NKX2-6

Summary

NKX2-6 (NK2 homeobox 6, HGNC:32940) is a protein-coding gene on chromosome 8p21.2, encoding Homeobox protein Nkx-2.6 (A6NCS4). Acts as a transcriptional activator.

This gene encodes a homeobox-containing protein that belongs to the NK-2 homeobox family. This protein is a vertebrate homolog of Drosophila homeobox-containing protein called ’tinman’, which has been shown to be essential for development of the heart-like dorsal vessel. In conjunction with related gene, NKX2-5, this gene may play a role in both pharyngeal and cardiac embryonic development. Mutations in this gene are associated with persistent truncus arteriosus.

Source: NCBI Gene 137814 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 29
• Clinical variants (ClinVar): 132 total — 3 likely-pathogenic
• Phenotypes (HPO): 65
• MANE Select transcript: NM_001136271

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:32940
Approved symbol	NKX2-6
Name	NK2 homeobox 6
Location	8p21.2
Locus type	gene with protein product
Status	Approved
Aliases	CSX2, NKX4-2
Ensembl gene	ENSG00000180053
Ensembl biotype	protein_coding
OMIM	611770
Entrez	137814

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000325017

RefSeq mRNA: 1 — MANE Select: NM_001136271 NM_001136271

Canonical transcript exons

ENST00000325017 — 2 exons

Exon	Start	End
ENSE00001324680	23706325	23706756
ENSE00003487472	23701740	23703082

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 57.11.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1157 / max 22.0800, expressed in 48 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
92340	0.1157	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	57.11	gold quality
minor salivary gland	UBERON:0001830	49.14	gold quality
saliva-secreting gland	UBERON:0001044	47.36	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	46.92	silver quality
heart	UBERON:0000948	43.64	gold quality
heart left ventricle	UBERON:0002084	42.95	gold quality
stromal cell of endometrium	CL:0002255	41.88	silver quality
bone marrow cell	CL:0002092	38.05	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	34.93	gold quality
duodenum	UBERON:0002114	33.36	silver quality
bone marrow	UBERON:0002371	32.71	gold quality
liver	UBERON:0002107	32.37	silver quality
muscle tissue	UBERON:0002385	32.20	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
tonsil	UBERON:0002372	31.78	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
urinary bladder	UBERON:0001255	27.62	gold quality
lymph node	UBERON:0000029	27.57	gold quality
blood	UBERON:0000178	27.48	gold quality
leukocyte	CL:0000738	26.67	gold quality
monocyte	CL:0000576	26.58	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.65

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
GJA5	Activation
MEF2A	Activation
TUBB3	Unknown

Literature-anchored findings (GeneRIF, showing 7)

• weakly activates transcription of a Cx40 promoter, may have role in heart development (PMID:15649947)
• 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)
• NKX2-6 plays a role in human cardiogenesis. (PMID:24421281)
• Heterozygous mutations in Nkx2.6, p.V176M and p.K177X, were identified in 2 unrelated patients, one with tetralogy of Fallot and one with double outlet of right ventricle and ventricular septal defect. Increased vulnerability to TOF or DORV is discussed. (PMID:25195019)
• Data associated genetically defective NK2 homeobox 6 (NKX2-6) with enhanced susceptibility to atrial fibrillation (AF). (PMID:25319568)
• This study firstly links NKX2.6 loss-of-function mutation with increased susceptibility to isolated VSD. (PMID:25380965)
• NKX2-6 related congenital heart disease: Biallelic homeodomain-disrupting variants and truncus arteriosus. (PMID:32198970)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
mus_musculus	Nkx2-6	ENSMUSG00000044186
rattus_norvegicus	Nkx2-6	ENSRNOG00000021910
drosophila_melanogaster	slou	FBGN0002941
drosophila_melanogaster	NK7.1	FBGN0024321
drosophila_melanogaster	HGTX	FBGN0040318
drosophila_melanogaster	vnd	FBGN0261930
drosophila_melanogaster	scro	FBGN0287186
caenorhabditis_elegans		WBGENE00000428
caenorhabditis_elegans	ceh-9	WBGENE00000434
caenorhabditis_elegans		WBGENE00000445
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), NKX2-5 (ENSG00000183072), NKX1-2 (ENSG00000229544), NKX1-1 (ENSG00000235608)

Protein

Protein identifiers

Homeobox protein Nkx-2.6 — A6NCS4 (reviewed: A6NCS4)

Alternative names: Homeobox protein NK-2 homolog F

All UniProt accessions (1): A6NCS4

UniProt curated annotations — full annotation on UniProt →

Function. Acts as a transcriptional activator. In conjunction with NKX2-5, may play a role in both pharyngeal and cardiac embryonic development.

