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Aliases for NKX2-1 Gene

Aliases for NKX2-1 Gene

  • NK2 Homeobox 1 2 3 5
  • Thyroid Transcription Factor 1 2 3 4
  • Thyroid-Specific Enhancer-Binding Protein 3 4
  • Homeobox Protein NK-2 Homolog A 3 4
  • Thyroid Nuclear Factor 1 3 4
  • NKX2A 3 4
  • TITF1 3 4
  • T/EBP 3 4
  • TTF-1 3 4
  • TTF1 3 4
  • Homeobox Protein Nkx-2.1 3
  • NK-2 Homolog A 3
  • Benign Chorea 2
  • NKX2.1 3
  • NMTC1 3
  • NK-2 3
  • TEBP 3
  • BCH 3
  • BHC 3

External Ids for NKX2-1 Gene

Previous HGNC Symbols for NKX2-1 Gene

  • NKX2A
  • BCH
  • TITF1

Previous GeneCards Identifiers for NKX2-1 Gene

  • GC14M036056
  • GC14M036985
  • GC14M017100

Summaries for NKX2-1 Gene

Entrez Gene Summary for NKX2-1 Gene

  • This gene encodes a protein initially identified as a thyroid-specific transcription factor. The encoded protein binds to the thyroglobulin promoter and regulates the expression of thyroid-specific genes but has also been shown to regulate the expression of genes involved in morphogenesis. Mutations and deletions in this gene are associated with benign hereditary chorea, choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress, and may be associated with thyroid cancer. Multiple transcript variants encoding different isoforms have been found for this gene. This gene shares the symbol/alias 'TTF1' with another gene, transcription termination factor 1, which plays a role in ribosomal gene transcription. [provided by RefSeq, Feb 2014]

GeneCards Summary for NKX2-1 Gene

NKX2-1 (NK2 Homeobox 1) is a Protein Coding gene. Diseases associated with NKX2-1 include Choreoathetosis And Congenital Hypothyroidism With Or Without Pulmonary Dysfunction and Chorea, Benign Hereditary. Among its related pathways are Circadian rythm related genes and FOXA2 and FOXA3 transcription factor networks. Gene Ontology (GO) annotations related to this gene include DNA binding transcription factor activity and enzyme binding. An important paralog of this gene is NKX2-4.

UniProtKB/Swiss-Prot for NKX2-1 Gene

  • Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation. Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (By similarity).

Gene Wiki entry for NKX2-1 Gene

Additional gene information for NKX2-1 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for NKX2-1 Gene

Genomics for NKX2-1 Gene

GeneHancer (GH) Regulatory Elements for NKX2-1 Gene

Promoters and enhancers for NKX2-1 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH14I036517 Promoter/Enhancer 1.8 EPDnew Ensembl ENCODE dbSUPER 550.8 +1.9 1916 4.2 ELF3 PKNOX1 INSM2 DMAP1 GLI4 ZNF2 ZNF48 RAD21 RFX5 ZNF335 NKX2-1 NKX2-1-AS1 ENSG00000257520 PAX9 NKX2-8 SFTA3 ENSG00000283098
GH14I036521 Enhancer 0.7 ENCODE dbSUPER 550.8 -0.7 -712 0.1 CTCF SUZ12 CEBPA CEBPB CEBPG EZH2 LOC105370453 NKX2-1 NKX2-1-AS1 ENSG00000283098
GH14I036515 Enhancer 0.9 FANTOM5 ENCODE dbSUPER 19.5 +6.3 6300 0.6 SUZ12 CTBP2 EZH2 SFTA3 NKX2-1 MBIP NKX2-1-AS1 ENSG00000257520 ENSG00000283098
GH14I036508 Enhancer 0.9 FANTOM5 dbSUPER 16.3 +12.8 12771 0.1 ZBTB10 MAZ RNF2 ZNF189 ZNF335 CBX8 GLIS2 ZBTB48 SMARCA4 PATZ1 NKX2-1 SFTA3 MBIP ENSG00000257520 GC14P036424 ENSG00000283098
GH14I036676 Enhancer 0.7 Ensembl ENCODE dbSUPER 10 -155.2 -155214 0.3 SP1 NKX2-8 RPL29P3 NKX2-1 NKX2-1-AS1 SFTA3 LOC105370455 PAX9 ENSG00000258690
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around NKX2-1 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the NKX2-1 gene promoter:

Genomic Locations for NKX2-1 Gene

Genomic Locations for NKX2-1 Gene
chr14:36,516,392-36,521,149
(GRCh38/hg38)
Size:
4,758 bases
Orientation:
Minus strand
chr14:36,985,602-36,990,354
(GRCh37/hg19)

Genomic View for NKX2-1 Gene

Genes around NKX2-1 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NKX2-1 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NKX2-1 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NKX2-1 Gene

Proteins for NKX2-1 Gene

  • Protein details for NKX2-1 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P43699-NKX21_HUMAN
    Recommended name:
    Homeobox protein Nkx-2.1
    Protein Accession:
    P43699
    Secondary Accessions:
    • D3DSA3
    • O14954
    • O14955
    • Q7KZF6
    • Q9BRJ8

    Protein attributes for NKX2-1 Gene

    Size:
    371 amino acids
    Molecular mass:
    38596 Da
    Quaternary structure:
    • Interacts with WWTR1.
    SequenceCaution:
    • Sequence=AAH06221.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305}; Sequence=BAA23527.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

    Alternative splice isoforms for NKX2-1 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NKX2-1 Gene

Post-translational modifications for NKX2-1 Gene

Other Protein References for NKX2-1 Gene

No data available for DME Specific Peptides for NKX2-1 Gene

Domains & Families for NKX2-1 Gene

Gene Families for NKX2-1 Gene

HGNC:
Human Protein Atlas (HPA):
  • Cancer-related genes
  • Disease related genes
  • Predicted intracellular proteins
  • Transcription factors

Protein Domains for NKX2-1 Gene

Suggested Antigen Peptide Sequences for NKX2-1 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

P43699

UniProtKB/Swiss-Prot:

NKX21_HUMAN :
  • Belongs to the NK-2 homeobox family.
Family:
  • Belongs to the NK-2 homeobox family.
genes like me logo Genes that share domains with NKX2-1: view

Function for NKX2-1 Gene

Molecular function for NKX2-1 Gene

UniProtKB/Swiss-Prot Function:
Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor. Crucial in the maintenance of the thyroid differentiation phenotype. May play a role in lung development and surfactant homeostasis. Forms a regulatory loop with GRHL2 that coordinates lung epithelial cell morphogenesis and differentiation. Activates the transcription of GNRHR and plays a role in enhancing the circadian oscillation of its gene expression. Represses the transcription of the circadian transcriptional repressor NR1D1 (By similarity).

Phenotypes From GWAS Catalog for NKX2-1 Gene

Gene Ontology (GO) - Molecular Function for NKX2-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000977 RNA polymerase II regulatory region sequence-specific DNA binding IDA 23143308
GO:0001012 RNA polymerase II regulatory region DNA binding IDA 23143308
GO:0001047 core promoter binding ISS --
GO:0001161 intronic transcription regulatory region sequence-specific DNA binding ISS --
GO:0003677 DNA binding IMP 7635972
genes like me logo Genes that share ontologies with NKX2-1: view
genes like me logo Genes that share phenotypes with NKX2-1: view

Human Phenotype Ontology for NKX2-1 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for NKX2-1 Gene

MGI Knock Outs for NKX2-1:

Animal Model Products

CRISPR Products

Targeted motifs for NKX2-1 Gene
HOMER Transcription Factor Regulatory Elements motif NKX2-1
  • Consensus sequence: RSCACTYRAG Submotif: canonical Cell Type: LungAC GEO ID: GSE43252

Clone Products

No data available for Enzyme Numbers (IUBMB) and Transcription Factor Targets for NKX2-1 Gene

Localization for NKX2-1 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NKX2-1 Gene

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NKX2-1 gene
Compartment Confidence
nucleus 5
extracellular 2
cytoskeleton 2
cytosol 2

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (1)
  • Vesicles (1)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NKX2-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005634 nucleus IEA,IDA 7713914
GO:0005654 nucleoplasm ISS --
GO:0005667 transcription factor complex IEA --
genes like me logo Genes that share ontologies with NKX2-1: view

Pathways & Interactions for NKX2-1 Gene

genes like me logo Genes that share pathways with NKX2-1: view

Pathways by source for NKX2-1 Gene

1 Cell Signaling Technology pathway for NKX2-1 Gene

SIGNOR curated interactions for NKX2-1 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for NKX2-1 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000122 negative regulation of transcription by RNA polymerase II IDA 23143308
GO:0001764 neuron migration IEA --
GO:0006351 transcription, DNA-templated IEA --
GO:0006355 regulation of transcription, DNA-templated IEA --
GO:0006357 regulation of transcription by RNA polymerase II IEA --
genes like me logo Genes that share ontologies with NKX2-1: view

