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

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: mouse all
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Genomic context

Location:: 5q35.1

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (173232109..173235206, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (173772181..173775278, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (172659112..172662209, complement)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

A Novel Splicing Mutation c.335-1 G > A in the Cardiac Transcription Factor NKX2-5 Leads to Familial Atrial Septal Defect Through miR-19 and PYK2.
Title: A Novel Splicing Mutation c.335-1 G &gt; A in the Cardiac Transcription Factor NKX2-5 Leads to Familial Atrial Septal Defect Through miR-19 and PYK2.
Mutational Assessment in NKX2-5 and ACTC1 Genes in Patients with Congenital Cardiac Septal Defect (CCSD) from Ethnic Kashmiri Population.
Title: Mutational Assessment in NKX2-5 and ACTC1 Genes in Patients with Congenital Cardiac Septal Defect (CCSD) from Ethnic Kashmiri Population.
NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis.
Title: NKX2-5 Variant in Two Siblings with Thyroid Hemiagenesis.
Functional analysis of novel genetic variants of NKX2-5 associated with nonsyndromic congenital heart disease.
Title: Functional analysis of novel genetic variants of NKX2-5 associated with nonsyndromic congenital heart disease.
lncENST Suppress the Warburg Effect Regulating the Tumor Progress by the Nkx2-5/ErbB2 Axis in Hepatocellular Carcinoma.
Title: lncENST Suppress the Warburg Effect Regulating the Tumor Progress by the Nkx2-5/ErbB2 Axis in Hepatocellular Carcinoma.
An update on genetic variants of the NKX2-5.
Title: An update on genetic variants of the NKX2-5.
Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.
Title: Association between congenital heart disease and NKX2.5 gene polymorphisms: systematic review and meta-analysis.
Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.
Title: Association of Maternal Diabetes Mellitus and Polymorphisms of the NKX2.5 Gene in Children with Congenital Heart Disease: A Single Centre-Based Case-Control Study.
Identification of FOXH1 mutations in patients with sporadic conotruncal heart defect.
Title: Identification of FOXH1 mutations in patients with sporadic conotruncal heart defect.
Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.
Title: Crystal Structures of Ternary Complexes of MEF2 and NKX2-5 Bound to DNA Reveal a Disease Related Protein-Protein Interaction Interface.

Submit: New GeneRIF Correction See all GeneRIFs (160)

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

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 EBI GWAS CatalogPubMed
Genome-wide association study of PR interval. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

Homologs of the NKX2-5 gene: The NKX2-5 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 449 organisms have orthologs with human gene NKX2-5
Orthologs

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	PubMed
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	PubMed
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 ventricle formation	IEA Inferred from Electronic Annotation more info
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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 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 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	PubMed
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 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
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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

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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)

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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

5107..8204

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_671

mRNA and Protein(s)

NM_001166175.2 → NP_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
NM_001166176.2 → NP_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
NM_004387.4 → NP_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

E9PBU6, P52952

UniProtKB/TrEMBL

A0A0S2Z383

Related

ENSP00000327758.4, ENST00000329198.5

Conserved Domains (1) summary

pfam00046
Location:145 → 194

Homeobox; Homeobox domain