NKX2-5

Summary

NKX2-5 (NK2 homeobox 5, HGNC:2488) is a protein-coding gene on chromosome 5q35.1, encoding Homeobox protein Nkx-2.5 (P52952). Transcription factor required for the development of the heart and the spleen. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a homeobox-containing transcription factor. This transcription factor functions in heart formation and development. Mutations in this gene cause atrial septal defect with atrioventricular conduction defect, and also tetralogy of Fallot, which are both heart malformation diseases. Mutations in this gene can also cause congenital hypothyroidism non-goitrous type 5, a non-autoimmune condition. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 1482 — RefSeq curated summary.

At a glance

• Gene–disease (curated): NKX2.5-related congenital, conduction and myopathic heart disease (Definitive, ClinGen) — +8 more curated relationships
• GWAS associations: 28
• Clinical variants (ClinVar): 826 total — 95 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 144
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 78 downstream targets (CollecTRI)
• MANE Select transcript: NM_004387

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2488
Approved symbol	NKX2-5
Name	NK2 homeobox 5
Location	5q35.1
Locus type	gene with protein product
Status	Approved
Aliases	CSX1, NKX2.5, NKX4-1
Ensembl gene	ENSG00000183072
Ensembl biotype	protein_coding
OMIM	600584
Entrez	1482

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000329198, ENST00000424406, ENST00000517440, ENST00000521848

RefSeq mRNA: 3 — MANE Select: NM_004387 NM_001166175, NM_001166176, NM_004387

CCDS: CCDS4387, CCDS54949, CCDS54950

Canonical transcript exons

ENST00000329198 — 2 exons

Exon	Start	End
ENSE00001298509	173232109	173233209
ENSE00002119720	173234750	173235206

Expression profiles

Bgee: expression breadth broad, 98 present calls, max score 98.52.

FANTOM5 (CAGE): breadth broad, TPM avg 2.8225 / max 622.5670, expressed in 231 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
64945	2.1126	189
64947	0.3659	97
64946	0.2559	105
64944	0.0545	27
203797	0.0335	13

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
apex of heart	UBERON:0002098	98.52	gold quality
right atrium auricular region	UBERON:0006631	98.22	gold quality
cardiac atrium	UBERON:0002081	97.51	gold quality
heart left ventricle	UBERON:0002084	97.07	gold quality
cardiac ventricle	UBERON:0002082	96.92	gold quality
heart right ventricle	UBERON:0002080	92.48	gold quality
left ventricle myocardium	UBERON:0006566	91.36	gold quality
myocardium	UBERON:0002349	90.93	gold quality
heart	UBERON:0000948	90.47	gold quality
cardiac muscle of right atrium	UBERON:0003379	88.58	gold quality
spleen	UBERON:0002106	87.42	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	84.29	gold quality
pancreatic ductal cell	CL:0002079	70.65	silver quality
vena cava	UBERON:0004087	69.56	gold quality
oocyte	CL:0000023	68.63	gold quality
triceps brachii	UBERON:0001509	68.54	gold quality
inferior olivary complex	UBERON:0002127	67.00	gold quality
gluteal muscle	UBERON:0002000	66.89	gold quality
lateral globus pallidus	UBERON:0002476	66.80	gold quality
body of tongue	UBERON:0011876	66.47	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	66.40	gold quality
periodontal ligament	UBERON:0008266	65.55	gold quality
lateral nuclear group of thalamus	UBERON:0002736	65.27	gold quality
substantia nigra pars reticulata	UBERON:0001966	64.08	gold quality
secondary oocyte	CL:0000655	64.04	gold quality
tongue	UBERON:0001723	63.76	silver quality
cervix squamous epithelium	UBERON:0006922	63.68	gold quality
nasal cavity epithelium	UBERON:0005384	63.46	gold quality
biceps brachii	UBERON:0001507	63.03	gold quality
subthalamic nucleus	UBERON:0001906	62.57	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.84

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

78 targets.

Target	Regulation
ACOT11
ACTA2
ACTC1	Activation
ACTG2
ADORA1	Activation
ANK2	Unknown
ANKRD1	Activation
ANKRD2
AR
BMP10
BMP2
C2
CALCA
CALR
CTNNB1	Unknown
DACT1	Repression
DACT2	Repression
DACT3	Repression
DHX9
DIO2	Activation
DKK1
E2F1	Repression
EP300
ETV2	Unknown
FGF10
FGFR1
GATA4	Activation
GJA1
GJA5	Activation
HCN4

JASPAR motifs

Motif	Name	Family
MA0063.2	NKX2-5	NK
MA0063.3	NKX2-5	NK

JASPAR matrix evidence (PMIDs): PMID:27013732

Upstream regulators (CollecTRI, top): BHLHA15, CREB1, FOXP1, GATA4, GATA5, GATA6, HIF1A, HMGA2, ISL1, NKX2-5, PBX1, SHOX2, SMAD1, SMAD4, SPI1, STAT3, TBX20, YY1

miRNA regulators (miRDB)

56 targeting NKX2-5, 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-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-3162-3P	100.00	65.37	363
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
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-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4325	99.49	72.20	1342
HSA-MIR-766-3P	99.47	65.24	1811

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• Csx/Nkx2-5 plays a critical role in maintaining highly differentiated cardiac phenotype and in protecting the heart from stresses (PMID:11889119)
• Novel point mutation is associated with congenital heart disease. (PMID:12074273)
• The Polycomb-group gene Rae28 sustains Nkx2.5/Csx expression and is essential for cardiac morphogenesis. (PMID:12122109)
• Nkx-2.5 and GATA-4 play prime roles in Dio2 gene regulation in the human heart and suggests that it is their synergistic action in humans that causes the differential expression of the cardiac Dio2 gene between humans and rats. (PMID:12775767)
• NKX2-5 mutations are a relatively infrequent cause of sporadic ASD (atrial septal defect) and HLHS ( hypoplastic left heart syndrome). Screening for NKX2-5 mutations warranted in individuals with ASD family history, irrespective of AV conduction block. (PMID:12798584)
• Role in heart development and disease. Review. (PMID:12858530)
• effects of gene mutations on ventricular development (PMID:12858532)
• A novel variant t(5;14) whereby NKX2-5, a related (NK-like family) homeobox gene located approximately 2 Mb telomeric of TLX3, juxtaposes BCL11B in a subset of T-cell ALL cell lines is described. (PMID:14500364)
• NKX2.5 mutations occur in a small percentage of patients with various congenital heart diseases. NKX2.5 mutations in non-homeodomain regions may be important in the development of human structural cardiac defects. (PMID:14607454)
• Mutated in cardiac malformations (PMID:15161646)
• Nkx-2.5 is a novel relevant transcriptional regulator of mammary NIS (sodium/iodide symporter) (PMID:15340050)
• somatic nature of NKX2-5 mutations associated with complex cardiac malformations (PMID:15342699)
• mutation reduced transcription activating function, synergism with partners at the ANF and connexin-40 (Cx40) promoters (PMID:15649947)
• NKX2.5 inhibits myocyte differentiation and myotube formation, and up-regulates Gata4 and Tbx5 expression (PMID:15653675)
• mutations of somatic origin in the binding domains of NKX2-5 were associated specifically with atrioventricular or ventricular septal defects and resulted in loss of protein function (PMID:15917268)
• expression of GATA-4 and GATA-6 is up-regulated prior to the transcriptional activation of Nkx 2.5 during cardiogenesis (PMID:16137232)
• NF1 and Nkx2-5 might be involved in heart development and congenital heart disease (PMID:16138909)
• Nkx2-5(-/-) embryos exhibit thyroid bud hypoplasia, providing evidence that NKX2-5 plays a role in thyroid organogenesis (PMID:16418214)
• In T-cell acute lymphoblastic leukemia, alternative t(5;14)(q35;q32.2) forms effect dysregulation of either TLX3 or NKX2-5 homeobox genes at 5q35 by juxtaposition with 14q32.2 breakpoints dispersed across the BCL11B downstream genomic desert. (PMID:17308084)
• Tbx18 interacts with Gata4 and Nkx2-5 and competes Tbx5-mediated activation of the cardiac Natriuretic peptide precursor type a-promoter. Tbx18 down-regulates Tbx6-activated Delta-like 1 expression in the somitic mesoderm in vivo (PMID:17584735)
• Our results do not provide strong genetic evidence for the pathogenecity of the p.Arg25Cys alteration in the NKX2-5 gene. (PMID:17891434)
• it is very likely that this novel mutation causes a complete loss of NKX2-5 function and haploinsufficiency is the pathophysiological mechanism underlying the autosomal-dominant inherited congenital heart disease in the family. (PMID:17891520)
• Mutations in NKX2.5,are infrequently found in patients with congenital cardiac septal defects (PMID:18076106)
• NKX2-5 expression in T-ALL cell lines reactivates embryonal pathways contributing to leukemogenesis. MEF2C is activated by NKX2-5 at both the RNA and protein levels. (PMID:18079734)
• Transgene expression resulted in cardiac conduction defects, increased expression of the cardiac-specific transcription factor NKX2-5 and profound disturbances in connexin 40 and connexin 43. (PMID:18084293)
• analysis of transcriptional activation of the cardiac homeobox gene CSX1/NKX2-5 in a B-cell chronic lymphoproliferative disorder [case report] (PMID:18492690)
• immunohistostaining was positive for Nkx2.5 in 6 of 9 patients with yolk sac tumor (YST), suggesting a certain function of Nkx2.5 in YST (PMID:18547965)
• SUMO1 modification serves as a positive regulator for Nkx2.5 transcriptional activity (PMID:18579533)
• Nkx2-5 function is critical not only during cardiac development in transgenic mice but also in perinatal hearts, by regulating expression of several important gene products involved in conduction and contraction. (PMID:18689573)
• NKX2.5/NKX2.6 mutations are not a common cause of isolated type 1 truncus arteriosus in a small cohort of multiethnic cases. (PMID:18939937)
• Clinical analysis revealed distinct hormonal patterns in thyroid hypoplasia when compared with other variants of thyroid dysgenesis, with genetic abnormalities identified only in few cases in the TSH-R, PAX8, and NKX2.5 genes. (PMID:18976153)
• Translocation of the transcription factors NKX2.5 and GATA4 to the nucleus was observed in all the cultures of mesenchymal stem cells during the differentiation process. (PMID:18983250)
• IN thks study, the NKX2.5 homeodomain has been crystallized in complex with a specific DNA element, the -242 promoter region of atrial natriuretic factor. (PMID:18997347)
• We have identified a mutation in the NKX2.5 gene responsible for autosomal dominantly inherited atrial septal defect in the oval fossa combined with disturbances of atrioventricular conduction in 7 patients spanning 4 generations. (PMID:19049681)
• The association of NKX2.5 mutations is present in a small percentage of patients with non-syndromic congenital heart defects and may explain only a few cases of the disease (PMID:19073351)
• Somatic mutations in NKX2-5 do not represent an important aetiologic pathway in pathologic cardiac development in patients with cardiac septal defects. (PMID:19181906)
• Heterozygous mutations in NKX2.5 transcription factor provide evidence for the genetic causes of congenital heart disease. (PMID:19217179)
• The results provided the primary data on congenital heart disease phenotype associated with GATA4 mutation in the Chinese Uygur population. (PMID:19302747)
• NKX2.5 mutations are extremely rare in congenital heart disease patients of the Chinese Han nationality. (PMID:19371212)
• mutations of NKX2-5 in peripheral blood DNA were barely detected in patients with stroke and patent foramen ovale (PMID:19464101)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	nkx2.5	ENSDARG00000018004
mus_musculus	Nkx2-5	ENSMUSG00000015579
rattus_norvegicus	Nkx2-5	ENSRNOG00000020747
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), NKX2-1 (ENSG00000136352), NKX6-2 (ENSG00000148826), NKX6-1 (ENSG00000163623), NKX6-3 (ENSG00000165066), NKX3-1 (ENSG00000167034), NKX2-6 (ENSG00000180053), NKX1-2 (ENSG00000229544), NKX1-1 (ENSG00000235608)

Protein

Protein identifiers

Homeobox protein Nkx-2.5 — P52952 (reviewed: P52952)

Alternative names: Cardiac-specific homeobox, Homeobox protein CSX, Homeobox protein NK-2 homolog E

All UniProt accessions (4): P52952, A0A0S2Z383, A0A0S2Z3K2, E5RH49

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required for the development of the heart and the spleen. During heart development, acts as a transcriptional activator of NPPA/ANF in cooperation with GATA4. May cooperate with TBX2 to negatively modulate expression of NPPA/ANF in the atrioventricular canal. Binds to the core DNA motif of NPPA promoter. Together with PBX1, required for spleen development through a mechanism that involves CDKN2B repression. Positively regulates transcription of genes such as COL3A1 and MMP2, resulting in increased pulmonary endothelial fibrosis in response to hypoxia.

Subunit / interactions. Homodimer (via the homeobox); binds DNA as homodimer. Interacts (via the homeobox) with TBX5 (via the T-box); this complex binds DNA. Interacts with HIPK1 and HIPK2, but not HIPK3. Interacts with the C-terminal zinc finger of GATA4 through its homeobox domain. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts with FBLIM1. Interacts with TBX18. Interacts with histone methyltransferase NSD2 (via HMG box). Interacts with NEDD9. Interacts with TBX1.

Subcellular location. Nucleus.

Tissue specificity. Expressed only in the heart.

Disease relevance. Atrial septal defect 7, with or without atrioventricular conduction defects (ASD7) [MIM:108900] A congenital heart malformation characterized by incomplete closure of the wall between the atria resulting in blood flow from the left to the right atria, and atrioventricular conduction defects in some cases. The disease is caused by variants affecting the gene represented in this entry. Tetralogy of Fallot (TOF) [MIM:187500] A congenital heart anomaly which consists of pulmonary stenosis, ventricular septal defect, dextroposition of the aorta (aorta is on the right side instead of the left) and hypertrophy of the right ventricle. In this condition, blood from both ventricles (oxygen-rich and oxygen-poor) is pumped into the body often causing cyanosis. The disease is caused by variants affecting the gene represented in this entry. Conotruncal heart malformations (CTHM) [MIM:217095] A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. The disease is caused by variants affecting the gene represented in this entry. Hypothyroidism, congenital, non-goitrous, 5 (CHNG5) [MIM:225250] A non-autoimmune condition characterized by resistance to thyroid-stimulating hormone (TSH) leading to increased levels of plasma TSH and low levels of thyroid hormone. CHNG5 presents variable severity depending on the completeness of the defect. Most patients are euthyroid and asymptomatic, with a normal sized thyroid gland. Only a subset of patients develop hypothyroidism and present a hypoplastic thyroid gland. The disease is caused by variants affecting the gene represented in this entry. Ventricular septal defect 3 (VSD3) [MIM:614432] A common form of congenital cardiovascular anomaly that may occur alone or in combination with other cardiac malformations. It can affect any portion of the ventricular septum, resulting in abnormal communications between the two lower chambers of the heart. Classification is based on location of the communication, such as perimembranous, inlet, outlet (infundibular), central muscular, marginal muscular, or apical muscular defect. Large defects that go unrepaired may give rise to cardiac enlargement, congestive heart failure, pulmonary hypertension, Eisenmenger’s syndrome, delayed fetal brain development, arrhythmias, and even sudden cardiac death. The disease is caused by variants affecting the gene represented in this entry. Hypoplastic left heart syndrome 2 (HLHS2) [MIM:614435] A syndrome due to defective development of the aorta proximal to the entrance of the ductus arteriosus, and hypoplasia of the left ventricle and mitral valve. As a result of the abnormal circulation, the ductus arteriosus and foramen ovale are patent and the right atrium, right ventricle, and pulmonary artery are enlarged. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The homeobox domain binds to double-stranded DNA.

