GATA4

Summary

GATA4 (GATA binding protein 4, HGNC:4173) is a protein-coding gene on chromosome 8p23.1, encoding Transcription factor GATA-4 (P43694). Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the GATA family of zinc-finger transcription factors. Members of this family recognize the GATA motif which is present in the promoters of many genes. This protein is thought to regulate genes involved in embryogenesis and in myocardial differentiation and function, and is necessary for normal testicular development. Mutations in this gene have been associated with cardiac septal defects. Additionally, alterations in gene expression have been associated with several cancer types. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 2626 — RefSeq curated summary.

At a glance

• Gene–disease (curated): structural congenital heart disease, multiple types - GATA4 (Definitive, ClinGen) — +11 more curated relationships
• GWAS associations: 74
• Clinical variants (ClinVar): 1,094 total — 32 pathogenic, 10 likely-pathogenic
• Phenotypes (HPO): 151
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• Transcription factor: yes — 149 downstream targets (CollecTRI)
• MANE Select transcript: NM_001308093

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4173
Approved symbol	GATA4
Name	GATA binding protein 4
Location	8p23.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000136574
Ensembl biotype	protein_coding
OMIM	600576
Entrez	2626

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 27 protein_coding, 1 retained_intron

ENST00000335135, ENST00000526021, ENST00000526716, ENST00000526974, ENST00000528712, ENST00000532059, ENST00000532977, ENST00000622443, ENST00000886845, ENST00000886846, ENST00000886847, ENST00000886848, ENST00000886849, ENST00000886850, ENST00000886851, ENST00000886852, ENST00000886853, ENST00000886854, ENST00000886855, ENST00000952123, ENST00000952124, ENST00000952125, ENST00000952126, ENST00000952127, ENST00000952128, ENST00000952129, ENST00000952130, ENST00000952131

RefSeq mRNA: 5 — MANE Select: NM_001308093 NM_001308093, NM_001308094, NM_001374273, NM_001374274, NM_002052

CCDS: CCDS5983, CCDS78303, CCDS78304

Canonical transcript exons

ENST00000532059 — 7 exons

Exon	Start	End
ENSE00000924802	11756935	11757083
ENSE00000924803	11755046	11755133
ENSE00001334448	11707856	11708928
ENSE00001359375	11758293	11760002
ENSE00001612139	11750111	11750236
ENSE00003572742	11748916	11749085
ENSE00003903869	11704202	11704304

Expression profiles

Bgee: expression breadth broad, 85 present calls, max score 96.29.

FANTOM5 (CAGE): breadth broad, TPM avg 5.8398 / max 254.4446, expressed in 402 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
87414	4.9933	393
87413	0.3638	100
87410	0.1573	62
87408	0.1460	57
87407	0.1294	59
87409	0.0500	25

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right atrium auricular region	UBERON:0006631	96.29	gold quality
heart left ventricle	UBERON:0002084	96.17	gold quality
duodenum	UBERON:0002114	96.15	gold quality
apex of heart	UBERON:0002098	95.61	gold quality
left ovary	UBERON:0002119	95.42	gold quality
heart	UBERON:0000948	95.09	gold quality
ovary	UBERON:0000992	94.86	gold quality
right coronary artery	UBERON:0001625	92.80	gold quality
right ovary	UBERON:0002118	92.41	gold quality
body of pancreas	UBERON:0001150	91.54	gold quality
left coronary artery	UBERON:0001626	90.14	gold quality
right testis	UBERON:0004534	90.01	gold quality
right lobe of liver	UBERON:0001114	89.76	gold quality
left testis	UBERON:0004533	89.60	gold quality
testis	UBERON:0000473	89.50	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.82	gold quality
liver	UBERON:0002107	87.77	gold quality
placenta	UBERON:0001987	86.24	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.62	gold quality
pancreas	UBERON:0001264	84.90	gold quality
body of stomach	UBERON:0001161	83.77	gold quality
stomach	UBERON:0000945	83.34	gold quality
mucosa of stomach	UBERON:0001199	81.71	gold quality
gall bladder	UBERON:0002110	79.62	gold quality
fundus of stomach	UBERON:0001160	77.20	gold quality
islet of Langerhans	UBERON:0000006	71.57	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.42	gold quality
right adrenal gland cortex	UBERON:0035827	62.30	gold quality
left adrenal gland cortex	UBERON:0035825	58.32	gold quality
right adrenal gland	UBERON:0001233	58.12	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	73.64
E-ANND-3	yes	6.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

149 targets.

Target	Regulation
ABCG8
ACOT11
ACOT13
ACTA2	Activation
ADA	Activation
ADAM2
ADCYAP1	Unknown
ADORA1	Activation
AGTR1	Unknown
ALPI	Activation
AMH	Activation
ANKRD1	Unknown
APC
AR
ATP2A2
BCL2	Unknown
BCL2L1	Unknown
BCL2L11	Repression
BMP2
CALCA	Activation
CCNA2	Unknown
CCND1	Activation
CCND2	Activation
CD2
CD44
CDK4
CDKN2B	Activation
CEBPB	Activation
CEBPD
CISH

JASPAR motifs

Motif	Name	Family
MA0482.2	GATA4	C4-GATA-related
MA0482.3	GATA4	C4-GATA-related

JASPAR matrix evidence (PMIDs): PMID:7791790

Upstream regulators (CollecTRI, top): ARRB2, ATRX, BHLHA15, BMP2, ERG, ESRRG, ETS1, FLI1, FOXA2, GATA4, GATA6, HAND2, HEY1, HEY2, HIF1A, HYDIN, KLF2, LHX9, MAZ, MYC, MYOG, NANOG, NFYB, NKX2-5, NR0B1, NR2F1, POU5F1, SOX7, SP1, STAT3, TAL1, TP53, USF2, ZBED1, ZBTB16, ZFPM2, ZNF260

miRNA regulators (miRDB)

76 targeting GATA4, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-499A-5P	99.98	70.79	1323
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-3617-5P	99.75	69.41	1968
HSA-MIR-641	99.75	69.35	1975
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4306	99.72	70.50	3630
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-4470	99.66	69.35	1767
HSA-MIR-6512-3P	99.65	66.07	1468
HSA-MIR-6720-5P	99.65	66.22	1459
HSA-MIR-7156-5P	99.64	68.81	1369
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4273	99.45	67.93	1206

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• GATA-4 and GATA-6 mRNAs are readily detectable from gestational week 19 in human adrenal cortex. (PMID:12530677)
• role in trans-activation of bone morphogenetic protein 4 and regulation of mammalian organogenesis (PMID:12606287)
• In postnatal ovary, granulosa cells of growing follicles express FOG-2, partially overlapping with expression of mullerian-inhibiting substance. Important role for FOG-2 and GATA transcription factors in developing ovary. (PMID:12606418)
• 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)
• results implicate GATA4 as a genetic cause of human cardiac septal defects, perhaps through its interaction with TBX5 (PMID:12845333)
• Wild-type SF1 but not SF1 G35E is a potent transactvator in GAGA4-expressing cells. Results strengthen the importance of a GATA-4/SF-1 cooperation for MIS transcription; disruption of this synergism might lead to abnormal sex differentiation. (PMID:12907682)
• GATA-4 is critical for transcription of the erythropoietin (Epo) gene in hepatocytes and may contribute to the switch in the site of Epo gene expression from the fetal liver to the adult kidney (PMID:14583613)
• in colorectal cancer and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 (PMID:14612389)
• plays a transactivator role in the regulation of the transcription of the microsomal epoxide hydrolase gene (EPHX1) (PMID:14984931)
• transcription factors GATA4 and YY1 are involved in the regulation of FcgammaRIIb expression, and that the expression variants of FcgammaRIIb lead to altered cell signaling, which may contribute to autoimmune pathogenesis in humans. (PMID:15153544)
• A novel atrial septal defect causative GATA4 mutation in a Japanese family. (PMID:15235040)
• GATA4 is a SUMO-1-targeted transcription factor and together with PIAS1 is a potent regulator of cardiac gene activity (PMID:15337742)
• optimal claudin-2 expression in the gut relies on the presence of GATA-4, suggesting a role for this factor in intestinal regionalization (PMID:15389642)
• Hypermethylation of the GATA4 is associated with lung cancer (PMID:15585625)
• NKX2.5 inhibits myocyte differentiation and myotube formation, and up-regulates Gata4 and Tbx5 expression (PMID:15653675)
• Steroidogenically active human adrenocortical cells were weakly positive for GATA-4, whereas steroidogenically inactive cells were totally GATA-4 negative. In contrast, both cell lines expressed GATA-6. (PMID:15666845)
• GATA-4 detected in ovarian GCTs has retained normal function (PMID:16110260)
• expression of GATA-4 and GATA-6 is up-regulated prior to the transcriptional activation of Nkx 2.5 during cardiogenesis (PMID:16137232)
• Aggressive granulosa cell tumors(GCTs) retain high GATA-4 expression, whereas larger tumors lose proliferation-suppressing anti-Mullerian hormone expression. High GATA-4 expression in GCTs may serve as marker of poor prognosis. (PMID:16159935)
• Methylation of GATA-4 was associated with ovarian carcinogenesis (PMID:16337738)
• a GATA4 mutation may have a role in Tetralogy of Fallot (PMID:16470721)
• two novel GATA4 mutations associated with congenital heart defects in Chinese patients. This suggests that the transcription factor GATA4 may play an important role in cardiogenesis (PMID:16604480)
• Altered histone modification of the promoter loci is one mechanism responsible for the silencing of GATA transcription factors. (PMID:16607277)
• Frequent silencing of GATA-4 and GATA-5 in human esophageal neoplasia is associated with gene promoter hypermethylation. (PMID:16823849)
• Data show that Oct-4, Rex-1, and Gata-4 expression in human mesenchymal stem cells increases cell differentiation efficiency but not hTERT expression. (PMID:17211834)
• GATA4 mutations are relatively rare among congenital heart disease patients. (PMID:17253934)
• TGF-beta signaling regulates gut epithelial gene expression by targeting GATA4. (PMID:17290010)
• GATA4 mutations that result in deficits in transactivation ability are consistently associated with congenital heart disease suggesting that normal transactivation properties of GATA4 are required for proper cardiac development. (PMID:17352393)
• Cooperative interaction between HNFA4 and GATA4 and GATA6 regulates ABCG5 and ABCG8. (PMID:17403900)
• analysis of the nuclear shuttling pathways of GATA-4 that represent an additional mechanism of gene regulation (PMID:17548362)
• 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)
• somatic GATA4 mutations in the 3’-UTR may provide an additional molecular rationale for congenital heart disease (PMID:17592645)
• These data establish the phenotypic spectrum of heterozygous Gata4 mutation in mice, and suggest that heterozygous GATA4 mutation leads to partially overlapping phenotypes in humans. (PMID:17643447)
• While hypermethylation of GATA-5 seems to be a universal feature among human tumors, infrequent methylation of GATA-4, and its corresponding overexpression, appears unique to pancreatic cancer from other tumor types reported thus far. (PMID:17912029)
• 4 missense sequence variants (Gly93Ala, Gln316Glu, Ala411Val, Asp425Asn) occurred in patients with cardiac septal defects. 2 led to polarity changes. Non-synonymous GATA4 sequence variants sometimes occur in septal defects & rarely in conotruncal defects. (PMID:18055909)
• identification of a novel GATA4 mutation in a patients with ASDII (PMID:18076106)
• the majority of the ovarian surface epithelial carcinomas retained GATA-4 expression, whereas approximately two-thirds of the carcinomas had mislocalization or loss of GATA-6 expression (PMID:18227727)
• The results suggest differential but overlapping functions for GATA-4 and GATA-6 in the normal gastrointestinal mucosa. Furthermore, GATA-4, GATA-6 and Ihh expression is altered in premalignant dysplastic lesions and reduced in overt cancer. (PMID:18405344)
• HNF4alpha regulates thyroid hormone homeostasis through transcriptional regulation of the Dio1 gene with GATA4 and KLF9 (PMID:18426912)
• GATA-4 influences granulosa cell fate by transactivating Bcl-2. (PMID:18653721)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gata4	ENSDARG00000098952
mus_musculus	Gata4	ENSMUSG00000021944
rattus_norvegicus	Gata4	ENSRNOG00000010708
drosophila_melanogaster	GATAe	FBGN0038391
caenorhabditis_elegans		WBGENE00001250
caenorhabditis_elegans		WBGENE00001252

Paralogs (7): GATA1 (ENSG00000102145), TRPS1 (ENSG00000104447), GATA3 (ENSG00000107485), GATA5 (ENSG00000130700), GATA6 (ENSG00000141448), GATA2 (ENSG00000179348), ZGLP1 (ENSG00000220201)

Protein

Protein identifiers

Transcription factor GATA-4 — P43694 (reviewed: P43694)

Alternative names: GATA-binding factor 4

All UniProt accessions (6): A0A087WZ09, B3KUF4, B6DU75, E9PKS4, P43694, R4GND5

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional activator that binds to the consensus sequence 5’-AGATAG-3’ and plays a key role in cardiac development and function. In cooperation with TBX5, it binds to cardiac super-enhancers and promotes cardiomyocyte gene expression, while it down-regulates endocardial and endothelial gene expression. Involved in bone morphogenetic protein (BMP)-mediated induction of cardiac-specific gene expression. Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions. Acts as a transcriptional activator of ANF in cooperation with NKX2-5. Promotes cardiac myocyte enlargement. Required during testicular development. May play a role in sphingolipid signaling by regulating the expression of sphingosine-1-phosphate degrading enzyme, sphingosine-1-phosphate lyase.

Subunit / interactions. Interacts with ZNF260. Interacts with the homeobox domain of NKX2-5 through its C-terminal zinc finger. Also interacts with JARID2 which represses its ability to activate transcription of ANF. Interacts (via the second Zn finger) with NFATC4. Interacts with LMCD1. Forms a complex made of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates hypertrophy in cardiomyocytes. Interacts with NR5A1, ZFPM2 and TBX5. Interacts with TBX18. Interacts with GLYR1; the interaction is required for a synergistic activation of GATA4 target genes transcription. Interacts with PHF7; the interaction promotes GATA4 binding to its transcription targets.

Subcellular location. Nucleus.

Post-translational modifications. Methylation at Lys-300 attenuates transcriptional activity.

Disease relevance. Atrial septal defect 2 (ASD2) [MIM:607941] 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. Patients show other heart abnormalities including ventricular and atrioventricular septal defects, pulmonary valve thickening or insufficiency of the cardiac valves. The disease is not associated with defects in the cardiac conduction system or non-cardiac abnormalities. The disease is caused by variants affecting the gene represented in this entry. Ventricular septal defect 1 (VSD1) [MIM:614429] 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. 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. Atrioventricular septal defect 4 (AVSD4) [MIM:614430] A congenital heart malformation characterized by a common atrioventricular junction coexisting with deficient atrioventricular septation. The complete form involves underdevelopment of the lower part of the atrial septum and the upper part of the ventricular septum; the valve itself is also shared. A less severe form, known as ostium primum atrial septal defect, is characterized by separate atrioventricular valvar orifices despite a common junction. The disease is caused by variants affecting the gene represented in this entry. Testicular anomalies with or without congenital heart disease (TACHD) [MIM:615542] A 46,XY disorder of sex development with variable clinical presentation and defects in testicular differentiation and function. Clinical features include ambiguous genitalia, fused labioscrotal folds, hypospadias, microphallus, and bilateral inguinal hernia containing gonads. The disease is caused by variants affecting the gene represented in this entry. GATA4 mutations can predispose to dilated cardiomyopathy (CMD), a disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.

Isoforms (2)

UniProt ID	Names	Canonical?
P43694-1	1	yes
P43694-2	2

RefSeq proteins (5): NP_001295022, NP_001295023, NP_001361202, NP_001361203, NP_002043 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000679	Znf_GATA	Domain
IPR008013	GATA_N	Domain
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR016375	TF_GATA_4/5/6	Family
IPR039355	Transcription_factor_GATA	Family

Pfam: PF00320, PF05349

UniProt features (53 total): sequence variant 30, sequence conflict 6, compositionally biased region 4, region of interest 3, zinc finger region 2, turn 2, strand 2, chain 1, modified residue 1, splice variant 1, helix 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
8VG1	ELECTRON MICROSCOPY	2.48
8VG0	ELECTRON MICROSCOPY	3.07
2M9W	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43694-F1	58.64	0.20

Functional residue map

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

Post-translational modifications (1): 300

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-2032785	YAP1- and WWTR1 (TAZ)-stimulated gene expression
R-HSA-400511	Synthesis, secretion, and inactivation of Glucose-dependent Insulinotropic Polypeptide (GIP)
R-HSA-5578768	Physiological factors
R-HSA-9690406	Transcriptional regulation of testis differentiation
R-HSA-9733709	Cardiogenesis
R-HSA-9758920	Formation of lateral plate mesoderm
R-HSA-9823730	Formation of definitive endoderm
R-HSA-983231	Factors involved in megakaryocyte development and platelet production
R-HSA-9925561	Developmental Lineage of Pancreatic Acinar Cells
R-HSA-9925563	Developmental Lineage of Pancreatic Ductal Cells
R-HSA-9937080	Developmental Lineage of Multipotent Pancreatic Progenitor Cells

MSigDB gene sets: 675 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, CREL_01, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GOBP_CELLULAR_RESPONSE_TO_CARBOHYDRATE_STIMULUS, GOBP_POSITIVE_REGULATION_OF_VASCULATURE_DEVELOPMENT, GOBP_GROWTH

GO Biological Process (46): negative regulation of transcription by RNA polymerase II (GO:0000122), heart looping (GO:0001947), atrioventricular node development (GO:0003162), aortic valve morphogenesis (GO:0003180), atrioventricular valve formation (GO:0003190), endocardial cushion development (GO:0003197), cardiac ventricle morphogenesis (GO:0003208), cardiac right ventricle morphogenesis (GO:0003215), ventricular septum development (GO:0003281), atrial septum primum morphogenesis (GO:0003289), atrial septum secundum morphogenesis (GO:0003290), regulation of DNA-templated transcription (GO:0006355), cell-cell signaling (GO:0007267), endoderm development (GO:0007492), male gonad development (GO:0008584), response to xenobiotic stimulus (GO:0009410), response to mechanical stimulus (GO:0009612), negative regulation of autophagy (GO:0010507), positive regulation of vascular endothelial growth factor production (GO:0010575), negative regulation of cardiac muscle cell apoptotic process (GO:0010667), positive regulation of BMP signaling pathway (GO:0030513), response to vitamin A (GO:0033189), embryonic heart tube anterior/posterior pattern specification (GO:0035054), atrioventricular canal development (GO:0036302), wound healing (GO:0042060), cell fate commitment (GO:0045165), positive regulation of angiogenesis (GO:0045766), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), embryonic foregut morphogenesis (GO:0048617), transdifferentiation (GO:0060290), atrial septum morphogenesis (GO:0060413), intestinal epithelial cell differentiation (GO:0060575), cardiac muscle tissue regeneration (GO:0061026), cell growth involved in cardiac muscle cell development (GO:0061049), cellular response to glucose stimulus (GO:0071333), regulation of cardiac muscle cell contraction (GO:0086004), negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway (GO:1902176), negative regulation of apoptotic signaling pathway (GO:2001234), regulation of transcription by RNA polymerase II (GO:0006357)

GO Molecular Function (19): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II transcription regulatory region sequence-specific DNA binding (GO:0000977), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription activator activity (GO:0001216), DNA-binding transcription activator activity, RNA polymerase II-specific (GO:0001228), DNA binding (GO:0003677), zinc ion binding (GO:0008270), protein kinase binding (GO:0019901), sequence-specific DNA binding (GO:0043565), NFAT protein binding (GO:0051525), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), co-SMAD binding (GO:0070410), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA-binding transcription factor activity (GO:0003700), protein binding (GO:0005515), metal ion binding (GO:0046872), DNA-binding transcription factor binding (GO:0140297)

GO Cellular Component (5): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), RNA polymerase II transcription regulator complex (GO:0090575)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Developmental Cell Lineages of the Exocrine Pancreas	3
Developmental Biology	2
Gastrulation	2
Generic Transcription Pathway	1
Incretin synthesis, secretion, and inactivation	1
Cardiac conduction	1
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription cis-regulatory region binding	4
RNA polymerase II transcription regulatory region sequence-specific DNA binding	3
regulation of transcription by RNA polymerase II	2
cardiac ventricle development	2
atrial septum morphogenesis	2
DNA-binding transcription factor activity	2
cellular anatomical structure	2
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
embryonic heart tube morphogenesis	1
determination of heart left/right asymmetry	1
cardiac conduction system development	1
cardiac muscle tissue development	1
aortic valve development	1
heart valve morphogenesis	1
atrioventricular valve morphogenesis	1
heart valve formation	1
heart development	1
mesenchyme development	1
cardiac chamber morphogenesis	1
cardiac ventricle morphogenesis	1
cardiac septum development	1
septum primum development	1
septum secundum development	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell communication	1
signaling	1
tissue development	1
gonad development	1
development of primary male sexual characteristics	1
response to chemical	1
response to external stimulus	1
response to abiotic stimulus	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
positive regulation of cytokine production	1
vascular endothelial growth factor production	1

Protein interactions and networks

STRING

4518 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATA4	NKX2-5	P52952	999
GATA4	TBX5	Q99593	998
GATA4	ZFPM2	Q8WW38	997
GATA4	TBX20	Q9UMR3	990
GATA4	HAND2	P61296	985
GATA4	SMARCD3	Q6STE5	974
GATA4	MEF2C	Q06413	968
GATA4	EP300	Q09472	946
GATA4	SRF	P11831	920
GATA4	NPPA	P01160	895
GATA4	SOX17	Q9H6I2	875
GATA4	WT1	P19544	863
GATA4	NFATC4	Q14934	854
GATA4	NANOG	Q9H9S0	846
GATA4	FOXA2	Q9Y261	845

IntAct

22 interactions, top by confidence:

A	B	Type	Score
NKX2-5	GATA4	psi-mi:“MI:0915”(physical association)	0.520
GATA4	NKX2-5	psi-mi:“MI:0915”(physical association)	0.520
GATA4	KLF13	psi-mi:“MI:0915”(physical association)	0.520
KLF13	GATA4	psi-mi:“MI:0915”(physical association)	0.520
GATA4	H1-5	psi-mi:“MI:0915”(physical association)	0.400
GATA4		psi-mi:“MI:0915”(physical association)	0.400
CYP2C19	GATA4	psi-mi:“MI:0915”(physical association)	0.400
GATA4	ALX4	psi-mi:“MI:0915”(physical association)	0.370
GATA4	ZBTB3	psi-mi:“MI:0915”(physical association)	0.370
FOXE1	DDX39A	psi-mi:“MI:0914”(association)	0.350
KSR1	FBLL1	psi-mi:“MI:0914”(association)	0.350
KSR1	FAM168B	psi-mi:“MI:0914”(association)	0.350
ARHGEF19	NUP42	psi-mi:“MI:0914”(association)	0.350
GATA4	PCCA	psi-mi:“MI:0914”(association)	0.350
CANX	HLA-A	psi-mi:“MI:0914”(association)	0.350
ERG	BCL9	psi-mi:“MI:2364”(proximity)	0.270
FEV	TAF4	psi-mi:“MI:2364”(proximity)	0.270
PAX9	BCL9	psi-mi:“MI:2364”(proximity)	0.270
SOX2	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (454): GATA4 (Affinity Capture-MS), GATA4 (Protein-peptide), GATA4 (Proximity Label-MS), NKX2-5 (Affinity Capture-Western), GATA4 (Affinity Capture-Western), TBX5 (Affinity Capture-Western), GATA4 (Affinity Capture-Western), GATA4 (Reconstituted Complex), GNB2L1 (Reconstituted Complex), EP300 (Reconstituted Complex), EP300 (Affinity Capture-Western), GNB2L1 (Affinity Capture-Western), HAND2 (Reconstituted Complex), HAND2 (Affinity Capture-Western), GATA4 (Reconstituted Complex)

