NKX2-1: NK2 Homeobox 1
Thyroid Transcription Factor 1 (TTF-1) - Key Regulator of Lung, Thyroid, and Brain Development
Gene Information Card
| Symbol | NKX2-1 |
|---|---|
| Full Name | NK2 Homeobox 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 14q13.3 |
| NCBI Gene ID | 7080 ncbi.nlm.nih.gov/gene/7080 |
| Ensembl ID | ENSG00000136352 |
| UniProt ID | P43699 |
| OMIM ID | 600635 |
| HGNC ID | 11825 |
| Aliases | TTF1, TTF-1, NKX2A, BCH, BHC, TEBP |
Description
The NKX2-1 gene (also known as TTF-1) encodes a homeodomain-containing transcription factor critical for the development and function of the thyroid, lung, and ventral forebrain. It regulates the expression of genes involved in thyroid hormone synthesis (e.g., TG, TPO, TSHR), pulmonary surfactant production (e.g., SFTPB, SFTPC), and neuronal migration. Mutations in NKX2-1 cause brain-lung-thyroid syndrome (OMIM #610978), characterized by choreoathetosis, congenital hypothyroidism, and neonatal respiratory distress. NKX2-1 is also a lineage-specific oncogene in lung adenocarcinoma and a diagnostic marker for primary lung and thyroid carcinomas.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Brain-Lung-Thyroid Syndrome | Loss-of-function mutations in NKX2-1 disrupt development of thyroid, lung, and basal ganglia | OMIM #610978; ClinVar |
| Congenital Hypothyroidism | Impaired NKX2-1 function reduces expression of thyroid-specific genes (TG, TPO, TSHR) | OMIM #600635; NCBI Gene |
| Choreoathetosis, Familial Benign | NKX2-1 haploinsufficiency leads to abnormal basal ganglia development | OMIM #118700; ClinVar |
| Respiratory Distress Syndrome in Newborns | Deficient NKX2-1 reduces surfactant protein expression (SFTPB, SFTPC) | OMIM #610978; NCBI Gene |
| Lung Adenocarcinoma | NKX2-1 amplification and overexpression drive tumorigenesis in lung adenocarcinoma | COSMIC; NCBI Gene |
| Thyroid Carcinoma | NKX2-1 (TTF-1) is a diagnostic marker; aberrant expression linked to tumor progression | UniProt; NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lung | 49.8 | High |
| Thyroid | 38.2 | High |
| Brain (basal ganglia) | 12.1 | Medium |
| Brain (cerebellum) | 1.5 | Low |
| Heart | 0.2 | Not detected |
| Liver | 0.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| A549 (lung adenocarcinoma) | 62.3 | High expression; used as positive control for TTF-1 |
| NCI-H441 (lung papillary adenocarcinoma) | 55.1 | High expression |
| NCI-H1299 (lung carcinoma) | 0.8 | Low/undetectable |
| HeLa (cervical carcinoma) | 0.1 | Not detected |
| HEK293 (embryonic kidney) | 0.2 | Not detected |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.251C>T (p.Pro84Leu) | Missense | Rare | Loss of DNA-binding activity; associated with brain-lung-thyroid syndrome |
| c.373C>T (p.Arg125Trp) | Missense | Rare | Reduced transactivation of surfactant genes; linked to respiratory distress |
| c.490C>T (p.Arg164*) | Nonsense | Rare | Premature truncation; loss of function; choreoathetosis and hypothyroidism |
| Whole gene deletion | Copy number loss | Rare | Haploinsufficiency; severe brain-lung-thyroid phenotype |
| Amplification (14q13.3) | Copy number gain | Frequent in lung adenocarcinoma | Oncogenic; increased proliferation and lineage survival |
Mutation functional classification
Loss of Function (LOF)
Missense, nonsense, frameshift, and whole gene deletions that impair DNA binding or transactivation; cause brain-lung-thyroid syndrome.
Gain of Function (GOF)
Gene amplification and overexpression in lung adenocarcinoma; promotes tumor growth and lineage dependency.
Dominant Negative (DN)
Not well documented; some missense mutations may interfere with wild-type NKX2-1 function in heterozygous state.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Thyroid hormone synthesis (Reactome: R-HSA-209968)
• Surfactant metabolism (Reactome: R-HSA-5683826)
• Developmental biology (Reactome: R-HSA-1266738)
• Transcriptional regulation by NKX2-1 (PID: NKX2-1 pathway)
Protein Summary
NKX2-1 (TTF-1) is a 42 kDa homeodomain transcription factor containing an N-terminal tinman domain and a C-terminal NK2-specific domain. It binds to the consensus sequence 5'-CAAG-3' in target gene promoters. The protein is essential for organogenesis of the thyroid, lung, and ventral forebrain. In the thyroid, it activates thyroglobulin (TG), thyroperoxidase (TPO), and TSH receptor (TSHR) genes. In the lung, it regulates surfactant proteins SFTPB, SFTPC, and ABCA3. In the brain, it controls neuronal migration and differentiation in the basal ganglia. Post-translational modifications include phosphorylation and acetylation, which modulate its transcriptional activity. NKX2-1 is a well-established immunohistochemical marker for primary lung adenocarcinoma and thyroid carcinoma.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NKX2-1 Knockout HEK293 Cell Line | EDJ-KQ1558 | Human | 7080 | Details Get a Quote |
| NKX2-1 Knockout HeLa Cell Line | EDJ-KQ54662 | Human | 7080 | Details Get a Quote |
| NKX2-1 Knockout A-549 Cell Line | EDJ-KQ63143 | Human | 7080 | Details Get a Quote |
| NKX2-1 Knockout HCT 116 Cell Line | EDJ-KQ71617 | Human | 7080 | Details Get a Quote |
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