LEFTY2

Summary

LEFTY2 (left-right determination factor 2, HGNC:3122) is a protein-coding gene on chromosome 1q42.12, encoding Left-right determination factor 2 (O00292). Required for left-right (L-R) asymmetry determination of organ systems in mammals.

This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate the mature protein, which plays a role in left-right asymmetry determination of organ systems during development. The protein may also play a role in endometrial bleeding. Mutations in this gene have been associated with left-right axis malformations, particularly in the heart and lungs. Some types of infertility have been associated with dysregulated expression of this gene in the endometrium. This gene is closely linked to both a related family member and a related pseudogene. This gene encodes multiple isoforms that may undergo similar proteolytic processing.

Source: NCBI Gene 7044 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 204 total
• MANE Select transcript: NM_003240

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3122
Approved symbol	LEFTY2
Name	left-right determination factor 2
Location	1q42.12
Locus type	gene with protein product
Status	Approved
Aliases	LEFTA, LEFTYA
Ensembl gene	ENSG00000143768
Ensembl biotype	protein_coding
OMIM	601877
Entrez	7044

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000366820, ENST00000420304, ENST00000474493

RefSeq mRNA: 2 — MANE Select: NM_003240 NM_001172425, NM_003240

CCDS: CCDS1549, CCDS53479

Canonical transcript exons

ENST00000366820 — 4 exons

Exon	Start	End
ENSE00001899342	225940891	225941220
ENSE00001956200	225936603	225937804
ENSE00002390847	225939361	225939600
ENSE00002394066	225939756	225940002

Expression profiles

Bgee: expression breadth ubiquitous, 170 present calls, max score 94.32.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 2.1259 / max 155.8351, expressed in 152 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
17735	2.0869	146
17737	0.0301	18
17736	0.0088	2

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
decidua	UBERON:0002450	94.32	gold quality
body of uterus	UBERON:0009853	90.55	gold quality
choroid plexus epithelium	UBERON:0003911	90.47	gold quality
myometrium	UBERON:0001296	89.60	gold quality
sperm	CL:0000019	87.46	gold quality
adult organism	UBERON:0007023	86.97	gold quality
blood vessel layer	UBERON:0004797	86.63	gold quality
left ovary	UBERON:0002119	85.63	gold quality
male germ cell	CL:0000015	85.17	gold quality
endocervix	UBERON:0000458	84.84	gold quality
descending thoracic aorta	UBERON:0002345	84.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	84.45	gold quality
ascending aorta	UBERON:0001496	84.24	gold quality
thoracic aorta	UBERON:0001515	84.24	gold quality
right ovary	UBERON:0002118	84.03	gold quality
right coronary artery	UBERON:0001625	83.30	gold quality
cauda epididymis	UBERON:0004360	82.15	gold quality
aorta	UBERON:0000947	81.71	gold quality
ovary	UBERON:0000992	81.32	gold quality
popliteal artery	UBERON:0002250	79.91	gold quality
tibial artery	UBERON:0007610	79.90	gold quality
caput epididymis	UBERON:0004358	79.40	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	78.33	gold quality
smooth muscle tissue	UBERON:0001135	76.45	gold quality
coronary artery	UBERON:0001621	75.40	gold quality
left coronary artery	UBERON:0001626	75.28	gold quality
uterus	UBERON:0000995	75.06	gold quality
adenohypophysis	UBERON:0002196	72.70	gold quality
corpus epididymis	UBERON:0004359	72.54	gold quality
hair follicle	UBERON:0002073	71.27	gold quality

Single-cell (SCXA)

Detected in 6 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-9388	yes	11436.36
E-MTAB-3929	yes	241.46
E-MTAB-10287	yes	61.11
E-MTAB-6108	no	603.09
E-MTAB-8060	no	45.91
E-ANND-3	no	1.67

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): DLX5, EOMES, FOXH1, FOXO1, GATA6, HLX, HSF1, ID2, PITX2, POU5F1, TBX18, TBXT, ZFP42

miRNA regulators (miRDB)

60 targeting LEFTY2, 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-4262	100.00	73.26	3931
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-4659A-3P	99.80	72.62	4248
HSA-MIR-4659B-3P	99.80	72.62	4248
HSA-MIR-6739-5P	99.80	67.87	2806
HSA-MIR-6733-5P	99.74	67.94	2759
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-3685	99.62	68.83	1621
HSA-MIR-4310	99.59	68.84	2527

Literature-anchored findings (GeneRIF, showing 17)

