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

Summary

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Official Symbol: NKX2-5provided by HGNC
Official Full Name: NK2 homeobox 5provided by HGNC
Primary source: 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]

Genomic context

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Location :: 5q34

Sequence :: Chromosome: 5; NC_000005.9 (172659107..172662315, complement)

See NKX2-5 in Epigenomics, MapViewer

Chromosome 5 - NC_000005.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

Bibliography

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GeneRIFs: Gene References Into Functions What's a GeneRIF?

Absence of mutations in PAX8, NKX2.5, and TSH receptor genes demonstrate the rare genetic etiology in sporadic cases of thyroid dysgenesis.
Title: Absence of mutations in PAX8, NKX2.5, and TSH receptor genes in patients with thyroid dysgenesis.
The responsiveness of WP to exercise, the long-term stability of the WP rhythm, and the mild asymptomatic structural features expand the phenotypic presentation of diseases related to mutations in NKX2.5.
Title: Wenckebach periodicity at rest that normalizes with tachycardia in a family with a NKX2.5 mutation.
Variants within the cardiac enhancer in the NKX2-5 gene is not associated with ventricular septal defects.
Title: Genetic analysis of an enhancer of the NKX2-5 gene in ventricular septal defects.
The high resolution crystal structure of NKX2.5 protein provides a detailed picture of protein and DNA interactions, which allows to predict DNA binding of mutants identified in human patients.
Title: Crystal structure of the human NKX2.5 homeodomain in complex with DNA target.
Rescue of Nkx2.5 phenotype establishes a model for ensuring electrophysiological function within the adult heart.
Title: Epistatic rescue of Nkx2.5 adult cardiac conduction disease phenotypes by prospero-related homeobox protein 1 and HDAC3.
Genetic data suggest that a heterozygous missense mutation (P236H) in NKX2-5 is associated with isolated congenital asplenia (ICA).
Title: Congenital asplenia in mice and humans with mutations in a Pbx/Nkx2-5/p15 module.
In addition to reporting two novel mutations of NKX2-5 in congenital heart defects, we describe families where multiple individual mutations seem to have an additive effect over the pathogenesis.
Title: Combined mutation screening of NKX2-5, GATA4, and TBX5 in congenital heart disease: multiple heterozygosity and novel mutations.
Three novel heterozygous missense NKX2-5 mutations, p.Q22K, p.R36S, and p.E54K, are responsible for congenital heart disease in cohort of Chinese patients.
Title: Novel NKX2-5 mutations responsible for congenital heart disease.
Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
Title: Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.
Data reveal highly complex regulatory mechanisms driven by SUMOylation to modulate Nkx2-5 activity.
Title: Complex SUMO-1 regulation of cardiac transcription factor Nkx2-5.

Submit: New GeneRIF Correction See all (74)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Common variants near MBNL1 and NKX2-5 are associated with infantile hypertrophic pyloric stenosis.

Genome-wide association study of PR interval.

Interactions

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Products	Interactant	Other Gene	Source	Pubs	Description
NP_004378.1	NP_002043.2	GATA4	BIND	PubMed	Nkx2.5 interacts with GATA4.
NP_004378.1	NP_004964.2	JARID2	BIND	PubMed	JMJ interacts with Nkx2.5.
P52952	O94983	CAMTA2	HPRD	PubMed
P52952	P68400	CSNK2A1	HPRD	PubMed
P52952	O75593	FOXH1	HPRD	PubMed
P52952	P43694	GATA4	HPRD	PubMed
P52952	Q86Z02	HIPK1	HPRD	PubMed
P52952	Q9H2X6	HIPK2	HPRD	PubMed
P52952	Q92833	JARID2	HPRD	PubMed
P52952	P11831	SRF	HPRD	PubMed
P52952	Q13207	TBX2	HPRD	PubMed
P52952	Q99593	TBX5	HPRD	PubMed
BioGRID:107864	BioGRID:116744	CAMTA2	BioGRID	PubMed	Reconstituted Complex
BioGRID:107864	BioGRID:108896	GATA4	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107864	BioGRID:109315	HDAC1	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107864	BioGRID:109623	ID1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107864	BioGRID:109624	ID2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107864	BioGRID:109625	ID3	BioGRID	PubMed	Affinity Capture-Western
BioGRID:107864	BioGRID:109923	JARID2	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107864	BioGRID:113246	KDM6A	BioGRID	PubMed	Affinity Capture-Western; Two-hybrid
BioGRID:107864	BioGRID:110264	SMAD4	BioGRID	PubMed	Affinity Capture-RNA
BioGRID:107864	BioGRID:112773	TBX5	BioGRID	PubMed	Affinity Capture-Western; Reconstituted Complex
BioGRID:107864	BioGRID:112943	TLE1	BioGRID	PubMed	Two-hybrid

Pathways from BioSystems

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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.
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...

General gene information

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Genotypes

See NKX2-5 SNP Geneview Report
See NKX2-5 SNP Genotype Report
See NKX2-5 SNP Variation Viewer Report

Homology

Homologs of the NKX2-5 gene: The NKX2-5 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Map Viewer (Mouse, Rat)
OrthoDB: The Hierarchical Catalog of Eukaryotic Orthologs

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 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 receptor 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	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of apoptotic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
negative regulation of canonical Wnt receptor 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-dependent	ISS Inferred from Sequence or Structural Similarity more info	PubMed
outflow tract septum morphogenesis	IMP Inferred from Mutant Phenotype more info
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-dependent	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of transcription, DNA-dependent	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
sarcomere organization	IEA Inferred from Electronic Annotation more info
septum secundum 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 development	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
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

General protein information

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Preferred Names: homeobox protein Nkx-2.5

Names: homeobox protein Nkx-2.5; tinman paralog; homeobox protein CSX; cardiac-specific homeobox 1; homeobox protein NK-2 homolog E; NK2 transcription factor related, locus 5

NCBI Reference Sequences (RefSeq)

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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

NG_013340.1 RefSeqGene

Range

5001..8209

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

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
NM_001166176.1 → NP_001159648.1 homeobox protein Nkx-2.5 isoform 3

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
NM_004387.3 → NP_004378.1 homeobox protein Nkx-2.5 isoform 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:145 – 197
Blast Score: 173

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 104

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

Reference GRCh37.p10 Primary Assembly

Genomic

NC_000005.9 Reference GRCh37.p10 Primary Assembly

Range

172659107..172662315, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000137.1 Alternate HuRef

Range

167754405..167757613, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate CHM1_1.0

Genomic

NC_018916.1 Alternate CHM1_1.0

Range

172886255..172889464, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	ABBA01044025.1 (46128..49336)	None
genomic	AC008412.8 (40386..43510)	None
genomic	AMYH01015823.1 (99487..102696)	None
genomic	CH471062.2	EAW61404.1
mRNA	AB021133.1	BAA35181.1
mRNA	AI609745.1	None
mRNA	AK290615.1	BAF83304.1
mRNA	AK297844.1	BAG60178.1
mRNA	AK307218.1	None
mRNA	AK307247.1	None
mRNA	AK307249.1	None
mRNA	AK309495.1	None
mRNA	BC025711.1	AAH25711.1
mRNA	DA559427.1	None
mRNA	U34962.1	AAC50470.1
other-genetic	DQ893313.2	ABM84239.1
other-genetic	DQ894104.2	ABM85030.1
other-genetic	DQ896627.2	ABM87626.1