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    NKX2-5 NK2 homeobox 5 [ Homo sapiens (human) ]

    Gene ID: 1482, updated on 12-Jun-2016
    Official Symbol
    NKX2-5provided by HGNC
    Official Full Name
    NK2 homeobox 5provided by HGNC
    Primary source
    HGNC:HGNC:2488
    See related
    Ensembl:ENSG00000183072 HPRD:02787; MIM:600584; Vega:OTTHUMG00000130522
    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
    CSX; CSX1; VSD3; CHNG5; HLHS2; NKX2E; NKX2.5; NKX4-1
    Summary
    This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]
    Orthologs
    Location:
    5q34
    Exon count:
    3
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 5 NC_000005.10 (173232104..173235312, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (172659107..172662315, complement)

    Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene BCL2 interacting protein 1 Neighboring gene ribosomal protein L7a pseudogene 33 Neighboring gene uncharacterized LOC105377731 Neighboring gene RNA, 5S ribosomal pseudogene 200 Neighboring gene stanniocalcin 2

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Atrial septal defect 7 with or without atrioventricular conduction defects
    MedGen: C1862388 OMIM: 108900 GeneReviews: Not available
    Compare labs
    Conotruncal heart malformations
    MedGen: C1857586 OMIM: 217095 GeneReviews: Not available
    Compare labs
    Hypoplastic left heart syndrome 2
    MedGen: C3280795 OMIM: 614435 GeneReviews: Not available
    Compare labs
    Hypothyroidism, congenital, nongoitrous, 5
    MedGen: C2673630 OMIM: 225250 GeneReviews: Not available
    Compare labs
    Tetralogy of Fallot
    MedGen: C0039685 OMIM: 187500 GeneReviews: Not available
    Compare labs
    Ventricular septal defect 3
    MedGen: C3280785 OMIM: 614432 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2011-12-15)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2011-12-15)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

    Description
    Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
    NHGRI GWA Catalog
    Genome-wide association study of PR interval.
    NHGRI GWA Catalog
    Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
    NHGRI GWA Catalog
    • Cardiac Progenitor Differentiation, organism-specific biosystem (from WikiPathways)
      Cardiac Progenitor Differentiation, organism-specific biosystemFactors involved in the induction of cardiac differentiation in vitro and in vivo. This model was based on the below two review articles.
    • Cardiac conduction, organism-specific biosystem (from REACTOME)
      Cardiac conduction, organism-specific biosystemThe normal sequence of contraction of atria and ventricles of the heart require activation of groups of cardiac cells. The mechanism must elicit rapid changes in heart rate and respond to changes in ...
    • 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...
    • Heart Development, organism-specific biosystem (from WikiPathways)
      Heart Development, organism-specific biosystemThis pathway has been largely adapted from an article by Deepak Srivastava, Cell. 2006 Sep 22;126(6):1037-48. In this pathway are known transcription factors, miRNAs and regulatory proteins that impa...
    • Muscle contraction, organism-specific biosystem (from REACTOME)
      Muscle contraction, organism-specific biosystemIn this module, the processes by which calcium binding triggers actin - myosin interactions and force generation in smooth and striated muscle tissues are annotated.
    • Physiological factors, organism-specific biosystem (from REACTOME)
      Physiological factors, organism-specific biosystemCardiovascular homeostasis can be regulated by natriuretic peptides (Pandey 2014).
    • 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
    • SRF and miRs in Smooth Muscle Differentiation and Proliferation, organism-specific biosystem (from WikiPathways)
      SRF and miRs in Smooth Muscle Differentiation and Proliferation, organism-specific biosystemSmooth muscle cells exhibit a unique plasticity, in that they are able to oscillate between proliferative and more quiescent, differentiated states. These two states are determined, in part, by a net...
    • 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...
    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Clone Names

    • FLJ52202, FLJ97166, FLJ97195, FLJ97197, FLJ99536

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    RNA polymerase II core promoter proximal region sequence-specific DNA binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    RNA polymerase II transcription cofactor activity IEA
    Inferred from Electronic Annotation
    more info
     
    chromatin binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    protein heterodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    protein homodimerization activity IEA
    Inferred from Electronic Annotation
    more info
     
    sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    serum response element binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding IEA
    Inferred from Electronic Annotation
    more info
     
    transcription factor activity, sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to transcription factor activity, sequence-specific DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor activity, sequence-specific DNA binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcription factor binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    transcription regulatory region DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcriptional activator activity, RNA polymerase II transcription factor binding IEA
    Inferred from Electronic Annotation
    more info
     
    transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    BMP signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    Purkinje myocyte differentiation IEA
    Inferred from Electronic Annotation
    more info
     
    adult heart development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    apoptotic process involved in heart morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    atrial cardiac muscle cell development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    atrial septum morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    atrioventricular node cell development IEA
    Inferred from Electronic Annotation
    more info
     
    atrioventricular node cell fate commitment IEA
    Inferred from Electronic Annotation
    more info
     
    bundle of His development IEA
    Inferred from Electronic Annotation
    more info
     