ESM2 similar proteins: A2XAV5, A2XED8, A2XLF4, A2XVI8, A2Y3I2, A2Y5N0, A2YG32, A2YWA6, A2Z259, B8AH02, B8AIK3, B8AX53, O09100, O82268, P17678, P23769, P43694, P46152, P56721, P84551, Q08369, Q0DZF3, Q0E3M2, Q0Q0E4, Q10DV5, Q5W659, Q62431, Q652I1, Q688U3, Q69Z36, Q6ATW6, Q6K5X1, Q6NNI3, Q6YXH5, Q6ZB90, Q7X7N3, Q7XDD0, Q7XRS1, Q8BX46, Q8GVZ6

Diamond homologs: B4XXY3, B7WN96, G5EB20, G5EGF4, G5EGN3, N4XMB0, O09100, O13412, O13415, O13508, O61924, O94720, P15976, P17429, P17678, P17679, P19212, P23767, P23768, P23769, P23770, P23771, P23772, P23773, P23824, P23825, P26343, P28515, P40349, P42944, P43429, P43574, P43691, P43692, P43693, P43694, P43695, P43696, P46152, P46153

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
POU5F1	“down-regulates quantity by repression”	GATA4	“transcriptional regulation”
NANOG	“down-regulates quantity by repression”	GATA4	“transcriptional regulation”
NKX2-5	“up-regulates quantity by expression”	GATA4	“transcriptional regulation”
GATA4	“up-regulates quantity by expression”	HAMP	“transcriptional regulation”
HYDIN	“up-regulates quantity by expression”	GATA4	“transcriptional regulation”
GATA4	up-regulates	Differentiation
GATA4	“up-regulates quantity by expression”	CTNNA3	“transcriptional regulation”
GATA4	“up-regulates quantity by expression”	α-Catenin	“transcriptional regulation”
PKA	“up-regulates activity”	GATA4	phosphorylation
CDK4	“down-regulates quantity by destabilization”	GATA4	phosphorylation
CDK4	“up-regulates activity”	GATA4	phosphorylation
ZFPM2	“down-regulates activity”	GATA4	binding
JARID2	“down-regulates activity”	GATA4	binding
ATRX	“down-regulates quantity by repression”	GATA4	“transcriptional regulation”
ZBED1	“down-regulates quantity by repression”	GATA4	“transcriptional regulation”
GATA4	“down-regulates quantity by repression”	TDO2	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

1094 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	32
Likely pathogenic	10
Uncertain significance	552
Likely benign	397
Benign	51

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1338850	NM_001308093.3(GATA4):c.691C>T (p.Arg231Ter)	Pathogenic
1361119	NM_001308093.3(GATA4):c.54C>A (p.Tyr18Ter)	Pathogenic
1452170	NM_001308093.3(GATA4):c.54C>G (p.Tyr18Ter)	Pathogenic
1458733	NM_001308093.3(GATA4):c.854G>A (p.Arg285His)	Pathogenic
1459470	NM_001308093.3(GATA4):c.266G>A (p.Trp89Ter)	Pathogenic
219226	NM_001308093.3(GATA4):c.23C>A (p.Ala8Asp)	Pathogenic
219228	NM_001308093.3(GATA4):c.383A>T (p.Glu128Val)	Pathogenic
219229	NM_001308093.3(GATA4):c.397A>T (p.Ser133Cys)	Pathogenic
219230	NM_001308093.3(GATA4):c.685T>A (p.Trp229Arg)	Pathogenic
219231	NM_001308093.3(GATA4):c.27C>A (p.Ala9=)	Pathogenic
219232	NM_001308093.3(GATA4):c.1266C>T (p.Ser422=)	Pathogenic
219233	NM_001308093.3(GATA4):c.1000+2T>G	Pathogenic
2424349	NC_000008.10:g.(?11565822)(11566457_?)del	Pathogenic
253407	GRCh37/hg19 8p23.3-22(chr8:158991-13304906)x3	Pathogenic
2711491	NM_001308093.3(GATA4):c.409G>T (p.Gly137Ter)	Pathogenic
2752218	NM_001308093.3(GATA4):c.923C>G (p.Pro308Arg)	Pathogenic
2812933	NM_001308093.3(GATA4):c.655_656del (p.Val219fs)	Pathogenic
2820525	NM_001308093.3(GATA4):c.887G>C (p.Cys296Ser)	Pathogenic
30098	NM_001308093.3(GATA4):c.889G>T (p.Gly297Cys)	Pathogenic
30106	NM_001308093.3(GATA4):c.889G>C (p.Gly297Arg)	Pathogenic
3245522	NC_000008.10:g.(?11565822)(11615984_?)del	Pathogenic
3631539	NM_001308093.3(GATA4):c.686G>A (p.Trp229Ter)	Pathogenic
4056393	NM_001308093.3(GATA4):c.786+1G>A	Pathogenic
433018	NM_001308093.3(GATA4):c.913-55T>C	Pathogenic
4723478	NM_001308093.3(GATA4):c.947_957del (p.Ile316fs)	Pathogenic
539991	NC_000008.11:g.(?11703278)(11758495_?)del	Pathogenic
805889	NM_001308093.3(GATA4):c.687G>C (p.Trp229Cys)	Pathogenic
831284	NC_000008.11:g.(?11703278)(11759996_?)del	Pathogenic
88838	NM_001308093.3(GATA4):c.664G>A (p.Gly222Arg)	Pathogenic
9031	NM_001308093.3(GATA4):c.1078del (p.Glu360fs)	Pathogenic

