GATA3

GATA binding protein 3, the group of GATA zinc finger domain containing

Basic information

Region (hg38): 10:8045378-8075198

Links

ENSG00000107485 ∙ NCBI:2625 ∙ OMIM:131320 ∙ HGNC:4172 ∙ Uniprot:P23771 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• hypoparathyroidism-deafness-renal disease syndrome (Strong), mode of inheritance: AD
• hypoparathyroidism-deafness-renal disease syndrome (Definitive), mode of inheritance: AD
• hypoparathyroidism-deafness-renal disease syndrome (Strong), mode of inheritance: AD
• hypoparathyroidism-deafness-renal disease syndrome (Supportive), mode of inheritance: AD
• hypoparathyroidism-deafness-renal disease syndrome (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome	AD	Audiologic/Otolaryngologic; Endocrine; Renal	Early recognition of electrolyte abnormalitities (eg, hypocalcemia) can allow prompt treatment in order to avoid severe sequelae; Individuals may also have deafness of varying ages of onset, and may benefit from early recognition and treatment of hearing impairment	Audiologic/Otolaryngologic; Endocrine; Renal	10935639; 11389161; 17309062; 19248180; 9253381; 21399899; 21242646; 21834031; 21157112; 21120445

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the GATA3 gene.

• not provided (26 variants)
• Hypoparathyroidism, deafness, renal disease syndrome (15 variants)
• Stage 5 chronic kidney disease (1 variants)
• Dominant congenital non-syndromic sensorineural hearing loss (1 variants)
• GATA3-related disorder (1 variants)
• Inborn genetic diseases (1 variants)
• See cases (1 variants)
• Deafness, autosomal dominant (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the GATA3 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			7	56	5	68
missense	5	7	84	4		100
nonsense	5	2				7
start loss						0
frameshift	25	7				32
inframe indel			1	1		2
splice donor/acceptor (+/-2bp)	5	3				8
splice region			2	2		4
non coding			30	25	40	95
Total	40	19	122	86	45

Highest pathogenic variant AF is 0.00000660

Variants in GATA3

This is a list of pathogenic ClinVar variants found in the GATA3 region.

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

Position	Type	Phenotype	Significance	ClinVar
10-8054700-G-T		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 12, 2018)
10-8054743-T-TAA		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jun 14, 2016)
10-8054766-G-C		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 13, 2018)
10-8054848-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 12, 2018)
10-8054906-CT-C		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jun 14, 2016)
10-8054906-C-CT		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jun 14, 2016)
10-8055276-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 13, 2018)
10-8055297-G-A		Hypoparathyroidism, deafness, renal disease syndrome	Benign/Likely benign (Dec 22, 2018)
10-8055305-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jan 13, 2018)
10-8055369-G-A		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 13, 2018)
10-8055392-G-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jan 13, 2018)
10-8055405-G-A		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Mar 31, 2019)
10-8055508-A-G		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 12, 2018)
10-8055561-G-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jan 13, 2018)
10-8055576-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 12, 2018)
10-8055587-G-A		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jan 13, 2018)
10-8055596-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jun 21, 2018)
10-8055598-C-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign (Jun 16, 2018)
10-8055607-C-T		Hypoparathyroidism, deafness, renal disease syndrome • not specified	Benign (Jan 13, 2018)
10-8055608-G-T		Hypoparathyroidism, deafness, renal disease syndrome	Benign/Likely benign (Jun 16, 2018)
10-8055616-G-A		Hypoparathyroidism, deafness, renal disease syndrome	Uncertain significance (Jan 12, 2018)
10-8055665-A-G			Uncertain significance (Oct 07, 2022)
10-8055673-C-T			Likely benign (Dec 25, 2021)
10-8055683-T-G			Uncertain significance (Sep 18, 2020)
10-8055688-G-C			Likely benign (Apr 14, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
GATA3	protein_coding	protein_coding	ENST00000379328	5	21595

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.899	0.101	125745	0	3	125748	0.0000119

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.91	181	269	0.672	0.0000157	2847
Missense in Polyphen		40	79.867	0.50083		867
Synonymous	-2.91	169	127	1.33	0.00000882	911
Loss of Function	3.27	2	16.2	0.123	8.83e-7	168

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.00	0.00
Finnish	0.0000489	0.0000462
European (Non-Finnish)	0.00000879	0.00000879
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Transcriptional activator which binds to the enhancer of the T-cell receptor alpha and delta genes. Binds to the consensus sequence 5'-AGATAG-3'. Required for the T-helper 2 (Th2) differentiation process following immune and inflammatory responses. {ECO:0000269|PubMed:23824597}.
• Disease: DISEASE: Hypoparathyroidism, sensorineural deafness, and renal disease (HDR) [MIM:146255]: A disease characterized by steroid- resistant nephrosis with progressive renal failure, hypoparathyroidism, sensorineural deafness, and renal dysplasia. {ECO:0000269|PubMed:10935639, ECO:0000269|PubMed:11389161, ECO:0000269|PubMed:26514990}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Inflammatory bowel disease (IBD) - Homo sapiens (human);Th17 cell differentiation - Homo sapiens (human);Th1 and Th2 cell differentiation - Homo sapiens (human);WNT-Ncore;White fat cell differentiation;Adipogenesis;Mesodermal Commitment Pathway;Preimplantation Embryo;IL-4 Signaling Pathway;Development and heterogeneity of the ILC family;Interleukin-4 and 13 signaling;White fat cell differentiation;Transcriptional cascade regulating adipogenesis;Notch Signaling Pathway;T-Cell antigen Receptor (TCR) Signaling Pathway;Sudden Infant Death Syndrome (SIDS) Susceptibility Pathways;Signal Transduction;Gene expression (Transcription);gata3 participate in activating the th2 cytokine genes expression;Generic Transcription Pathway;Factors involved in megakaryocyte development and platelet production;Post-translational protein modification;Metabolism of proteins;RNA Polymerase II Transcription;Glucocorticoid receptor regulatory network;Hemostasis;Ub-specific processing proteases;Deubiquitination;Signaling by Nuclear Receptors;C-MYB transcription factor network;Notch signaling pathway;Estrogen-dependent gene expression;RUNX1 regulates transcription of genes involved in differentiation of HSCs;ESR-mediated signaling;Transcriptional regulation by RUNX1;IL27-mediated signaling events;Calcineurin-regulated NFAT-dependent transcription in lymphocytes;Regulation of nuclear SMAD2/3 signaling (Consensus)