    canonical Wnt signaling pathway IEA
    Inferred from Electronic Annotation
    more info
     
    cardiac conduction system development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cardiac muscle cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    cardiac muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    cardiac muscle contraction IEA
    Inferred from Electronic Annotation
    more info
     
    cardiac muscle tissue morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    cardiac ventricle formation IEA
    Inferred from Electronic Annotation
    more info
     
    cell differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    embryonic heart tube development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    embryonic heart tube left/right pattern formation IEA
    Inferred from Electronic Annotation
    more info
     
    heart looping ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    heart morphogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    heart trabecula formation IEA
    Inferred from Electronic Annotation
    more info
     
    hemopoiesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    negative regulation of apoptotic process ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    negative regulation of canonical Wnt signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    negative regulation of cardiac muscle cell apoptotic process IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of myotube differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of transcription from RNA polymerase II promoter IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    negative regulation of transcription from RNA polymerase II promoter ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    negative regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    outflow tract septum morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    pharyngeal system development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of cardioblast differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of cell proliferation ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of heart contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    positive regulation of neuron differentiation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of sodium ion transport ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    positive regulation of transcription from RNA polymerase II promoter ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of transcription initiation from RNA polymerase II promoter ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of transcription via serum response element binding ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    positive regulation of transcription, DNA-templated IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of transcription, DNA-templated ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    proepicardium development IEA
    Inferred from Electronic Annotation
    more info
     
    pulmonary myocardium development IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of cardiac conduction ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    regulation of cardiac muscle cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    regulation of cardiac muscle contraction ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    right ventricular cardiac muscle tissue morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    sarcomere organization IEA
    Inferred from Electronic Annotation
    more info
     
    septum secundum development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    spleen development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    spleen development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    thyroid gland development IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    transcription from RNA polymerase II promoter IEA
    Inferred from Electronic Annotation
    more info
     
    vasculogenesis ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    ventricular cardiac muscle cell development ISS
    Inferred from Sequence or Structural Similarity
    more info
    PubMed 
    ventricular cardiac myofibril assembly IEA
    Inferred from Electronic Annotation
    more info
     
    ventricular septum morphogenesis IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    ventricular trabecula myocardium morphogenesis IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    RNA polymerase II transcription factor complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
     
    nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    transcription factor complex IC
    Inferred by Curator
    more info
    PubMed 
    Preferred Names
    homeobox protein Nkx-2.5
    Names
    NK2 transcription factor related locus 5
    NK2 transcription factor related, locus 5
    NKX 2-5
    cardiac-specific homeobox 1
    homeobox protein CSX
    homeobox protein NK-2 homolog E
    homeobox protein NKX 2-5
    tinman paralog

    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_013340.1 RefSeqGene

      Range
      5001..8209
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001166175.1NP_001159647.1  homeobox protein Nkx-2.5 isoform 2

      See identical proteins and their annotated locations for NP_001159647.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (2) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AI609745, AK290615, AK307247, DA559427
      Consensus CDS
      CCDS54950.1
      UniProtKB/Swiss-Prot
      P52952
      UniProtKB/TrEMBL
      A0A0S2Z3K2
      Related
      ENSP00000395378, OTTHUMP00000225425, ENST00000424406, OTTHUMT00000317804
    2. NM_001166176.1NP_001159648.1  homeobox protein Nkx-2.5 isoform 3

      See identical proteins and their annotated locations for NP_001159648.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has a distinct C-terminus and is shorter than isoform 1.
      Source sequence(s)
      AI609745, AK290615, AK297844, DA559427
      Consensus CDS
      CCDS54949.1
      UniProtKB/Swiss-Prot
      P52952
      Related
      ENSP00000427906, OTTHUMP00000225426, ENST00000521848, OTTHUMT00000317805
    3. NM_004387.3NP_004378.1  homeobox protein Nkx-2.5 isoform 1

      See identical proteins and their annotated locations for NP_004378.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the shortest transcript but encodes the longest isoform (1).
      Source sequence(s)
      AI609745, BC025711, DA559427
      Consensus CDS
      CCDS4387.1
      UniProtKB/Swiss-Prot
      P52952
      UniProtKB/TrEMBL
      A0A0S2Z383
      Related
      ENSP00000327758, OTTHUMP00000161080, ENST00000329198, OTTHUMT00000252942
      Conserved Domains (1) summary
      cd00086
      Location:145197
      homeodomain; Homeodomain; DNA binding domains involved in the transcriptional regulation of key eukaryotic developmental processes; may bind to DNA as monomers or as homo- and/or heterodimers, in a sequence-specific manner.

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...

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

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000005.10 Reference GRCh38.p7 Primary Assembly

      Range
      173232104..173235312 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017009071.1XP_016864560.1  

      Related
      ENSP00000429905, OTTHUMP00000225427, ENST00000517440, OTTHUMT00000317803

    Alternate CHM1_1.1

    Genomic

    1. NC_018916.2 Alternate CHM1_1.1

      Range
      172091589..172094797 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)