Similarity. Belongs to the NK-2 homeobox family.

Isoforms (3)

UniProt ID	Names	Canonical?
P52952-1	1	yes
P52952-2	2
P52952-3	3

RefSeq proteins (3): NP_001159647, NP_001159648, NP_004378* (*=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 (64 total): sequence variant 55, splice variant 4, helix 3, chain 1, DNA-binding region 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
3RKQ	X-RAY DIFFRACTION	1.7
6WC2	X-RAY DIFFRACTION	2.1
4S0H	X-RAY DIFFRACTION	2.82
6WC5	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P52952-F1	64.14	0.20

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-5578768	Physiological factors
R-HSA-9733709	Cardiogenesis

MSigDB gene sets: 568 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_OUTFLOW_TRACT_SEPTUM_MORPHOGENESIS, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GU_PDEF_TARGETS_DN, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_HEART_TRABECULA_MORPHOGENESIS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_NEGATIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (72): negative regulation of transcription by RNA polymerase II (GO:0000122), vasculogenesis (GO:0001570), heart looping (GO:0001947), heart morphogenesis (GO:0003007), outflow tract septum morphogenesis (GO:0003148), cardiac conduction system development (GO:0003161), atrioventricular node development (GO:0003162), bundle of His development (GO:0003166), Purkinje myocyte differentiation (GO:0003168), aortic valve morphogenesis (GO:0003180), cardiac ventricle formation (GO:0003211), right ventricular cardiac muscle tissue morphogenesis (GO:0003221), ventricular trabecula myocardium morphogenesis (GO:0003222), atrial cardiac muscle tissue development (GO:0003228), apoptotic process involved in heart morphogenesis (GO:0003278), septum secundum development (GO:0003285), proepicardium development (GO:0003342), pulmonary myocardium development (GO:0003350), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), transcription by RNA polymerase II (GO:0006366), heart development (GO:0007507), adult heart development (GO:0007512), positive regulation of cell population proliferation (GO:0008284), positive regulation of gene expression (GO:0010628), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of sodium ion transport (GO:0010765), negative regulation of myotube differentiation (GO:0010832), hemopoiesis (GO:0030097), cell differentiation (GO:0030154), epithelial cell differentiation (GO:0030855), thyroid gland development (GO:0030878), embryonic heart tube development (GO:0035050), negative regulation of apoptotic process (GO:0043066), positive regulation of neuron differentiation (GO:0045666), positive regulation of heart contraction (GO:0045823), 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), spleen development (GO:0048536)

GO Molecular Function (13): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), chromatin binding (GO:0003682), DNA-binding transcription factor activity (GO:0003700), protein homodimerization activity (GO:0042803), sequence-specific DNA binding (GO:0043565), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), sequence-specific double-stranded DNA binding (GO:1990837), protein binding (GO:0005515)

GO Cellular Component (10): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytosol (GO:0005829), protein-containing complex (GO:0032991), protein-DNA complex (GO:0032993), RNA polymerase II transcription regulator complex (GO:0090575), Nkx-2.5 complex (GO:1990664), cytoplasm (GO:0005737)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Generic Transcription Pathway	1
Cardiac conduction	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cardiac muscle tissue development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
transcription by RNA polymerase II	2
ventricular cardiac muscle tissue morphogenesis	2
regulation of DNA-templated transcription	2
DNA-binding transcription factor activity	2
transcription cis-regulatory region binding	2
binding	2
protein-containing complex	2
negative regulation of DNA-templated transcription	1
cell differentiation	1
blood vessel morphogenesis	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
heart development	1
animal organ morphogenesis	1
outflow tract morphogenesis	1
cardiac septum morphogenesis	1
cardiac conduction system development	1
His-Purkinje system development	1
ventricular cardiac muscle tissue development	1
Purkinje myocyte development	1
His-Purkinje system cell differentiation	1
aortic valve development	1
heart valve morphogenesis	1
cardiac chamber formation	1
cardiac ventricle morphogenesis	1
cardiac right ventricle morphogenesis	1
heart trabecula morphogenesis	1
heart morphogenesis	1
apoptotic process involved in morphogenesis	1
atrial septum development	1
septum transversum development	1
mesenchyme development	1
striated muscle tissue development	1
venous blood vessel development	1
DNA-templated transcription	1
regulation of gene expression	1

Protein interactions and networks

STRING

2208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKX2-5	TBX5	Q99593	999
NKX2-5	GATA4	P43694	999
NKX2-5	TBX20	Q9UMR3	990
NKX2-5	HAND2	P61296	981
NKX2-5	SRF	P11831	979
NKX2-5	MEF2C	Q06413	970
NKX2-5	NSD2	O96028	941
NKX2-5	NPPA	P01160	934
NKX2-5	SMARCD3	Q6STE5	916
NKX2-5	TNNT2	P45379	903
NKX2-5	SMARCA4	P51532	901
NKX2-5	GJA5	P36382	873
NKX2-5	TBX3	O15119	867
NKX2-5	ISL1	P20663	860
NKX2-5	HCN4	Q9Y3Q4	858

IntAct

53 interactions, top by confidence:

A	B	Type	Score
KPNA4	MYC	psi-mi:“MI:0915”(physical association)	0.780
SMAD4	SMAD9	psi-mi:“MI:0914”(association)	0.750
GRB2	WIPF3	psi-mi:“MI:0914”(association)	0.730
NKX2-5	TBX5	psi-mi:“MI:0915”(physical association)	0.640
TBX5	NKX2-5	psi-mi:“MI:0915”(physical association)	0.640
NKX2-5	TBX5	psi-mi:“MI:0407”(direct interaction)	0.640
JUN	NFATC1	psi-mi:“MI:0914”(association)	0.610
NKX2-5	RBPMS	psi-mi:“MI:0915”(physical association)	0.560
NKX2-5	KRTAP8-1	psi-mi:“MI:0915”(physical association)	0.560
SHOX	NKX2-5	psi-mi:“MI:0915”(physical association)	0.560
NKX2-5	TRIP10	psi-mi:“MI:0915”(physical association)	0.560
FBLIM1	NKX2-5	psi-mi:“MI:0915”(physical association)	0.550
KSR2	POLR3A	psi-mi:“MI:0914”(association)	0.530
Fblim1	NKX2-5	psi-mi:“MI:0915”(physical association)	0.520
NKX2-5	Fblim1	psi-mi:“MI:0915”(physical association)	0.520
NKX2-5	GATA4	psi-mi:“MI:0915”(physical association)	0.520
GATA4	NKX2-5	psi-mi:“MI:0915”(physical association)	0.520
	NKX2-5	psi-mi:“MI:0407”(direct interaction)	0.440
NKX2-5		psi-mi:“MI:0407”(direct interaction)	0.440
NKX2-5	TLE1	psi-mi:“MI:0915”(physical association)	0.370
FOXA1	NFIC	psi-mi:“MI:0914”(association)	0.350
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350

BioGRID (94): NKX2-5 (Reconstituted Complex), FBXO25 (Reconstituted Complex), NKX2-5 (Proximity Label-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-MS), NKX2-5 (Affinity Capture-Western), TBX5 (Affinity Capture-Western), NKX2-5 (Two-hybrid), NKX2-5 (Two-hybrid), KRTAP8-1 (Two-hybrid), SHOX (Two-hybrid)

ESM2 similar proteins: A0A8I6AGW3, A2A9A2, A6NMB9, A8MYZ6, E9PZZ1, J3QK54, O02755, O02756, O35392, O35767, O60548, O70220, P05554, P17676, P21272, P28033, P35713, P42582, P49715, P49716, P52952, P53566, P58012, Q12952, Q13461, Q14526, Q60843, Q61345, Q63244, Q63250, Q6BEB4, Q6VFT5, Q6VFT6, Q6ZQN5, Q70KY4, Q8IU81, Q8MIP2, Q8NDY6, Q8R2I0, Q98937

Diamond homologs: A0JPN1, A1YG85, A5PKG8, A6NJ46, A6NMT0, A7MB54, A9L937, B0VXK3, D2KQB0, E7FDX5, M0R6D8, O08686, O13023, O35762, O42365, O43364, O43711, O55144, O88181, O93366, O93367, O93590, P0C1T1, P10035, P14652, P14837, P20009, P28468, P31245, P31246, P31261, P31314, P42583, P42584, P43120, P43345, P43688, P50219, P52945, P52950

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
NKX2-5	“down-regulates quantity by repression”	CTNNB1	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	GATA4	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	LYL1	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	MEF2C	“transcriptional regulation”
JARID2	“down-regulates activity”	NKX2-5	binding
NKX2-5	“up-regulates quantity by expression”	MYL2	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	ANKRD1	“transcriptional regulation”
CSNK2A1	“up-regulates activity”	NKX2-5	phosphorylation
NKX2-5	unknown	NPPB	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	TBX5	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 43 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
Diseases of signal transduction by growth factor receptors and second messengers	6	11.4×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
anatomical structure morphogenesis	5	17.9×	5e-04
transcription by RNA polymerase II	5	9.0×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	95
Likely pathogenic	30
Uncertain significance	381
Likely benign	238
Benign	16

