IRX4

Summary

IRX4 (iroquois homeobox 4, HGNC:6129) is a protein-coding gene on chromosome 5p15.33, encoding Iroquois-class homeodomain protein IRX-4 (P78413). Likely to be an important mediator of ventricular differentiation during cardiac development.

Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Predicted to be involved in cell development; neuron differentiation; and regulation of DNA-templated transcription. Predicted to act upstream of or within heart development. Predicted to be located in chromatin. Predicted to be active in nucleus.

Source: NCBI Gene 50805 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart disease (Limited, ClinGen) — +1 more curated relationship
• GWAS associations: 40
• Clinical variants (ClinVar): 129 total — 3 pathogenic
• MANE Select transcript: NM_016358

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6129
Approved symbol	IRX4
Name	iroquois homeobox 4
Location	5p15.33
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000113430
Ensembl biotype	protein_coding
OMIM	606199
Entrez	50805

Gene structure

Transcript identifiers

Ensembl transcripts: 20 — 15 protein_coding, 3 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000231357, ENST00000505790, ENST00000505938, ENST00000508261, ENST00000511126, ENST00000513692, ENST00000717757, ENST00000717758, ENST00000718124, ENST00000718125, ENST00000879326, ENST00000879327, ENST00000879328, ENST00000919728, ENST00000919729, ENST00000919730, ENST00000919731, ENST00000950949, ENST00000950950, ENST00000950951

RefSeq mRNA: 5 — MANE Select: NM_016358 NM_001278632, NM_001278633, NM_001278634, NM_001278635, NM_016358

CCDS: CCDS3867, CCDS75225

Canonical transcript exons

ENST00000231357 — 5 exons

Exon	Start	End
ENSE00001083972	1882603	1882925
ENSE00004034212	1881808	1882059
ENSE00004034213	1877413	1878792
ENSE00004034215	1879504	1879832
ENSE00004034216	1880725	1880834

Expression profiles

Bgee: expression breadth broad, 93 present calls, max score 87.54.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2125 / max 65.4414, expressed in 231 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60833	0.2697	84
60830	0.2311	45
60829	0.1840	40
60834	0.1502	72
60837	0.1112	53
60832	0.0960	34
60836	0.0890	38
60835	0.0812	48

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
skin of abdomen	UBERON:0001416	87.54	gold quality
apex of heart	UBERON:0002098	87.43	gold quality
cervix squamous epithelium	UBERON:0006922	86.76	silver quality
lower esophagus mucosa	UBERON:0035834	85.85	gold quality
skin of leg	UBERON:0001511	85.44	gold quality
hair follicle	UBERON:0002073	84.03	silver quality
zone of skin	UBERON:0000014	83.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	83.61	gold quality
esophagus mucosa	UBERON:0002469	83.11	gold quality
heart left ventricle	UBERON:0002084	83.05	gold quality
cardiac ventricle	UBERON:0002082	82.49	gold quality
minor salivary gland	UBERON:0001830	78.88	gold quality
mouth mucosa	UBERON:0003729	76.94	gold quality
saliva-secreting gland	UBERON:0001044	75.13	gold quality
vagina	UBERON:0000996	71.97	gold quality
heart right ventricle	UBERON:0002080	70.88	silver quality
epithelium of mammary gland	UBERON:0003244	70.18	silver quality
nipple	UBERON:0002030	70.07	gold quality
prostate gland	UBERON:0002367	69.83	gold quality
mammary duct	UBERON:0001765	69.45	silver quality
epithelium of esophagus	UBERON:0001976	68.03	gold quality
tongue squamous epithelium	UBERON:0006919	67.99	gold quality
buccal mucosa cell	CL:0002336	67.96	gold quality
upper leg skin	UBERON:0004262	66.31	gold quality
gingiva	UBERON:0001828	66.28	silver quality
secondary oocyte	CL:0000655	66.04	silver quality
esophagus squamous epithelium	UBERON:0006920	66.01	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	64.96	gold quality
gingival epithelium	UBERON:0001949	64.84	silver quality
penis	UBERON:0000989	64.69	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

5 targets.