Subcellular location. Nucleus.

Disease relevance. 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 may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the NK-2 homeobox family.

RefSeq proteins (1): NP_001129743* (*=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 (7 total): sequence variant 3, chain 1, DNA-binding region 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NCS4-F1	64.31	0.21

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 204 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_STRIATED_MUSCLE_CELL_DIFFERENTIATION, GOBP_VENTRICULAR_CARDIAC_MUSCLE_CELL_DIFFERENTIATION, GOBP_TONGUE_DEVELOPMENT, GOBP_FOREBRAIN_DEVELOPMENT, GOBP_HYPOTHALAMUS_DEVELOPMENT, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_EMBRYONIC_HEART_TUBE_DEVELOPMENT, GOBP_MUSCLE_STRUCTURE_DEVELOPMENT, chr8p21, GOBP_CARDIAC_MUSCLE_CELL_DIFFERENTIATION, GOBP_HEAD_DEVELOPMENT, GOBP_CARDIOCYTE_DIFFERENTIATION

GO Biological Process (22): regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of cell population proliferation (GO:0008284), hypothalamus development (GO:0021854), cell differentiation (GO:0030154), epithelial cell differentiation (GO:0030855), embryonic heart tube development (GO:0035050), negative regulation of apoptotic process (GO:0043066), tongue development (GO:0043586), positive regulation of transcription by RNA polymerase II (GO:0045944), digestive tract development (GO:0048565), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679), atrial cardiac muscle cell development (GO:0055014), ventricular cardiac muscle cell development (GO:0055015), pharyngeal system development (GO:0060037), pericardium development (GO:0060039), epithelial cell apoptotic process (GO:1904019), negative regulation of epithelial cell apoptotic process (GO:1904036), regulation of DNA-templated transcription (GO:0006355), apoptotic process (GO:0006915), heart development (GO:0007507), cell population proliferation (GO:0008283)

GO Molecular Function (5): 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, RNA polymerase II-specific (GO:0001228), DNA-binding transcription factor activity (GO:0003700), DNA binding (GO:0003677)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
epithelium development	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
cell population proliferation	2
heart development	2
tube development	2
apoptotic process	2
regulation of transcription by RNA polymerase II	2
cardiac muscle cell development	2
regulation of cell population proliferation	1
positive regulation of cellular process	1
diencephalon development	1
limbic system development	1
anatomical structure development	1
cellular developmental process	1
cell differentiation	1
embryonic organ development	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
sensory organ development	1
positive regulation of DNA-templated transcription	1
digestive system development	1
positive regulation of cell population proliferation	1
epithelial cell proliferation	1
regulation of epithelial cell proliferation	1
atrial cardiac muscle cell differentiation	1
ventricular cardiac muscle cell differentiation	1
chordate embryonic development	1
system development	1
negative regulation of apoptotic process	1
epithelial cell apoptotic process	1
regulation of epithelial cell apoptotic process	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
programmed cell death	1
apoptotic signaling pathway	1
execution phase of apoptosis	1
cis-regulatory region sequence-specific DNA binding	1

Protein interactions and networks

STRING

540 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NKX2-6	CFC1	P0CG37	779
NKX2-6	GDF1	P27539	693
NKX2-6	TBX1	O43435	645
NKX2-6	UFD1	Q92890	388
NKX2-6	GATA4	P43694	384
NKX2-6	TBX5	Q99593	364
NKX2-6	TBX20	Q9UMR3	359
NKX2-6	LYZL4	Q96KX0	338
NKX2-6	FOXD4L5	Q5VV16	320
NKX2-6	GATA5	Q9BWX5	319
NKX2-6	POU4F3	Q15319	318
NKX2-6	ZBTB7B	O15156	316
NKX2-6	HAND2	P61296	315
NKX2-6	CDC45	O75419	314
NKX2-6	TPBGL	P0DKB5	309
NKX2-6	POU6F2	P78424	309

IntAct

2 interactions, top by confidence:

A	B	Type	Score
NKX2-6	RPS9	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (1): RPS9 (Proximity Label-MS)

