NKX2-1

Summary

NKX2-1 (NK2 homeobox 1, HGNC:11825) is a protein-coding gene on chromosome 14q13.3, encoding Homeobox protein Nkx-2.1 (P43699). Transcription factor that binds and activates the promoter of thyroid specific genes such as thyroglobulin, thyroperoxidase, and thyrotropin receptor.

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.

Source: NCBI Gene 7080 — RefSeq curated summary.

At a glance

• Gene–disease (curated): NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 7
• Clinical variants (ClinVar): 549 total — 66 pathogenic, 42 likely-pathogenic
• Phenotypes (HPO): 114
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types
• Transcription factor: yes — 69 downstream targets (CollecTRI)
• MANE Select transcript: NM_001079668

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11825
Approved symbol	NKX2-1
Name	NK2 homeobox 1
Location	14q13.3
Locus type	gene with protein product
Status	Approved
Aliases	TTF-1, TTF1
Ensembl gene	ENSG00000136352
Ensembl biotype	protein_coding
OMIM	600635
Entrez	7080

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000354822, ENST00000498187, ENST00000518149, ENST00000522719

RefSeq mRNA: 2 — MANE Select: NM_001079668 NM_001079668, NM_003317

CCDS: CCDS41945, CCDS9659

Canonical transcript exons

ENST00000354822 — 3 exons

Exon	Start	End
ENSE00000000246	36516397	36518020
ENSE00002242032	36520053	36520232
ENSE00003523259	36518985	36519370

Expression profiles

Bgee: expression breadth ubiquitous, 101 present calls, max score 99.00.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5414 / max 164.5053, expressed in 210 samples.

FANTOM5 promoters (17 alternative TSS)

Promoter ID	TPM avg	Samples expressed
142936	0.3987	50
142943	0.2925	96
142948	0.2421	122
142939	0.2073	91
142947	0.1270	69
142938	0.1200	70
142944	0.0926	58
142940	0.0873	30
142946	0.0873	61
142933	0.0743	31

Top tissues by expression

260 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of thyroid gland	UBERON:0001119	99.00	gold quality
left lobe of thyroid gland	UBERON:0001120	98.78	gold quality
thyroid gland	UBERON:0002046	98.47	gold quality
lower lobe of lung	UBERON:0008949	96.80	gold quality
right lung	UBERON:0002167	95.82	gold quality
upper lobe of lung	UBERON:0008948	94.01	gold quality
upper lobe of left lung	UBERON:0008952	93.75	gold quality
lung	UBERON:0002048	93.73	gold quality
buccal mucosa cell	CL:0002336	92.45	gold quality
triceps brachii	UBERON:0001509	80.55	gold quality
gluteal muscle	UBERON:0002000	80.30	gold quality
epithelium of bronchus	UBERON:0002031	80.20	gold quality
bronchial epithelial cell	CL:0002328	80.04	gold quality
bronchus	UBERON:0002185	79.55	gold quality
visceral pleura	UBERON:0002401	78.97	gold quality
tendon of biceps brachii	UBERON:0008188	77.42	gold quality
adult organism	UBERON:0007023	76.11	gold quality
medial globus pallidus	UBERON:0002477	72.78	silver quality
globus pallidus	UBERON:0001875	69.43	silver quality
hypothalamus	UBERON:0001898	68.87	gold quality
nucleus accumbens	UBERON:0001882	68.68	gold quality
myocardium	UBERON:0002349	68.19	gold quality
caudate nucleus	UBERON:0001873	68.12	gold quality
epithelium of esophagus	UBERON:0001976	68.08	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	67.99	gold quality
esophagus squamous epithelium	UBERON:0006920	67.54	gold quality
oocyte	CL:0000023	67.47	gold quality
heart right ventricle	UBERON:0002080	66.69	gold quality
putamen	UBERON:0001874	66.09	gold quality
biceps brachii	UBERON:0001507	65.77	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-8894	yes	514.40
E-HCAD-1	yes	80.94
E-ANND-3	yes	27.02
E-GEOD-93593	yes	8.81

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

69 targets.

Target	Regulation
ABCA3	Activation
ADCYAP1	Unknown
AFP
AGER	Repression
APRT
BMP4	Unknown
BTK
CALCA	Activation
CCL11	Activation
CCNB1	Activation
CCNB2	Activation
CEBPA	Unknown
CHRNA2
CHRNA7
CIP2A
DAXX
E2F3	Activation
EBP
FLT1	Activation
GH1	Unknown
GJA5
GLB1
HGF
HHEX	Activation
HLA-A	Unknown
HMGA2	Repression
IKBKB
IL6	Activation
INS-IGF2
IRF2BPL	Unknown

Upstream regulators (CollecTRI, top): AP1, BMAL1, CLOCK, FOXA1, FOXA2, FOXP2, GATA6, GLI1, GRHL2, HOXB3, NKX2-1, PAX6, PAX8, POU3F2, SMAD2, SMAD4, SOX2, SP1, SP3, TP53, TTF1

miRNA regulators (miRDB)

49 targeting NKX2-1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-568	99.98	69.86	2084
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-6753-3P	99.93	66.57	637
HSA-MIR-7107-3P	99.93	66.73	627
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-4530	99.69	66.47	1509
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-365A-3P	99.43	70.02	836

Literature-anchored findings (GeneRIF, showing 40)

