GATAD2B

Chr 1AD

GATA zinc finger domain containing 2B

Also known as: GANDS, MRD18, P66beta, p68

NCBI Gene: 57459 ENSG00000143614 UniProt: Q8WXI9 OMIM: 614998

This gene encodes a transcriptional repressor that functions as a component of the histone deacetylase NuRD complex, which remodels chromatin and represses gene expression. Mutations cause GAND syndrome, characterized by intellectual disability and dysmorphic features, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.097), indicating that even single functional copies are critical for normal development.

OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a zinc finger protein transcriptional repressor. The encoded protein is part of the methyl-CpG-binding protein-1 complex, which represses gene expression by deacetylating methylated nucleosomes. Mutations in this gene are linked to intellectual disability and dysmorphic features associated with cognitive disability. [provided by RefSeq, Jun 2016]

OMIM ResearchGenerating clinical summary…

LOFmechanismADLOEUF 0.101 OMIM phenotype

Clinical Summary— GATAD2B

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Gene-Disease Validity (ClinGen)

severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

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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.

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ClinVar Variants

115 unique Pathogenic / Likely Pathogenic· 277 VUS of 679 total submissions

Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Dual constrained — LoF & missense intolerant

LoF Constraint?

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?

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?

LoF OE?0.00 (0.00–0.10)

0≤0.351.4

Missense OE?0.52 (0.46–0.59)

0≤0.61.4

Synonymous OE?1.01

0≤1.21.6

LoF obs/exp: 0 / 30.6Missense obs/exp: 182 / 347.9Syn Z: -0.12

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveGATAD2B-related nonspecific severe intellectual disabilityLOFAD

This gene — mechanism propensity

0.2299th %ile

GOF

0.1799th %ile

LOF

0.89top 5%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · 1 literature citation · 90% of P/LP variants are LoF · LOEUF 0.10 · ClinGen HI: Sufficient evidence for dosage pathogenicity

Literature Evidence

LOFGATAD2B loss-of-function mutations cause a recognisable syndrome with intellectual disability and are associated with learning deficits and synaptic undergrowth in Drosophila1

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

References

1.PMID 23644463 ↗

ClinVar Variant Classifications

679 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic82

Likely Pathogenic33

VUS277

Likely Benign218

Benign33

Conflicting20

Pathogenic

Likely Pathogenic

277

VUS

218

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	75	4	3	0	82
Likely Pathogenic	29	3	1	0	33
VUS	6	249	15	7	277
Likely Benign	0	7	82	129	218
Benign	0	1	32	0	33
Conflicting	—				20
Total	110	264	133	136	663

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

View in ClinVar →

15 pathogenic / likely-pathogenic (of 25) ClinVar copy-number / structural variants overlap GATAD2B — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →