{"entity":{"id":"nkx2-1","kind":"target","name":"NKX2-1","aka":["NK2 homeobox 1","Homeobox protein Nkx-2.1","TTF-1","TTF1","NKX2A","TITF1"],"tldr":"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.","summary":"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.\n\nOpen 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.","asOf":"2026-09-23","links":[{"label":"HGNC HGNC:11825","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11825"},{"label":"UniProt P43699","url":"https://www.uniprot.org/uniprotkb/P43699/entry"},{"label":"NCBI Gene 7080","url":"https://www.ncbi.nlm.nih.gov/gene/7080"},{"label":"Ensembl ENSG00000136352","url":"https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000136352"}],"tags":["cancer-genes-wave"],"related":["open-targets","intogen"],"cancers":["thyroid","lung-cancer","skin-cancer","melanoma","nsclc"],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015"],"journals":[],"dependsOn":[],"notes":["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.","Lung cancer: high-level amplification in 8 to 14% of adenocarcinomas and about 3% of squamous tumours (cBioPortal). It is the adenocarcinoma lineage gene and the TTF-1 stain the pathologist reads; low expression with CDKN2A or CDKN2B loss defines the mucinous KC subset of KRAS-mutant disease (Skoulidis 2015), and TTF-1 is also low in the POU2F3 and double-negative subtypes of small-cell cancer (Baine 2020)."],"provenance":{"editedBy":"scripts/fetch-cancer-genes.ts (CIViC, Open Targets, IntOGen, HGNC, UniProt)","editedOn":"2026-09-23"},"symbol":"NKX2-1","role":["tumour-suppressor"],"evidenceTier":"cohort-driver","sources":[{"label":"HGNC HGNC:11825","url":"https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:11825","note":"approved symbol, name, aliases, locus and cross-references (hgnc_complete_set.txt)"},{"label":"UniProt P43699","url":"https://www.uniprot.org/uniprotkb/P43699/entry","note":"protein name, function text, keywords and locations (REST API)"},{"label":"Open Targets ENSG00000136352","url":"https://platform.opentargets.org/target/ENSG00000136352/associations","note":"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)"},{"label":"IntOGen NKX2-1","url":"https://www.intogen.org/search?gene=NKX2-1","note":"driver in 1 cohort (Act 0, LoF 1); Compendium_Cancer_Genes.tsv release 20240920, CC0 1.0"}],"specificitySources":[],"hgnc":"HGNC:11825","ensembl":"ENSG00000136352","uniprot":"P43699","entrez":"7080","firstDescribed":1995,"firstDescribedBasis":"sequence","firstDescribedNote":"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\".","firstDescribedSource":"https://pubmed.ncbi.nlm.nih.gov/7711079/","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).","whereFound":["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)","Non-small-cell lung cancer: high-level amplification (lineage survival gene) 8-14%"],"targetClass":"tumor-suppressor","prevalence":[{"cancerId":"nsclc","pct":"8-14","measure":"High-level amplification (lineage survival gene)","source":"https://www.cbioportal.org/study/summary?id=luad_mskcc_2023_met_organotropism","note":"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."}]},"route":"/targets/nkx2-1/","neighbours":{"collection":[{"id":"intogen","kind":"collection","name":"IntOGen","route":"/collections/intogen/"},{"id":"open-targets","kind":"collection","name":"Open Targets Platform","route":"/collections/open-targets/"}],"cancer":[{"id":"lung-cancer","kind":"cancer","name":"Lung cancer (all types)","route":"/cancers/lung-cancer/"},{"id":"melanoma","kind":"cancer","name":"Melanoma","route":"/cancers/melanoma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"skin-cancer","kind":"cancer","name":"Skin cancer (all types)","route":"/cancers/skin-cancer/"},{"id":"thyroid","kind":"cancer","name":"Thyroid cancer","route":"/cancers/thyroid/"}],"paper":[{"id":"paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015","kind":"paper","name":"Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities","route":"/key-papers/paper-skoulidis-kras-co-mutation-subsets-cancer-discov-2015/"},{"id":"paper-tcga-lung-adenocarcinoma-nature-2014","kind":"paper","name":"Comprehensive molecular profiling of lung adenocarcinoma","route":"/key-papers/paper-tcga-lung-adenocarcinoma-nature-2014/"},{"id":"paper-baine-sclc-subtype-immunohistochemistry-jto-2020","kind":"paper","name":"SCLC subtypes defined by ASCL1, NEUROD1, POU2F3, and YAP1: a comprehensive immunohistochemical and histopathologic characterization","route":"/key-papers/paper-baine-sclc-subtype-immunohistochemistry-jto-2020/"}]}}