GATA5

Summary

GATA5 (GATA binding protein 5, HGNC:15802) is a protein-coding gene on chromosome 20q13.33, encoding Transcription factor GATA-5 (Q9BWX5). Transcription factor required during cardiovascular development.

The protein encoded by this gene is a transcription factor that contains two GATA-type zinc fingers. The encoded protein is known to bind to hepatocyte nuclear factor-1alpha (HNF-1alpha), and this interaction is essential for cooperative activation of the intestinal lactase-phlorizin hydrolase promoter. In other organisms, similar proteins may be involved in the establishment of cardiac smooth muscle cell diversity.

Source: NCBI Gene 140628 — RefSeq curated summary.

At a glance

• Gene–disease (curated): congenital heart defects, multiple types, 5 (Moderate, GenCC) — +3 more curated relationships
• GWAS associations: 8
• Clinical variants (ClinVar): 634 total — 4 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 43
• Transcription factor: yes — 43 downstream targets (CollecTRI)
• MANE Select transcript: NM_080473

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15802
Approved symbol	GATA5
Name	GATA binding protein 5
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	bB379O24.1, GATAS
Ensembl gene	ENSG00000130700
Ensembl biotype	protein_coding
OMIM	611496
Entrez	140628

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 4 protein_coding

ENST00000252997, ENST00000861188, ENST00000861189, ENST00000914293

RefSeq mRNA: 1 — MANE Select: NM_080473 NM_080473

CCDS: CCDS13499

Canonical transcript exons

ENST00000252997 — 7 exons

Exon	Start	End
ENSE00000897947	62474999	62475542
ENSE00002431888	62463497	62464991
ENSE00002451771	62466426	62466551
ENSE00002458871	62465340	62465464
ENSE00002469558	62473403	62473578
ENSE00002512498	62465834	62465921
ENSE00002703284	62475930	62475995

Expression profiles

Bgee: expression breadth ubiquitous, 106 present calls, max score 87.67.

FANTOM5 (CAGE): breadth broad, TPM avg 0.8455 / max 64.6045, expressed in 186 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
188270	0.8455	186

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ileal mucosa	UBERON:0000331	87.67	gold quality
left uterine tube	UBERON:0001303	80.91	gold quality
jejunal mucosa	UBERON:0000399	79.30	gold quality
duodenum	UBERON:0002114	78.06	gold quality
right testis	UBERON:0004534	76.53	gold quality
left testis	UBERON:0004533	75.98	gold quality
body of stomach	UBERON:0001161	75.09	gold quality
testis	UBERON:0000473	75.02	gold quality
right adrenal gland cortex	UBERON:0035827	72.72	gold quality
stomach	UBERON:0000945	72.60	gold quality
right adrenal gland	UBERON:0001233	72.26	gold quality
urinary bladder	UBERON:0001255	72.21	gold quality
fundus of stomach	UBERON:0001160	72.19	gold quality
germinal epithelium of ovary	UBERON:0001304	71.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	70.76	gold quality
small intestine	UBERON:0002108	70.61	gold quality
left adrenal gland cortex	UBERON:0035825	70.38	gold quality
left adrenal gland	UBERON:0001234	70.11	gold quality
cardiac muscle of right atrium	UBERON:0003379	69.77	gold quality
adrenal cortex	UBERON:0001235	69.65	gold quality
left ventricle myocardium	UBERON:0006566	69.56	gold quality
apex of heart	UBERON:0002098	69.52	gold quality
mucosa of stomach	UBERON:0001199	69.51	gold quality
superficial temporal artery	UBERON:0001614	68.25	silver quality
right atrium auricular region	UBERON:0006631	68.20	gold quality
cardiac atrium	UBERON:0002081	68.09	gold quality
jejunum	UBERON:0002115	66.97	gold quality
body of uterus	UBERON:0009853	66.62	gold quality
adrenal gland	UBERON:0002369	66.51	gold quality
vena cava	UBERON:0004087	65.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.19

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

43 targets.