ESM2 similar proteins: A0A1W2PRP0, A6NCS4, A7Y7W2, O14512, O43638, O57601, O70220, O96004, P07812, P09023, P10085, P10284, P17483, P22091, P24899, P50548, P52954, P52955, P55318, P57100, P63156, P63157, P70447, P79772, P97832, Q02346, Q05917, Q0VCE2, Q12952, Q1XID0, Q28555, Q3I5G5, Q3Y598, Q60688, Q61660, Q63244, Q63250, Q64279, Q64305, Q64731

Diamond homologs: A1YF16, A1YG93, A2RU54, A2T764, A6NCS4, A6NHT5, G5EE18, M0R6D8, O02786, O35767, O42230, O57601, O60479, O70218, P10181, P13297, P15857, P19601, P20009, P23410, P28360, P28361, P28362, P35548, P35993, P40764, P42580, P42581, P43687, P43688, P48031, P50219, P50223, P50574, P50575, P50576, P50577, P52953, P53547, P53770

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	3
Uncertain significance	80
Likely benign	33
Benign	12

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
133345	NM_001136271.3(NKX2-6):c.453_454insT (p.Lys152Ter)	Likely pathogenic
2432235	NM_001136271.3(NKX2-6):c.568C>T (p.Gln190Ter)	Likely pathogenic
791	NM_001136271.3(NKX2-6):c.451T>C (p.Phe151Leu)	Likely pathogenic

SpliceAI

454 predictions. Top by Δscore:

Variant	Effect	Δscore
8:23706319:A:AC	donor_gain	1.0000
8:23706320:C:CC	donor_gain	1.0000
8:23706320:CTCA:C	donor_gain	1.0000
8:23706323:A:AC	donor_gain	1.0000
8:23706324:C:CC	donor_gain	1.0000
8:23706324:CGTGG:C	donor_gain	1.0000
8:23703079:GGCT:G	acceptor_gain	0.9900
8:23703080:GCTC:G	acceptor_loss	0.9900
8:23703081:CT:C	acceptor_gain	0.9900
8:23703082:TCTAA:T	acceptor_loss	0.9900
8:23703083:C:CC	acceptor_gain	0.9900
8:23703084:T:A	acceptor_loss	0.9900
8:23706318:TAC:T	donor_loss	0.9900
8:23706320:C:CA	donor_loss	0.9900
8:23706320:CT:C	donor_gain	0.9900
8:23706321:T:TA	donor_loss	0.9900
8:23703078:GGGCT:G	acceptor_gain	0.9800
8:23703083:C:A	acceptor_gain	0.9800
8:23706317:TTAC:T	donor_loss	0.9800
8:23706324:CG:C	donor_gain	0.9800
8:23703080:GCT:G	acceptor_gain	0.9700
8:23703081:CTC:C	acceptor_gain	0.9700
8:23703082:TCTA:T	acceptor_gain	0.9700
8:23706319:ACT:A	donor_gain	0.9700
8:23706320:CTC:C	donor_gain	0.9700
8:23706324:CGT:C	donor_gain	0.9600
8:23704956:C:A	donor_gain	0.9500
8:23703090:C:CT	acceptor_gain	0.9400
8:23704149:T:C	acceptor_gain	0.9400
8:23704915:G:C	donor_gain	0.9400

AlphaMissense

1885 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:23702817:G:C	F180L	1.000
8:23702817:G:T	F180L	1.000
8:23702819:A:G	F180L	1.000
8:23702799:T:A	K186N	0.999
8:23702799:T:G	K186N	0.999
8:23702812:T:A	N182I	0.999
8:23702812:T:C	N182S	0.999
8:23702812:T:G	N182T	0.999
8:23702813:T:C	N182D	0.999
8:23702814:C:A	Q181H	0.999
8:23702814:C:G	Q181H	0.999
8:23702818:A:C	F180C	0.999
8:23702818:A:G	F180S	0.999
8:23702819:A:C	F180V	0.999
8:23702819:A:T	F180I	0.999
8:23702820:C:A	W179C	0.999
8:23702820:C:G	W179C	0.999
8:23702904:G:C	F151L	0.999
8:23702904:G:T	F151L	0.999
8:23702905:A:G	F151S	0.999
8:23702906:A:G	F151L	0.999
8:23702940:A:C	F139L	0.999
8:23702940:A:T	F139L	0.999
8:23702941:A:C	F139C	0.999
8:23702942:A:G	F139L	0.999
8:23702793:C:A	K188N	0.998
8:23702793:C:G	K188N	0.998
8:23702801:T:C	K186E	0.998
8:23702811:G:C	N182K	0.998
8:23702811:G:T	N182K	0.998

