NKX2-6 (NK2 homeobox 6)

Gene

• Entrez ID: 137814
• Gene name: NK2 homeobox 6
• Gene symbol: NKX2-6
• Synonyms (NCBI Gene): CSX2, CTHM, NKX2F, NKX4-2
• Chromosome: 8
• Chromosome location: 8p21.2
• Summary: This gene encodes a homeobox-containing protein that belongs to the NK-2 homeobox family. This protein is a vertebrate homolog of Drosophila homeobox-containing protein called `tinman`, which has been shown to be essential for development of the heart-lik

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000785	Component	Chromatin	ISA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IBA
GO:0000978	Function	RNA polymerase II cis-regulatory region sequence-specific DNA binding	IMP	15649947
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IBA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	IEA
GO:0000981	Function	DNA-binding transcription factor activity, RNA polymerase II-specific	ISA
GO:0001228	Function	DNA-binding transcription activator activity, RNA polymerase II-specific	IMP	15649947
GO:0003677	Function	DNA binding	IEA
GO:0003700	Function	DNA-binding transcription factor activity	IDA	15649947
GO:0005634	Component	Nucleus	IBA
GO:0005634	Component	Nucleus	IC	15649947
GO:0005634	Component	Nucleus	IEA
GO:0006355	Process	Regulation of DNA-templated transcription	IEA
GO:0006357	Process	Regulation of transcription by RNA polymerase II	IBA
GO:0006915	Process	Apoptotic process	IEA
GO:0007507	Process	Heart development	IEA
GO:0008283	Process	Cell population proliferation	IEA
GO:0008284	Process	Positive regulation of cell population proliferation	ISS
GO:0021854	Process	Hypothalamus development	IEA
GO:0021854	Process	Hypothalamus development	ISS
GO:0030154	Process	Cell differentiation	IBA
GO:0030154	Process	Cell differentiation	ISS
GO:0030855	Process	Epithelial cell differentiation	IEA
GO:0035050	Process	Embryonic heart tube development	IEA
GO:0035050	Process	Embryonic heart tube development	IMP	15649947
GO:0035050	Process	Embryonic heart tube development	ISS
GO:0043066	Process	Negative regulation of apoptotic process	ISS
GO:0043586	Process	Tongue development	IEA
GO:0043586	Process	Tongue development	ISS
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IMP	15649947
GO:0048565	Process	Digestive tract development	IEA
GO:0048565	Process	Digestive tract development	ISS
GO:0050673	Process	Epithelial cell proliferation	IEA
GO:0050679	Process	Positive regulation of epithelial cell proliferation	IEA
GO:0055014	Process	Atrial cardiac muscle cell development	IEA
GO:0055014	Process	Atrial cardiac muscle cell development	ISS
GO:0055015	Process	Ventricular cardiac muscle cell development	IEA
GO:0055015	Process	Ventricular cardiac muscle cell development	ISS
GO:0060037	Process	Pharyngeal system development	IEA
GO:0060037	Process	Pharyngeal system development	ISS
GO:0060039	Process	Pericardium development	IEA
GO:0060039	Process	Pericardium development	ISS
GO:1904019	Process	Epithelial cell apoptotic process	IEA
GO:1904036	Process	Negative regulation of epithelial cell apoptotic process	IEA

Other IDs

• MIM: 611770
• HGNC: 32940
• e!Ensembl: ENSG00000180053

Protein

• UniProt ID: A6NCS4
• Protein name: Homeobox protein Nkx-2.6 (Homeobox protein NK-2 homolog F)
• Protein function: Acts as a transcriptional activator (PubMed:15649947). In conjunction with NKX2-5, may play a role in both pharyngeal and cardiac embryonic development.
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00046	Homeodomain	133 → 189	Homeodomain	Domain

• Sequence:

  MLLSPVTSTPFSVKDILRLERERSCPAASPHPRVRKSPENFQYLRMDAEPRGSEVHNAGG
  GGGDRKLDGSEPPGGPCEAVLEMDAERMGEPQPGLNAASPLGGGTRVPERGVGNSGDSVR
  GGRSEQPKARQRRKPRVLFSQAQVLALERRFKQQRYLSAPEREHLASALQLTSTQVKIWF
  QNRRYKCKRQRQDKSLELAGHPLTPRRVAVPVLVRDGKPCLGPGPGAPAFPSPYSAAVSP
  YSCYGGYSGAPYGAGYGTCYAGAPSGPAPHTPLASAGFGHGGQNATPQGHLAATLQGVRA
  W

