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

Gene ID: 1482, updated on 4-Oct-2020

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
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

Genomic context

See NKX2-5 in Genome Data Viewer
Location:
5q35.1
Exon count:
3
Annotation release Status Assembly Chr Location
109.20200815 current GRCh38.p13 (GCF_000001405.39) 5 NC_000005.10 (173232109..173235321, 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 VISTA enhancer hs2185 Neighboring gene uncharacterized LOC105377731 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 with or without atrioventricular conduction defects
MedGen: C3276096 OMIM: 108900 GeneReviews: Not available
Compare labs
Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
GeneReviews: Not available
Conotruncal heart malformations
MedGen: C1857586 OMIM: 217095 GeneReviews: Not available
Compare labs
Genome-wide association study of PR interval.
GeneReviews: Not available
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
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders.
GeneReviews: Not available
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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
DNA-binding transcription activator activity, RNA polymerase II-specific IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription activator activity, RNA polymerase II-specific IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
contributes_to DNA-binding transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
DNA-binding transcription factor activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
DNA-binding transcription factor activity, RNA polymerase II-specific ISA
Inferred from Sequence Alignment
more info
 
DNA-binding transcription factor activity, RNA polymerase II-specific ISM
Inferred from Sequence Model
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
RNA polymerase II proximal promoter sequence-specific DNA binding ISS
Inferred from Sequence or Structural Similarity
more info
PubMed 
chromatin binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
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 double-stranded DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor binding IPI
Inferred from Physical Interaction
more info
PubMed 
transcription regulatory region sequence-specific DNA binding IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
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
 
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 IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
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 by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
negative regulation of transcription by RNA polymerase II 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 by RNA polymerase II IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of transcription by RNA polymerase II IGI
Inferred from Genetic Interaction
more info
PubMed 
positive regulation of transcription by RNA polymerase II IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription by RNA polymerase II 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 
regulation of transcription by RNA polymerase II IBA
Inferred from Biological aspect of Ancestor
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 
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
 
nuclear chromatin ISA
Inferred from Sequence Alignment
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 
protein-DNA complex IDA
Inferred from Direct Assay
more info
PubMed 
protein-containing complex IDA
Inferred from Direct Assay
more info
PubMed 
transcription factor 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)

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)

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/Swiss-Prot
    P52952
    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
    P52952
    UniProtKB/TrEMBL
    A0A0S2Z383
    Related
    ENSP00000327758.4, ENST00000329198.5
    Conserved Domains (1) summary
    pfam00046
    Location:145194
    Homeobox; Homeobox domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20200815

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000005.10 Reference GRCh38.p13 Primary Assembly

    Range
    173232109..173235321 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017009071.2XP_016864560.1  homeobox protein Nkx-2.5 isoform X1

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