dbSNP variants (sampled 300 via entrez): RS1000892942 (8:23705248 C>A,T), RS1001263040 (8:23705499 G>A), RS1001829636 (8:23701436 T>C), RS1002395947 (8:23705596 C>T), RS1002865966 (8:23702154 G>A), RS1003016561 (8:23708234 G>C), RS1003047601 (8:23708542 C>A,T), RS1003194518 (8:23701777 A>G), RS1003230665 (8:23703648 A>C), RS1003370053 (8:23707040 G>A), RS1003891059 (8:23708395 A>G), RS1004022424 (8:23702851 A>C), RS1004554623 (8:23704417 C>T), RS1004578049 (8:23708543 T>C), RS1005033593 (8:23707453 T>G)

Disease associations

OMIM: gene MIM:611770 | disease phenotypes: MIM:217095

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Strong	Autosomal recessive
conotruncal heart malformations	Moderate	Autosomal recessive

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AR

Mondo (4): conotruncal heart malformations (MONDO:0016581), cerebral palsy (MONDO:0006497), persistent truncus arteriosus (MONDO:0018072), congenital heart disease (MONDO:0005453)

Orphanet (3): Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426)

HPO phenotypes

65 total (30 of 65 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000233	Thin vermilion border
HP:0000268	Dolichocephaly
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000520	Proptosis
HP:0000778	Hypoplasia of the thymus
HP:0000849	Adrenocortical abnormality
HP:0000961	Cyanosis
HP:0001156	Brachydactyly
HP:0001279	Syncope
HP:0001511	Intrauterine growth retardation
HP:0001627	Abnormal heart morphology
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001640	Cardiomegaly
HP:0001642	Pulmonic stenosis
HP:0001643	Patent ductus arteriosus
HP:0001649	Tachycardia
HP:0001654	Abnormal heart valve morphology
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001660	Truncus arteriosus
HP:0001667	Right ventricular hypertrophy
HP:0001669	Transposition of the great arteries
HP:0001674	Complete atrioventricular canal defect
HP:0001680	Coarctation of aorta
HP:0001719	Double outlet right ventricle

GWAS associations

29 associations (top):

Study	Trait	p-value
GCST001402_4	Treatment response for severe sepsis	7.000000e-06
GCST003783_6	Multiple system atrophy (pathologically confirmed)	1.000000e-06
GCST004063_60	Waist circumference adjusted for body mass index	9.000000e-06
GCST004063_70	Waist circumference adjusted for body mass index	2.000000e-10
GCST004500_66	Waist circumference adjusted for BMI (adjusted for smoking behaviour)	1.000000e-10
GCST004501_118	Waist circumference adjusted for BMI (joint analysis main effects and smoking interaction)	3.000000e-10
GCST004504_88	Waist circumference adjusted for BMI in non-smokers	5.000000e-10
GCST004505_88	Waist-to-hip ratio adjusted for BMI (adjusted for smoking behaviour)	1.000000e-11
GCST004508_20	Waist-to-hip ratio adjusted for BMI in non-smokers	4.000000e-07
GCST004562_240	Waist circumference adjusted for body mass index	4.000000e-09
GCST004562_34	Waist circumference adjusted for body mass index	1.000000e-06
GCST004563_178	Waist circumference adjusted for BMI (joint analysis main effects and physical activity interaction)	4.000000e-08
GCST004564_29	Waist circumference adjusted for BMI in active individuals	1.000000e-07
GCST004567_24	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	4.000000e-07
GCST004567_6	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-09
GCST004567_86	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	1.000000e-07
GCST004567_98	Waist-to-hip ratio adjusted for BMI (joint analysis for main effect and physical activity interaction)	2.000000e-09
GCST004576_10	Waist-to-hip ratio adjusted for body mass index	3.000000e-12
GCST004576_109	Waist-to-hip ratio adjusted for body mass index	2.000000e-08
GCST004576_8	Waist-to-hip ratio adjusted for body mass index	2.000000e-11
GCST004576_9	Waist-to-hip ratio adjusted for body mass index	2.000000e-07
GCST004578_38	Waist-to-hip ratio adjusted for BMI in active individuals	3.000000e-07
GCST004578_54	Waist-to-hip ratio adjusted for BMI in active individuals	1.000000e-09
GCST004578_76	Waist-to-hip ratio adjusted for BMI in active individuals	7.000000e-07
GCST004578_99	Waist-to-hip ratio adjusted for BMI in active individuals	1.000000e-09
GCST005957_7	Waist-to-hip ratio adjusted for BMI (age <50)	3.000000e-06
GCST005958_10	Waist-to-hip ratio adjusted for BMI (age >50)	3.000000e-08
GCST005959_22	Waist-to-hip ratio adjusted for BMI x sex interaction	5.000000e-08
GCST005962_21	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	5.000000e-11