Target	Regulation
ADAM2
APC
BMP4	Activation
CDC5L
CDH13
CDH5	Activation
CTNND1
EPHB4	Activation
ERBB2	Activation
FABP1
GATA5
GNRH1	Unknown
HEY1	Activation
JAG1	Activation
LCT	Repression
MEF2C	Activation
MGMT
MUC17
MUC2	Activation
MUC4	Activation
MUC5B	Unknown
MUC6
MYH7
MYL3	Activation
NELFE
NKX2-5	Activation
NOS3	Activation
NOTCH1	Activation
NPPA	Repression
NPPB	Repression

JASPAR motifs

Motif	Name	Family
MA0766.1	GATA5	C4-GATA-related
MA0766.2	GATA5	C4-GATA-related
MA0766.3	GATA5	C4-GATA-related

JASPAR matrix evidence (PMIDs): PMID:1638017, PMID:14612389

Upstream regulators (CollecTRI, top): CDX1, GATA5, USF1

miRNA regulators (miRDB)

38 targeting GATA5, 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-30E-5P	100.00	76.32	3242
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-4283	100.00	66.42	2097
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-187-5P	99.74	70.26	1404
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-6757-3P	99.63	66.88	1089
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4284	99.36	65.25	1293
HSA-MIR-130A-5P	99.33	70.26	2623
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-4651	99.06	67.57	2002
HSA-MIR-608	98.93	67.83	2013
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-6728-3P	98.63	67.63	1534
HSA-MIR-3135B	98.61	65.33	1470
HSA-MIR-323A-5P	98.59	65.13	651
HSA-MIR-6818-3P	98.56	68.23	1307
HSA-MIR-4718	98.55	68.61	814
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6826-3P	98.19	66.32	1153
HSA-MIR-4483	98.09	64.12	1642
HSA-MIR-6810-3P	97.96	64.57	1023

Literature-anchored findings (GeneRIF, showing 40)

