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

Gene ID: 1482, updated on 27-Nov-2024

Summary

Official Symbol
NKX2-5provided by HGNC
Official Full Name
NK2 homeobox 5provided by HGNC
Primary source
HGNC:HGNC:2488
See related
Ensembl:ENSG00000183072 MIM:600584; AllianceGenome:HGNC:2488
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]
Expression
Restricted expression toward heart (RPKM 9.4) See more
Orthologs
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Try the new Transcript table

Genomic context

See NKX2-5 in Genome Data Viewer
Location:
5q35.1
Exon count:
3
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 5 NC_000005.10 (173232109..173235206, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 5 NC_060929.1 (173772181..173775278, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 5 NC_000005.9 (172659112..172662209, complement)

Chromosome 5 - NC_000005.10Genomic Context describing neighboring genes Neighboring gene H3K27ac hESC enhancer GRCh37_chr5:172571727-172572255 Neighboring gene BCL2 interacting protein 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16636 Neighboring gene ReSE screen-validated silencer GRCh37_chr5:172633891-172634070 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:172656189-172656855 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:172659129-172660008 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr5:172660009-172660888 Neighboring gene ribosomal protein L7a pseudogene 33 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:172665705-172666278 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr5:172672012-172672748 Neighboring gene VISTA enhancer hs2185 Neighboring gene uncharacterized LOC105377731 Neighboring gene MPRA-validated peak5581 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 16637 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23652 Neighboring gene uncharacterized LOC124901136 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 23653 Neighboring gene RNA, 5S ribosomal pseudogene 200

Genomic regions, transcripts, and products

Expression

  • 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 Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Atrial septal defect 7
MedGen: C3276096 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 2020-07-22)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated 2020-07-22)

ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
EBI GWAS Catalog
Genome-wide association study of PR interval.
EBI GWAS Catalog
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
EBI GWAS Catalog

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Clone Names

  • FLJ52202, FLJ97166, FLJ97195, FLJ97197, FLJ99536

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables DNA-binding transcription activator activity IDA
Inferred from Direct Assay
more info
PubMed 
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 IMP
Inferred from Mutant Phenotype
more info
PubMed 
contributes_to DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
enables DNA-binding transcription factor activity IMP
Inferred from Mutant Phenotype
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 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 IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
enables RNA polymerase II-specific DNA-binding transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables chromatin binding IDA
Inferred from Direct Assay
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables protein homodimerization activity IEA
Inferred from Electronic Annotation
more info
 
enables sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables sequence-specific double-stranded DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
enables transcription cis-regulatory region binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
involved_in Purkinje myocyte differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in adult heart development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in aortic valve morphogenesis TAS
Traceable Author Statement
more info
PubMed 
involved_in apoptotic process involved in heart morphogenesis IEA
Inferred from Electronic Annotation
more info
 
involved_in atrial cardiac muscle cell development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in atrial cardiac muscle tissue development ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in atrial septum morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in atrioventricular node cell development IEA
Inferred from Electronic Annotation
more info
 
involved_in atrioventricular node cell fate commitment IEA
Inferred from Electronic Annotation
more info
 
involved_in atrioventricular node development ISS
Inferred from Sequence or Structural Similarity
more info
 
acts_upstream_of_or_within bundle of His development ISS
Inferred from Sequence or Structural Similarity
more info
 
acts_upstream_of_or_within cardiac conduction system development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cardiac conduction system development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cardiac muscle cell development ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cardiac muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in cardiac muscle contraction IEA
Inferred from Electronic Annotation
more info
 
involved_in cardiac muscle tissue morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cardiac muscle tissue morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in cardiac septum morphogenesis ISO
Inferred from Sequence Orthology
more info
 
involved_in cardiac ventricle formation IEA
Inferred from Electronic Annotation
more info
 
involved_in cell differentiation IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in cell differentiation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in embryonic heart tube development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in embryonic heart tube left/right pattern formation IEA
Inferred from Electronic Annotation
more info
 
involved_in epithelial cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
involved_in epithelial cell differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in heart development ISO
Inferred from Sequence Orthology
more info
 
involved_in heart looping ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in heart morphogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in heart trabecula formation IEA
Inferred from Electronic Annotation
more info
 
involved_in hemopoiesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in negative regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in negative regulation of apoptotic process ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in negative regulation of canonical Wnt signaling pathway ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in negative regulation of cardiac muscle cell apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of epithelial cell apoptotic process IEA
Inferred from Electronic Annotation
more info
 
involved_in negative regulation of myotube differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in outflow tract septum morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in pharyngeal system development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of DNA-templated transcription ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of cardioblast differentiation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of cell population proliferation ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of epithelial cell proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of gene expression IEA
Inferred from Electronic Annotation
more info
 
involved_in positive regulation of heart contraction ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of neuron differentiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of sodium ion transport ISS
Inferred from Sequence or Structural Similarity
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 
involved_in positive regulation of transcription by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in positive regulation of transcription initiation by RNA polymerase II ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in proepicardium development IEA
Inferred from Electronic Annotation
more info
 
involved_in pulmonary myocardium development IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of DNA-templated transcription IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of cardiac conduction ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in regulation of cardiac muscle cell proliferation IEA
Inferred from Electronic Annotation
more info
 
involved_in regulation of cardiac muscle contraction ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
more info
 
involved_in right ventricular cardiac muscle tissue morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in septum secundum development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in spleen development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in spleen development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in thyroid gland development IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
 
involved_in vasculogenesis ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in ventricular cardiac muscle cell development ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
involved_in ventricular cardiac myofibril assembly IEA
Inferred from Electronic Annotation
more info
 
involved_in ventricular septum morphogenesis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in ventricular trabecula myocardium morphogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
part_of Nkx-2.5 complex IPI
Inferred from Physical Interaction
more info
PubMed 
part_of RNA polymerase II transcription regulator complex IDA
Inferred from Direct Assay
more info
PubMed 
located_in chromatin ISA
Inferred from Sequence Alignment
more info
 
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
 
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 
part_of protein-DNA complex IDA
Inferred from Direct Assay
more info
PubMed 
part_of protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
part_of transcription regulator complex IC
Inferred by Curator
more info
PubMed 

General protein information

Preferred Names
homeobox protein Nkx-2.5
Names
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 homolog
tinman paralog

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

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
    5107..8204
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_671

mRNA and Protein(s)

  1. NM_001166175.2NP_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
    Consensus CDS
    CCDS54950.1
    UniProtKB/TrEMBL
    A0A0S2Z3K2
    Related
    ENSP00000395378.2, ENST00000424406.2
  2. NM_001166176.2NP_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
    Consensus CDS
    CCDS54949.1
    UniProtKB/Swiss-Prot
    P52952
    Related
    ENSP00000427906.1, ENST00000521848.1
  3. NM_004387.4NP_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)
    BC025711, DA559427
    Consensus CDS
    CCDS4387.1
    UniProtKB/Swiss-Prot
    A8K3K0, B4DNB6, E9PBU6, P52952
    UniProtKB/TrEMBL
    A0A0S2Z383
    Related
    ENSP00000327758.4, ENST00000329198.5
    Conserved Domains (1) summary
    pfam00046
    Location:145194
    Homeobox; Homeobox domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p14 Primary Assembly

    Range
    173232109..173235206 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009071.3XP_016864560.1  homeobox protein Nkx-2.5 isoform X1

    UniProtKB/TrEMBL
    E5RH49
    Related
    ENSP00000429905.1, ENST00000517440.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060929.1 Alternate T2T-CHM13v2.0

    Range
    173772181..173775278 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054351717.1XP_054207692.1  homeobox protein Nkx-2.5 isoform X1

    UniProtKB/TrEMBL
    E5RH49