GeneBe

GATA3

protein-coding

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

Gene summary

This gene encodes a protein which belongs to the GATA family of transcription factors. The protein contains two GATA-type zinc fingers and is an important regulator of T-cell development and plays an important role in endothelial cell biology. Defects in this gene are the cause of hypoparathyroidism with sensorineural deafness and renal dysplasia. [provided by RefSeq, Nov 2009]

MANE transcript

NM_001002295.2

Inheritance

AD

ClinVar variants

P:123U:174B:98

Top phenotype

Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome

gnomAD constraint

pLI —, LoF o/e 0.12

Max pathogenic AF

—

Genomic locus

chr10:8,045,378-8,075,198

External References & Databases

Ensembl (ENSG00000107485)NCBI Gene (2625)OMIM (131320)HGNC:4172GenCCUniProt (P23771)AlphaFoldClinVar (GATA3)gnomADPubMedJAXSFARI

Transcript & Mutation Effects

hg38 • Region Span ~29.8 kb
Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

hypoparathyroidism-deafness-renal disease syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007797

Submitter: ClinGen

GATA3 was reported in relation to autosomal dominant hypoparathyroidism-deafness-renal disease syndrome in 1995 (Pandolfi PMID: 7550312). At least 8 unique variant (missense, nonsense, frameshift, etc.) have been reported in humans. Evidence supporting this gene-disease relationship includes case-level, segregation and experimental data. Variants in this gene have been reported in at least 9 probands in 7 publications (PMIDs: 10935639, 11389161, 21120445, 26316437, 25771973, 27387476, 30396722). More evidence is available in the literature, but the maximum score for genetic evidence (12 pt.) has been reached. In summary, GATA3 is definitively associated with autosomal dominant hypoparathyroidism-deafness-renal disease syndrome. This has been repeatedly demonstrated in both the research and clinical diagnostic settings, and has been upheld over time. This classification was approved by the ClinGen Hearing Loss Gene Curation Expert Panel on 6/18/19.

hypoparathyroidism-deafness-renal disease syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007797

Submitter: PanelApp Australia

hypoparathyroidism-deafness-renal disease syndromeSUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007797

Submitter: Orphanet

hypoparathyroidism-deafness-renal disease syndromeDEFINITIVE

Inheritance Pattern: AD

Disease ID:MONDO:0007797

Submitter: G2P

hypoparathyroidism-deafness-renal disease syndromeSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007797

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Hypoparathyroidism, sensorineural deafness, and renal dysplasia syndromeAD

Manifestation: Audiologic/Otolaryngologic; Endocrine; Renal

Intervention: Audiologic/Otolaryngologic; Endocrine; Renal

Rationale: 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

Refs: 10935639; 11389161; 17309062; 19248180; 9253381; 21399899; 21242646; 21834031; 21157112; 21120445Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GATA3 variants in ClinVar

15 Conditions Cataloged
not providedTotal: 283
Hypoparathyroidism, deafness, renal disease syndromeTotal: 164
Inborn genetic diseasesTotal: 42
GATA3-related disorderTotal: 24
not specifiedTotal: 17
Hearing impairmentTotal: 3
Neurodevelopmental disorderTotal: 1
Stage 5 chronic kidney diseaseTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001002295.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

EffectPLPVUSLBBSum
synonymous
9
clinvar
83
clinvar
4
clinvar
 96
missense
10
clinvar
19
clinvar
155
clinvar
10
clinvar
 194
nonsense
12
clinvar
5
clinvar
1
clinvar
 18
start loss
0
frameshift
44
clinvar
21
clinvar
8
clinvar
 73
splice donor/acceptor (+/-2bp)
6
clinvar
6
clinvar
1
clinvar
1
clinvar
 14
Total7251174944395

Highest pathogenic variant AF is 0.00001672823

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 38 transcripts
Transcript IDSourceProtein IDCoding ExonsMANE Status
NM_001002295.2RefSeqNP_001002295.15MANE Select
ENST00000379328.9EnsemblENSP00000368632.35MANE Select
NM_001441115.1RefSeqNP_001428044.15Standard
NM_001441116.1RefSeqNP_001428045.15Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / ModelOrganismObserved Phenotype
gata3Danio rerio

Structure: pronephric distal late tubule

Quality: decreased object quality

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

  • 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

Biological Process

  • negative regulation of transcription by RNA polymerase II
  • in utero embryonic development
  • cell fate determination
  • neuron migration
  • type IV hypersensitivity

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

Cellular Component

  • nuclear chromatin
  • nucleus
  • nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type
protein_coding
Transcript type
protein_coding
Transcript
ENST00000379328
Coding exons
5
Length
21595
Individuals with no LoFs
125745
Homozygous LoFs
0
Heterozygous LoFs
3
Defined
125748
p
0.0000119
Z-ScoreObservedExpectedObserved/ExpectedMutation RateTotal Possible
Missense1.911812690.6720.00001572847
Missense (PolyPhen)4079.8670.50083867
Synonymous-2.911691271.330.00000882911
Loss of Function3.27216.20.1238.83e-7168

Population LoF Frequency

PopulationCAFp-valueStatus
African00.0absent
Latino/Admixed American00.0absent
Ashkenazi Jewish0.0000990.000099rare
East Asian00.0absent
Finnish0.0000490.000046rare
European (Non-Finnish)0.00000880.0000088rare
South Asian00.0absent
Other00.0absent

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec
0.826

Intolerance Scores

LoFtool
0.0252
RVIS EVS
-0.65
RVIS percentile EVS
16.36

Essentials

Essential (CRISPR)
N
Essential (CRISPR2)
N
Essential (gene trap)
N
Indispensability pred.
E
Indispensability score
1.00

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium
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