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1068493	NM_004387.4(NKX2-5):c.270del (p.Ala91fs)	Pathogenic
1069411	NM_004387.4(NKX2-5):c.281del (p.Pro94fs)	Pathogenic
1071005	NM_004387.4(NKX2-5):c.462del (p.Glu154fs)	Pathogenic
1072792	NM_004387.4(NKX2-5):c.598_599del (p.Gln200fs)	Pathogenic
1299661	NM_004387.4(NKX2-5):c.261del (p.Ala88fs)	Pathogenic
1323366	NM_004387.4(NKX2-5):c.530_536del (p.Leu177fs)	Pathogenic
1358436	NM_004387.4(NKX2-5):c.377_378del (p.Glu126fs)	Pathogenic
1364905	NM_004387.4(NKX2-5):c.340_341del (p.Cys114fs)	Pathogenic
1375957	NM_004387.4(NKX2-5):c.340_341dup (p.Leu116fs)	Pathogenic
1401094	NM_004387.4(NKX2-5):c.585del (p.Gln196fs)	Pathogenic
1409300	NM_004387.4(NKX2-5):c.744C>A (p.Tyr248Ter)	Pathogenic
1417309	NM_004387.4(NKX2-5):c.437C>A (p.Ser146Ter)	Pathogenic
1432308	NM_004387.4(NKX2-5):c.212del (p.Ala71fs)	Pathogenic
1432865	NM_004387.4(NKX2-5):c.423dup (p.Arg142fs)	Pathogenic
1443937	NM_004387.4(NKX2-5):c.253_256dup (p.Phe86fs)	Pathogenic
1451578	NM_004387.4(NKX2-5):c.512T>C (p.Leu171Pro)	Pathogenic
1452531	NM_004387.4(NKX2-5):c.270dup (p.Ala91fs)	Pathogenic
1452571	NM_004387.4(NKX2-5):c.230del (p.Pro77fs)	Pathogenic
1456175	NM_004387.4(NKX2-5):c.778_784dup (p.Ala262fs)	Pathogenic
1515823	NM_004387.4(NKX2-5):c.433T>C (p.Phe145Leu)	Pathogenic
156158	NM_004387.4(NKX2-5):c.461A>G (p.Glu154Gly)	Pathogenic
156159	NM_004387.4(NKX2-5):c.618del (p.Leu207fs)	Pathogenic
156160	NM_004387.4(NKX2-5):c.721_728del (p.Tyr241fs)	Pathogenic
159255	NM_004387.4(NKX2-5):c.471_472del (p.Phe157fs)	Pathogenic
1805774	NM_004387.4(NKX2-5):c.487del (p.Leu163fs)	Pathogenic
190839	NM_004387.4(NKX2-5):c.554_555insC (p.Trp185fs)	Pathogenic
195219	NM_004387.4(NKX2-5):c.685_686dup (p.Cys230fs)	Pathogenic
1993512	NM_004387.4(NKX2-5):c.328A>T (p.Lys110Ter)	Pathogenic
1999808	NM_004387.4(NKX2-5):c.168C>G (p.Tyr56Ter)	Pathogenic
2029887	NM_004387.4(NKX2-5):c.554G>A (p.Trp185Ter)	Pathogenic

SpliceAI

387 predictions. Top by Δscore:

Variant	Effect	Δscore
5:173233205:CAGCT:C	acceptor_gain	1.0000
5:173234049:T:C	donor_gain	1.0000
5:173234060:C:CA	donor_gain	1.0000
5:173234746:TCA:T	donor_loss	1.0000
5:173234747:CACCT:C	donor_loss	1.0000
5:173234748:ACCT:A	donor_loss	1.0000
5:173234749:CCTTT:C	donor_gain	1.0000
5:173233207:GCT:G	acceptor_gain	0.9900
5:173233208:CT:C	acceptor_gain	0.9900
5:173233208:CTC:C	acceptor_gain	0.9900
5:173233209:TC:T	acceptor_loss	0.9900
5:173233209:TCT:T	acceptor_gain	0.9900
5:173233210:C:CC	acceptor_gain	0.9900
5:173233210:C:G	acceptor_gain	0.9900
5:173234744:CCTCA:C	donor_loss	0.9900
5:173234745:CTCA:C	donor_loss	0.9900
5:173233206:AGCT:A	acceptor_gain	0.9800
5:173234748:A:AC	donor_gain	0.9800
5:173234749:C:CC	donor_gain	0.9800
5:173233221:C:CT	acceptor_gain	0.9700
5:173234015:T:TA	donor_gain	0.9600
5:173234061:C:A	donor_gain	0.9600
5:173234460:T:TA	donor_gain	0.9600
5:173233952:G:A	donor_gain	0.9500
5:173234743:T:TA	donor_gain	0.9500
5:173233317:G:A	donor_gain	0.9400
5:173234225:T:A	donor_gain	0.9400
5:173233346:CT:C	donor_gain	0.9300
5:173234005:C:A	donor_gain	0.9200
5:173233345:A:AC	donor_gain	0.9100

AlphaMissense

2042 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:173232962:C:A	K194N	1.000
5:173232962:C:G	K194N	1.000
5:173232963:T:A	K194M	1.000
5:173232964:T:C	K194E	1.000
5:173232968:C:A	K192N	1.000
5:173232968:C:G	K192N	1.000
5:173232969:T:A	K192M	1.000
5:173232970:T:C	K192E	1.000
5:173232970:T:G	K192Q	1.000
5:173232972:T:C	Y191C	1.000
5:173232973:A:G	Y191H	1.000
5:173232976:G:A	R190C	1.000
5:173232976:G:C	R190G	1.000
5:173232976:G:T	R190S	1.000
5:173232978:C:G	R189P	1.000
5:173232979:G:C	R189G	1.000
5:173232980:G:C	N188K	1.000
5:173232980:G:T	N188K	1.000
5:173232981:T:A	N188I	1.000
5:173232981:T:C	N188S	1.000
5:173232981:T:G	N188T	1.000
5:173232982:T:C	N188D	1.000
5:173232982:T:G	N188H	1.000
5:173232983:C:A	Q187H	1.000
5:173232983:C:G	Q187H	1.000
5:173232984:T:G	Q187P	1.000
5:173232985:G:T	Q187K	1.000
5:173232986:G:C	F186L	1.000
5:173232986:G:T	F186L	1.000
5:173232987:A:C	F186C	1.000

dbSNP variants (sampled 300 via entrez): RS1000529990 (5:173235180 G>T), RS1001059393 (5:173236769 G>A,T), RS1002445763 (5:173237112 G>A), RS1002469920 (5:173233762 G>A,C), RS1002628434 (5:173237067 G>A,T), RS1003034022 (5:173233746 A>G), RS1003777077 (5:173232502 C>T), RS1003904687 (5:173232267 C>A,G,T), RS1004442524 (5:173234640 C>T), RS1004876197 (5:173234318 C>T), RS1004963332 (5:173235240 C>G), RS1004973072 (5:173235589 G>T), RS1005179646 (5:173233312 G>A,T), RS1005473839 (5:173235842 G>A,C,T), RS1005638568 (5:173232346 AC>A)