• highly sensitive and specific immunomarker distinguishing between metastatic pulmonary and extrapulmonary adenocarcinoma in effusion cytology specimens (PMID:11836702)
• haploinsufficiency of the TTF1 gene results in a predominantly neurological phenotype and secondary hyperthyrotropinemia (PMID:11854318)
• the association of symptoms in the patients with NKX2-1 mutations points to an important role of human NKX2-1 in the development and function of thyroid, basal ganglia, and lung, as already described for rodents (PMID:11854319)
• TTF-1 and Pax 8 cooperatively activate their target genes and their synergistic activity requires the cross-talk between enhancer and gene promoter (PMID:11923479)
• results show that TTF-1 is not expressed in normal and hyperplastic neuroendocrine(NE) cells or in carcinoids, but is expressed in high-grade NE proliferations and in lung adenocarcinomas (PMID:11957142)
• evidence that mutations in TITF-1 are associated with benign hereditary chorea (PMID:11971878)
• review on use in differentiating neoplasm types (PMID:12051643)
• Data suggest that SMAD3 interactions with the positive regulators NKX2.1 and HNF-3 underlie the molecular basis for TGF-beta-induced repression of surfactant protein B gene transcription. (PMID:12161428)
• the significance of thyroid transcription factor-1 (TTF-1) in the histogenesis of pulmonary sclerosing hemangioma (PSH) (PMID:12408771)
• directly interacts with Pax8 and synergistically activates transcription (PMID:12441357)
• nuclear staining of TTF-1 was observed in two of six adenocarcinoma cell lines, none of seven small cell lung cancer cell lines, and none of three squamous lung cancer cell lines (PMID:12499091)
• -1 is expressed in pulmonary adenocarcinomas and SCLCs (PMID:12923324)
• Glucocorticoid receptor inhibits SP-A promoter activity through the ttf-1 binding element (PMID:14633512)
• Examination of different immunohistochemical markers including TTF-1 is helpful in the diagnosis and differential diagnosis of pulmonary sclerosing hemangioma. (PMID:14720435)
• TTF-1 immunoreactivity favors a diagnosis of primary thyroid medullary carcinoma over laryngeal moderately differentiated neuroendocrine carcinoma. (PMID:15098009)
• NFAT and thyroid transcription factor-1 have roles in regulating transcription of the surfactant protein D gene (PMID:15173172)
• significantly increased the amount of protein-bound radioiodide and prolonged the iodide efflux (PMID:15271884)
• nuclear galectin-3 and TTF-1 have roles in progression of non-small cell lung carcinoma (PMID:15279903)
• Site-specific mutagenesis identifies that lysine-182 in the TTF-1 homeodomain is acetylated in respiratory epithelial cells. Mutation at this acetylation site shows a dominant negative effect on human surfactant protein B gene transcription. (PMID:15449938)
• results demonstrate that interleukin-10 induces uteroglobin related protein 1(UGRP1) gene expression in lung epithelial cells through transcription factor T/EBP/NKX2.1-dependent pathway (PMID:15485815)
• TTF-1 in orbital tissues suggests that it may play an important role in extrathyroidal, as it does in thyroidal, thyrotropin receptor expression (PMID:15929662)
• Presented is a pedigree with infancy-onset benign hereditary chorea (BHC) caused by a novel nonsense mutation in exon 3 (523G–>T, E175X) of the TITF-1 (Nkx2.1) gene. (PMID:15955952)
• a nonsense mutation in the TITF1 gene may be the genetic cause of benign hereditary chorea in a Portuguese family (PMID:16220345)
• pendrin and thyroglobulin are downstream targets in vivo of TTF-1, whose action is a prime factor in controlling thyroid differentiation in vivo (PMID:16260629)
• Thyroid transcription factor 1 gene is not associated with mental retardation in iodine-deficient areas in China. (PMID:16314749)
• PARP-2 and PARP-1 interact with TTF-1 and regulate the expression of surfactant protein B, a protein required for lung function (PMID:16461352)
• p23 forms a specific complex with Hsp90 primarily through binding to its middle domain (PMID:16565516)
• Erm is involved in SP-C regulation, which results from an interaction with TTF-1 (PMID:16613858)
• Via promoter mutation analysis, adjacent TTF-1 binding sites within the proximal promoter region of SP-C were found to be essential for TTF-1/TAP26-enhanced SP-C promoter activity. (PMID:16630564)
• 42-kD TTF-1 is required for induction of a subset of regulated genes during type II cell differentiation. (PMID:16960125)
• study supports the fact that TTF-1 could be included in further prospective trials studying prognostic factors in NSCLC (PMID:16980598)
• New syndromic form of benign hereditary chorea is associated with a deletion of TITF-1 and PAX-9 contiguous genes. (PMID:17044090)
• Although morphogenesis of both the pallidum and the hypothalamus requires the presence of transgenic TTF1, only the hypothalamus necessitates the continuous expression of TTF1 to carry out specific differentiated functions. (PMID:17182767)
• GST-FOXA1 fusion protein interferes with the formation of NKX2.1 transcriptional complexes by potentially masking the latter’s homeodomain DNA binding function (PMID:17220277)
• calcitonin gene expression could be directly activated by Nkx2.1, whereas Pax9 is not involved in transcription from the 2kbp calcitonin promoter (PMID:17412341)
• Our results suggest that an immunohistochemical panel consisting of TTF-1, CEA, CA-125, and OCT-4 is helpful in distinguishing most pulmonary and ovarian carcinomas with clear cell features. (PMID:17413979)
• TTF-1 expression may be crucial for survival of a subset of adenocarcinomas that express TTF-1, providing credence for the lineage-specific dependency model (PMID:17616654)
• Met3Leu reduced the activity of the RET promoter by 100% in the presence of the wild-type or HSCR-associated RET promoter SNP alleles. (PMID:17640327)
• Anaplastic thyroid carcinoma tissue express TTF1 mRNA abundantly. (PMID:17671725)
• a new splicing mutation (376-2A>C) of the TITF-1 gene was detected in a mother and her daughter in this study. (PMID:17702043)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkx2.1	ENSDARG00000019835
mus_musculus	Nkx2-1	ENSMUSG00000001496
rattus_norvegicus	Nkx2-1	ENSRNOG00000008644
drosophila_melanogaster	NK7.1	FBGN0024321
drosophila_melanogaster	HGTX	FBGN0040318
drosophila_melanogaster	scro	FBGN0287186
caenorhabditis_elegans	ceh-9	WBGENE00000434
caenorhabditis_elegans		WBGENE00000447
caenorhabditis_elegans		WBGENE00000450
caenorhabditis_elegans		WBGENE00000584

