GATA6

GATA binding protein 6, the group of GATA zinc finger domain containing

Basic information

Region (hg38): 18:22169589-22202528

Links

ENSG00000141448 ∙ NCBI:2627 ∙ OMIM:601656 ∙ HGNC:4174 ∙ Uniprot:Q92908 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• atrioventricular septal defect 5 (Definitive), mode of inheritance: AD
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Definitive), mode of inheritance: AD
• atrial septal defect 9 (Definitive), mode of inheritance: AD
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Strong), mode of inheritance: AD
• neonatal diabetes mellitus (Strong), mode of inheritance: AD
• metabolic syndrome (Strong), mode of inheritance: AD
• tetralogy of fallot (Moderate), mode of inheritance: AD
• conotruncal heart malformations (Limited), mode of inheritance: AR
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Strong), mode of inheritance: AD
• atrial septal defect 9 (Limited), mode of inheritance: AD
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Supportive), mode of inheritance: AD
• familial atrial fibrillation (Supportive), mode of inheritance: AD
• pancreatic hypoplasia-diabetes-congenital heart disease syndrome (Strong), mode of inheritance: AD
• atrioventricular septal defect 5 (Limited), mode of inheritance: AD
• GATA6-related congenital heart disease with or without pancreatic agenesis or neonatal diabetes (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Heart defects, congenital, and other congenital anomalies; Atrial septal defect 9; Atrioventricular septal defect 5; Persistent truncus arteriosus; Tetralogy of Fallot	AD	Cardiovascular; Gastrointestinal	In Heart defects, congenital, and other congenital anomalies, the condition may include pancreatic a/hypogenesis, and individuals may manifest neonatally with severe sequelae of endocrine and exocrine pancreatic insufficiency, and prompt detection can allow potentially beneficial management (eg, with insulin treatment and replacement of exocrine pancreatic enzymes); In conditions that involve congenital heart anomalies, individuals may present with frank, obvious congenital cardiac malformations that require intervention, and more subtle presentations in individuals with variants in this gene have also been described, including valvular anomalies, and surveillance (eg, with electrocardiogram and echocardiogram) may allow early detection and treatment of manifestations	Cardiovascular; Endocrine; Gastrointestinal; Musculoskeletal; Neurologic	19666519; 20631719; 20581743; 22158542; 22750565; 22824924; 22962692; 23020118; 23158662; 23223019; 23635550; 23639568; 24385578

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GATA6 gene.

• Atrioventricular septal defect 5 (7 variants)
• not provided (6 variants)
• Pancreatic hypoplasia-diabetes-congenital heart disease syndrome (6 variants)
• Congenital diaphragmatic hernia;Abnormal cardiovascular system morphology (2 variants)
• Tetralogy of Fallot (1 variants)
• GATA6-related disorder (1 variants)
• Persistent truncus arteriosus (1 variants)
• Abnormal cardiovascular system morphology;Congenital diaphragmatic hernia (1 variants)
• Conotruncal heart malformations (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GATA6 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			3	149	4	156
missense	3	1	260	7	1	272
nonsense	10		1			11
start loss			1			1
frameshift	8	3	1			12
inframe indel			16	3		19
splice donor/acceptor (+/-2bp)						0
splice region			6	5	1	12
non coding				33	8	41
Total	21	4	282	192	13