Target	Regulation
KCND2
MYH1	Activation
MYL7
SLIT1	Unknown
SOX2	Unknown

Upstream regulators (CollecTRI, top): IRX5, NR2F2

miRNA regulators (miRDB)

24 targeting IRX4, 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-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-574-5P	100.00	66.01	989
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-3605-5P	99.96	67.12	932
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-4276	99.56	67.66	2514
HSA-MIR-7160-5P	99.11	67.17	2207
HSA-MIR-6877-3P	98.98	65.83	560
HSA-MIR-6819-3P	98.95	65.57	572
HSA-MIR-4742-5P	98.89	68.41	1542
HSA-MIR-6884-3P	98.05	65.32	750
HSA-MIR-4294	97.86	65.72	1110
HSA-MIR-3198	97.84	65.64	579
HSA-MIR-4309	97.84	65.45	588
HSA-MIR-1289	97.46	65.37	655
HSA-MIR-6514-5P	95.07	66.02	655
HSA-MIR-4745-3P	83.50	60.58	126

Literature-anchored findings (GeneRIF, showing 8)

• Polymorphism A381>G of the Irx4 gene may have a modifier effect on septal thickness, resulting in increased corrected QT dispersion and higher outflow gradients. (PMID:18497553)
• IRX4 had a potential causative impact on the development of congenital heart disease, particularly ventricular septal defect. (PMID:21544582)
• Among migraineurs with aura rs7698623 in MEPE (OR = 6.37; 95% CI 3.15-12.90; p = 2.7x10(-7)) and rs4975709 in IRX4 (OR = 5.06; 95% CI 2.66-9.62; p = 7.7x10(-7)) appeared to be associated with ischemic stroke. (PMID:21779381)
• the prostate cancer (PC)-susceptibility locus represented by rs12653946 at 5p15 is likely to regulate IRX4 expression in prostate which could suppress PC growth by interacting with the VDR pathway, conferring to PC susceptibility (PMID:22323358)
• We independently validated IRX4 as a potential prostate cancer risk gene through cis-expression quantitative trait loci analysis of prostate cancer risk variants. (PMID:24022300)
• Epigenetic inactivation of IRX4 is responsible for acceleration of cell growth in human pancreatic cancer. (PMID:32894817)
• Identification and Characterization of Alternatively Spliced Transcript Isoforms of IRX4 in Prostate Cancer. (PMID:33919200)
• Dynamics and recognition of homeodomain containing protein-DNA complex of IRX4. (PMID:37861198)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	irx4a	ENSDARG00000035648
mus_musculus	Irx4	ENSMUSG00000021604
rattus_norvegicus	Irx4	ENSRNOG00000012720

Paralogs (6): MKX (ENSG00000150051), IRX6 (ENSG00000159387), IRX1 (ENSG00000170549), IRX2 (ENSG00000170561), IRX5 (ENSG00000176842), IRX3 (ENSG00000177508)

Protein

Protein identifiers

Iroquois-class homeodomain protein IRX-4 — P78413 (reviewed: P78413)

Alternative names: Homeodomain protein IRXA3, Iroquois homeobox protein 4

All UniProt accessions (3): D6RAS8, D6RC00, P78413

UniProt curated annotations — full annotation on UniProt →

Function. Likely to be an important mediator of ventricular differentiation during cardiac development.

Subunit / interactions. Interacts with the vitamin D receptor VDR but doesn’t affect its transactivation activity.

Subcellular location. Nucleus.

Tissue specificity. Predominantly expressed in cardiac ventricles.

Similarity. Belongs to the TALE/IRO homeobox family.

Isoforms (2)

UniProt ID	Names	Canonical?
P78413-1	1	yes
P78413-2	2

RefSeq proteins (5): NP_001265561, NP_001265562, NP_001265563, NP_001265564, NP_057442* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001356	HD	Domain
IPR003893	Iroquois_homeo	Domain
IPR008422	KN_HD	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017970	Homeobox_CS	Conserved_site

Pfam: PF05920

UniProt features (9 total): compositionally biased region 3, chain 1, DNA-binding region 1, region of interest 1, splice variant 1, sequence variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P78413-F1	54.03	0.10

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 144 (showing top): ATF_B, YAATNRNNNYNATT_UNKNOWN, BENPORATH_ES_WITH_H3K27ME3, GOBP_AXIS_SPECIFICATION, JAEGER_METASTASIS_DN, GCANCTGNY_MYOD_Q6, AREB6_01, GOBP_NEUROGENESIS, CREBP1_Q2, LHX3_01, CHX10_01, CAGCTG_AP4_Q5, NKX61_01, CREB_Q4, CDP_01

GO Biological Process (9): negative regulation of transcription by RNA polymerase II (GO:0000122), regulation of transcription by RNA polymerase II (GO:0006357), heart development (GO:0007507), neuron differentiation (GO:0030182), positive regulation of DNA-templated transcription (GO:0045893), cell development (GO:0048468), establishment of animal organ orientation (GO:0048561), regulation of DNA-templated transcription (GO:0006355), positive regulation of transcription by RNA polymerase II (GO:0045944)

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 (GO:0003677), protein binding (GO:0005515)