Paralogs (13): NKX3-2 (ENSG00000109705), NKX2-3 (ENSG00000119919), NKX2-4 (ENSG00000125816), NKX2-2 (ENSG00000125820), NKX2-8 (ENSG00000136327), NKX6-2 (ENSG00000148826), NKX6-1 (ENSG00000163623), NKX6-3 (ENSG00000165066), NKX3-1 (ENSG00000167034), NKX2-6 (ENSG00000180053), NKX2-5 (ENSG00000183072), NKX1-2 (ENSG00000229544), NKX1-1 (ENSG00000235608)

Protein

Protein identifiers

Homeobox protein Nkx-2.1 — P43699 (reviewed: P43699)

Alternative names: Homeobox protein NK-2 homolog A, Thyroid nuclear factor 1, Thyroid transcription factor 1, Thyroid-specific enhancer-binding protein

All UniProt accessions (2): A0A7P0P5T6, P43699

UniProt curated annotations — full annotation on UniProt →

Function. 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.

Subunit / interactions. Interacts with WWTR1.

Subcellular location. Nucleus.

Tissue specificity. Thyroid and lung.

Post-translational modifications. Phosphorylated on serine residues by STK3/MST2.

Disease relevance. Chorea, hereditary benign (BHC) [MIM:118700] A rare autosomal dominant movement disorder, defined by early onset in childhood, a stable or non-progressive course of chorea, and no mental deterioration. Chorea is characterized by involuntary, forcible, rapid, jerky movements that may be subtle or become confluent, markedly altering normal patterns of movement. The disease is caused by variants affecting the gene represented in this entry. Choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (CAHTP) [MIM:610978] An autosomal dominant disorder that manifests in infancy with neurological disturbances, hypothyroidism, and respiratory problems. It is characterized by movement abnormalities beginning with muscular hypotonia followed by the development of chorea, athetosis, dystonia, ataxia, and dysarthria. The disease is caused by variants affecting the gene represented in this entry. Thyroid cancer, non-medullary, 1 (NMTC1) [MIM:188550] A form of non-medullary thyroid cancer (NMTC), a cancer characterized by tumors originating from the thyroid follicular cells. NMTCs represent approximately 95% of all cases of thyroid cancer and are classified into papillary, follicular, Hurthle cell, and anaplastic neoplasms. Disease susceptibility is associated with variants affecting the gene represented in this entry.

Similarity. Belongs to the NK-2 homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
P43699-1	1	yes
P43699-3	3

RefSeq proteins (2): NP_001073136, NP_003308 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site
IPR020479	HD_metazoa	Domain
IPR050394	Homeobox_NK-like	Family

Pfam: PF00046

UniProt features (21 total): sequence variant 8, sequence conflict 4, compositionally biased region 3, region of interest 2, chain 1, DNA-binding region 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
9U19	X-RAY DIFFRACTION	1.18
9U18	X-RAY DIFFRACTION	1.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43699-F1	58.30	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 254

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 598 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, GOBP_CIRCADIAN_RHYTHM, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, MYAATNNNNNNNGGC_UNKNOWN, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_BEHAVIOR, PAX4_01, GOBP_DNA_TEMPLATED_TRANSCRIPTION_TERMINATION, PID_HNF3B_PATHWAY, NKX25_02

GO Biological Process (50): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), phospholipid metabolic process (GO:0006644), axon guidance (GO:0007411), brain development (GO:0007420), endoderm development (GO:0007492), locomotory behavior (GO:0007626), response to hormone (GO:0009725), gene expression (GO:0010467), positive regulation of gene expression (GO:0010628), negative regulation of epithelial to mesenchymal transition (GO:0010719), globus pallidus development (GO:0021759), hippocampus development (GO:0021766), cerebral cortex cell migration (GO:0021795), forebrain dorsal/ventral pattern formation (GO:0021798), hypothalamus development (GO:0021854), forebrain neuron fate commitment (GO:0021877), cerebral cortex GABAergic interneuron differentiation (GO:0021892), pituitary gland development (GO:0021983), cell differentiation (GO:0030154), lung development (GO:0030324), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), thyroid gland development (GO:0030878), forebrain development (GO:0030900), developmental induction (GO:0031128), Leydig cell differentiation (GO:0033327), positive regulation of circadian rhythm (GO:0042753), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), rhythmic process (GO:0048511), anatomical structure formation involved in morphogenesis (GO:0048646), oligodendrocyte differentiation (GO:0048709), lung saccule development (GO:0060430), epithelial tube branching involved in lung morphogenesis (GO:0060441), club cell differentiation (GO:0060486), type II pneumocyte differentiation (GO:0060510), interneuron migration (GO:1904936)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), intronic transcription regulatory region sequence-specific DNA binding (GO:0001161), DNA binding (GO:0003677), DNA-binding transcription factor activity (GO:0003700), enzyme binding (GO:0019899), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565)