Highest pathogenic variant AF is 0.0000131

Variants in GATA6

This is a list of pathogenic ClinVar variants found in the GATA6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
18-22170849-C-T			Likely benign (Oct 01, 2018)
18-22171070-G-C			Likely benign (Dec 17, 2018)
18-22171144-G-A			Uncertain significance (Feb 12, 2024)
18-22171146-T-A		Atrioventricular septal defect 5	Uncertain significance (Nov 22, 2022)
18-22171159-C-G		GATA6-related disorder	Uncertain significance (Jan 20, 2024)
18-22171160-G-A		Atrioventricular septal defect 5 • Inborn genetic diseases	Uncertain significance (Jan 21, 2024)
18-22171160-G-C		Atrioventricular septal defect 5	Uncertain significance (Mar 18, 2022)
18-22171162-C-A		Atrioventricular septal defect 5	Likely benign (Mar 22, 2021)
18-22171163-G-A		Atrioventricular septal defect 5	Uncertain significance (May 24, 2023)
18-22171167-G-A		Tetralogy of Fallot	Pathogenic (-)
18-22171169-T-A		not specified	Uncertain significance (Oct 13, 2021)
18-22171176-C-T		Atrioventricular septal defect 5	Uncertain significance (Aug 09, 2021)
18-22171177-G-A		Atrioventricular septal defect 5	Likely benign (Apr 25, 2022)
18-22171187-G-A		Atrioventricular septal defect 5	Likely benign (Sep 11, 2023)
18-22171187-G-C		not specified • Monogenic diabetes • Atrioventricular septal defect 5 • GATA6-related disorder	Benign/Likely benign (Jun 24, 2024)
18-22171192-C-A		Atrioventricular septal defect 5	Likely benign (Aug 15, 2021)
18-22171192-C-G		Atrioventricular septal defect 5	Likely benign (Nov 11, 2021)
18-22171194-C-G		Atrioventricular septal defect 5	Uncertain significance (Jun 20, 2023)
18-22171196-G-C		Atrioventricular septal defect 5	Uncertain significance (Feb 04, 2019)
18-22171200-C-A		Atrioventricular septal defect 5	Uncertain significance (Dec 21, 2023)
18-22171201-G-A		Atrioventricular septal defect 5	Likely benign (Nov 22, 2022)
18-22171205-G-T		Atrioventricular septal defect 5	Uncertain significance (May 13, 2023)
18-22171206-C-G		Atrioventricular septal defect 5	Likely benign (Jan 15, 2024)
18-22171210-C-A			Uncertain significance (Apr 06, 2023)
18-22171211-GA-TT		Atrioventricular septal defect 5	Uncertain significance (Jan 22, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GATA6	protein_coding	protein_coding	ENST00000269216	6	33088

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.997	0.00291	116244	0	1	116245	0.00000430

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.28	222	283	0.785	0.0000147	3705
Missense in Polyphen		57	98.178	0.58058		1220
Synonymous	-0.171	134	132	1.02	0.00000764	1320
Loss of Function	3.84	0	17.2	0.00	8.35e-7	214

