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

Gene ID: 1482, updated on 19-Apr-2015
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
See NKX2-5 in MapViewer
Location:
5q34
Exon count:
2
Annotation release Status Assembly Chr Location
107 current GRCh38.p2 (GCF_000001405.28) 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/adenovirus E1B 19kDa interacting protein 1 Neighboring gene ribosomal protein L7a pseudogene 33 Neighboring gene uncharacterized LOC105377731 Neighboring gene RNA, 5S ribosomal pseudogene 200

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.
  • 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...
  • 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 core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription IMP
Inferred from Mutant Phenotype
more info
PubMed 
RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II transcription cofactor activity IEA
Inferred from Electronic Annotation
more info
 
RNA polymerase II transcription factor binding transcription factor activity involved in positive regulation of transcription 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 
sequence-specific DNA binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to sequence-specific DNA binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
sequence-specific DNA binding transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
serum response element binding ISS
Inferred from Sequence or Structural Similarity
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 
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 
positive regulation of voltage-gated calcium channel activity 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 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
homeobox protein Nkx-2.5
NK2 transcription factor related, locus 5
cardiac-specific homeobox 1
homeobox protein CSX
homeobox protein NK-2 homolog E
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
  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
  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
    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 107

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

Reference GRCh38.p2 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p2 Primary Assembly

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

Alternate CHM1_1.1

Genomic

  1. NC_018916.2 Alternate CHM1_1.1

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