GATAD1

protein-coding

GATA zinc finger domain containing 1, the group of GATA zinc finger domain containing|EMSY complex

Gene summary

The protein encoded by this gene contains a zinc finger at the N-terminus, and is thought to bind to a histone modification site that regulates gene expression. Mutations in this gene have been associated with autosomal recessive dilated cardiomyopathy. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2012]

MANE transcript

NM_021167.5

Inheritance

AR, AD

ClinVar variants

P:1U:164B:94

Top phenotype

Cardiomyopathy, dilated, 2B

gnomAD constraint

pLI —, LoF o/e 0.21

Max pathogenic AF

—

Genomic locus

chr7:92,447,482-92,460,075

External References & Databases

Ensembl (ENSG00000157259)

Transcript & Mutation Effects

hg38 • Region Span ~12.6 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

dilated cardiomyopathy 2BLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013848

Submitter: Ambry Genetics

dilated cardiomyopathy 2BLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013848

Submitter: Labcorp Genetics (formerly Invitae)

dilated cardiomyopathy 2BLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013848

Submitter: ClinGen

GATAD1 was evaluated for autosomal recessive dilated cardiomyopathy (DCM). GATAD1 was originally evaluated for DCM by the ClinGen DCM GCEP on September 27, 2019. Evidence of the association of this gene with DCM was re-evaluated using SOP v10 on June 28, 2024. As a result, the classification did not change. A summary of the information contributing to the classification of this gene at the time of re-evaluation is summarized herein. Human genetic evidence supporting this gene-disease relationship includes case-level data and segregation data. The human genetic level evidence remains limited to one paper (Theis et al, 2011, PMID: 21965549) which reports on a consanguineous family with adult-onset DCM. A homozygous missense variant in GATAD1 was reported in three affected siblings. Segregation data gave a LOD score of 3.1. In addition, this gene-disease assertion is supported by animal models and expression studies. The missense variant reported by Theis et al (2011, PMID 21965549) was shown to affect expression in cardiac tissue. Yang et al (2016, PMID: 28955713) report on a knockout zebrafish model and a model with the missense variant previously reported. The knockout zebrafish only developed a phenotype consistent with DCM when exposed to stressors, and only 1 out of 6 transgenic fish with the mutant allele developed a significantly increased heart size. In summary, there is limited evidence to support this gene-disease relationship. More evidence is needed to support the relationship of GATAD1 with autosomal recessive DCM. This classification was approved by the ClinGen Dilated Cardiomyopathy Working Group June 28, 2024 (SOP Version 10).

familial dilated cardiomyopathyLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0016333

Submitter: G2P

dilated cardiomyopathy 2BLIMITED

Inheritance Pattern: AR

Disease ID:MONDO:0013848

Submitter: PanelApp Australia

familial isolated dilated cardiomyopathySUPPORTIVE

Inheritance Pattern: AD

Disease ID:MONDO:0015470

Submitter: Orphanet

Clinical Genomic Database (CGD)

Cardiomyopathy, dilated, 2BAR

Manifestation: Cardiovascular

Intervention: Cardiovascular

Rationale: Surveillance (eg, echocardiography/electocardiography), preventive measures and medical management (including ICD placement) may be helpful to decrease morbidity and mortality

Refs: 21965549

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to GATAD1 variants in ClinVar

6 Conditions Cataloged

Cardiovascular phenotypeTotal: 199

Dilated cardiomyopathy 2BTotal: 174

not specifiedTotal: 32

not providedTotal: 22

GATAD1-related disorderTotal: 6

Hypertrophic cardiomyopathy 2Total: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_021167.5. 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.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			4 clinvar	88 clinvar		92
missense	1 clinvar		150 clinvar	5 clinvar	1 clinvar	157
nonsense			2 clinvar			2
start loss						0
frameshift			6 clinvar			6
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	1	0	164	93	1	259

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 8 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_021167.5	RefSeq	NP_066990.3	5	MANE Select
ENST00000287957.5	Ensembl	ENSP00000287957.3	5	MANE Select
ENST00000645746.1	Ensembl	ENSP00000493785.1	4	Standard
ENST00001031143.1	Ensembl	ENSP00000700960.1	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

regulation of transcription by RNA polymerase II
chromatin assembly

Molecular Function

DNA-binding transcription factor activity, RNA polymerase II-specific
zinc ion binding
sequence-specific DNA binding

Cellular Component

nucleus
nucleoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000287957
Coding exons: 5
Length: 11384
Individuals with no LoFs: 125738
Homozygous LoFs: 0
Heterozygous LoFs: 8
Defined: 125746
p: 0.0000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	68	110	0.620	0.00000517	1716
Missense (PolyPhen)		18	35.759	0.50337		489
Synonymous	-0.735	45	39.1	1.15	0.00000194	545
Loss of Function	2.28	2	9.64	0.207	4.03e-7	150

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000029	0.000029	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.000053	0.000053	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Component of some chromatin complex recruited to chromatin sites methylated 'Lys-4' of histone H3 (H3K4me). {ECO:0000269|PubMed:20850016}.;

Recessive Scores

pRec: 0.101

Intolerance Scores

LoFtool: 0.116
RVIS EVS: -0.01
RVIS percentile EVS: 53.19

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.932

Gene Damage Prediction

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