Disease associations

OMIM: gene MIM:600584 | disease phenotypes: MIM:108900, MIM:187500, MIM:225250, MIM:614432, MIM:614435, MIM:217095, MIM:108800, MIM:611603, MIM:271400, MIM:610805

GenCC curated gene-disease

Disease	Classification	Inheritance
atrial septal defect 7	Definitive	Autosomal dominant
conotruncal heart malformations	Definitive	Semidominant
hypothyroidism, congenital, nongoitrous, 5	Definitive	Autosomal dominant
tetralogy of fallot	Definitive	Autosomal dominant
NKX2.5-related congenital, conduction and myopathic heart disease	Strong	Autosomal dominant
familial isolated congenital asplenia	Supportive	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant
familial bicuspid aortic valve	Supportive	Autosomal dominant
athyreosis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
NKX2.5-related congenital, conduction and myopathic heart disease	Definitive	AD

Mondo (22): atrial septal defect 7 (MONDO:0007173), tetralogy of fallot (MONDO:0008542), hypothyroidism, congenital, nongoitrous, 5 (MONDO:0009154), ventricular septal defect 3 (MONDO:0013749), hypoplastic left heart syndrome 2 (MONDO:0013752), conotruncal heart malformations (MONDO:0016581), long QT syndrome (MONDO:0002442), congenital heart disease (MONDO:0005453), NKX2.5-related congenital, conduction and myopathic heart disease (MONDO:0800441), atrial septal defect (MONDO:0006664), lissencephaly due to TUBA1A mutation (MONDO:0012703), familial isolated congenital asplenia (MONDO:0010066), double outlet right ventricle (MONDO:0018089), dilated cardiomyopathy (MONDO:0005021), congenital anomaly of kidney and urinary tract (MONDO:0019719)

Orphanet (14): Atrial septal defect-atrioventricular conduction defects syndrome (Orphanet:1479), Hypoplastic left heart syndrome (Orphanet:2248), Conotruncal heart malformations (Orphanet:2445), Tetralogy of Fallot (Orphanet:3303), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426), Thyroid ectopia (Orphanet:95712), Interatrial communication (Orphanet:1478), Lissencephaly due to TUBA1A mutation (Orphanet:171680), Familial isolated congenital asplenia (Orphanet:101351), Dilated cardiomyopathy (Orphanet:217604), Renal or urinary tract malformation (Orphanet:93545), Rare hypertrophic cardiomyopathy (Orphanet:217569), Aortic arch interruption (Orphanet:2299)

HPO phenotypes

144 total (30 of 144 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000158	Macroglossia
HP:0000233	Thin vermilion border
HP:0000239	Large fontanelles
HP:0000256	Macrocephaly
HP:0000268	Dolichocephaly
HP:0000271	Abnormality of the face
HP:0000280	Coarse facial features
HP:0000282	Facial edema
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000470	Short neck
HP:0000520	Proptosis
HP:0000768	Pectus carinatum
HP:0000820	Abnormality of the thyroid gland
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0000851	Congenital hypothyroidism
HP:0000952	Jaundice
HP:0000958	Dry skin
HP:0000961	Cyanosis
HP:0001156	Brachydactyly
HP:0001249	Intellectual disability
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001262	Excessive daytime somnolence
HP:0001263	Global developmental delay

GWAS associations

28 associations (top):

Study	Trait	p-value
GCST000562_7	PR interval	9.000000e-13
GCST001399_3	Infantile hypertrophic pyloric stenosis	1.000000e-15
GCST001969_17	Heart rate	2.000000e-12
GCST002987_18	Stroke	5.000000e-07
GCST003818_67	Resting heart rate	4.000000e-16
GCST006061_40	Atrial fibrillation	3.000000e-14
GCST006061_41	Atrial fibrillation	1.000000e-14
GCST006414_58	Atrial fibrillation	2.000000e-11
GCST006414_92	Atrial fibrillation	5.000000e-22
GCST007045_5	PR interval	6.000000e-21
GCST010321_139	PR interval	5.000000e-55
GCST010346_38	TPE interval (resting)	2.000000e-14
GCST010346_44	TPE interval (resting)	3.000000e-08
GCST010796_4982	Electrocardiogram morphology (amplitude at temporal datapoints)	7.000000e-10
GCST010796_4983	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-12
GCST010796_4984	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-14
GCST010796_4985	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-15
GCST010796_4986	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-18
GCST010796_4987	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-18
GCST010796_4988	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-18
GCST010796_4989	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-17
GCST010796_4990	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-16
GCST010796_4991	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-17
GCST010796_4992	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-18
GCST010796_4993	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-16
GCST010796_4994	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-13
GCST010796_4995	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-11
GCST010796_4996	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004644	TPE interval measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (13)

