle morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of cell population proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic heart tube development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within embryonic heart tube left/right pattern formation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in endoderm development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of epithelial cell apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within epithelial cell differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of epithelial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within heart contraction	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within heart development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within heart development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart looping	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in heart morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within heart trabecula formation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within hemopoiesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within multicellular organism development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of cardiac muscle cell apoptotic process	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of epithelial cell apoptotic process	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of myotube differentiation	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in negative regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within outflow tract morphogenesis	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within outflow tract morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in outflow tract septum morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within pharyngeal system development	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of cardioblast differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of epithelial cell proliferation	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of heart contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of neuron differentiation	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of sodium ion transport	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in positive regulation of transcription initiation by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within proepicardium development	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within pulmonary myocardium development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of DNA-templated transcription	ISO Inferred from Sequence Orthology more info
involved_in regulation of cardiac conduction	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within regulation of cardiac muscle cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of cardiac muscle contraction	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in right ventricular cardiac muscle tissue morphogenesis	ISO Inferred from Sequence Orthology more info
involved_in septum secundum development	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within spleen development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in spleen development	ISO Inferred from Sequence Orthology more info
involved_in spleen development	TAS Traceable Author Statement more info	PubMed
involved_in thyroid gland development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in thyroid gland development	ISO Inferred from Sequence Orthology more info
involved_in tongue development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of transcription by RNA polymerase II	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within vasculogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventricular cardiac muscle cell development	TAS Traceable Author Statement more info	PubMed
acts_upstream_of_or_within ventricular cardiac myofibril assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in ventricular septum morphogenesis	ISO Inferred from Sequence Orthology more info
acts_upstream_of_or_within ventricular trabecula myocardium morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
part_of Nkx-2.5 complex	ISO Inferred from Sequence Orthology more info
part_of RNA polymerase II transcription regulator complex	ISO Inferred from Sequence Orthology more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
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	ISO Inferred from Sequence Orthology more info
part_of protein-DNA complex	ISO Inferred from Sequence Orthology more info
part_of protein-containing complex	ISO Inferred from Sequence Orthology more info
part_of transcription regulator complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: homeobox protein Nkx-2.5

Names: Drosophila NK2 transcription factor related, locus 5; NK2 transcription factor related, locus 5; cardiac-specific homeobox; homeobox protein CSX; homeobox protein NK-2 homolog E

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.