Human Gene NKX2-5 (ENST00000329198.5_7) from GENCODE V47lift37
  Description: NK2 homeobox 5, transcript variant 1 (from RefSeq NM_004387.4)
Gencode Transcript: ENST00000329198.5_7
Gencode Gene: ENSG00000183072.10_11
Transcript (Including UTRs)
   Position: hg19 chr5:172,659,112-172,662,209 Size: 3,098 Total Exon Count: 2 Strand: -
Coding Region
   Position: hg19 chr5:172,659,572-172,662,086 Size: 2,515 Coding Exon Count: 2 

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Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:172,659,112-172,662,209)mRNA (may differ from genome)Protein (324 aa)
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UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: NKX25_HUMAN
DESCRIPTION: RecName: Full=Homeobox protein Nkx-2.5; AltName: Full=Cardiac-specific homeobox; AltName: Full=Homeobox protein CSX; AltName: Full=Homeobox protein NK-2 homolog E;
FUNCTION: Implicated in commitment to and/or differentiation of the myocardial lineage. Acts as a transcriptional activator of ANF in cooperation with GATA4 (By similarity).
SUBUNIT: Interacts with HIPK1 and HIPK2, but not HIPK3. Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts with FBLIM1 (By similarity).
INTERACTION: Q99593-1:TBX5; NbExp=6; IntAct=EBI-936601, EBI-304423;
SUBCELLULAR LOCATION: Nucleus (Probable).
TISSUE SPECIFICITY: Expressed only in the heart.
DISEASE: Defects in NKX2-5 are the cause of atrial septal defect type 7 with or without atrioventricular conduction defects (ASD7) [MIM:108900]. A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria, and atrioventricular conduction defects in some cases.
DISEASE: Defects in NKX2-5 are a cause of tetralogy of Fallot (TOF) [MIM:187500]. TOF is a congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. This condition results in a blue baby at birth due to inadequate oxygenation. Surgical correction is emergent.
DISEASE: Defects in NKX2-5 are a cause of conotruncal heart malformations (CTHM) [MIM:217095]. CTMH is a group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle.
DISEASE: Defects in NKX2-5 are the cause of congenital hypothyroidism non-goitrous type 5 (CHNG5) [MIM:225250]. CHNG5 is a non-autoimmune condition characterized by resistance to thyroid- stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG5 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland.
DISEASE: Defects in NKX2-5 are a cause of ventricular septal defect type 3 (VSD3) [MIM:614432]. VSD3 is a common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger's syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death.
DISEASE: Defects in NKX2-5 are a cause of hypoplastic left heart syndrome type 2 (HLHS2) [MIM:614435]. HLHS2 is a syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged.
SIMILARITY: Belongs to the NK-2 homeobox family.
SIMILARITY: Contains 1 homeobox DNA-binding domain.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NKX25ID42958ch5q35.html";
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NKX2-5";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: NKX2-5
Diseases sorted by gene-association score: atrial septal defect 7, with or without av conduction defects* (1650), tetralogy of fallot* (1384), ventricular septal defect 3* (1329), hypothyroidism, congenital nongoitrous, 5* (1300), hypoplastic left heart syndrome 2* (629), conotruncal heart malformations* (518), patent foramen ovale* (382), heart disease* (327), asplenia, isolated congenital* (247), thyroid ectopia* (247), athyreosis* (202), familial bicuspid aortic valve* (175), familial atrial fibrillation* (103), hypoplastic left heart syndrome* (71), ventricular septal defect (55), atrial heart septal defect (28), heart septal defect (27), atrioventricular block (23), deletion 5q35* (18), ebstein anomaly (17), hypothyroidism (17), hypertrophic pyloric stenosis (17), pyloric stenosis (16), transposition of the great arteries (14), familial progressive cardiac conduction defect* (12), holt-oram syndrome (12), congenital hypothyroidism (10), atrioventricular septal defect (7), arrhythmogenic right ventricular dysplasia 5 (7), wolff-parkinson-white syndrome (6), ovarian endodermal sinus tumor (6), ovarian primitive germ cell tumor (6), tricuspid atresia (5), tricuspid valve disease (5), char syndrome (5), chromosome 17q11.2 deletion syndrome, 1.4-mb (5), cardiomyopathy, dilated, 1e (4), dilated cardiomyopathy (1)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 72.95 RPKM in Heart - Left Ventricle
Total median expression: 161.13 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -62.60123-0.509 Picture PostScript Text
3' UTR -175.90460-0.382 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017970 - Homeobox_CS
IPR020479 - Homeobox_metazoa
IPR001356 - Homeodomain
IPR009057 - Homeodomain-like

Pfam Domains:
PF00046 - Homeodomain

SCOP Domains:
46689 - Homeodomain-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3RKQ - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P52952
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGDEnsembl   
      
      

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001104 RNA polymerase II transcription cofactor activity
GO:0001190 transcriptional activator activity, RNA polymerase II transcription factor binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003682 chromatin binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0005515 protein binding
GO:0008134 transcription factor binding
GO:0010736 serum response element binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001570 vasculogenesis
GO:0001947 heart looping
GO:0003007 heart morphogenesis
GO:0003148 outflow tract septum morphogenesis
GO:0003151 outflow tract morphogenesis
GO:0003161 cardiac conduction system development
GO:0003162 atrioventricular node development
GO:0003166 bundle of His development
GO:0003168 Purkinje myocyte differentiation
GO:0003208 cardiac ventricle morphogenesis
GO:0003211 cardiac ventricle formation
GO:0003221 right ventricular cardiac muscle tissue morphogenesis
GO:0003222 ventricular trabecula myocardium morphogenesis
GO:0003278 apoptotic process involved in heart morphogenesis
GO:0003285 septum secundum development
GO:0003342 proepicardium development
GO:0003350 pulmonary myocardium development
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006366 transcription from RNA polymerase II promoter
GO:0007275 multicellular organism development
GO:0007507 heart development
GO:0007512 adult heart development
GO:0008284 positive regulation of cell proliferation
GO:0010628 positive regulation of gene expression
GO:0010667 negative regulation of cardiac muscle cell apoptotic process
GO:0010735 positive regulation of transcription via serum response element binding
GO:0010765 positive regulation of sodium ion transport
GO:0010832 negative regulation of myotube differentiation
GO:0030097 hemopoiesis
GO:0030154 cell differentiation
GO:0030509 BMP signaling pathway
GO:0030878 thyroid gland development
GO:0035050 embryonic heart tube development
GO:0043066 negative regulation of apoptotic process
GO:0045214 sarcomere organization
GO:0045666 positive regulation of neuron differentiation
GO:0045823 positive regulation of heart contraction
GO:0045892 negative regulation of transcription, DNA-templated
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0048536 spleen development
GO:0048738 cardiac muscle tissue development
GO:0051891 positive regulation of cardioblast differentiation
GO:0055005 ventricular cardiac myofibril assembly
GO:0055007 cardiac muscle cell differentiation
GO:0055008 cardiac muscle tissue morphogenesis
GO:0055014 atrial cardiac muscle cell development
GO:0055015 ventricular cardiac muscle cell development
GO:0055117 regulation of cardiac muscle contraction
GO:0060037 pharyngeal system development
GO:0060038 cardiac muscle cell proliferation
GO:0060043 regulation of cardiac muscle cell proliferation
GO:0060047 heart contraction
GO:0060048 cardiac muscle contraction
GO:0060070 canonical Wnt signaling pathway
GO:0060261 positive regulation of transcription initiation from RNA polymerase II promoter
GO:0060347 heart trabecula formation
GO:0060412 ventricular septum morphogenesis
GO:0060413 atrial septum morphogenesis
GO:0060928 atrioventricular node cell development
GO:0060929 atrioventricular node cell fate commitment
GO:0060971 embryonic heart tube left/right pattern formation
GO:0072358 cardiovascular system development
GO:0090090 negative regulation of canonical Wnt signaling pathway
GO:1903779 regulation of cardiac conduction

Cellular Component:
GO:0005634 nucleus
GO:0005667 transcription factor complex
GO:0005737 cytoplasm
GO:0032991 macromolecular complex
GO:0032993 protein-DNA complex
GO:0090575 RNA polymerase II transcription factor complex


