Loading
NKX2-1 (Homeobox protein Nkx-2.1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer, Lung cancer, Skin cancer and 1 more.
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.
Open Targets scores its association with cancer at 0.76 (direct and indirect evidence; datatypes genetic literature 0.61, literature 0.96, genetic association 0.66, somatic mutation 0.81, animal model 0.79). IntOGen calls it a driver in 1 cohort (0 activating, 1 loss-of-function), covering Low-Grade Glioma, NOS.
In plain words · NKX2-1 (Homeobox protein Nkx-2.1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer, Lung cancer, Skin cancer and 1 more.
NKX2-1 (Homeobox protein Nkx-2.1) is a gene whose normal job is to hold cell growth in check. The public catalogues list it as a tumour suppressor, and it is called a cancer driver by mutation analysis of patient cohorts. Tied to Thyroid cancer, Lung cancer, Skin cancer and 1 more.
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.
No product in this corpus aims at NKX2-1 yet. Because the protein is lost rather than overactive, drugs either restore its function or exploit the weakness its loss leaves (synthetic lethality).
First described 1995. Earliest sequence paper UniProt cites for the protein: Oguchi et al, Biochim. Biophys. Acta, 1995, "The complete nucleotide sequence of the mouse thyroid-specific enhancer-binding protein (T/EBP) gene: extensive identity of the deduced amino acid sequence with the human protein". Source.
Sources: HGNC HGNC:11825 (approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)); UniProt P43699 (protein name, function text, keywords and locations (REST API)); Open Targets ENSG00000136352 (association with cancer (MONDO_0004992) 0.76; per-cancer scores at or above 0.5: melanoma 0.51, thyroid cancer 0.58, skin cancer 0.52, lung cancer 0.54 (GraphQL API, CC0)); IntOGen NKX2-1 (driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0)
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. Location: Nucleus (UniProt). Locus 14q13.3 (HGNC).
| Cancer | Prevalence | Measure | Note | Source |
|---|---|---|---|---|
| Non-small-cell lung cancer | 8-14% | High-level amplification (lineage survival gene) | cBioPortal high-level amplification: 261 of 2,422, 10.8%, in luad_mskcc_2023_met_organotropism; 75 of 915, 8.2%, in lung_msk_2017; 67 of 511, 13.1%, in luad_tcga_pan_can_atlas_2018; 32 of 230, 13.9%, in luad_tcga_pub; 11 of 302, 3.6%, in luad_oncosg_2020; 13 of 487, 2.7%, in lusc_tcga_pan_can_atlas_2018. | cBioPortal (TCGA) |
Approximate, population-level figures; the measure column says what was counted. Ranges show the midpoint as a bar.
It is the reality check on the subtype model and it has a direct consequence for treatment: the DLL3-directed medicines are aimed at the neuroendocrine-high subtypes, and the POU2F3 and double-negative tumours will not express the target.
It is the origin of the idea, now central to lung oncology, that the co-mutation and not the driver decides how a KRAS-mutant tumour behaves and whether immunotherapy will work.
It is the reference table the field still argues against, and it made two practical points that outlived it: a tumour with no driver on a standard panel usually has one that the panel did not look for, and pathway activity measured on protein does not follow from the mutation list.
Query for this target: (TITLE:"NKX2-1" OR ABSTRACT:"NKX2-1" OR TITLE:"NK2 homeobox 1" OR ABSTRACT:"NK2 homeobox 1" OR TITLE:"Homeobox protein Nkx-2.1" OR ABSTRACT:"Homeobox protein Nkx-2.1" OR TITLE:"TTF-1" OR ABSTRACT:"TTF-1" OR TITLE:"TTF1" OR ABSTRACT:"TTF1" OR TITLE:"NKX2A" OR ABSTRACT:"NKX2A") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about NKX2-1, not a curated reading list.
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, IntOGen, Lung cancer (all types), Open Targets Platform.
Shares Thyroid cancer, IntOGen, Lung cancer (all types), Open Targets Platform.
Shares Comprehensive molecular profiling of lung adenocarcinoma, IntOGen, Lung cancer (all types), Open Targets Platform.
Shares Thyroid cancer, Lung cancer (all types), Open Targets Platform, Non-small-cell lung cancer.
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).
Shares Thyroid cancer, Skin cancer (all types), IntOGen, Lung cancer (all types).