• demonstrate that GATA-5 and HNF-1alpha physically associate both in vivo and in vitro and that this interaction is necessary for cooperative activation of the lactase-phlorizin hydrolase promoter (PMID:12011060)
• in colorectal cancer and gastric cancer promoter hypermethylation and transcriptional silencing are frequent for GATA-4 and -5 (PMID:14612389)
• Hypermethylation of the GATA5 is associated with lung cancer (PMID:15585625)
• Methylation of GATA-5 was associated with ovarian carcinogenesis (PMID:16337738)
• Frequent silencing of GATA-4 and GATA-5 in human esophageal neoplasia is associated with gene promoter hypermethylation. (PMID:16823849)
• 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)
• Methylation of GATA4/5 is a common and specific event in colorectal carcinomas, and GATA4/5 exhibit tumor suppressive effects in colorectal cancer cells in vitro. GATA4 methylation in fecal DNA may be of interest for colorectal cancer detection. (PMID:19509152)
• Epigenetic inactivation of GATA-5 by methylation of CpG islands is an early frequent event during gastric carcinogenesis and is significantly correlated with H. pylori infection. (PMID:20222162)
• Two new epigenetic subgroups of gastroesophageal adenocarcinomas were identified that differ to some extent in their survival rates, risk factors of exposure, and GATA5 DNA methylation. (PMID:22028801)
• the prevalence and spectrum of GATA5 mutations in patients with familial atrial fibrillation (PMID:22483626)
• USF1 transactivates GATA5 expression by binding to the E-box in its promoter (PMID:22625849)
• Rare non-synonymous variations in the functionally important GATA5 transcriptional activation domains may be important in the pathogenesis of BAV disease in humans. (PMID:22641149)
• GATA5 protein mutataion is reposnsible for congenital ventriculoseptal defect. (PMID:22961344)
• GATA5 mutations were associated with congenital heart disease. (PMID:23031282)
• A novel heterozygous GATA5 loss-of-function mutation of p.W200G identified in a family with lone atrial fibrillation is reported. (PMID:23175127)
• In the present study, two novel heterozygous mutations of GATA5, p.R187G and p.H207R, were identified in 2 families with TOF. In each family, the mutant allele was present in all the affected family members (PMID:23289003)
• The findings expand the spectrum of GATA5 mutations linked to atrial fibrillation and provide novel insights into the molecular mechanism involved in the pathogenesis of atrial fibrillation (PMID:23295592)
• Reduced GATA5 mRNA levels are associated with a poor clinical outcome, indicating a possible role of GATA5 for the development of aggressive clear cell renal cell carcinoma. (PMID:24533449)
• Epigenetic alterations in GATA family members may be associated with aggressive tumor phenotypes in renal cell cancer (PMID:24549248)
• Results of this study showed an association of somatic GATA5 mutations with TOF, providing further insight into the underlying molecular mechanism of TOF. (PMID:24573614)
• study provides genetic evidence on the association of GATA5 loss-of-function mutations with enhanced susceptibility to bicuspid aortic valve (BAV), providing novel insight into the molecular mechanism involved in human BAV (PMID:24638895)
• GATA5, possibly through upregulation of eNOS, plays a role in the development of aortic dilatation in patients with unicuspid and bicuspid aortic valves. (PMID:24766859)
• Rare sequence variants, p.Gln3Arg and p.Leu233Pro, in GATA5 are associated with human bicuspid aortic valve. (PMID:24796370)
• Promoter hypermethylation is an important mechanism of the transcriptional inactivation of GATA5 in invasive ductal breast carcinoma. (PMID:25148870)
• A new potentially pathogenic variant in GATA5 contributes to the development of bicuspid aortic valve syndrome. (PMID:25449525)
• DSVs in the GATA5 gene promoter may increase the susceptibility to the development of VSD as a risk factor. (PMID:25515806)
• This study firstly links GATA5 mutation to DCM, which provides novel insight into the molecular mechanisms of DCM, suggesting a potential molecular target for the prenatal prophylaxis and allele-specific treatment of DCM. (PMID:25543888)
• A combination of GATA5 and SFRP2 methylation could be promising as a marker for the detection and diagnosis of colorectal cancers and adenomas. (PMID:25759530)
• Transcriptomic analysis of human microvascular endothelial cells with GATA5 knockdown reveals that GATA5 affects several genes and pathways critical for endothelial function. (PMID:26617239)
• Evidence supporting a genetic basis includes the autosomal dominance of Bicuspid aortic valve inheritance patterns, and the identification of mutations in GATA binding protein 5 transcription factor. (PMID:26766164)
• The Correlation between GATA5, WT1 and PAX5 methylation and clinical/histological parameters is suggestive of applicability of these markers in non-invasive (epi)genetic testing in hepatocellular carcinoma (HCC). (PMID:27171388)
• A multivariate regression model revealed that the effects of both the promoter methylation and the exonic SNPs in GATA5 were independent.This interaction between GATA5 variants and GATA5 promoter methylation indicates that the association of either factor with gastric disease progression is modified by the other (PMID:27225266)
• These results suggest that the induction of GATA-6 dysfunction may be more effective for chemotherapy for colorectal cancer, although the mechanism underlying the synergistic effect of 5-FU and anisomycin remains unknown. (PMID:27404124)
• we identified gene promoter methylation signatures (WT1, MSH6, GATA5 and PAX5) that are strongly correlated to, and can have a predictive value for the clinical outcome of oral squamous cell carcinoma patients (PMID:27491556)
• findings show that GATA5 mutations, in addition to heart diseases, can result in congenital abnormalities of the female genitourinary tract in humans (PMID:28180938)
• H. pylori upregulates GATA-5 mRNA levels after 6, 24, and 48 h of infection in gastric epithelial cells compared to uninfected cells, in parallel with a progressive increase in TFF1 mRNA levels. (PMID:30083861)
• The findings support the fact that rare functional variants especially in GATA5 could be associated with BAV, adding novel genetic factors to the list of variants associated with the phenotypic expression of this genetically complex pathology. (PMID:30229885)
• GATA5 inhibits hepatocellular carcinoma cells malignant behavior by blocking expression of beta-catenin and reprogramming genes. (PMID:30672133)
• Molecular genetic study on GATA5 gene promoter in acute myocardial infarction. (PMID:33684162)
• GATA binding protein 5 (GATA5) induces Rho GTPase activating protein 9 (ARHGAP9) to inhibit the malignant process of lung adenocarcinoma cells. (PMID:35040754)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	gata5	ENSDARG00000017821
mus_musculus	Gata5	ENSMUSG00000015627
rattus_norvegicus	Gata5	ENSRNOG00000058983
drosophila_melanogaster	pnr	FBGN0003117
caenorhabditis_elegans		WBGENE00001250
caenorhabditis_elegans		WBGENE00001252