Recessive Scores

• pRec: 0.826

Intolerance Scores

• loftool: 0.0252
• rvis_EVS: -0.65
• rvis_percentile_EVS: 16.36

Haploinsufficiency Scores

• pHI: 0.690
• hipred: Y
• hipred_score: 0.853
• ghis: 0.602

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 1.00

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Gata3
• Phenotype: vision/eye phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hearing/vestibular/ear phenotype; digestive/alimentary phenotype; skeleton phenotype; renal/urinary system phenotype; immune system phenotype; embryo phenotype; pigmentation 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); normal phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region 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; craniofacial phenotype; muscle phenotype; cellular phenotype; homeostasis/metabolism phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); endocrine/exocrine gland phenotype

Zebrafish Information Network

• Gene name: gata3
• Affected structure: pronephric distal late tubule
• Phenotype tag: abnormal
• Phenotype quality: decreased object quality

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;in utero embryonic development;cell fate determination;neuron migration;type IV hypersensitivity;kidney development;mesonephros development;lens development in camera-type eye;immune system development;pro-T cell differentiation;aortic valve morphogenesis;cardiac right ventricle morphogenesis;ventricular septum development;chromatin remodeling;transcription by RNA polymerase II;defense response;humoral immune response;signal transduction;axon guidance;blood coagulation;negative regulation of cell population proliferation;male gonad development;response to virus;anatomical structure morphogenesis;post-embryonic development;positive regulation of signal transduction;response to gamma radiation;positive regulation of endothelial cell migration;regulation of neuron projection development;phosphatidylinositol 3-kinase signaling;protein deubiquitination;cytokine-mediated signaling pathway;erythrocyte differentiation;regulation of epithelial cell differentiation;TOR signaling;negative regulation of interferon-gamma production;negative regulation of interleukin-2 production;positive regulation of interleukin-4 production;negative regulation of mammary gland epithelial cell proliferation;embryonic hemopoiesis;cellular response to interferon-alpha;ureter maturation;parathyroid hormone secretion;regulation of cytokine biosynthetic process;norepinephrine biosynthetic process;inner ear morphogenesis;regulation of CD4-positive, alpha-beta T cell differentiation;regulation of neuron apoptotic process;ear development;response to estrogen;thymic T cell selection;T-helper 2 cell differentiation;innate immune response;response to ethanol;positive regulation of T cell differentiation;negative regulation of fat cell differentiation;negative regulation of cell cycle;negative regulation of transcription, DNA-templated;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II;cell maturation;sympathetic nervous system development;thymus development;embryonic organ development;developmental growth;anatomical structure formation involved in morphogenesis;negative regulation of inflammatory response;T cell receptor signaling pathway;regulation of histone H3-K4 methylation;positive regulation of protein kinase B signaling;parathyroid gland development;pharyngeal system development;uterus development;mesenchymal to epithelial transition;mast cell differentiation;ureteric bud formation;regulation of histone H3-K27 methylation;canonical Wnt signaling pathway involved in metanephric kidney development;cellular response to interleukin-4;cellular response to tumor necrosis factor;positive regulation of histone H3-K14 acetylation;otic vesicle development;cellular response to BMP stimulus;positive regulation of ureteric bud formation;nephric duct morphogenesis;nephric duct formation;regulation of nephron tubule epithelial cell differentiation;interleukin-4 secretion;interferon-gamma secretion;lymphocyte migration;cochlea development;negative regulation of DNA demethylation;regulation of hematopoietic stem cell differentiation;regulation of establishment of cell polarity;negative regulation of cell motility;negative regulation of endothelial cell apoptotic process;positive regulation of T-helper 2 cell cytokine production;negative regulation of cell proliferation involved in mesonephros development;positive regulation of thyroid hormone generation;positive regulation of histone H3-K9 acetylation;positive regulation of interleukin-5 secretion;positive regulation of interleukin-13 secretion;positive regulation of transcription regulatory region DNA binding;regulation of cellular response to X-ray;negative regulation of fibroblast growth factor receptor signaling pathway involved in ureteric bud formation;negative regulation of glial cell-derived neurotrophic factor receptor signaling pathway involved in ureteric bud formation
• Cellular component: nuclear chromatin;nucleus;nucleoplasm
• Molecular function: transcription regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;proximal promoter sequence-specific DNA binding;enhancer sequence-specific DNA binding;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;DNA-binding transcription factor activity;transcription coactivator activity;interleukin-2 receptor binding;protein binding;transcription factor binding;zinc ion binding;transcription regulatory region DNA binding;protein dimerization activity;E-box binding;HMG box domain binding