• may provide a crucial signal for endometrial breakdown and bleeding by triggering expression of several matrix metalloproteinases (PMID:12215426)
• nodal and the inhibitors of Nodal signaling, lefty-A and lefty-B, are down-regulated very early upon differentiation of human embryonic stem cells (PMID:15308665)
• Addition of recombinant LEFTY-A to explants induced MMP-9 in most samples, a response prevented by ovarian steroids. (PMID:15536155)
• LEFTY proteins, which are known to play a major role during mouse gastrulation, are transiently expressed during human embryonic stem cell differentiation. (PMID:17038673)
• Findings suggest that Lefty2 is negatively modulated by miR-302s in hESCs, which plays an important role in maintaining the balance between pluripotency and germ layer specification. (PMID:21266536)
• Findings show that during embryonic development, EBAF/LEFTY B plays important roles in decidualization and embryo implantation. (PMID:21401636)
• Lefty A may account for the tumor suppressive activity of human adult stem cells. (PMID:22469982)
• LeftyA leads to disruption of Rac1 and Pak1 activity with subsequent actin depolymerization, cell softening and cell shrinkage. (PMID:27404958)
• LEFTY2 down-regulates MKi67 expression and FAK activity, up-regulates miR-200a and E-cadherin, and is thus a powerful negative regulator of endometrial cell proliferation and migration. (PMID:27497669)
• LEFTY2 regulates the expression and activity of ENaC in endometrial epithelial cells via SGK1. (PMID:27606670)
• functional role of LEFTY during progesterone therapy for endometrial carcinoma (PMID:29268772)
• In a reaction-diffusion pattern, the effective range of Nodal is 3.5 times narrower than that of Lefty2. (PMID:30575724)
• The present study demonstrates a novel role of LEFTY2 in up-regulating transcript levels and protein abundance of the Na+ coupled glucose transporter SGLT1, thus stimulating cellular glucose uptake and cellular formation of glycogen in endometrial cancer cells. (PMID:32236143)
• LEFTY2 alleviates hepatic stellate cell activation and liver fibrosis by regulating the TGF-beta1/Smad3 pathway. (PMID:32745796)
• Requirements of LEFTY and Nodal overexpression for tumor cell survival under hypoxia in glioblastoma. (PMID:33111989)
• Association of maternal hypertension and diabetes with variants of the NKX2-5, LEFTY1 and LEFTY2 genes in children with congenital heart defects: a case-control study from Pakistani Population. (PMID:37097539)
• findings show that the TGFB4 (ebaf) mRNA has distinct tumor specific expression (PMID:9230066)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	lft1	ENSDARG00000019920
danio_rerio	lft2	ENSDARG00000044059
mus_musculus	Lefty1	ENSMUSG00000038793
mus_musculus	Lefty2	ENSMUSG00000066652
rattus_norvegicus	Lefty1	ENSRNOG00000003263
rattus_norvegicus	Lefty2	ENSRNOG00000060325

Paralogs (31): TGFB2 (ENSG00000092969), BMP7 (ENSG00000101144), TGFB1 (ENSG00000105329), BMP5 (ENSG00000112175), BMP8B (ENSG00000116985), TGFB3 (ENSG00000119699), INHBA (ENSG00000122641), INHA (ENSG00000123999), BMP4 (ENSG00000125378), BMP2 (ENSG00000125845), GDF5 (ENSG00000125965), GDF1 (ENSG00000130283), BMP15 (ENSG00000130385), GDF15 (ENSG00000130513), GDF11 (ENSG00000135414), MSTN (ENSG00000138379), INHBE (ENSG00000139269), GDF7 (ENSG00000143869), BMP3 (ENSG00000152785), BMP6 (ENSG00000153162), GDF6 (ENSG00000156466), NODAL (ENSG00000156574), INHBB (ENSG00000163083), BMP10 (ENSG00000163217), GDF9 (ENSG00000164404), INHBC (ENSG00000175189), BMP8A (ENSG00000183682), GDF3 (ENSG00000184344), LEFTY1 (ENSG00000243709), GDF2 (ENSG00000263761), GDF10 (ENSG00000266524)

Protein

Protein identifiers

Left-right determination factor 2 — O00292 (reviewed: O00292)

Alternative names: Endometrial bleeding-associated factor, Left-right determination factor A, Protein lefty-2, Protein lefty-A, Transforming growth factor beta-4

All UniProt accessions (1): O00292

UniProt curated annotations — full annotation on UniProt →

Function. Required for left-right (L-R) asymmetry determination of organ systems in mammals. May play a role in endometrial bleeding.