Paralogs (7): GATA1 (ENSG00000102145), TRPS1 (ENSG00000104447), GATA3 (ENSG00000107485), GATA4 (ENSG00000136574), GATA6 (ENSG00000141448), GATA2 (ENSG00000179348), ZGLP1 (ENSG00000220201)

Protein

Protein identifiers

Transcription factor GATA-5 — Q9BWX5 (reviewed: Q9BWX5)

Alternative names: GATA-binding factor 5

All UniProt accessions (1): Q9BWX5

UniProt curated annotations — full annotation on UniProt →

Function. Transcription factor required during cardiovascular development. Plays an important role in the transcriptional program(s) that underlies smooth muscle cell diversity. Binds to the functionally important CEF-1 nuclear protein binding site in the cardiac-specific slow/cardiac troponin C transcriptional enhancer.

Subcellular location. Nucleus.

Disease relevance. Congenital heart defects, multiple types, 5 (CHTD5) [MIM:617912] A disorder characterized by congenital developmental abnormalities involving structures of the heart. Common defects include transposition of the great arteries, aortic stenosis, atrial septal defect, ventricular septal defect, pulmonic stenosis, patent ductus arteriosus, and tetralogy of Fallot. Some patients also have cardiac arrhythmias, which may be due to the anatomic defect itself or to surgical interventions. CHTD5 inheritance can be autosomal dominant or recessive. The disease is caused by variants affecting the gene represented in this entry.

RefSeq proteins (1): NP_536721* (*=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 (33 total): sequence variant 23, compositionally biased region 4, zinc finger region 2, region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9BWX5-F1	59.91	0.23

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-983231	Factors involved in megakaryocyte development and platelet production

MSigDB gene sets: 256 (showing top): GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_ENDOCARDIAL_CUSHION_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_NOTCH_SIGNALING_PATHWAY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, SCHLESINGER_METHYLATED_DE_NOVO_IN_CANCER, GOBP_DEVELOPMENTAL_INDUCTION, GOBP_CELLULAR_RESPONSE_TO_OXYGEN_CONTAINING_COMPOUND, GOBP_ENDOCARDIAL_CUSHION_MORPHOGENESIS, GOBP_DNA_CATABOLIC_PROCESS, GOBP_CELL_CELL_ADHESION, GOBP_DIGESTIVE_SYSTEM_DEVELOPMENT, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, OHM_METHYLATED_IN_ADULT_CANCERS

GO Biological Process (24): negative regulation of transcription by RNA polymerase II (GO:0000122), heart induction (GO:0003129), aortic valve morphogenesis (GO:0003180), endocardial cushion fusion (GO:0003274), negative regulation of cardiac muscle hypertrophy (GO:0010614), positive regulation of gene expression (GO:0010628), negative regulation of gene expression (GO:0010629), cell fate commitment (GO:0045165), positive regulation of Notch signaling pathway (GO:0045747), positive regulation of transcription by RNA polymerase II (GO:0045944), cardiac muscle tissue development (GO:0048738), intestinal epithelial cell differentiation (GO:0060575), positive regulation of cardiac endothelial to mesenchymal transition (GO:0062000), cellular response to hydrogen peroxide (GO:0070301), cellular response to nitric oxide (GO:0071732), cellular response to BMP stimulus (GO:0071773), positive regulation of apoptotic DNA fragmentation (GO:1902512), regulation of DNA-templated transcription (GO:0006355), regulation of transcription by RNA polymerase II (GO:0006357), heart development (GO:0007507), anatomical structure morphogenesis (GO:0009653), tissue development (GO:0009888), cell differentiation (GO:0030154), positive regulation of DNA-templated transcription (GO:0045893)

GO Molecular Function (11): transcription cis-regulatory region binding (GO:0000976), RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), DNA-binding transcription factor activity, RNA polymerase II-specific (GO:0000981), DNA-binding transcription factor activity (GO:0003700), zinc ion binding (GO:0008270), sequence-specific double-stranded DNA binding (GO:1990837), cis-regulatory region sequence-specific DNA binding (GO:0000987), DNA binding (GO:0003677), protein binding (GO:0005515), sequence-specific DNA binding (GO:0043565), metal ion binding (GO:0046872)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

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
regulation of gene expression	3
gene expression	2
regulation of DNA-templated transcription	2
RNA polymerase II transcription regulatory region sequence-specific DNA binding	2
transcription cis-regulatory region binding	2
cellular anatomical structure	2
negative regulation of DNA-templated transcription	1
organ induction	1
heart field specification	1
regulation of heart morphogenesis	1
aortic valve development	1
heart valve morphogenesis	1
endocardial cushion morphogenesis	1
cell adhesion involved in heart morphogenesis	1
cell-cell adhesion	1
cardiac muscle hypertrophy	1
regulation of cardiac muscle hypertrophy	1
negative regulation of muscle hypertrophy	1
positive regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule biosynthetic process	1
cell differentiation	1
cellular developmental process	1
Notch signaling pathway	1
regulation of Notch signaling pathway	1
positive regulation of signal transduction	1
positive regulation of DNA-templated transcription	1
heart development	1
striated muscle tissue development	1
columnar/cuboidal epithelial cell differentiation	1
digestive tract development	1
positive regulation of cell differentiation	1
positive regulation of multicellular organismal process	1
regulation of cardiac endothelial to mesenchymal transition	1
cardiac endothelial to mesenchymal transition	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
response to nitric oxide	1
cellular response to oxygen-containing compound	1

Protein interactions and networks

STRING

2400 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATA5	NKX2-5	P52952	847
GATA5	LCT	P09848	818
GATA5	TBX20	Q9UMR3	737
GATA5	HNF1A	P20823	720
GATA5	FOXA2	Q9Y261	674
GATA5	FABP2	P12104	671
GATA5	FOXA1	P55317	627
GATA5	ZFPM2	Q8WW38	627
GATA5	TBX5	Q99593	602
GATA5	PCBD1	P61457	596
GATA5	QRSL1	Q9H0R6	596
GATA5	HAND2	P61296	586
GATA5	LMO2	P25791	555
GATA5	MCM6	Q14566	549
GATA5	SFRP1	Q8N474	518

IntAct

22 interactions, top by confidence:

A	B	Type	Score
HPCA	GATA5	psi-mi:“MI:0915”(physical association)	0.560
GATA5	MAGED1	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	GATA5	psi-mi:“MI:0915”(physical association)	0.560
PLA2G10	GATA5	psi-mi:“MI:0915”(physical association)	0.560
PPARG	GATA5	psi-mi:“MI:0915”(physical association)	0.560
ARID5A	GATA5	psi-mi:“MI:0915”(physical association)	0.560
HPCAL1	GATA5	psi-mi:“MI:0915”(physical association)	0.560
GATA5	MAGED1	psi-mi:“MI:0915”(physical association)	0.000
GATA5	CYSRT1	psi-mi:“MI:0915”(physical association)	0.000
GATA5	PLA2G10	psi-mi:“MI:0915”(physical association)	0.000
GATA5	PPARG	psi-mi:“MI:0915”(physical association)	0.000
GATA5	ARID5A	psi-mi:“MI:0915”(physical association)	0.000
GATA5	HPCAL1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (12): GATA5 (Two-hybrid), GATA5 (Two-hybrid), GATA5 (Two-hybrid), PPARG (Two-hybrid), MAGED1 (Two-hybrid), ARID5A (Two-hybrid), CYSRT1 (Two-hybrid), GATA5 (Positive Genetic), KLF2 (Two-hybrid), GATA5 (Co-localization), GATA5 (Affinity Capture-Western), CTNNB1 (Affinity Capture-Western)

ESM2 similar proteins: A0A059XKS9, A0A120KVR5, A0A120KVR8, A0A120KVW2, A4HK17, A4I1H7, A9V196, B5APK2, B9VXQ2, F5HF49, F5HG95, F5HIG1, O83683, P09705, P12304, P14348, P16749, P16753, P16789, P16801, P16827, P16848, P40572, Q07762, Q384Y0, Q4CTY5, Q4D7L5, Q4Q9W0, Q57W26, Q57XK8, Q57XV5, Q57Y77, Q68101, Q6SVX2, Q6SW04, Q6SW48, Q6SW62, Q6SW65, Q6SW73, Q6SW82

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

1 interactions.

