NKX2-1 NK2 homeobox 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: NKX2-1provided by HGNC
Official Full Name: NK2 homeobox 1provided by HGNC
Primary source: HGNC:HGNC:11825
See related: Ensembl:ENSG00000136352 MIM:600635; AllianceGenome:HGNC:11825
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: BCH; BHC; NK-2; TEBP; TTF1; NKX2A; NMTC1; T/EBP; TITF1; TTF-1; NKX2.1
Summary: 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]
Annotation information: Note: TTF1 (GeneID 7270) and NKX2-1 (GeneID 7080) loci share the TTF1 symbol/alias in common. TTF1 is a widely used alternative name for thyroid transcription factor 1 (NKX2-1) conflicting with the official symbol for transcription termination factor, RNA polymerase I (TTF1). [13 Feb 2013]
Expression: Biased expression in lung (RPKM 35.0) and thyroid (RPKM 29.1) See more
Orthologs: mouse all
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Genomic context

Location:: 14q13.3

Exon count:: 3

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (36516397..36520232, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (30705671..30709516, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (36985602..36989437, complement)

Chromosome 14 - NC_000014.9 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?

Functional characterization of two novel NKX2-1 frameshift variants that cause pulmonary surfactant dysfunction.
Title: Functional characterization of two novel NKX2-1 frameshift variants that cause pulmonary surfactant dysfunction.
Transcription factor NKX2-1 drives serine and glycine synthesis addiction in cancer.
Title: Transcription factor NKX2-1 drives serine and glycine synthesis addiction in cancer.
Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma.
Title: Genotype-phenotype mapping of a patient-derived lung cancer organoid biobank identifies NKX2-1-defined Wnt dependency in lung adenocarcinoma.
Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1.
Title: Expression landscapes in non-small cell lung cancer shaped by the thyroid transcription factor 1.
Exploring the values, preferences, and information needs of patients with NKX2-1-related disorders: A qualitative study protocol.
Title: Exploring the values, preferences, and information needs of patients with NKX2-1-related disorders: A qualitative study protocol.
Relationship between brain metastasis and thyroid transcription factor 1.
Title: Relationship between brain metastasis and thyroid transcription factor 1.
Transcriptional Circuitry of NKX2-1 and SOX1 Defines an Unrecognized Lineage Subtype of Small-Cell Lung Cancer.
Title: Transcriptional Circuitry of NKX2-1 and SOX1 Defines an Unrecognized Lineage Subtype of Small-Cell Lung Cancer.
Optimized thyroid transcription factor-1 core promoter-driven microRNA-7 expression effectively inhibits the growth of human non-small-cell lung cancer cells.
Title: Optimized thyroid transcription factor-1 core promoter-driven microRNA-7 expression effectively inhibits the growth of human non-small-cell lung cancer cells.
FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma.
Title: FoxA1 and FoxA2 control growth and cellular identity in NKX2-1-positive lung adenocarcinoma.
Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH).
Title: Mutational and bioinformatics analysis of the NKX2.1 gene in a cohort of Iranian pediatric patients with congenital hypothyroidism (CH).

Submit: New GeneRIF Correction See all GeneRIFs (286)

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
Benign hereditary chorea MedGen: C0393584 OMIM: 118700 GeneReviews: NKX2-1-Related Disorders	Compare labs
Brain-lung-thyroid syndrome MedGen: C1970269 OMIM: 610978 GeneReviews: NKX2-1-Related Disorders	Compare labs
Thyroid cancer, nonmedullary, 1 MedGen: C4721429 OMIM: 188550 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome wide association study of age at menarche in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of ten loci associated with height highlights new biological pathways in human growth. 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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Markers