Drugs & Compounds for NKX2-1 Gene

(16) Drugs for NKX2-1 Gene - From: ClinicalTrials and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Protein C Approved Pharma 126
Pulmonary Surfactants Pharma 122
Respiratory System Agents Pharma 5297

(10) Additional Compounds for NKX2-1 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with NKX2-1: view

Transcripts for NKX2-1 Gene

Unigene Clusters for NKX2-1 Gene

NK2 homeobox 1:
Representative Sequences:

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for NKX2-1 Gene

No ASD Table

Relevant External Links for NKX2-1 Gene

GeneLoc Exon Structure for
NKX2-1
ECgene alternative splicing isoforms for
NKX2-1

Expression for NKX2-1 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for NKX2-1 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for NKX2-1 Gene

This gene is overexpressed in Thyroid (x35.6) and Lung (x12.7).

Protein differential expression in normal tissues from HIPED for NKX2-1 Gene

This gene is overexpressed in Fetal heart (69.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, and MOPED for NKX2-1 Gene



Protein tissue co-expression partners for NKX2-1 Gene

SOURCE GeneReport for Unigene cluster for NKX2-1 Gene:

Hs.94367

mRNA Expression by UniProt/SwissProt for NKX2-1 Gene:

P43699-NKX21_HUMAN
Tissue specificity: Thyroid and lung.

Evidence on tissue expression from TISSUES for NKX2-1 Gene

  • Lung(4.8)
  • Thyroid gland(4.8)
  • Nervous system(2.5)
  • Intestine(2.4)
  • Liver(2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for NKX2-1 Gene

Germ Layers:
  • ectoderm
  • endoderm
  • mesoderm
Systems:
  • cardiovascular
  • digestive
  • endocrine
  • immune
  • integumentary
  • nervous
  • reproductive
  • respiratory
  • skeletal muscle
Regions:
Head and neck:
  • brain
  • ear
  • eye
  • head
  • hypothalamus
  • neck
  • pituitary gland
  • thyroid
Thorax:
  • heart
  • lung
Abdomen:
  • intestine
  • large intestine
  • small intestine
Pelvis:
  • uterus
General:
  • blood
  • coagulation system
  • peripheral nerve
  • peripheral nervous system
  • red blood cell
  • skin
genes like me logo Genes that share expression patterns with NKX2-1: view

Orthologs for NKX2-1 Gene

This gene was present in the common ancestor of animals.

Orthologs for NKX2-1 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia NKX2-1 33 34
  • 99.5 (n)
cow
(Bos Taurus)
Mammalia NKX2-1 34
  • 97 (a)
OneToOne
LOC613713 33
  • 94.68 (n)
mouse
(Mus musculus)
Mammalia Nkx2-1 33 16 34
  • 92.63 (n)
rat
(Rattus norvegicus)
Mammalia Nkx2-1 33
  • 92.18 (n)
oppossum
(Monodelphis domestica)
Mammalia NKX2-1 34
  • 84 (a)
OneToOne
chicken
(Gallus gallus)
Aves NKX2-1 33 34
  • 76.58 (n)
lizard
(Anolis carolinensis)
Reptilia NKX2-1 34
  • 73 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia nkx2-1 33
  • 73.22 (n)
African clawed frog
(Xenopus laevis)
Amphibia titf1-A 33
zebrafish
(Danio rerio)
Actinopterygii nkx2.1b 33 34
  • 68.41 (n)
titf1b 33
fruit fly
(Drosophila melanogaster)
Insecta scro 34
  • 34 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea ceh-24 34
  • 32 (a)
OneToMany
sea squirt
(Ciona savignyi)
Ascidiacea CS-TTF1 34
  • 27 (a)
OneToMany
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.14238 33
Species where no ortholog for NKX2-1 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • dog (Canis familiaris)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for NKX2-1 Gene

ENSEMBL:
Gene Tree for NKX2-1 (if available)
TreeFam:
Gene Tree for NKX2-1 (if available)

Paralogs for NKX2-1 Gene

Paralogs for NKX2-1 Gene

(2) SIMAP similar genes for NKX2-1 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with NKX2-1: view

Variants for NKX2-1 Gene

Sequence variations from dbSNP and Humsavar for NKX2-1 Gene

SNP ID Clin Chr 14 pos Variation AA Info Type
rs10139625 benign, Choreoathetosis, hypothyroidism, and neonatal respiratory distress, Benign hereditary chorea 36,517,068(-) A/T 3_prime_UTR_variant
rs137852692 pathogenic, Choreoathetosis, hypothyroidism, and neonatal respiratory distress, Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP) [MIM:610978] 36,517,781(-) C/A coding_sequence_variant, missense_variant
rs137852693 pathogenic, Choreoathetosis, hypothyroidism, and neonatal respiratory distress 36,517,871(-) C/A/G coding_sequence_variant, missense_variant, stop_gained
rs137852694 pathogenic, Benign hereditary chorea 36,517,739(-) G/A coding_sequence_variant, stop_gained
rs140427692 benign, Choreoathetosis, hypothyroidism, and neonatal respiratory distress, Benign hereditary chorea 36,516,986(-) CCCC/CCCCC 3_prime_UTR_variant

Structural Variations from Database of Genomic Variants (DGV) for NKX2-1 Gene

Variant ID Type Subtype PubMed ID
esv23132 CNV loss 19812545
nsv564346 CNV loss 21841781
nsv819045 CNV gain 19587683

Variation tolerance for NKX2-1 Gene

Residual Variation Intolerance Score: 49% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.26; 25.25% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NKX2-1 Gene

Human Gene Mutation Database (HGMD)
NKX2-1
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NKX2-1

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for NKX2-1 Gene

Disorders for NKX2-1 Gene

MalaCards: The human disease database

(87) MalaCards diseases for NKX2-1 Gene - From: HGMD, OMIM, ClinVar, GTR, Orphanet, Swiss-Prot, DISEASES, Novoseek, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

NKX21_HUMAN
  • Chorea, hereditary benign (BHC) [MIM:118700]: A rare autosomal dominant movement disorder, defined by early onset in childhood, a stable or non-progressive course of chorea, and no mental deterioration. Chorea is characterized by involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. {ECO:0000269 PubMed:11971878, ECO:0000269 PubMed:15955952, ECO:0000269 PubMed:24453141, ECO:0000269 PubMed:26723978}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP) [MIM:610978]: An autosomal dominant disorder that manifests in infancy with neurological disturbances, hypothyroidism, and respiratory problems. It is characterized by movement abnormalities beginning with muscular hypotonia followed by the development of chorea, athetosis, dystonia, ataxia, and dysarthria. {ECO:0000269 PubMed:11854318, ECO:0000269 PubMed:11854319, ECO:0000269 PubMed:15289765, ECO:0000269 PubMed:15955952, ECO:0000269 PubMed:24714694}. Note=The disease is caused by mutations affecting the gene represented in this entry.
  • Thyroid cancer, non-medullary, 1 (NMTC1) [MIM:188550]: A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. {ECO:0000269 PubMed:19176457}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for NKX2-1

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with NKX2-1: view

No data available for Genatlas for NKX2-1 Gene

Publications for NKX2-1 Gene

  1. A germline mutation (A339V) in thyroid transcription factor-1 (TITF-1/NKX2.1) in patients with multinodular goiter and papillary thyroid carcinoma. (PMID: 19176457) Ngan ES … Garcia-Barceló MM (Journal of the National Cancer Institute 2009) 3 4 44 58
  2. Gene structure and expression of human thyroid transcription factor-1 in respiratory epithelial cells. (PMID: 7713914) Ikeda K … Whitsett JA (The Journal of biological chemistry 1995) 3 4 22 58
  3. A novel mutation of NKX2-1 affecting 2 generations with hypothyroidism and choreoathetosis: part of the spectrum of brain-thyroid-lung syndrome. (PMID: 24453141) Williamson S … Goudie D (Journal of child neurology 2014) 3 4 58
  4. A large-scale candidate gene association study of age at menarche and age at natural menopause. (PMID: 20734064) He C … Hunter DJ (Human genetics 2010) 3 44 58
  5. Utility of thyroid transcription factor-1 and CDX-2 in determining the primary site of metastatic adenocarcinomas in serous effusions. (PMID: 20518411) Kim JH … Choi C (Acta cytologica 2010) 3 22 58

Products for NKX2-1 Gene

Sources for NKX2-1 Gene

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