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.00000937	0.00000937
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator (PubMed:19666519, PubMed:27756709, PubMed:22750565, PubMed:22824924). Regulates SEMA3C and PLXNA2 (PubMed:19666519). Involved in gene regulation specifically in the gastric epithelium (PubMed:9315713). May regulate genes that protect epithelial cells from bacterial infection (PubMed:16968778). Involved in bone morphogenetic protein (BMP)-mediated cardiac-specific gene expression (By similarity). Binds to BMP response element (BMPRE) DNA sequences within cardiac activating regions (By similarity). {ECO:0000250|UniProtKB:Q61169, ECO:0000269|PubMed:16968778, ECO:0000269|PubMed:19666519, ECO:0000269|PubMed:22750565, ECO:0000269|PubMed:22824924, ECO:0000269|PubMed:27756709, ECO:0000269|PubMed:9315713}.
• Disease: DISEASE: Note=Rare variants in GATA6 may be a cause of susceptibility to atrial fibrillation, a common sustained cardiac rhythm disturbance. Atrial fibrillation is characterized by disorganized atrial electrical activity and ineffective atrial contraction promoting blood stasis in the atria and reduces ventricular filling. It can result in palpitations, syncope, thromboembolic stroke, and congestive heart failure. {ECO:0000269|PubMed:22750565, ECO:0000269|PubMed:22824924, ECO:0000269|PubMed:27756709}.; DISEASE: Conotruncal heart malformations (CTHM) [MIM:217095]: A group of congenital heart defects involving the outflow tracts. Examples include truncus arteriosus communis, double-outlet right ventricle and transposition of great arteries. Truncus arteriosus communis is characterized by a single outflow tract instead of a separate aorta and pulmonary artery. In transposition of the great arteries, the aorta arises from the right ventricle and the pulmonary artery from the left ventricle. In double outlet of the right ventricle, both the pulmonary artery and aorta arise from the right ventricle. {ECO:0000269|PubMed:19666519}. Note=The disease is caused by mutations affecting the gene represented in this entry. GATA6 mutations have been found in patients with non- syndromic persistent truncus arteriosus (PubMed:19666519). {ECO:0000269|PubMed:19666519}.; DISEASE: Atrial septal defect 9 (ASD9) [MIM:614475]: 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. Some patients manifest tricuspid valve disease, pulmonary valve disease, and pulmonary artery hypertension. {ECO:0000269|PubMed:20631719}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:20581743, ECO:0000269|PubMed:20631719}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Atrioventricular septal defect 5 (AVSD5) [MIM:614474]: 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. {ECO:0000269|PubMed:20581743}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Pancreatic agenesis and congenital heart defects (PACHD) [MIM:600001]: An autosomal dominant disease characterized by pancreatic severe hypoplasia or agenesis, diabetes mellitus, and congenital heart abnormalities including ventricular septal defect, patent ductus arteriosus, pulmonary artery stenosis, truncus arteriosus and tetralogy of Fallot. {ECO:0000269|PubMed:22158542}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Heart Development;Endoderm Differentiation;Mesodermal Commitment Pathway;Ectoderm Differentiation;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Developmental Biology;Factors involved in megakaryocyte development and platelet production;Surfactant metabolism;Metabolism of proteins;POU5F1 (OCT4), SOX2, NANOG repress genes related to differentiation;Hemostasis;Transcriptional regulation of pluripotent stem cells;Notch-mediated HES/HEY network (Consensus)

Recessive Scores

• pRec: 0.409

Haploinsufficiency Scores

• pHI: 0.635
• ghis: 0.559

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.947

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Gata6
• Phenotype: growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; normal phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; limbs/digits/tail phenotype

Zebrafish Information Network

• Gene name: gata6
• Affected structure: heart tube
• Phenotype tag: abnormal
• Phenotype quality: malformed

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;liver development;outflow tract septum morphogenesis;type B pancreatic cell differentiation;pancreatic A cell differentiation;transcription by RNA polymerase II;phospholipid metabolic process;endodermal cell fate determination;blood coagulation;male gonad development;cardiac muscle hypertrophy in response to stress;epithelial cell differentiation;negative regulation of transforming growth factor beta1 production;negative regulation of transforming growth factor beta2 production;tube morphogenesis;response to drug;negative regulation of apoptotic process;response to estrogen;cellular protein metabolic process;positive regulation of angiogenesis;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;animal organ formation;smooth muscle cell differentiation;positive regulation of cardioblast differentiation;cardiac muscle cell differentiation;positive regulation of cardiac muscle cell proliferation;lung saccule development;Clara cell differentiation;type II pneumocyte differentiation;intestinal epithelial cell differentiation;cardiac vascular smooth muscle cell differentiation;response to growth factor;positive regulation of cell cycle arrest;cellular response to gonadotropin stimulus;cellular response to hypoxia;cellular response to BMP stimulus;positive regulation of cardiac muscle myoblast proliferation
• Cellular component: nucleus;nucleoplasm;transcription factor complex;nuclear membrane
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;RNA polymerase II repressing transcription factor binding;chromatin binding;DNA-binding transcription factor activity;protein binding;transcription factor binding;zinc ion binding;protein kinase binding;transcription regulatory region DNA binding