Subcellular location. Secreted.

Tissue specificity. Mesenchymal cells of the endometrial stroma.

Post-translational modifications. The processing of the protein may also occur at the second R-X-X-R site located at AA 132-135. Processing appears to be regulated in a cell-type specific manner.

Disease relevance. Left-right axis malformations (LRAM) [MIM:601877] The defect includes left pulmonary isomerism, with cardiac anomalies characterized by complete atrioventricular canal defect and hypoplastic left ventricle, and interrupted inferior vena cava. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the TGF-beta family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00292-1	1	yes
O00292-2	2

RefSeq proteins (2): NP_001165896, NP_003231* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001111	TGF-b_propeptide	Domain
IPR001839	TGF-b_C	Domain
IPR003942	LRDF	Family
IPR015615	TGF-beta-like	Family
IPR017948	TGFb_CS	Conserved_site
IPR029034	Cystine-knot_cytokine	Homologous_superfamily

Pfam: PF00019, PF00688

UniProt features (14 total): disulfide bond 4, sequence variant 3, sequence conflict 2, signal peptide 1, propeptide 1, chain 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00292-F1	79.01	0.23

Functional residue map

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

Disulfide bonds (4): 251–264, 263–316, 293–351, 297–353

Glycosylation sites (1): 158

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-1181150	Signaling by NODAL
R-HSA-1433617	Regulation of signaling by NODAL
R-HSA-109582	Hemostasis
R-HSA-1266738	Developmental Biology
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 112 (showing top): GOBP_AXIS_SPECIFICATION, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOMF_GROWTH_FACTOR_ACTIVITY, GOBP_ANTERIOR_POSTERIOR_PATTERN_SPECIFICATION, GOBP_RESPONSE_TO_BMP, GOBP_RESPONSE_TO_GROWTH_FACTOR, BENPORATH_NOS_TARGETS, GOMF_CYTOKINE_ACTIVITY, GOBP_ANTERIOR_POSTERIOR_AXIS_SPECIFICATION, CERVERA_SDHB_TARGETS_1_UP, GOMF_SIGNALING_RECEPTOR_BINDING, TESAR_ALK_TARGETS_HUMAN_ES_4D_DN, GOCC_PLATELET_ALPHA_GRANULE, GOCC_SECRETORY_VESICLE

GO Biological Process (2): anterior/posterior axis specification (GO:0009948), BMP signaling pathway (GO:0030509)

GO Molecular Function (3): cytokine activity (GO:0005125), transforming growth factor beta receptor binding (GO:0005160), growth factor activity (GO:0008083)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), extracellular matrix (GO:0031012), platelet alpha granule lumen (GO:0031093)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Developmental Biology	1
Signaling by NODAL	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
receptor ligand activity	2
axis specification	1
anterior/posterior pattern specification	1
cellular response to BMP stimulus	1
transforming growth factor beta receptor superfamily signaling pathway	1
cytokine receptor binding	1
cellular anatomical structure	1
external encapsulating structure	1
platelet alpha granule	1
secretory granule lumen	1

Protein interactions and networks

STRING

1076 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LEFTY2	ZIC3	O60481	920
LEFTY2	PITX2	Q99697	920
LEFTY2	ACVR2B	Q13705	896
LEFTY2	CRIPTO	P13385	885
LEFTY2	CFC1	P0CG37	873
LEFTY2	NODAL	Q96S42	868
LEFTY2	FOXH1	O75593	760
LEFTY2	NANOG	Q9H9S0	729
LEFTY2	POU5F1	P31359	713
LEFTY2	CER1	O95813	709
LEFTY2	GJA1	P17302	708
LEFTY2	SOX2	P48431	698
LEFTY2	FOXA2	Q9Y261	693
LEFTY2	GDF1	P27539	686
LEFTY2	RTTN	Q86VV8	637

IntAct

6 interactions, top by confidence:

A	B	Type	Score
LEFTY1	LEFTY2	psi-mi:“MI:0914”(association)	0.530
MAPK8IP2	LEFTY2	psi-mi:“MI:0915”(physical association)	0.370
LEFTY2	ACSS3	psi-mi:“MI:0915”(physical association)	0.370
RPL28	LEFTY2	psi-mi:“MI:0914”(association)	0.350