A	Effect	B	Mechanism
USF1	“up-regulates quantity by expression”	GATA5	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	4
Likely pathogenic	1
Uncertain significance	346
Likely benign	235
Benign	25

Top pathogenic / likely-pathogenic (5)

Variant ID	HGVS	Classification
496599	NM_080473.5(GATA5):c.569T>C (p.Val190Ala)	Pathogenic
496600	NM_080473.5(GATA5):c.595C>G (p.Leu199Val)	Pathogenic
496601	NM_080473.5(GATA5):c.598T>G (p.Trp200Gly)	Pathogenic
496602	NM_080473.5(GATA5):c.46T>G (p.Tyr16Asp)	Pathogenic
4277395	NM_080473.5(GATA5):c.699+1G>A	Likely pathogenic

SpliceAI

843 predictions. Top by Δscore:

Variant	Effect	Δscore
20:62465334:CCTTA:C	donor_loss	1.0000
20:62465335:CTTA:C	donor_loss	1.0000
20:62465336:TTACC:T	donor_loss	1.0000
20:62465337:TACCT:T	donor_loss	1.0000
20:62465339:CCTG:C	donor_loss	1.0000
20:62465460:GGATC:G	acceptor_gain	1.0000
20:62465461:GATC:G	acceptor_gain	1.0000
20:62465463:TC:T	acceptor_gain	1.0000
20:62465463:TCC:T	acceptor_loss	1.0000
20:62465464:CC:C	acceptor_gain	1.0000
20:62465465:C:CC	acceptor_gain	1.0000
20:62465465:CTGGA:C	acceptor_loss	1.0000
20:62466422:TCAC:T	donor_loss	1.0000
20:62466423:CAC:C	donor_loss	1.0000
20:62466424:A:AC	donor_gain	1.0000
20:62466424:AC:A	donor_gain	1.0000
20:62466424:ACC:A	donor_gain	1.0000
20:62466424:ACCC:A	donor_gain	1.0000
20:62466425:C:CC	donor_gain	1.0000
20:62466425:CC:C	donor_gain	1.0000
20:62466425:CCC:C	donor_gain	1.0000
20:62466425:CCCC:C	donor_gain	1.0000
20:62466547:GAGGA:G	acceptor_gain	1.0000
20:62466548:AGGA:A	acceptor_gain	1.0000
20:62466549:GGA:G	acceptor_gain	1.0000
20:62466550:GA:G	acceptor_gain	1.0000
20:62466551:AC:A	acceptor_loss	1.0000
20:62466552:C:CA	acceptor_loss	1.0000
20:62466552:C:CC	acceptor_gain	1.0000
20:62466554:G:C	acceptor_gain	1.0000

AlphaMissense

2531 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:62466431:G:C	H274D	1.000
20:62466445:A:G	L269P	1.000
20:62466451:C:T	C267Y	1.000
20:62466456:A:C	N265K	1.000
20:62466456:A:T	N265K	1.000
20:62466459:G:C	C264W	1.000
20:62466460:C:T	C264Y	1.000
20:62466461:A:G	C264R	1.000
20:62466489:C:A	W254C	1.000
20:62466489:C:G	W254C	1.000
20:62466491:A:G	W254R	1.000
20:62466491:A:T	W254R	1.000
20:62466514:C:G	C246S	1.000
20:62466515:A:T	C246S	1.000
20:62473502:C:A	W200C	1.000
20:62473502:C:G	W200C	1.000
20:62473504:A:G	W200R	1.000
20:62473504:A:T	W200R	1.000
20:62465915:G:C	R278G	0.999
20:62466433:A:G	L273P	0.999
20:62466442:T:C	Y270C	0.999
20:62466443:A:C	Y270D	0.999
20:62466445:A:T	L269H	0.999
20:62466448:C:T	G268D	0.999
20:62466450:G:C	C267W	0.999
20:62466451:C:A	C267F	0.999
20:62466451:C:G	C267S	0.999
20:62466452:A:G	C267R	0.999
20:62466452:A:T	C267S	0.999
20:62466457:T:A	N265I	0.999