RH79171 (e-PCR)
- UniSTS:28443

PMC152810P1 (e-PCR)
- UniSTS:271243

Titf1 (e-PCR), detects polymorphism
- UniSTS:464797

SHGC-35528 (e-PCR)
- UniSTS:9695

TITF1_2309 (e-PCR)
- UniSTS:281057

RH69670 (e-PCR)
- UniSTS:56823

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables DNA binding	IMP Inferred from Mutant Phenotype 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
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
enables RNA polymerase II cis-regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA polymerase II-specific DNA-binding transcription factor binding	IPI Inferred from Physical Interaction more info	PubMed
enables enzyme binding	IPI Inferred from Physical Interaction more info	PubMed
enables intronic transcription regulatory region sequence-specific DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables intronic transcription regulatory region sequence-specific DNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables transcription cis-regulatory region binding	IDA Inferred from Direct Assay more info	PubMed
enables transcription cis-regulatory region binding	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Leydig cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in anatomical structure formation involved in morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in axon guidance	IEA Inferred from Electronic Annotation more info
involved_in brain development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
involved_in cerebral cortex GABAergic interneuron differentiation	IEA Inferred from Electronic Annotation more info
involved_in cerebral cortex cell migration	IEA Inferred from Electronic Annotation more info
involved_in club cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in developmental induction	IEA Inferred from Electronic Annotation more info
involved_in endoderm development	IEA Inferred from Electronic Annotation more info
involved_in epithelial tube branching involved in lung morphogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in forebrain development	IEP Inferred from Expression Pattern more info	PubMed
involved_in forebrain dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
involved_in forebrain neuron fate commitment	IEA Inferred from Electronic Annotation more info
involved_in gene expression	IEA Inferred from Electronic Annotation more info
involved_in globus pallidus development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hippocampus development	IEA Inferred from Electronic Annotation more info
involved_in hypothalamus development	IEA Inferred from Electronic Annotation more info
involved_in interneuron migration	IEA Inferred from Electronic Annotation more info
involved_in locomotory behavior	IEA Inferred from Electronic Annotation more info
involved_in lung development	IEP Inferred from Expression Pattern more info	PubMed
involved_in lung saccule development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of cell migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of epithelial to mesenchymal transition	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within negative regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of transforming growth factor beta receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in oligodendrocyte differentiation	IEA Inferred from Electronic Annotation more info
involved_in phospholipid metabolic process	IEA Inferred from Electronic Annotation more info
involved_in pituitary gland development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of DNA-templated transcription	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of circadian rhythm	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of gene expression	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to hormone	IEP Inferred from Expression Pattern more info	PubMed
involved_in rhythmic process	IEA Inferred from Electronic Annotation more info
involved_in thyroid gland development	IEP Inferred from Expression Pattern more info	PubMed
involved_in thyroid gland development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in type II pneumocyte differentiation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
part_of chromatin	ISA Inferred from Sequence Alignment more info
located_in nucleoplasm	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of transcription regulator complex	IPI Inferred from Physical Interaction more info	PubMed

General protein information

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Preferred Names: homeobox protein Nkx-2.1

Names: NK-2 homolog A; homeobox protein NK-2 homolog A; thyroid nuclear factor 1; thyroid transcription factor 1; thyroid-specific enhancer-binding protein

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_013365.1 RefSeqGene

Range

4994..8829

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001079668.3 → NP_001073136.1 homeobox protein Nkx-2.1 isoform 1

See identical proteins and their annotated locations for NP_001073136.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer protein (isoform 1).

Source sequence(s)

AL132857, BM970287, U43203

Consensus CDS

CCDS41945.1

UniProtKB/Swiss-Prot

P43699

Related

ENSP00000346879.6, ENST00000354822.7

Conserved Domains (1) summary

pfam00046
Location:194 → 247

Homeobox; Homeobox domain
NM_003317.4 → NP_003308.1 homeobox protein Nkx-2.1 isoform 2

See identical proteins and their annotated locations for NP_003308.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding region compared to variant 1. The resulting protein (isoform 2) is shorter and has a distinct N-terminus compared to isoform 1.

Source sequence(s)

BC006221, BM970838, U33749

Consensus CDS

CCDS9659.1

UniProtKB/Swiss-Prot

D3DSA3, O14954, O14955, P43699, Q7KZF6, Q9BRJ8

Related

ENSP00000429607.2, ENST00000498187.6

Conserved Domains (1) summary

pfam00046
Location:164 → 217

Homeobox; Homeobox domain