-  Descriptions from all associated GenBank mRNAs
  BC025711 - Homo sapiens NK2 transcription factor related, locus 5 (Drosophila), mRNA (cDNA clone MGC:34495 IMAGE:5225103), complete cds.
JD563211 - Sequence 544235 from Patent EP1572962.
U34962 - Human transcription factor HCSX (hCsx) mRNA, complete cds.
JD195698 - Sequence 176722 from Patent EP1572962.
JD408498 - Sequence 389522 from Patent EP1572962.
JD384202 - Sequence 365226 from Patent EP1572962.
JD452254 - Sequence 433278 from Patent EP1572962.
JD532656 - Sequence 513680 from Patent EP1572962.
JD396356 - Sequence 377380 from Patent EP1572962.
JD126069 - Sequence 107093 from Patent EP1572962.
AK290615 - Homo sapiens cDNA FLJ76261 complete cds, highly similar to Homo sapiens NK2 transcription factor related, locus 5 (Drosophila) (NKX2-5), mRNA.
JD052592 - Sequence 33616 from Patent EP1572962.
JD542019 - Sequence 523043 from Patent EP1572962.
DQ893313 - Synthetic construct clone IMAGE:100005943; FLH196050.01X; RZPDo839C08154D NK2 transcription factor related, locus 5 (Drosophila) (NKX2-5) gene, encodes complete protein.
AB021133 - Homo sapiens Nkx-2.5 mRNA, complete cds.
KJ896668 - Synthetic construct Homo sapiens clone ccsbBroadEn_06062 NKX2-5 gene, encodes complete protein.
DQ894104 - Synthetic construct Homo sapiens clone IMAGE:100008564; FLH167757.01L; RZPDo839E1289D NK2 transcription factor related, locus 5 (Drosophila) (NKX2-5) gene, encodes complete protein.
DQ896627 - Synthetic construct Homo sapiens clone IMAGE:100011087; FLH196046.01L; RZPDo839C08153D NK2 transcription factor related, locus 5 (Drosophila) (NKX2-5) gene, encodes complete protein.
KU178001 - Homo sapiens NK2 transcription factor related locus 5 isoform 1 (NKX2-5) mRNA, partial cds.
KU178002 - Homo sapiens NK2 transcription factor related locus 5 isoform 2 (NKX2-5) mRNA, complete cds.
AB464641 - Synthetic construct DNA, clone: pF1KB8950, Homo sapiens NKX2-5 gene for NK2 transcription factor related, locus 5, without stop codon, in Flexi system.
AK309495 - Homo sapiens cDNA, FLJ99536.
AK297844 - Homo sapiens cDNA FLJ52202 complete cds, highly similar to Homeobox protein Nkx-2.5.
AK307249 - Homo sapiens cDNA, FLJ97197.
AK307218 - Homo sapiens cDNA, FLJ97166.
AK307247 - Homo sapiens cDNA, FLJ97195.
LF212701 - JP 2014500723-A/20204: Polycomb-Associated Non-Coding RNAs.
CU693024 - Synthetic construct Homo sapiens gateway clone IMAGE:100016706 5' read NKX2-5 mRNA.
JD365148 - Sequence 346172 from Patent EP1572962.
JD159580 - Sequence 140604 from Patent EP1572962.
JD549000 - Sequence 530024 from Patent EP1572962.
MA448278 - JP 2018138019-A/20204: Polycomb-Associated Non-Coding RNAs.

-  Biochemical and Signaling Pathways
  BioCarta from NCI Cancer Genome Anatomy Project
h_nfatPathway - NFAT and Hypertrophy of the heart (Transcription in the broken heart)
h_hopPathway - Hop Pathway in Cardiac Development
h_alkPathway - ALK in cardiac myocytes

-  Other Names for This Gene
  Alternate Gene Symbols: A8K3K0, B4DNB6, CSX, E9PBU6, ENST00000329198.1, ENST00000329198.2, ENST00000329198.3, ENST00000329198.4, NKX2.5, NKX25_HUMAN, NKX2E, NM_004387, P52952, uc317srg.1, uc317srg.2
UCSC ID: ENST00000329198.5_7
RefSeq Accession: NM_004387.4
Protein: P52952 (aka NKX25_HUMAN or NK25_HUMAN)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.