BioGRID (5): LEFTY2 (Two-hybrid), LEFTY2 (Affinity Capture-MS), LEFTY2 (Affinity Capture-MS), LEFTY2 (Two-hybrid), LEFTY2 (Two-hybrid)

ESM2 similar proteins: D3YZZ2, E7ERA6, F2Z333, H3BV60, O00292, O18796, O43508, O43612, O54907, O55232, O55241, O60391, O75462, O75610, O77668, O95633, O95685, P13224, P41155, P56717, Q02833, Q06643, Q14626, Q1LZB9, Q2TBM7, Q4V892, Q5RF19, Q5TM22, Q6IA17, Q6UXT9, Q6ZMM2, Q862Z7, Q86VR8, Q86YD3, Q8BQB4, Q8NBV8, Q8TAD2, Q99640, Q99MF4, Q9BZR6

Diamond homologs: O00292, O75610, P57785, Q64280, Q66KL4, P25703

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
POU5F1	“up-regulates quantity by expression”	LEFTY2	“transcriptional regulation”
SOX2/POU5F1	“up-regulates quantity by expression”	LEFTY2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	110
Likely benign	57
Benign	22

Top pathogenic / likely-pathogenic (0)

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
1:225937803:CT:C	acceptor_gain	1.0000
1:225939359:A:AC	donor_gain	1.0000
1:225939359:AC:A	donor_gain	1.0000
1:225939360:C:CC	donor_gain	1.0000
1:225939360:CC:C	donor_gain	1.0000
1:225939365:AGTC:A	donor_gain	1.0000
1:225939998:CACCT:C	acceptor_gain	1.0000
1:225940003:C:CC	acceptor_gain	1.0000
1:225937800:GAGCT:G	acceptor_gain	0.9900
1:225937802:GCT:G	acceptor_gain	0.9900
1:225937803:CTCTG:C	acceptor_gain	0.9900
1:225937804:TCT:T	acceptor_gain	0.9900
1:225937805:C:CC	acceptor_gain	0.9900
1:225939358:TA:T	donor_loss	0.9900
1:225939359:ACCCA:A	donor_loss	0.9900
1:225939368:C:A	donor_gain	0.9900
1:225939482:C:CA	donor_gain	0.9900
1:225939584:C:CT	acceptor_gain	0.9900
1:225939596:CCAGC:C	acceptor_gain	0.9900
1:225939597:CAGCC:C	acceptor_gain	0.9900
1:225939599:GCC:G	acceptor_loss	0.9900
1:225939601:C:CC	acceptor_gain	0.9900
1:225939999:ACCT:A	acceptor_gain	0.9900
1:225940000:CCTC:C	acceptor_gain	0.9900
1:225940001:CT:C	acceptor_gain	0.9900
1:225940003:C:CG	acceptor_loss	0.9900
1:225940004:T:A	acceptor_loss	0.9900
1:225940484:A:C	acceptor_gain	0.9900
1:225940886:CTCAC:C	donor_loss	0.9900
1:225940887:TCACC:T	donor_loss	0.9900

AlphaMissense

2350 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:225937595:C:G	C316S	0.989
1:225937596:A:T	C316S	0.989
1:225939436:A:C	F221C	0.988
1:225939573:C:A	W175C	0.987
1:225939573:C:G	W175C	0.987
1:225937664:C:G	C293S	0.985
1:225937665:A:T	C293S	0.985
1:225939813:A:T	V147D	0.985
1:225939537:C:A	W187C	0.982
1:225939537:C:G	W187C	0.982
1:225939760:A:G	S165P	0.982
1:225937490:C:G	C351S	0.981
1:225937491:A:T	C351S	0.981
1:225937596:A:G	C316R	0.981
1:225939951:A:C	F101C	0.981
1:225937484:C:G	C353S	0.980
1:225937485:A:T	C353S	0.980
1:225937711:C:A	W277C	0.980
1:225937711:C:G	W277C	0.980
1:225939907:C:G	A116P	0.979
1:225937665:A:G	C293R	0.978
1:225939900:A:G	L118P	0.978
1:225939435:A:C	F221L	0.976
1:225939435:A:T	F221L	0.976
1:225939437:A:G	F221L	0.976
1:225939565:A:G	F178S	0.976
1:225937594:A:C	C316W	0.974
1:225937652:C:G	C297S	0.974
1:225937653:A:T	C297S	0.974
1:225937699:C:A	W281C	0.974

dbSNP variants (sampled 300 via entrez): RS1000048782 (1:225936342 C>G), RS1000304635 (1:225939235 A>T), RS1002867972 (1:225942124 C>G,T), RS1002994228 (1:225941730 G>A), RS1003046289 (1:225941425 T>C), RS1003232059 (1:225943058 C>A,G), RS1004368014 (1:225941577 G>A), RS1004442853 (1:225939152 T>C), RS1004664278 (1:225942962 C>A,T), RS1004748414 (1:225942781 C>G), RS1005369769 (1:225936197 A>C,G), RS1005528113 (1:225941094 GCCAGGGGCAGCAC>G), RS1006165826 (1:225940179 C>T), RS1006522859 (1:225940607 C>G,T), RS1007260258 (1:225937237 C>T)

Disease associations

OMIM: gene MIM:601877 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant
visceral heterotaxy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Disputed	AD

Mondo (2): congenital heart disease (MONDO:0005453), visceral heterotaxy (MONDO:0018677)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Resveratrol	increases expression, decreases expression, affects cotreatment	3
bisphenol A	decreases expression, affects methylation	2
Triclosan	decreases reaction, increases expression, decreases expression	2
aristolochic acid I	increases expression	1
VX-agent	increases expression	1
manganese chloride	decreases expression	1
CGP 52608	affects binding, increases reaction	1
(+)-JQ1 compound	decreases expression	1
Ethanol	increases expression	1
Benzo(a)pyrene	increases mutagenesis	1
Copper	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Estradiol	affects cotreatment, decreases expression	1
Fluorocarbons	affects cotreatment, increases expression	1
Fluorouracil	decreases expression	1
Hydrocarbons, Chlorinated	increases expression, affects cotreatment	1
Lipopolysaccharides	decreases reaction, increases expression	1
Manganese	decreases expression	1
Metals	affects cotreatment, increases expression	1
Oxygen	increases expression	1
Pentachlorophenol	affects cotreatment, increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Polychlorinated Biphenyls	affects cotreatment, increases expression	1
Progesterone	affects cotreatment, decreases expression	1
Teratogens	increases expression	1
Valproic Acid	increases methylation	1
Zearalenone	decreases expression	1
Cyclosporine	decreases expression	1
Medroxyprogesterone Acetate	decreases expression	1
Antirheumatic Agents	increases expression	1

Clinical trials (associated diseases)

300 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
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
NCT06406517	PHASE3	UNKNOWN	Comparative Effectiveness of Gadopiclenol for Evaluation of Adult Congenital Heart Anatomy and Hemodynamics
NCT06693674	PHASE3	RECRUITING	Effect of Sacubitril-Valsartan on Cardiac Structure and Function
NCT06955260	PHASE3	NOT_YET_RECRUITING	SGLT2 Inhibition With Empagliflozin in Fontan Circulatory Failure
NCT00115375	PHASE2	COMPLETED	Platelet Aggregation Inhibition in Children on Clopidogrel (PICOLO)
NCT00350220	PHASE2	COMPLETED	Transfusion Strategies in Pediatric Cardiothoracic Surgery
NCT00374088	PHASE2	COMPLETED	N-Acetylcysteine in Neonatal Congenital Heart Surgery (INACT Study)
NCT00538785	PHASE2	COMPLETED	A Study to Evaluate MEDI-524 In Children With Hemodynamically Significant Congenital Heart Disease
NCT00770705	PHASE2	WITHDRAWN	Parenteral Phenoxybenzamine During Congenital Heart Disease Surgery
NCT00919945	PHASE2	TERMINATED	Impact of Early Enteral Feeding on Splanchnic Blood Flow After Surgery for Critical Heart Disease in the Newborn
NCT01063712	PHASE2	COMPLETED	Safety and Effectiveness of the Device Nit-Occlud® PDA-R
NCT01069510	PHASE2	COMPLETED	Spironolactone in Adult Congenital Heart Disease
NCT01189981	PHASE2	COMPLETED	Effect of eHealth Encouragements to Intensive Exercise in Adolescents With Congenital Heart Disease
NCT01330433	PHASE2	COMPLETED	Effects of CoSeal on Bleeding & Adhesions in Pediatric Heart Surgery
NCT01662037	PHASE2	COMPLETED	Bosentan Therapy in Children With Functional Single Ventricle
NCT01668264	PHASE2	UNKNOWN	Imaging Assessment of Diastolic Function
NCT01827059	PHASE2	UNKNOWN	Bosentan In Exercise Induced Pulmonary Arterial Hypertension in CongenitaL Heart diseasE