GO Cellular Component (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
diencephalon development	3
transcription cis-regulatory region binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
regulation of gene expression	2
regulation of DNA-templated transcription	2
limbic system development	2
anatomical structure development	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
DNA-templated transcription	1
regulation of RNA biosynthetic process	1
lipid metabolic process	1
organophosphate metabolic process	1
axonogenesis	1
neuron projection guidance	1
central nervous system development	1
animal organ development	1
head development	1
tissue development	1
behavior	1
response to endogenous stimulus	1
response to chemical	1
macromolecule biosynthetic process	1
gene expression	1
positive regulation of macromolecule biosynthetic process	1
epithelial to mesenchymal transition	1
regulation of epithelial to mesenchymal transition	1
negative regulation of cell differentiation	1
negative regulation of multicellular organismal process	1
neural nucleus development	1
pallium development	1
cerebral cortex development	1
telencephalon cell migration	1
dorsal/ventral pattern formation	1
forebrain regionalization	1
forebrain neuron differentiation	1
neuron fate commitment	1
cerebral cortex neuron differentiation	1

Protein interactions and networks

STRING

2186 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKX2-1	PAX8	Q06710	973
NKX2-1	TSHR	P16473	954
NKX2-1	FOXE1	O00358	948
NKX2-1	TG	P01266	923
NKX2-1	SFTPB	P07988	904
NKX2-1	NAPSA	O96009	874
NKX2-1	KRT7	P08729	871
NKX2-1	SMAD3	P84022	861
NKX2-1	GATA6	P78327	858
NKX2-1	SPDEF	O95238	850
NKX2-1	KRT20	P35900	841
NKX2-1	CLDN18	P56856	822
NKX2-1	SLC5A5	Q92911	813
NKX2-1	LHX6	Q9UPM6	800
NKX2-1	LIAT1	Q6ZQX7	781

IntAct

30 interactions, top by confidence:

A	B	Type	Score
NKX2-1	CCDC59	psi-mi:“MI:0915”(physical association)	0.580
CCDC59	NKX2-1	psi-mi:“MI:0915”(physical association)	0.580
Dlg4	NKX2-1	psi-mi:“MI:0407”(direct interaction)	0.440
ABL1	NKX2-1	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	CRK	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	SRC	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	FYN	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	GRB2	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	NCK1	psi-mi:“MI:0915”(physical association)	0.400
FOXA1	NKX2-1	psi-mi:“MI:0915”(physical association)	0.400
NKX2-1	SMAD3	psi-mi:“MI:0915”(physical association)	0.370
	NKX2-1	psi-mi:“MI:0915”(physical association)	0.370
NKX2-1	SREBF2	psi-mi:“MI:0914”(association)	0.350
NKX2-1		psi-mi:“MI:0914”(association)	0.350
DDX6	RPSA2	psi-mi:“MI:2364”(proximity)	0.270
NKX2-1	AKT1	psi-mi:“MI:2364”(proximity)	0.270
FBXW7	NKX2-1	psi-mi:“MI:2364”(proximity)	0.270
SMAD4	NKX2-1	psi-mi:“MI:2364”(proximity)	0.270
NKX2-1	SMAD4	psi-mi:“MI:2364”(proximity)	0.270
NKX2-1	SMARCA4	psi-mi:“MI:2364”(proximity)	0.270
SMARCA4	NKX2-1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (187): NKX2-1 (Reconstituted Complex), NKX2-1 (Biochemical Activity), NKX2-1 (Biochemical Activity), NKX2-1 (Biochemical Activity), DDB1 (Affinity Capture-Western), NKX2-1 (Affinity Capture-Western), PGD (Affinity Capture-MS), AMOTL2 (Affinity Capture-MS), APTX (Affinity Capture-MS), ATF2 (Affinity Capture-MS), ATF7 (Affinity Capture-MS), ATP5O (Affinity Capture-MS), BANF1 (Affinity Capture-MS), CEBPB (Affinity Capture-MS), MB21D1 (Affinity Capture-MS)

ESM2 similar proteins: A1YFU7, A8WL06, O14770, O35740, O42368, O46250, O76971, O77215, P07548, P09077, P09081, P20482, P20822, P23023, P25822, P31264, P40657, P40791, P43699, P54231, P54269, P56672, P83949, P83950, P91607, P91613, P91686, P91697, P91698, P91705, P91716, P92203, P97367, Q05201, Q0VCT9, Q24248, Q24255, Q24573, Q2Z1R2, Q5XGW7