dbSNP variants (sampled 300 via entrez): RS1000001877 (20:62465603 G>A), RS1000026040 (20:62463242 C>G,T), RS1001314859 (20:62473811 C>T), RS1001963000 (20:62466190 C>A), RS1002632012 (20:62464233 C>T), RS1003037710 (20:62476785 G>A), RS1003539173 (20:62473036 C>T), RS1003652675 (20:62468346 A>T), RS1003768645 (20:62468135 C>T), RS1003854456 (20:62465930 G>A,T), RS1003905404 (20:62466171 T>C), RS1004063546 (20:62472861 G>A), RS1005087376 (20:62470278 A>T), RS1005706988 (20:62468118 G>A), RS1006033450 (20:62469017 T>C)

Disease associations

OMIM: gene MIM:611496 | disease phenotypes: MIM:617912, MIM:610805, MIM:607086, MIM:109730

GenCC curated gene-disease

Disease	Classification	Inheritance
congenital heart defects, multiple types, 5	Moderate	Autosomal dominant
tetralogy of fallot	Supportive	Autosomal dominant
familial atrial fibrillation	Supportive	Autosomal dominant
familial bicuspid aortic valve	Supportive	Autosomal dominant

Mondo (9): congenital heart defects, multiple types, 5 (MONDO:0060663), congenital heart defects, multiple types (MONDO:0000119), congenital heart disease (MONDO:0005453), congenital anomaly of kidney and urinary tract (MONDO:0019719), familial thoracic aortic aneurysm and aortic dissection (MONDO:0019625), aortic valve disease 1 (MONDO:0024523), tetralogy of fallot (MONDO:0008542), familial atrial fibrillation (MONDO:0018054), familial bicuspid aortic valve (MONDO:0007194)

Orphanet (2): Renal or urinary tract malformation (Orphanet:93545), Familial thoracic aortic aneurysm and aortic dissection (Orphanet:91387)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000028	Cryptorchidism
HP:0000233	Thin vermilion border
HP:0000268	Dolichocephaly
HP:0000337	Broad forehead
HP:0000520	Proptosis
HP:0000822	Hypertension
HP:0001156	Brachydactyly
HP:0001279	Syncope
HP:0001511	Intrauterine growth retardation
HP:0001629	Ventricular septal defect
HP:0001631	Atrial septal defect
HP:0001636	Tetralogy of Fallot
HP:0001644	Dilated cardiomyopathy
HP:0001647	Bicuspid aortic valve
HP:0001650	Aortic valve stenosis
HP:0001658	Myocardial infarction
HP:0001659	Aortic regurgitation
HP:0001680	Coarctation of aorta
HP:0001719	Double outlet right ventricle
HP:0001727	Thromboembolic stroke
HP:0001907	Thromboembolism
HP:0001962	Palpitations
HP:0002094	Dyspnea
HP:0002321	Vertigo
HP:0003546	Exercise intolerance
HP:0003577	Congenital onset
HP:0003829	Typified by incomplete penetrance
HP:0004209	Clinodactyly of the 5th finger

GWAS associations

8 associations (top):

Study	Trait	p-value
GCST001942_4	Prostate cancer	4.000000e-08
GCST006416_6	Chronic central serous retinopathy	7.000000e-07
GCST007507_23	Benign prostatic hyperplasia and lower urinary tract symptoms	8.000000e-10
GCST007507_4	Benign prostatic hyperplasia and lower urinary tract symptoms	7.000000e-12
GCST009653_2	Central serous retinopathy	5.000000e-15
GCST009653_4	Central serous retinopathy	3.000000e-12
GCST90002383_308	Hematocrit	8.000000e-11
GCST90002384_479	Hemoglobin	2.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0009363	chronic central serous retinopathy
EFO:0008008	lower urinary tract symptom
EFO:0009784	central serous retinopathy
EFO:0004348	hematocrit
EFO:0004509	hemoglobin measurement

MeSH disease descriptors (3)