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007789	BMI-adjusted waist circumference
EFO:0004318	smoking behavior
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008002	physical activity measurement
EFO:0008343	sex interaction measurement
EFO:0008007	age at assessment

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D014339	Truncus Arteriosus, Persistent	C14.240.400.560.098.500; C14.280.400.560.098.500; C16.131.240.400.560.098.500

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

8 total (human), top 8 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol S	decreases methylation	1
Arsenic	increases methylation	1
Benzo(a)pyrene	increases methylation	1
Cadmium	decreases expression, increases abundance	1
Lead	affects methylation	1
Triclosan	decreases expression	1
Aflatoxin B1	decreases methylation	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00154830	PHASE4	COMPLETED	Alterations of Functional Activities and Leg Stiffness After Hamstring Lengthening in Cerebral Palsy Children
NCT00432055	PHASE4	COMPLETED	Effects of Botulinum Toxin Type A in Adults With Cerebral Palsy
NCT00549471	PHASE4	TERMINATED	Improvement After Botulinum Toxin Injections to the Arms in Children With Cerebral Palsy
NCT00752934	PHASE4	TERMINATED	Does Oral Baclofen Improve Care and Comfort in Spastic Children in Nursing Homes?
NCT00964639	PHASE4	COMPLETED	Postoperative Pain in Children With Cerebral Palsy After Pelvic and Femoral Osteotomies
NCT01386255	PHASE4	WITHDRAWN	Placebo Controlled Study of Baclofen for GERD in Children With Cerebral Palsy
NCT02546999	PHASE4	COMPLETED	Does Botulinum Toxin A Make Walking Easier in Children With Cerebral Palsy?
NCT02633241	PHASE4	COMPLETED	A Pilot Study of Dexmedetomidine-Propofol in Children Undergoing Magnetic Resonance Imaging
NCT03117322	PHASE4	COMPLETED	Synbiotic, Prebiotics and Probiotics in Children With Cerebral Palsy and Constipation
NCT03648658	PHASE4	UNKNOWN	Paracetamol Study in Patients With Low Muscle Mass
NCT04074265	PHASE4	COMPLETED	Peri-operative Use of a Pain Injection in Pediatric Patients With Cerebral Palsy
NCT04273737	PHASE4	TERMINATED	Amantadine in Treating Cognitive & Motor Impairments in Adolescents and Adults With Cerebral Palsy
NCT04523935	PHASE4	COMPLETED	Excessive Crying in Children With Cerebral Palsy and Communication Deficits
NCT05887765	PHASE4	COMPLETED	Effect of Systematic Dexamethasone on the Duration of Popliteal Nerve Block for Anesthesia After Pediatric Ankle Surgery
NCT06176430	PHASE4	UNKNOWN	Comparison of Twice Weekly Versus Daily Iron Therapy in Treating Anemia in Children With Cerebral Palsy
NCT06189781	PHASE4	RECRUITING	Pain Injection Versus Epidural Anesthesia for Hip Surgery in Pediatric Patients With Cerebral Palsy
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
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects
NCT03154476	PHASE3	COMPLETED	Role of Sildenafil for Fontan Associated Liver Disease (SiFALD) Study
NCT04536194	PHASE3	COMPLETED	Dopamine Versus Norepinephrine Under General Anesthesia
NCT04702373	PHASE3	ACTIVE_NOT_RECRUITING	Training in Exercise Activities and Motion for Growth (TEAM 4 Growth) RCT
NCT05049590	PHASE3	COMPLETED	Acute Normovolemic Hemodilution in Complex Cardiac Surgery