Diamond homologs: A1YF16, A1YG93, A2RU54, A2T764, A6NCS4, A6NHT5, G5EE18, O02786, O15522, O17319, O35767, O43763, O57601, O70218, O70584, O93590, O95096, P13297, P22711, P22808, P22809, P23410, P23441, P28360, P28361, P28362, P35548, P35993, P40764, P41936, P42581, P42582, P42583, P42584, P42586, P42587, P43687, P43688, P43697, P43698

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
WWTR1	up-regulates	NKX2-1	binding
SMAD3	“down-regulates activity”	NKX2-1	binding
NKX2-1	“up-regulates quantity by expression”	SFTPB	“transcriptional regulation”
NKX2-1	“up-regulates quantity by expression”	TPO	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 17 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
FCGR3A-mediated phagocytosis	6	74.9×	4e-08
VEGFA-VEGFR2 Pathway	5	46.4×	7e-06
Nervous system development	5	14.3×	3e-04
Cytokine Signaling in Immune system	5	13.6×	3e-04
Infectious disease	6	9.9×	3e-04

GO biological processes:

GO term	Partners	Fold	FDR
ephrin receptor signaling pathway	5	114.6×	3e-07
positive regulation of miRNA transcription	5	96.8×	3e-07
cellular response to transforming growth factor beta stimulus	5	92.1×	3e-07
intracellular signal transduction	5	12.7×	9e-04

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — LGGNOS.

Clinical variants and AI predictions

ClinVar

549 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	66
Likely pathogenic	42
Uncertain significance	277
Likely benign	95
Benign	22

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1189930	NM_001079668.3(NKX2-1):c.754_755insT (p.Asp252fs)	Pathogenic
1326865	NM_001079668.3(NKX2-1):c.338dup (p.Tyr116fs)	Pathogenic
1357268	NM_001079668.3(NKX2-1):c.313del (p.Val105fs)	Pathogenic
1376422	NC_000014.8:g.(?36986483)(36987245_?)del	Pathogenic
1377274	NM_001079668.3(NKX2-1):c.1066C>T (p.Gln356Ter)	Pathogenic
1417048	NM_001079668.3(NKX2-1):c.619G>T (p.Glu207Ter)	Pathogenic
1418530	NM_001079668.3(NKX2-1):c.1131_1132insACACCCAGTTCAGGTG (p.Ser378fs)	Pathogenic
1453656	NM_001079668.3(NKX2-1):c.463+1G>A	Pathogenic
1456475	NM_001079668.3(NKX2-1):c.532del (p.Asp178fs)	Pathogenic
1685985	NM_001079668.3(NKX2-1):c.533del (p.Asp178fs)	Pathogenic
1701230	NM_001079668.3(NKX2-1):c.501del (p.Met167fs)	Pathogenic
1712809	NM_001079668.3(NKX2-1):c.612C>A (p.Tyr204Ter)	Pathogenic
1722935	NM_001079668.3(NKX2-1):c.326C>A (p.Ser109Ter)	Pathogenic
2013969	NM_001079668.3(NKX2-1):c.474del (p.Phe158fs)	Pathogenic
2031146	NM_001079668.3(NKX2-1):c.198_222del (p.Pro67fs)	Pathogenic
217884	NM_001079668.3(NKX2-1):c.524C>A (p.Ser175Ter)	Pathogenic
2423626	NC_000014.8:g.(?36988170)(36989334_?)del	Pathogenic
2444747	NM_001079668.3(NKX2-1):c.351C>A (p.Cys117Ter)	Pathogenic
2498216	NM_001079668.3(NKX2-1):c.612C>G (p.Tyr204Ter)	Pathogenic
2498592	NM_001079668.3(NKX2-1):c.463+1_463+10del	Pathogenic
2506907	NM_001079668.3(NKX2-1):c.216del (p.Arg72fs)	Pathogenic
2506917	NM_001079668.3(NKX2-1):c.583del (p.Arg195fs)	Pathogenic
2506928	NM_001079668.3(NKX2-1):c.650C>A (p.Ser217Ter)	Pathogenic
2506933	NM_001079668.3(NKX2-1):c.711C>G (p.Ile237Met)	Pathogenic
2506934	NM_001079668.3(NKX2-1):c.622C>T (p.Arg208Ter)	Pathogenic
2506937	NM_001079668.3(NKX2-1):c.423del (p.Gly142fs)	Pathogenic
2506939	NM_001079668.3(NKX2-1):c.647del (p.Leu216fs)	Pathogenic
2506942	NM_001079668.3(NKX2-1):c.336_345del (p.Val113fs)	Pathogenic
2506943	NM_001079668.3(NKX2-1):c.196del (p.Ala66fs)	Pathogenic
2506944	NM_001079668.3(NKX2-1):c.456_457delinsACGG (p.Phe152fs)	Pathogenic

SpliceAI

2248 predictions. Top by Δscore:

Variant	Effect	Δscore
14:36518983:A:AC	donor_gain	1.0000
14:36518984:C:CC	donor_gain	1.0000
14:36518984:CTGG:C	donor_gain	1.0000
9:132379143:CACTT:C	acceptor_gain	1.0000
9:132386549:GTCTT:G	donor_loss	1.0000
9:132386550:TCTTA:T	donor_loss	1.0000
9:132386551:CTTA:C	donor_loss	1.0000
9:132386552:TTA:T	donor_loss	1.0000
9:132386553:TAC:T	donor_loss	1.0000
9:132386554:A:AC	donor_gain	1.0000
9:132386554:AC:A	donor_gain	1.0000
9:132386554:ACCC:A	donor_loss	1.0000
9:132386555:C:CC	donor_gain	1.0000
9:132386555:C:CT	donor_loss	1.0000
9:132386555:CC:C	donor_gain	1.0000
9:132386618:CAAC:C	acceptor_gain	1.0000
9:132388137:A:AT	donor_loss	1.0000
9:132388138:C:A	donor_loss	1.0000
9:132388224:CTGTC:C	acceptor_gain	1.0000
9:132388226:GTC:G	acceptor_gain	1.0000
9:132388227:TC:T	acceptor_gain	1.0000
9:132388228:CC:C	acceptor_gain	1.0000
9:132388228:CCTA:C	acceptor_loss	1.0000
9:132388232:CAT:C	acceptor_gain	1.0000
9:132388233:A:C	acceptor_gain	1.0000
9:132388234:T:TC	acceptor_gain	1.0000
9:132390596:CCA:C	donor_gain	1.0000
9:132390602:A:AC	donor_gain	1.0000
9:132390603:C:CC	donor_gain	1.0000
9:132390647:TTC:T	donor_gain	1.0000

AlphaMissense

2606 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:36517606:A:G	L263P	1.000
14:36517606:A:T	L263Q	1.000
14:36517609:A:T	V262D	1.000
14:36517741:C:G	R218P	1.000
14:36517742:G:A	R218C	1.000
14:36517742:G:T	R218S	1.000
14:36517743:C:A	K217N	1.000
14:36517743:C:G	K217N	1.000
14:36517744:T:A	K217M	1.000
14:36517745:T:C	K217E	1.000
14:36517749:T:A	K215N	1.000
14:36517749:T:G	K215N	1.000
14:36517750:T:A	K215I	1.000
14:36517750:T:G	K215T	1.000
14:36517751:T:C	K215E	1.000
14:36517751:T:G	K215Q	1.000
14:36517753:T:C	Y214C	1.000
14:36517753:T:G	Y214S	1.000
14:36517754:A:C	Y214D	1.000
14:36517754:A:G	Y214H	1.000
14:36517754:A:T	Y214N	1.000
14:36517756:C:A	R213L	1.000
14:36517756:C:G	R213P	1.000
14:36517756:C:T	R213H	1.000
14:36517757:G:A	R213C	1.000
14:36517757:G:C	R213G	1.000
14:36517757:G:T	R213S	1.000
14:36517758:G:C	H212Q	1.000
14:36517758:G:T	H212Q	1.000
14:36517759:T:A	H212L	1.000

dbSNP variants (sampled 300 via entrez): RS1000438679 (14:36518633 C>T), RS1000818307 (14:36518751 G>A,C), RS1000909186 (14:36517161 G>A,C,T), RS1001194608 (14:36517675 C>G,T), RS1002396872 (14:36520859 A>G), RS1002450872 (14:36521099 G>A,T), RS1002713210 (14:36518239 A>G), RS1002781589 (14:36521992 A>C), RS1002786833 (14:36522226 A>G), RS1002864748 (14:36521047 G>T), RS1002936342 (14:36516173 C>G), RS1002992360 (14:36516540 T>C), RS1003307358 (14:36519521 T>C), RS1003325893 (14:36518235 C>T), RS1003380206 (14:36520717 C>A,G,T)

Disease associations

OMIM: gene MIM:600635 | disease phenotypes: MIM:610978, MIM:118700, MIM:178500, MIM:218700, MIM:188550, MIM:608751, MIM:254500

GenCC curated gene-disease

Disease	Classification	Inheritance
NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction	Definitive	Autosomal dominant
brain-lung-thyroid syndrome	Definitive	Autosomal dominant
hereditary progressive chorea without dementia	Strong	Autosomal dominant
congenital hypothyroidism	Moderate	Autosomal dominant
choreatic disease	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction	Definitive	AD

Mondo (14): brain-lung-thyroid syndrome (MONDO:0012593), hereditary progressive chorea without dementia (MONDO:0021011), interstitial lung disease 2 (MONDO:0800497), choreatic disease (MONDO:0001595), hereditary ataxia (MONDO:0100309), lung adenocarcinoma (MONDO:0005061), squamous cell carcinoma (MONDO:0005096), hypothyroidism, congenital, nongoitrous, 2 (MONDO:0024264), thyroid cancer, nonmedullary, 1 (MONDO:0008567), hypertrophic cardiomyopathy 8 (MONDO:0012111), neurodevelopmental disorder (MONDO:0700092), plasma cell myeloma (MONDO:0009693), NKX2-1 related choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction (MONDO:0100520), congenital hypothyroidism (MONDO:0018612)

Orphanet (9): Brain-lung-thyroid syndrome (Orphanet:209905), Benign hereditary chorea (Orphanet:1429), Idiopathic pulmonary fibrosis (Orphanet:2032), Acute interstitial pneumonia (Orphanet:79126), Hereditary ataxia (Orphanet:183518), Thyroid ectopia (Orphanet:95712), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443), NON RARE IN EUROPE: Adenocarcinoma of the lung (Orphanet:415268)

HPO phenotypes

114 total (30 of 114 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000021	Megacystis
HP:0000047	Hypospadias
HP:0000076	Vesicoureteral reflux
HP:0000158	Macroglossia
HP:0000239	Large fontanelles
HP:0000252	Microcephaly
HP:0000271	Abnormality of the face
HP:0000280	Coarse facial features
HP:0000282	Facial edema
HP:0000407	Sensorineural hearing impairment
HP:0000465	Webbed neck
HP:0000668	Hypodontia
HP:0000707	Abnormality of the nervous system
HP:0000722	Compulsive behaviors
HP:0000726	Dementia
HP:0000736	Short attention span
HP:0000739	Anxiety
HP:0000752	Hyperactivity
HP:0000820	Abnormality of the thyroid gland
HP:0000821	Hypothyroidism
HP:0000824	Decreased response to growth hormone stimulation test
HP:0000829	Hypoparathyroidism
HP:0000851	Congenital hypothyroidism
HP:0000853	Goiter
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001256	Mild intellectual disability
HP:0001260	Dysarthria

GWAS associations

7 associations (top):

Study	Trait	p-value
GCST000176_11	Height	8.000000e-06
GCST000335_2	Thyroid cancer	2.000000e-09
GCST002013_8	Menarche (age at onset)	7.000000e-06
GCST004753_6	Papillary thyroid cancer	2.000000e-06
GCST004798_7	Differentiated thyroid cancer	1.000000e-07
GCST005867_11	Menarche (age at onset)	1.000000e-11
GCST005867_2	Menarche (age at onset)	2.000000e-15

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004703	age at menarche

MeSH disease descriptors (9)

Descriptor	Name	Tree numbers
D002294	Carcinoma, Squamous Cell	C04.557.470.200.400; C04.557.470.700.400
D002819	Chorea	C10.228.662.262.249; C10.597.350.250; C23.888.592.350.250
D003409	Congenital Hypothyroidism	C05.116.099.343.347; C05.116.132.256; C16.320.240.625; C19.297.155; C19.874.482.281
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
D065886	Neurodevelopmental Disorders	F03.625
C563866	Cardiomyopathy, Familial Hypertrophic, 8 (supp.)
C567034	Choreoathetosis, Hypothyroidism, And Neonatal Respiratory Distress (supp.)
C531684	Hereditary spinal ataxia (supp.)
C566852	Hypothyroidism, Congenital, Nongoitrous, 2 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

33 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
nitrofen	decreases expression, decreases reaction	3
Decitabine	affects expression, affects cotreatment, increases expression	3
Tretinoin	affects cotreatment, increases expression, decreases expression	3
Resveratrol	decreases reaction, increases expression, affects cotreatment, decreases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
sodium arsenite	affects methylation	1
butyraldehyde	increases expression	1
diallyl trisulfide	increases expression	1
pentanal	increases expression	1
2-ethyl-5-carboxypentyl phthalate	increases abundance, increases expression	1
mono(2-ethyl-5-oxohexyl)phthalate	increases abundance, increases expression	1
Chir 99021	affects cotreatment, increases expression	1
jinfukang	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Air Pollutants	increases expression, increases abundance	1
Aldehydes	increases expression	1
Ascorbic Acid	decreases expression, decreases reaction	1
Benzo(a)pyrene	decreases methylation, increases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Diethylhexyl Phthalate	increases abundance, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Vitamin A	decreases expression, decreases reaction	1
Vitamin E	decreases expression, decreases reaction	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1

Cellosaurus cell lines

7 cell lines: 4 embryonic stem cell, 3 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A4Q0	SEES3-1V human NKX2-1, clone1	Embryonic stem cell	Male
CVCL_A4Q1	SEES3-1V human NKX2-1, clone2	Embryonic stem cell	Male
CVCL_A4Q2	SEES3-1V human NKX2-1, clone3	Embryonic stem cell	Male
CVCL_A5HA	ESIBIe003-A-6	Embryonic stem cell	Female
CVCL_D3C4	T1 1Cr NKX2.1 Pt 1	Induced pluripotent stem cell	Female
CVCL_D3C5	T3 2Cr NKX2.1 Pt 3	Induced pluripotent stem cell	Female
CVCL_D3C6	T4 32Cr NKX2.1 Pt 4	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