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
C566906	Cakut (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	increases methylation, affects cotreatment, increases expression, affects expression	5
Benzo(a)pyrene	affects methylation, increases methylation	2
Polyamines	affects expression, increases expression	2
bisphenol F	affects cotreatment, increases methylation	1
propionaldehyde	increases expression	1
bisphenol A	decreases methylation	1
terbufos	increases methylation	1
butyraldehyde	increases expression	1
aflatoxin B2	increases methylation	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	increases expression, affects cotreatment	1
dorsomorphin	increases expression, affects cotreatment	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
Resveratrol	affects cotreatment, decreases expression	1
Decitabine	affects expression	1
Sunitinib	decreases expression	1
Fulvestrant	increases methylation, affects cotreatment	1
Microplastics	increases abundance, decreases expression	1
Arsenic	affects methylation	1
Biguanides	affects expression	1
Cisplatin	affects expression	1
Cytarabine	decreases expression	1
Diazinon	increases methylation	1
Diethylhexyl Phthalate	decreases expression	1
Doxorubicin	decreases expression	1
Fonofos	increases methylation	1
Lipopolysaccharides	increases expression, affects response to substance	1
Niclosamide	increases expression	1
Parathion	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01971593	PHASE4	TERMINATED	The Effects of Eplerenone on Markers of Myocardial Fibrosis in Adult Congenital Heart Disease
NCT00668824	PHASE4	UNKNOWN	Improved Diagnosis of Congenital Heart Disease by Magnetic Resonance Imaging Using Vasovist
NCT01368705	PHASE4	COMPLETED	Nitrogen Balance in Infants After Post Cardiothoracic Surgery
NCT01619982	PHASE4	COMPLETED	Pre-operative Prophylaxis With Vancomycin and Cefazolin in Pediatric Cardiovascular Surgery Patients
NCT02122679	PHASE4	WITHDRAWN	Tranexamic Acid Effect on Platelet Aggregation Following Infant Cardiopulmonary Bypass
NCT02527811	PHASE4	UNKNOWN	Ulinastatin Injection in in Pediatric Patients Undergoing Open Heart Surgery
NCT03014700	PHASE4	COMPLETED	Fibrinogen Concentrate vs Cryoprecipitate
NCT03408340	PHASE4	TERMINATED	Paravertebral Nerve Blocks in Neonates
NCT03630796	PHASE4	UNKNOWN	Effect of Sevoflurane in Postoperative Troponin I Levels in Children Undergoing Congenital Heart Defects Surgery
NCT03667703	PHASE4	COMPLETED	Stress Ulcer Prophylaxis Versus Placebo in Critically Ill Infants With Congenital Heart Disease
NCT04453761	PHASE4	UNKNOWN	Thiamine Influenced on Substrate Energy Effectiveness in Indonesian Children Undergoing Cardiopulmonary Bypass
NCT06668389	PHASE4	RECRUITING	Sodium-Glucose Cotransporter 2 Inhibitors for Repaired Tetralogy of Fallot Patients for Enhancement of Cardio-Pulmonary Status Trial
NCT07499154	PHASE4	NOT_YET_RECRUITING	Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery
NCT00564993	PHASE3	TERMINATED	Cardiac Function Under Stress for Early Detection of the Right Ventricular Insufficiency After Repair of Tetralogy of Fallot
NCT00000470	PHASE3	COMPLETED	Infant Heart Surgery: Central Nervous System Sequelae of Circulatory Arrest
NCT00000494	PHASE3	COMPLETED	Management of Patent Ductus in Premature Infants
NCT01134302	PHASE3	UNKNOWN	Hybrid Versus Norwood Management Strategies in Infants Undergoing Single Ventricle Palliation
NCT01607983	PHASE3	WITHDRAWN	Effects of Pulmonary Vasodilation Upon VA Coupling in Fontan Patients
NCT01662011	PHASE3	UNKNOWN	Application of Neurally Adjusted Ventilatory Assist to Children After Congenital Cardiac Surgery
NCT02320669	PHASE3	COMPLETED	Phase 3 Triiodothyronine Supplementation for Infants After Cardiopulmonary Bypass
NCT02615262	PHASE3	COMPLETED	Intraoperative Dexamethasone in Pediatric Cardiac Surgery
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
NCT00848393	PHASE2	COMPLETED	Measures to Lower the Stress Response in Pediatric Cardiac Surgery
NCT02010905	PHASE2	UNKNOWN	Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System
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