NKX2-1
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.
Overview
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.
- Target · the protein and the cell it sits on
- Drug · antibody, small molecule, cell or radioligand
- Effect · signal, damage or kill
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.
- 1 · What it is
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.
- 2 · What goes wrong in cancer
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.
- 3 · How drugs use it
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).
External identifiers
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)
Biology
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).
- Thyroid cancer: Open Targets association 0.58 with thyroid cancer (MONDO_0002108)
- Lung cancer: Open Targets association 0.54 with lung cancer (MONDO_0008903)
- Skin cancer: Open Targets association 0.52 with skin cancer (MONDO_0002898)
- Melanoma: Open Targets association 0.51 with melanoma (MONDO_0005105)
Notes
top- Written by scripts/fetch-cancer-genes.ts from CIViC, Open Targets, IntOGen, HGNC and UniProt; the function text is UniProt's, condensed and in UK spelling. Roles: IntOGen calls it a loss-of-function (LoF) driver in 1 cohort. Evidence tier "cohort-driver" is the strongest of those signals.
- Prevalence not recorded: none of the sources gives a positivity rate.
- Diseases the sources name that have no OnCo cancer page yet, so they are not linked: Low-Grade Glioma, NOS.
Latest papers
topQuery 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.
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