SpliceAI

1607 predictions. Top by Δscore:

Variant	Effect	Δscore
8:11704301:GCAG:G	donor_gain	1.0000
8:11704303:AGGT:A	donor_loss	1.0000
8:11704305:GTAG:G	donor_loss	1.0000
8:11704306:T:A	donor_loss	1.0000
8:11748899:T:TA	acceptor_gain	1.0000
8:11748909:A:AG	acceptor_gain	1.0000
8:11748910:A:G	acceptor_gain	1.0000
8:11748914:A:AG	acceptor_gain	1.0000
8:11748915:G:GA	acceptor_gain	1.0000
8:11748915:GT:G	acceptor_gain	1.0000
8:11748915:GTA:G	acceptor_gain	1.0000
8:11748915:GTAGA:G	acceptor_gain	1.0000
8:11749086:G:GG	donor_gain	1.0000
8:11750109:A:AG	acceptor_gain	1.0000
8:11750109:AGTCC:A	acceptor_gain	1.0000
8:11750110:G:GT	acceptor_gain	1.0000
8:11750110:GT:G	acceptor_gain	1.0000
8:11750110:GTC:G	acceptor_gain	1.0000
8:11750110:GTCC:G	acceptor_gain	1.0000
8:11750110:GTCCG:G	acceptor_gain	1.0000
8:11750234:GGG:G	donor_gain	1.0000
8:11750235:GG:G	donor_gain	1.0000
8:11750235:GGG:G	donor_gain	1.0000
8:11750235:GGGT:G	donor_loss	1.0000
8:11750236:GG:G	donor_gain	1.0000
8:11750237:G:GG	donor_gain	1.0000
8:11750237:GTAC:G	donor_loss	1.0000
8:11750238:T:TC	donor_loss	1.0000
8:11757081:CAGGT:C	donor_loss	1.0000
8:11757082:AGGTA:A	donor_loss	1.0000

AlphaMissense

2836 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
8:11748947:A:C	R215S	1.000
8:11748947:A:T	R215S	1.000
8:11748948:G:A	E216K	1.000
8:11748951:T:A	C217S	1.000
8:11748951:T:C	C217R	1.000
8:11748951:T:G	C217G	1.000
8:11748952:G:A	C217Y	1.000
8:11748952:G:C	C217S	1.000
8:11748952:G:T	C217F	1.000
8:11748953:T:G	C217W	1.000
8:11748955:T:A	V218D	1.000
8:11748957:A:G	N219D	1.000
8:11748959:C:A	N219K	1.000
8:11748959:C:G	N219K	1.000
8:11748960:T:A	C220S	1.000
8:11748960:T:C	C220R	1.000
8:11748960:T:G	C220G	1.000
8:11748961:G:A	C220Y	1.000
8:11748961:G:C	C220S	1.000
8:11748961:G:T	C220F	1.000
8:11748962:T:G	C220W	1.000
8:11748963:G:A	G221R	1.000
8:11748963:G:C	G221R	1.000
8:11748963:G:T	G221W	1.000
8:11748964:G:A	G221E	1.000
8:11748964:G:T	G221V	1.000
8:11748966:G:C	A222P	1.000
8:11748967:C:A	A222D	1.000
8:11748972:T:C	S224P	1.000
8:11748976:C:A	T225N	1.000

dbSNP variants (sampled 300 via entrez): RS1000047025 (8:11685175 A>C,G), RS1000050236 (8:11738305 C>A), RS1000074973 (8:11725081 G>A), RS1000144859 (8:11733284 A>G,T), RS1000179027 (8:11697127 G>C), RS1000186958 (8:11728293 A>G,T), RS1000227034 (8:11711098 G>A,T), RS1000237899 (8:11728483 C>A,G), RS1000240064 (8:11698980 G>T), RS1000253106 (8:11676917 G>A), RS1000304869 (8:11692613 G>C), RS1000312771 (8:11747145 C>G), RS1000319874 (8:11707960 G>C), RS1000341752 (8:11758324 G>A,T), RS1000381423 (8:11712469 G>C)

Disease associations

OMIM: gene MIM:600576 | disease phenotypes: MIM:614430, MIM:607941, MIM:615542, MIM:614429, MIM:187500, MIM:601144, MIM:612965, MIM:217095, MIM:100800, MIM:137920, MIM:265500

GenCC curated gene-disease

Disease	Classification	Inheritance
testicular anomalies with or without congenital heart disease	Definitive	Autosomal dominant
structural congenital heart disease, multiple types - GATA4	Definitive	Autosomal dominant
atrial septal defect 2	Definitive	Autosomal dominant
metabolic syndrome	Strong	Autosomal dominant
pancreatic hypoplasia-diabetes-congenital heart disease syndrome	Strong	Autosomal dominant
neonatal diabetes mellitus	Strong	Autosomal dominant
transient neonatal diabetes mellitus	Strong	Autosomal dominant
permanent neonatal diabetes mellitus	Strong	Autosomal dominant
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant
tetralogy of fallot	Supportive	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant
dilated cardiomyopathy	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
structural congenital heart disease, multiple types - GATA4	Definitive	AD

Mondo (26): atrioventricular septal defect 4 (MONDO:0013747), atrial septal defect 2 (MONDO:0011938), testicular anomalies with or without congenital heart disease (MONDO:0014239), ventricular septal defect 1 (MONDO:0013746), tetralogy of fallot (MONDO:0008542), congenital heart disease (MONDO:0005453), structural congenital heart disease, multiple types - GATA4 (MONDO:0100009), Brugada syndrome (MONDO:0015263), thoracic aortic aneurysm (MONDO:0005396), 46,XY sex reversal 3 (MONDO:0013066), microcephaly (MONDO:0001149), conotruncal heart malformations (MONDO:0016581), achondroplasia (MONDO:0007037), dilated cardiomyopathy (MONDO:0005021), intellectual disability (MONDO:0001071)