• Sequence length: 301

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Cerebral palsy	Likely pathogenic	rs757292066	RCV001796581	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Conotruncal heart malformations	Likely pathogenic	rs757292066, rs587777422, rs267606914, rs2486482243	RCV001780395 RCV000119845 RCV004585978 RCV003135428	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Persistent truncus arteriosus	Likely pathogenic	rs267606914	RCV000000827	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
ALZHEIMER DISEASE	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL 1	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 10	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 11	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 12	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 13	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 14	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 15	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 2	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 3	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 4	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 5	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 6	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 7	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 8	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ATRIAL FIBRILLATION, FAMILIAL, 9	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
BREAST CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
COLORECTAL CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONGENITAL HEART DISEASE	—	ClinGen, Disgenet, GWAS catalog ClinGen, Disgenet, GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CONOTRUNCAL CARDIAC DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
GOUT	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
HEREDITARY ATRIAL FIBRILLATION	—	Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
METABOLIC SYNDROME	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NKX2-6-related disorder	Uncertain significance; Benign; Likely benign; Conflicting classifications of pathogenicity	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CANCER	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PROSTATE CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TETRALOGY OF FALLOT	—	CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet CTD, Disgenet, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
TYPE 2 DIABETES MELLITUS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VASCULAR DEMENTIA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
VENTRICULAR SEPTAL DEFECTS	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Aortic coarctation	Aortic Coarctation	HPO_DG			★☆☆☆☆ Found in Text Mining only
Atrial Fibrillation	Atrial Fibrillation	BEFREE	25319568		★☆☆☆☆ Found in Text Mining only
ATRIAL FIBRILLATION, FAMILIAL, 1 (disorder)	Atrial Fibrillation	ORPHANET_DG	25319568		★☆☆☆☆ Found in Text Mining only
Atrioventricular Septal Defect	Atrioventricular septal defect	HPO_DG			★☆☆☆☆ Found in Text Mining only
Brachydactyly	Brachydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Clinodactyly of the 5th finger	Camptodactyly of fingers	HPO_DG			★☆☆☆☆ Found in Text Mining only
Congenital absence of thymus	Aplasia of the thymus	BEFREE	24421281		★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	GENOMICS_ENGLAND_DG	15649947		★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	UNIPROT_DG	15649947, 24421281, 25195019, 25380965		★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
CONOTRUNCAL HEART MALFORMATIONS (disorder)	Conotruncal heart defect	CTD_human_DG			★☆☆☆☆ Found in Text Mining only
Coronary heart disease	Coronary Heart Disease	BEFREE	27808268		★☆☆☆☆ Found in Text Mining only
Cryptorchidism	Cryptorchidism	HPO_DG			★☆☆☆☆ Found in Text Mining only
DiGeorge Syndrome	DiGeorge Syndrome	BEFREE	24421281		★☆☆☆☆ Found in Text Mining only
Double Outlet Right Ventricle	Double Outlet Right Ventricle	HPO_DG			★☆☆☆☆ Found in Text Mining only
Exophthalmos	Proptosis	HPO_DG			★☆☆☆☆ Found in Text Mining only
Familial atrial fibrillation	Atrial Fibrillation	Orphanet			★☆☆☆☆ Found in Text Mining only
Long narrow head	Dolichocephaly	HPO_DG			★☆☆☆☆ Found in Text Mining only
POLYDACTYLY, POSTAXIAL	Polydactyly	HPO_DG			★☆☆☆☆ Found in Text Mining only
Shprintzen-Goldberg syndrome	Shprintzen-Goldberg Syndrome	BEFREE	24421281		★☆☆☆☆ Found in Text Mining only
Tetralogy of Fallot	Tetralogy of Fallot	ORPHANET_DG	25195019		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tetralogy of Fallot	Tetralogy of Fallot	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Tetralogy of Fallot	Tetralogy of Fallot	HPO_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Transposition of Great Vessels	Transposition Of Great Vessels	HPO_DG			★☆☆☆☆ Found in Text Mining only
Truncus Arteriosus, Persistent	Persistent truncus arteriosus	ORPHANET_DG	15649947, 25195019		★☆☆☆☆ Found in Text Mining only
Truncus Arteriosus, Persistent	Persistent truncus arteriosus	GENOMICS_ENGLAND_DG			★☆☆☆☆ Found in Text Mining only
Truncus Arteriosus, Persistent	Persistent truncus arteriosus	CLINVAR_DG			★☆☆☆☆ Found in Text Mining only
Truncus Arteriosus, Persistent	Persistent truncus arteriosus	HPO_DG			★☆☆☆☆ Found in Text Mining only