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

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
regulation of transcription by RNA polymerase II	3
transcription by RNA polymerase II	3
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of DNA-templated transcription	2
cell differentiation	2
DNA-templated transcription	2
negative regulation of DNA-templated transcription	1
animal organ development	1
circulatory system development	1
generation of neurons	1
positive regulation of RNA biosynthetic process	1
anatomical structure development	1
cellular developmental process	1
animal organ morphogenesis	1
establishment of anatomical structure orientation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
positive regulation of DNA-templated transcription	1
cis-regulatory region sequence-specific DNA binding	1
chromatin	1
DNA-binding transcription factor activity	1
DNA-binding transcription factor activity, RNA polymerase II-specific	1
DNA-binding transcription activator activity	1
positive regulation of transcription by RNA polymerase II	1
nucleic acid binding	1
binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

1212 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
IRX4	NKX2-5	P52952	779
IRX4	HAND2	P61296	770
IRX4	AKAP11	Q9UKA4	729
IRX4	NPPA	P01160	646
IRX4	TBX5	Q99593	632
IRX4	MYL2	P10916	630
IRX4	MYL7	Q01449	615
IRX4	KCNJ3	P48549	606
IRX4	GPC5	P78333	601
IRX4	HEY2	Q9UBP5	555
IRX4	TBX20	Q9UMR3	552
IRX4	POSTN	Q15063	538
IRX4	GATA4	P43694	533
IRX4	NR2F2	P24468	528
IRX4	ISL1	P20663	516

IntAct

11 interactions, top by confidence:

A	B	Type	Score
IRX4	POU6F2	psi-mi:“MI:0915”(physical association)	0.560
IFNA10	IRX4	psi-mi:“MI:0915”(physical association)	0.370
IFNA16	IRX4	psi-mi:“MI:0915”(physical association)	0.370
IFNA17	IRX4	psi-mi:“MI:0915”(physical association)	0.370
IFNA21	IRX4	psi-mi:“MI:0915”(physical association)	0.370
IFNA4	IRX4	psi-mi:“MI:0915”(physical association)	0.370
MAGEA1	ANKRD17	psi-mi:“MI:0914”(association)	0.350
AFG2A	ESYT2	psi-mi:“MI:0914”(association)	0.350
IRX4	POU6F2	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (7): IRX4 (Protein-RNA), IRX4 (Two-hybrid), IRX4 (Affinity Capture-MS), IRX4 (Two-hybrid), IRX4 (Reconstituted Complex), RARA (Reconstituted Complex), IRX4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PQ73, A1YF16, A1YG93, A2RU54, A5PKG8, O02786, O14813, O15353, O35602, O43638, O57601, P13297, P19419, P28360, P35548, P41969, P42580, P43687, P49640, P50223, P50548, P52946, P52950, P63156, P63157, P70459, P78413, Q03358, Q14549, Q2VL78, Q2VL79, Q2VL82, Q2VL83, Q2VL84, Q2VL85, Q2VL86, Q2VL87, Q2VL88, Q5NSW5, Q61575

Diamond homologs: A1YGI6, A6NDR6, A8K0S8, A8WL06, B7ZRT8, O00470, O04136, O14770, O22300, O42261, O46339, O65685, O70477, P41779, P41817, P46606, P48000, P48001, P48002, P48731, P53147, P54269, P55347, P56659, P56660, P56664, P56665, P56669, P70284, P78412, P78413, P78414, P78415, P79937, P81067, P81068, P97367, P97368, Q0E3C3, Q0J6N4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 10 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.

GO biological processes:

GO term	Partners	Fold	FDR
B cell activation involved in immune response	5	526.6×	2e-12
natural killer cell activation involved in immune response	5	495.6×	2e-12
T cell activation involved in immune response	5	351.1×	1e-11
response to exogenous dsRNA	5	263.3×	4e-11
type I interferon-mediated signaling pathway	5	172.0×	3e-10
humoral immune response	5	140.4×	6e-10
cellular response to virus	5	100.3×	3e-09
adaptive immune response	5	42.1×	2e-07

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	3
Likely pathogenic	0
Uncertain significance	96
Likely benign	3
Benign	26

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2574127	NM_016358.3(IRX4):c.71G>A (p.Ser24Asn)	Pathogenic
2574128	NM_016358.3(IRX4):c.572C>T (p.Thr191Ile)	Pathogenic
3236540	NM_016358.3(IRX4):c.240G>A (p.Ser80=)	Pathogenic

SpliceAI

1190 predictions. Top by Δscore:

Variant	Effect	Δscore
5:1878789:GGCT:G	acceptor_gain	1.0000
5:1878791:CT:C	acceptor_gain	1.0000
5:1878792:TCTGC:T	acceptor_loss	1.0000
5:1878793:C:CC	acceptor_gain	1.0000
5:1878815:A:T	acceptor_gain	1.0000
5:1879499:CCCA:C	donor_loss	1.0000
5:1879500:CCAC:C	donor_loss	1.0000
5:1879501:CACCT:C	donor_loss	1.0000
5:1879502:A:T	donor_loss	1.0000
5:1879503:C:CA	donor_loss	1.0000
5:1879503:CCTG:C	donor_gain	1.0000
5:1880830:CTGTT:C	acceptor_gain	1.0000
5:1881804:TTA:T	donor_loss	1.0000
5:1881805:TACCA:T	donor_loss	1.0000
5:1881806:A:AC	donor_gain	1.0000
5:1881806:AC:A	donor_gain	1.0000
5:1881806:ACCAG:A	donor_gain	1.0000
5:1881807:C:CA	donor_gain	1.0000
5:1881807:CC:C	donor_gain	1.0000
5:1881807:CCA:C	donor_gain	1.0000
5:1881807:CCAG:C	donor_gain	1.0000
5:1881807:CCAGC:C	donor_gain	1.0000
5:1882060:C:CC	acceptor_gain	1.0000
5:1887060:ACCT:A	donor_loss	1.0000
5:1887061:C:A	donor_loss	1.0000
5:1878788:GGGCT:G	acceptor_gain	0.9900
5:1878805:A:AC	acceptor_gain	0.9900
5:1878805:A:C	acceptor_gain	0.9900
5:1878814:CAG:C	acceptor_gain	0.9900
5:1879563:T:TA	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000170293 (5:1887979 A>C), RS1000200742 (5:1887686 C>T), RS1000329956 (5:1883190 C>A,G), RS1000422628 (5:1881601 T>A,G), RS1000722262 (5:1887523 C>A), RS1000752855 (5:1882703 C>A), RS1000806631 (5:1883227 A>T), RS1000847638 (5:1882943 A>C), RS1000894248 (5:1879099 C>A), RS1000944922 (5:1888754 C>T), RS1001003737 (5:1888184 C>G,T), RS1001369705 (5:1877849 T>A,C), RS1001739539 (5:1884169 CG>C), RS1001897946 (5:1880064 A>G), RS1002342534 (5:1885360 T>C)

Disease associations

OMIM: gene MIM:606199 | disease phenotypes: MIM:614429, MIM:187500

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart disease	Limited	Autosomal dominant
ventricular septal defect 1	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
congenital heart disease	Limited	AD

Mondo (3): ventricular septal defect 1 (MONDO:0013746), tetralogy of fallot (MONDO:0008542), congenital heart disease (MONDO:0005453)

Orphanet (1): Tetralogy of Fallot (Orphanet:3303)

HPO phenotypes

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

GWAS associations

40 associations (top):

Study	Trait	p-value
GCST001157_2	Cardiovascular disease risk factors	8.000000e-07
GCST003148_7	Prostate cancer	2.000000e-12
GCST004519_14	Body mass index (adult)	8.000000e-07
GCST004519_26	Body mass index (adult)	7.000000e-09
GCST006218_90	Erosive tooth wear (severe vs non-severe)	8.000000e-07
GCST006226_15	Erosive tooth wear (severe vs none or mild)	5.000000e-06
GCST007626_4	Lack of perseverance	1.000000e-07
GCST008860_20	Prostate cancer	1.000000e-16
GCST009266_7	Dental caries (decayed and filled deciduous tooth surfaces)	4.000000e-06
GCST009306_4	Spatial processing	2.000000e-06
GCST010796_4297	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4298	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4299	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4300	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_4526	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4551	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_4552	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4553	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4554	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-08
GCST010796_4555	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-08
GCST010796_4556	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_4557	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_4558	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_4559	Electrocardiogram morphology (amplitude at temporal datapoints)	9.000000e-09
GCST010796_4560	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_4561	Electrocardiogram morphology (amplitude at temporal datapoints)	8.000000e-09
GCST010796_4562	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_4563	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-08
GCST010796_4564	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_4565	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006946	behavioural disinhibition measurement
EFO:0008354	cognitive function measurement
EFO:0004327	electrocardiography

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, increases methylation	4
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases oxidation, increases expression	2
Daunorubicin	decreases expression	2
Doxorubicin	decreases expression	2
Mitoxantrone	decreases expression	2
Ozone	affects cotreatment, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Silicon Dioxide	increases expression	2
Particulate Matter	decreases expression, increases abundance, increases expression	2
aristolochic acid I	increases expression	1
apocarotenal	decreases expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
tobacco tar	decreases expression	1
cupric chloride	increases expression	1
nickel sulfate	increases expression	1
pentanal	increases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(+)-JQ1 compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	increases expression	1
Decitabine	affects expression	1

Clinical trials (associated diseases)

369 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
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
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
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
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