Orphanet (14): Interatrial communication (Orphanet:1478), 46,XY partial gonadal dysgenesis (Orphanet:251510), Tetralogy of Fallot (Orphanet:3303), Brugada syndrome (Orphanet:130), Male infertility with azoospermia or oligozoospermia due to single gene mutation (Orphanet:399805), Conotruncal heart malformations (Orphanet:2445), Common arterial trunk (Orphanet:3384), Double outlet right ventricle (Orphanet:3426), Achondroplasia (Orphanet:15), Dilated cardiomyopathy (Orphanet:217604), HNF1B-related autosomal dominant tubulointerstitial kidney disease (Orphanet:93111), Transposition of the great arteries (Orphanet:216675), Congenital pulmonary valvar stenosis (Orphanet:3189), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

151 total (30 of 151 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000051	Perineal hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000252	Microcephaly
HP:0000268	Dolichocephaly
HP:0000286	Epicanthus
HP:0000293	Full cheeks
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000369	Low-set ears
HP:0000377	Abnormal pinna morphology
HP:0000426	Prominent nasal bridge
HP:0000431	Wide nasal bridge
HP:0000470	Short neck

GWAS associations

74 associations (top):

Study	Trait	p-value
GCST000847_5	Retinal vascular caliber	4.000000e-07
GCST001712_8	Myopia (pathological)	4.000000e-06
GCST004279_33	Systolic blood pressure	4.000000e-19
GCST004635_18	Testicular germ cell tumor	4.000000e-08
GCST004776_51	Systolic blood pressure	6.000000e-08
GCST005273_3	Polycystic ovary syndrome	8.000000e-10
GCST006061_17	Atrial fibrillation	1.000000e-06
GCST006187_21	Diastolic blood pressure (cigarette smoking interaction)	6.000000e-13
GCST006187_22	Diastolic blood pressure (cigarette smoking interaction)	2.000000e-10
GCST006188_1	Systolic blood pressure (cigarette smoking interaction)	6.000000e-18
GCST006188_37	Systolic blood pressure (cigarette smoking interaction)	1.000000e-22
GCST006258_36	Diastolic blood pressure	3.000000e-06
GCST006259_58	Systolic blood pressure	9.000000e-11
GCST006414_128	Atrial fibrillation	5.000000e-09
GCST006434_106	Systolic blood pressure x alcohol consumption interaction (2df test)	2.000000e-10
GCST006434_92	Systolic blood pressure x alcohol consumption interaction (2df test)	3.000000e-10
GCST007324_58	Adventurousness	3.000000e-17
GCST007325_176	General risk tolerance (MTAG)	1.000000e-08
GCST007709_175	General factor of neuroticism	1.000000e-09
GCST007709_177	General factor of neuroticism	2.000000e-09
GCST007709_188	General factor of neuroticism	5.000000e-11
GCST007709_49	General factor of neuroticism	8.000000e-12
GCST007928_50	Medication use (diuretics)	8.000000e-16
GCST007930_74	Medication use (agents acting on the renin-angiotensin system)	4.000000e-11
GCST010002_269	Refractive error	1.000000e-24
GCST010132_11	Processed meat consumption	4.000000e-10
GCST010132_14	Processed meat consumption	2.000000e-15
GCST010132_15	Processed meat consumption	1.000000e-09
GCST010136_40	Fruit consumption	1.000000e-10
GCST010136_5	Fruit consumption	9.000000e-09

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0004731	eye measurement
EFO:0004207	pathological myopia
EFO:0006335	systolic blood pressure
EFO:0006336	diastolic blood pressure
EFO:0006527	smoking status measurement
EFO:0004329	alcohol drinking
EFO:0008579	risk-taking behaviour
EFO:0007660	neuroticism measurement
EFO:0009928	Diuretic use measurement
EFO:0009931	Agents acting on the renin-angiotensin system use measurement
EFO:0008111	diet measurement
EFO:0004530	triglyceride measurement
EFO:0004346	neuroimaging measurement
EFO:0007789	BMI-adjusted waist circumference
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (14)

Descriptor	Name	Tree numbers
D000130	Achondroplasia	C05.116.099.343.110; C05.116.099.708.017; C16.320.240.500
D017545	Aortic Aneurysm, Thoracic	C14.907.055.239.125; C14.907.109.139.125
D053840	Brugada Syndrome	C14.280.067.322; C14.280.123.250; C16.320.100
D002311	Cardiomyopathy, Dilated	C14.280.195.160; C14.280.238.070; C16.320.488.750
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D013771	Tetralogy of Fallot	C14.240.400.849; C14.280.400.849; C16.131.240.400.849
D014188	Transposition of Great Vessels	C14.240.400.915; C14.280.400.915; C16.131.240.400.915
D014262	Tricuspid Valve Insufficiency	C14.280.484.856
C538263	Atrial septal defect 2 (supp.)
C563425	Diabetes Mellitus, Permanent Neonatal (supp.)
C564011	Pancreatic Hypoplasia, Congenital, with Diabetes Mellitus and Congenital Heart Disease (supp.)
C535520	Renal cysts and diabetes syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1687679 (SINGLE PROTEIN)

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

PharmGKB clinical annotations

3 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs13273672	Efficacy	3	Drugs used in alcohol dependence	Alcohol abuse
rs2645400	Dosage	3	warfarin
rs4841588	Dosage	3	warfarin

PharmGKB variants

37 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2645400	GATA4	3	0.00	1	warfarin
rs3735814	GATA4		0.00	0
rs4841588	GATA4	3	0.00	1	warfarin
rs10090884	GATA4		0.00	0
rs13273672	C8orf49, GATA4	3	2.25	1	Drugs used in alcohol dependence
rs6990313	GATA4		0.00	0
rs10105409	GATA4		0.00	0
rs6601604	GATA4		0.00	0
rs10112596	GATA4		0.00	0
rs12550668	GATA4		0.00	0
rs2898292	GATA4		0.00	0
rs4840579	GATA4		0.00	0
rs11250159	GATA4		0.00	0
rs17153694	GATA4		0.00	0
rs17153698	GATA4		0.00	0
rs6983129	GATA4		0.00	0
rs2898295	GATA4		0.00	0
rs11250163	GATA4		0.00	0
rs13275657	GATA4		0.00	0
rs2029969	GATA4		0.00	0
rs2173117	GATA4		0.00	0
rs3779664	GATA4		0.00	0
rs2740434	GATA4		0.00	0
rs2645399	GATA4		0.00	0
rs11784693	GATA4		0.00	0
rs804283	GATA4		0.00	0
rs17153747	GATA4		0.00	0
rs804282	GATA4		0.00	0
rs13264774	GATA4		0.00	0
rs804280	GATA4		0.00	0
rs3729856	GATA4		0.00	0
rs867858	GATA4		0.00	0
rs1062219	GATA4		0.00	0
rs804290	C8orf49, GATA4		0.00	0
rs11785481	C8orf49, GATA4		0.00	0
rs12458	C8orf49, GATA4		0.00	0
rs3203358	C8orf49, GATA4		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, increases methylation	4
sodium arsenite	affects methylation, affects cotreatment, decreases expression, affects splicing	3
Benzo(a)pyrene	increases mutagenesis, affects methylation, decreases expression, decreases methylation	3
Tretinoin	affects expression, affects cotreatment, increases expression	3
methylmercuric chloride	decreases expression, increases expression	2
bisphenol A	affects cotreatment, increases methylation, decreases expression	2
Panobinostat	decreases expression, affects cotreatment	2
Cadmium	decreases expression	2
Aflatoxin B1	affects methylation, decreases methylation	2
dicrotophos	increases expression	1
tributyltin	increases expression	1
terbufos	increases methylation	1
tris(2-butoxyethyl) phosphate	affects expression	1
arsenite	increases methylation	1
monoisoamyl-2,3-dimercaptosuccinate	decreases expression, affects cotreatment	1
1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene	affects cotreatment, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
Arsenic Trioxide	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Glyphosate	increases expression	1
Arsenic	affects methylation	1
Carbamazepine	affects expression	1
Dexamethasone	increases expression	1
Diclofenac	affects expression	1
Dimethyl Sulfoxide	decreases expression, increases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Malathion	decreases expression	1

ChEMBL screening assays

5 unique, capped per target: 5 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1687099	Binding	Inhibition of GATA4-DNA interaction in HEK293 nuclear extract at 50 uM after 15 mins by EMSA assay	Identification of new GATA4-small molecule inhibitors by structure-based virtual screening. — Bioorg Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A8WK	WAe007-A-1	Embryonic stem cell	Female
CVCL_B8GS	Abcam HCT 116 GATA4 KO	Cancer cell line	Male
CVCL_B9J0	Abcam A-549 GATA4 KO	Cancer cell line	Male
CVCL_D2FD	Abcam MCF-7 GATA4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00374465	PHASE4	UNKNOWN	Therapy With Verapamil or Carvedilol in Chronic Heart Failure
NCT01293903	PHASE4	COMPLETED	Study of Qiliqiangxin Capsule to Treat Dilated Cardiomyopathy
NCT01557140	PHASE4	COMPLETED	A Randomized Trial of Carvedilol in Chronic Chagas Cardiomyopathy
NCT01917149	PHASE4	COMPLETED	Supramaximal Titrated Inhibition of RAAS in Dilated Cardiomyopathy
NCT02115581	PHASE4	COMPLETED	Coenzyme Q10 Supplementation in Children With Idiopathic Dilated Cardiomyopathy
NCT06236022	PHASE4	RECRUITING	The Effects of Sirolimus in Patients With Dilated Cardiomyopathy Infected With Kaposi Sarcoma-associated Virus
NCT02624817	PHASE4	COMPLETED	Long-Term Sulfonylurea Response in KCNJ11 Neonatal Diabetes
NCT02624830	PHASE4	UNKNOWN	Long-Term Sulfonylurea Response in ABCC8 Neonatal Diabetes (SuResponsSUR)
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
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
NCT00333827	PHASE3	COMPLETED	Cell Therapy In Dilated Cardiomyopathy
NCT00505154	PHASE3	COMPLETED	Effect of Rosuvastatin on Left Ventricular Remodeling
NCT01223703	PHASE3	COMPLETED	PUFAs and Left Ventricular Function in Heart Failure
NCT01583114	PHASE3	TERMINATED	PREclinical Mutation CARriers From Families With DIlated Cardiomyopathy and ACE Inhibitors
NCT01914081	PHASE3	UNKNOWN	Resveratrol: A Potential Anti- Remodeling Agent in Heart Failure, From Bench to Bedside
NCT02989181	PHASE3	UNKNOWN	Continues Positive Airway Pressure Treatment for Patients With Dilated Cardiomyopathy and Obstructive Sleep Apnea
NCT03439514	PHASE3	TERMINATED	A Study of ARRY-371797 (PF-07265803) in Patients With Symptomatic Dilated Cardiomyopathy Due to a Lamin A/C Gene Mutation
NCT05237323	PHASE3	COMPLETED	Micophenolate Mofetil Versus Azathioprine in Myocarditis
NCT05849766	PHASE3	COMPLETED	Effect of Dapagliflozin on Cardiac Structure, Function and Secondary Mitral Regurgitation in Patients with Left Ventricle Dysfunction
NCT06250257	PHASE3	RECRUITING	Bromocriptine in Dilated Cardiomyopathy Among Women of Reproductive Age
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
NCT03153137	PHASE3	COMPLETED	Clinical Study Assessing the Efficacy and Safety of Macitentan in Fontan-palliated Subjects