322 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT05228184	PHASE4	TERMINATED	Use of Tirosint®-SOL or Tablet Formulations of Levothyroxine in Pediatric Patients With Congenital Hypothyroidism (CH)
NCT05371262	PHASE4	COMPLETED	Influence of Initial Levothyroxine Dose on Neurodevelopmental and Growth Outcomes in Congenital Hypothyroidism
NCT02399566	PHASE4	UNKNOWN	Clinical Trial of Erlotinib and Pemetrexed for Maintenance Treatment in Lung Adenocarcinoma
NCT02804646	PHASE4	UNKNOWN	Endostar Durative Transfusion Combined With Chemotherapy in the Treatment of Advanced Lung Adenocarcinoma
NCT00868088	PHASE4	COMPLETED	Photodynamic Therapy to Treat Actinic Damage in Patients With Squamous Cell Carcinoma (SCC) of the Lip
NCT02088515	PHASE4	COMPLETED	Nedaplatin (Jiebaishu®) Combined With Docetaxel for Advanced Lung Squamous Cell Carcinoma
NCT02151149	PHASE4	COMPLETED	Safety and Efficacy Study of Abraxane in Combination With Carboplatin to Treat Advanced NSCL Cancer in the Elderly
NCT03388931	PHASE4	WITHDRAWN	Radiotherapy Dose Escalation in Locally Advanced Squamous Cell Carcinoma of the Larynx or Hypopharynx
NCT00002852	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage I Non-small Cell Lung Cancer
NCT00005838	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy With or Without AE-941 in Treating Patients With Stage III Non-small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00020709	PHASE3	COMPLETED	Combination Chemotherapy and Radiation Therapy With or Without Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer That Cannot Be Removed By Surgery
NCT00049543	PHASE3	COMPLETED	Gefitinib in Treating Patients With Stage IB, II, or IIIA Non-small Cell Lung Cancer That Was Completely Removed by Surgery
NCT00946712	PHASE3	TERMINATED	S0819: Carboplatin and Paclitaxel With or Without Bevacizumab and/or Cetuximab in Treating Patients With Stage IV or Recurrent Non-Small Cell Lung Cancer
NCT01798485	PHASE3	TERMINATED	A Phase 3 Study of Ganetespib in Combination With Docetaxel Versus Docetaxel Alone in Patients With Advanced NSCLC
NCT02011997	PHASE3	UNKNOWN	Comparison of cVATS Segmentectomy Versus Lobectomy for Lung Adenocarcinoma in Situ and With Microinvasion
NCT03391869	PHASE3	ACTIVE_NOT_RECRUITING	Nivolumab and Ipilimumab With or Without Local Consolidation Therapy in Treating Patients With Stage IV Non-Small Cell Lung Cancer
NCT03676192	PHASE3	COMPLETED	To Compare Efficacy and Safety of CT-P16 and European Union-Approved Avastin as First-Line Treatment for Metastatic or Recurrent Non-Squamous Non-Small Cell Lung Cancer
NCT04339218	PHASE3	RECRUITING	Cryoablation in Combination (or Not) With Pembrolizumab and Pemetrexed-carboplatin in 1st-line Treatment for Patients With Metastatic Lung Adenocarcinoma
NCT05204758	PHASE3	COMPLETED	Prophylactic TCM for Mitigation of EGFR-TKI Related Dermatological Adverse Effect
NCT05717803	PHASE3	RECRUITING	Segmentectomy for Ground Glass-dominant Invasive Lung Cancer (ECTOP-1012)
NCT05943795	PHASE3	ACTIVE_NOT_RECRUITING	A Clinical Study of SI-B001 Combined With Docetaxel in the Treatment of Non-small Cell Lung Adenocarcinoma and Lung Squamous Cell Carcinoma
NCT06031181	PHASE3	RECRUITING	Sublobar Resection for Adenocarcinoma in Situ/Minimally Invasive Adenocarcinoma Diagnosed by Intraoperative Frozen Section (ECTOP-1019)
NCT06031246	PHASE3	RECRUITING	Selective Lymph Node Dissection for cT1N0M0 Invasive NSCLC With CTR>0.5 Located in the Apical Segment (ECTOP-1018)
NCT06634966	PHASE3	RECRUITING	Segmentectomy for Solid-dominant Lung Cancer
NCT07169903	PHASE3	NOT_YET_RECRUITING	Segmentectomy vs Lobectomy for 2 - 3cm IASLC Grade 1-2 Lung Adenocarcinoma: A Multi-center RCT
NCT07481786	PHASE3	RECRUITING	Bevacizumab Plus FSRT Versus Hippocampus-Avoidant WBRT in Lung Adenocarcinoma With Extensive Brain Metastases
NCT00101582	PHASE3	COMPLETED	Palifermin for the Reduction of Oral Mucositis in Patients With Locally Advanced Head and Neck Cancer
NCT00201279	PHASE3	COMPLETED	Chemoprevention Study of Oral Cavity Squamous Cell Carcinoma
NCT00201383	PHASE3	COMPLETED	Post-Operative Adjuvant Concurrent Chemoradiotherapy For High Risk Oral Cavity Squamous Cell Carcinoma Patients
NCT00382031	PHASE3	COMPLETED	Zalutumumab in Patients With Non-curable Head and Neck Cancer
NCT00472459	PHASE3	COMPLETED	Photodynamic Therapy (PDT) With Metvix® 160 Milligrams/Gram Cream in Organ Transplant Participants With Non-melanoma Skin Cancer
NCT00559351	PHASE3	TERMINATED	RCT on the Combined Modality Treatment of Squamous Cell Carcinoma of the Esophagus
NCT01161498	PHASE3	TERMINATED	Study of Safety and Efficacy of Talimogene Laherparepvec With Cisplatin and Radiotherapy for Treatment of Locally Advanced Head and Neck Cancer
NCT01363466	PHASE3	TERMINATED	Evaluation of Hysterectomy After Chemoradiation Therapy for Stage IB2/II Cervical Cancer
NCT01532453	PHASE3	TERMINATED	Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients
NCT01706939	PHASE3	ACTIVE_NOT_RECRUITING	The Quarterback Trial: Reduced Dose Radiotherapy for HPV+ Oropharynx Cancer
NCT03115476	PHASE3	TERMINATED	A Trial to Compare the Incidence of Squamous Cell Carcinoma (SCC) and Other Skin Neoplasia on Skin Areas Treated With Ingenol Disoxate Gel or Vehicle Gel for Actinic Keratosis on Face and Chest or Scalp
NCT03257267	PHASE3	COMPLETED	Study of Cemiplimab in Adults With Cervical Cancer
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
NCT00040794	PHASE2	COMPLETED	Combination Chemotherapy, Radiation Therapy, and Gefitinib in Treating Patients With Stage III Non-Small Cell Lung Cancer