Descriptor	Name	Tree numbers
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D002312	Cardiomyopathy, Hypertrophic	C14.280.238.100; C14.280.484.048.750.070.160
D004310	Double Outlet Right Ventricle	C14.240.400.560.540.500; C14.240.400.915.300; C14.280.400.560.540.500; C14.280.400.915.300; C16.131.240.400.560.540.500; C16.131.240.400.915.300
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D006344	Heart Septal Defects, Atrial	C14.240.400.560.375; C14.280.400.560.375; C16.131.240.400.560.375
D008133	Long QT Syndrome	C14.280.067.565; C14.280.123.625; C16.131.240.400.715; C23.550.073.547
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
D014339	Truncus Arteriosus, Persistent	C14.240.400.560.098.500; C14.280.400.560.098.500; C16.131.240.400.560.098.500
D014693	Ventricular Fibrillation	C14.280.067.922; C23.550.073.922
C566906	Cakut (supp.)
C567123	Hypothyroidism, Congenital, Nongoitrous, 5 (supp.)
C566908	Lissencephaly 3 (supp.)
C563028	Splenic Hypoplasia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Cadmium	decreases expression	2
Cisplatin	affects cotreatment, increases expression	2
Cadmium Chloride	decreases expression	2
arsenite	increases methylation	1
CGP 52608	increases reaction, affects binding	1
CD 437	decreases expression	1
1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene	affects cotreatment, increases expression	1
3-(4’-hydroxy-3’-adamantylbiphenyl-4-yl)acrylic acid	decreases expression	1
nutlin 3	affects cotreatment, increases expression	1
abrine	increases expression	1
licochalcone B	increases expression	1
jinfukang	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Azacitidine	increases expression	1
Benzo(a)pyrene	affects methylation, decreases methylation	1
Camptothecin	increases expression	1
Chelating Agents	affects binding, decreases expression	1
Copper	affects binding, decreases expression	1
Dactinomycin	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Phenylbutyrates	affects cotreatment, increases expression	1
Phthalic Acids	increases methylation	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	increases expression	1
Testosterone	decreases expression	1
Tretinoin	affects cotreatment, increases expression	1
Trichloroethylene	increases expression	1
Triclosan	decreases expression	1

Cellosaurus cell lines

124 cell lines: 120 cancer cell line, 3 embryonic stem cell, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_0138	ACH-2	Cancer cell line	Female
CVCL_0207	CCRF-CEM	Cancer cell line	Female
CVCL_0R18	CEM-TART clone 1A2	Cancer cell line	Female
CVCL_0U11	CEM/MX1	Cancer cell line	Female
CVCL_1B35	CEM/VM-1	Cancer cell line	Female
CVCL_1E04	Rev-CEM	Cancer cell line	Female
CVCL_1G53	CEM-GFP	Cancer cell line	Female
CVCL_1G54	EGFP-CEM-NKr	Cancer cell line	Female
CVCL_2265	1301	Cancer cell line	Female
CVCL_3484	8E5(CEM)	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT02513940	PHASE4	COMPLETED	Influence of Testosterone Administration on Drug-Induced QT Interval Prolongation and Torsades de Pointes
NCT03834883	PHASE4	COMPLETED	Reducing the Risk of Drug-Induced QT Interval Lengthening in Women
NCT04169100	PHASE4	UNKNOWN	Novel Form of Acquired Long QT Syndrome
NCT04675788	PHASE4	COMPLETED	Novel Approaches for Minimizing Drug-Induced QT Interval Lengthening
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905	PHASE2	UNKNOWN	Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
NCT01648205	PHASE2	COMPLETED	Long-term Efficacy Study of Sodium Channel Blocker in LQT3 Patients
NCT02412709	PHASE2	UNKNOWN	Long QT Syndrome Screening in Newborns
NCT04581408	PHASE2	COMPLETED	Mutation-specific Therapy for the Long QT Syndrome
NCT00573066	PHASE1	COMPLETED	Understanding Dexmedetomidine In Infants Post-Operative From Cardiac Surgery
NCT01915277	PHASE1	COMPLETED	A Phase I Study of Dexmedetomidine Bolus and Infusion in Corrective Infant Cardiac Surgery: Safety and Pharmacokinetics
NCT04713657	PHASE1	RECRUITING	Beta-blocker Administration for Cardiomyocyte Division
NCT00316459	PHASE1	COMPLETED	Study Evaluating the Effects of Multiple Oral Doses of ERB-041 on Cardiac Repolarization in Healthy Subjects
NCT01849003	PHASE1	COMPLETED	Study of the Effect of GS-6615 in Subjects With LQT-3
NCT02365532	PHASE1	COMPLETED	Effect of Oral GS-6615 on Dofetilide-Induced QT Prolongation, Safety, and Tolerability in Healthy Adults
NCT02412098	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Hepatic Function
NCT02441829	PHASE1	COMPLETED	Pharmacokinetics of Eleclazine in Adults With Normal and Impaired Renal Function
NCT05759962	PHASE1	COMPLETED	Phase 1 Study of LQT-1213 in Healthy Adults
NCT00004361	Not specified	COMPLETED	Study of the Relationship Between Calcium Levels and Intact Parathyroid Hormone (iPTH) in Adults With Repaired or Palliated Conotruncal Cardiac Defects