GATAD2B

Chr 1AD

GATA zinc finger domain containing 2B

NCBI Gene: 57459ENSG00000143614UniProt: Q8WXI9

Transcriptional repressor (PubMed:12183469, PubMed:16415179). Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin (PubMed:16428440, PubMed:28977666). Enhances MBD2-mediated repression (PubMed:12183469, PubMed:16415179). Efficient repression requires the presence of GATAD2A (PubMed:16415179). Targets MBD3 to discrete loci in the nucleus (PubMed:11756549). May play a role in synapse development (PubMed:23644463)

Primary Disease Associations & Inheritance

GAND syndromeMIM #615074
AD
584
ClinVar variants
65
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— GATAD2B
🧬
Gene-Disease Validity (ClinGen)
severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
65 Pathogenic / Likely Pathogenic· 269 VUS of 584 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Dual constrained — LoF & missense intolerant
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.10LOEUF
pLI 1.000
Z-score 5.13
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
3.16Z-score
OE missense 0.52 (0.46–0.59)
182 obs / 347.9 exp
Constrained

Highly missense-constrained (top ~0.1%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.52 (0.46–0.59)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.01
0≤1.21.6
LoF obs/exp: 0 / 30.6Missense obs/exp: 182 / 347.9Syn Z: -0.12

ClinVar Variant Classifications

584 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic45
Likely Pathogenic20
VUS269
Likely Benign202
Benign33
Conflicting15
45
Pathogenic
20
Likely Pathogenic
269
VUS
202
Likely Benign
33
Benign
15
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
25
2
18
0
45
Likely Pathogenic
16
0
4
0
20
VUS
2
239
21
7
269
Likely Benign
0
2
80
120
202
Benign
0
1
32
0
33
Conflicting
—15
Total43244155127584

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

GATAD2B · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

GATAD2B-related nonspecific severe intellectual disability

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

GAND syndrome

MIM #615074

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
De novo mutations in moderate or severe intellectual disability.
Hamdan FF et al.·PLoS Genet
2014
De novo variants underlying monogenic syndromes with intellectual disability in a neurodevelopmental cohort from India.
Pande S et al.·Eur J Hum Genet
2024Cohort
GATAD2B-related developmental and epileptic encephalopathy (DEE): Extending the epilepsy phenotype and a literature appraisal.
Scorrano G et al.·Epilepsia Open
2025Review
GATAD2B-related intellectual disability due to parental mosaicism and review of literature.
Kaur P et al.·Clin Dysmorphol
2019Review
GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder.
Shieh C et al.·Genet Med
2020
The NuRD complex and macrocephaly associated neurodevelopmental disorders.
Pierson TM et al.·Am J Med Genet C Semin Med Genet
2019Review
1q21.3 deletion involving GATAD2B: An emerging recurrent microdeletion syndrome.
Tim-Aroon T et al.·Am J Med Genet A
2017Review
GATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila.
Willemsen MH et al.·J Med Genet
2013
Gatad2b, associated with the neurodevelopmental syndrome GAND, plays a critical role in neurodevelopment and cortical patterning.
Abad C et al.·Transl Psychiatry
2024
Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND).
Vera G et al.·Eur J Med Genet
2020Case report
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools