GATAD2B

Summary

GATAD2B (GATA zinc finger domain containing 2B, HGNC:30778) is a protein-coding gene on chromosome 1q21.3, encoding Transcriptional repressor p66-beta (Q8WXI9). Transcriptional repressor. It is haploinsufficient (ClinGen: sufficient evidence).

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.

Source: NCBI Gene 57459 — RefSeq curated summary.

At a glance

• Gene–disease (curated): severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (Definitive, ClinGen)
• GWAS associations: 24
• Clinical variants (ClinVar): 678 total — 82 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 56
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_020699

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:30778
Approved symbol	GATAD2B
Name	GATA zinc finger domain containing 2B
Location	1q21.3
Locus type	gene with protein product
Status	Approved
Aliases	P66beta
Ensembl gene	ENSG00000143614
Ensembl biotype	protein_coding
OMIM	614998
Entrez	57459

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 12 protein_coding, 3 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000368655, ENST00000634401, ENST00000634408, ENST00000634544, ENST00000634564, ENST00000634645, ENST00000634791, ENST00000636008, ENST00000636014, ENST00000637331, ENST00000637918, ENST00000638051, ENST00000703630, ENST00000867096, ENST00000867097, ENST00000867098

RefSeq mRNA: 1 — MANE Select: NM_020699 NM_020699

CCDS: CCDS1054

Canonical transcript exons

ENST00000368655 — 11 exons

Exon	Start	End
ENSE00000961120	153818791	153818922
ENSE00000961121	153818040	153818171
ENSE00000961122	153817372	153817542
ENSE00000961123	153816273	153816588
ENSE00000961124	153813250	153813452
ENSE00000961125	153812022	153812132
ENSE00000961126	153811731	153811848
ENSE00001175700	153819606	153819735
ENSE00001447683	153804725	153810310
ENSE00001447689	153828013	153828348
ENSE00001447691	153922733	153922972

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.08.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 30.2289 / max 249.5938, expressed in 1802 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14733	26.3001	1798
14732	3.4347	1310
14719	0.3250	154
14725	0.1689	57

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
colonic epithelium	UBERON:0000397	94.08	gold quality
corpus callosum	UBERON:0002336	93.57	gold quality
cortical plate	UBERON:0005343	92.08	gold quality
bone marrow cell	CL:0002092	90.77	gold quality
skeletal muscle tissue	UBERON:0001134	90.05	gold quality
blood	UBERON:0000178	89.90	gold quality
tonsil	UBERON:0002372	89.70	gold quality
ganglionic eminence	UBERON:0004023	89.11	gold quality
sural nerve	UBERON:0015488	88.84	gold quality
muscle tissue	UBERON:0002385	88.05	gold quality
bone marrow	UBERON:0002371	87.67	gold quality
adrenal tissue	UBERON:0018303	87.15	gold quality
ventricular zone	UBERON:0003053	87.00	gold quality
cerebellum	UBERON:0002037	86.71	gold quality
cerebellar cortex	UBERON:0002129	86.64	gold quality
cerebellar hemisphere	UBERON:0002245	86.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.28	gold quality
gastrocnemius	UBERON:0001388	85.73	gold quality
muscle of leg	UBERON:0001383	85.61	gold quality
uterine cervix	UBERON:0000002	85.36	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.05	gold quality
leukocyte	CL:0000738	84.76	gold quality
superior frontal gyrus	UBERON:0002661	84.64	gold quality
stromal cell of endometrium	CL:0002255	84.59	gold quality
monocyte	CL:0000576	84.54	gold quality
primary visual cortex	UBERON:0002436	84.37	gold quality
urinary bladder	UBERON:0001255	84.10	gold quality
islet of Langerhans	UBERON:0000006	84.05	gold quality
skin of leg	UBERON:0001511	84.02	gold quality
granulocyte	CL:0000094	83.88	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-CURD-89	no	53.30
E-ANND-3	no	2.38

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

1 targets.

Target	Regulation
SHC1

miRNA regulators (miRDB)

284 targeting GATAD2B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3134	100.00	66.43	777
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-92A-3P	99.98	75.21	1960

Functional genomics

ClinGen dosage: haploinsufficiency 3 (sufficient evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 12)

• identification as potent transcriptional repressors interacting with MBD2 and MBD3 (PMID:12183469)
• Detailed clinical description showed that all four individuals with a GATAD2B aberration had a distinctive phenotype with childhood hypotonia, severe intellectual disability. (PMID:23644463)
• p66beta might be important for the regulation of LOX in the nucleus. (PMID:25118846)
• This is the first report of GATAD2B in Chinese ID patients. Our findings will broaden the spectrum of GATAD2B mutations and facilitate genetic diagnosis and counseling. (PMID:28077840)
• This data suggests that 1q21.3 microdeletion is a recurrent microdeletion syndrome with distinguishable phenotypes, and loss of function of GATAD2B is the major contributor of the characteristic facies and ID. (PMID:28211977)
• findings suggest that GATAD2B serves as an important mediator of progesterone-progesterone receptor suppression of proinflammatory and contractile genes during pregnancy; decreased GATAD2B expression near term may contribute to the decline in progesterone receptor function, leading to labor (PMID:28576827)
• GATAD2B interacts with C-MYC to enhance KRAS driven tumor growth. (PMID:30013058)
• Our report further supports the importance of GATAD2B in neurodevelopment and contributes to delineation of the phenotype of the recently identified GAND. Mosaicism for the pathogenic variant in unaffected mothers of cases prompts detailed genetic testing with the use of NGS technology and genetic counseling for the parents of children with GAND. (PMID:30346093)
• GATAD2B-related intellectual disability is a rare condition with subtle yet recognizable clinical features. In this article, we highlight a consistent clinical profile of subjects with GATAD2B-related intellectual disability. (PMID:31205050)
• GATAD2B-associated neurodevelopmental disorder (GAND): clinical and molecular insights into a NuRD-related disorder. (PMID:31949314)
• The enhancer activity of long interspersed nuclear element derived microRNA 625 induced by NF-kappaB. (PMID:33542430)
• Tissue-specific DNase I footprint analysis confirms the association of GATAD2B Q470* variant with intellectual disability. (PMID:34470925)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gatad2b	ENSDARG00000005834
mus_musculus	Gatad2b	ENSMUSG00000042390
rattus_norvegicus	Gatad2b	ENSRNOG00000015553
drosophila_melanogaster	simj	FBGN0010762
caenorhabditis_elegans	dcp-66	WBGENE00000938

Paralogs (1): GATAD2A (ENSG00000167491)

Protein

Protein identifiers

Transcriptional repressor p66-beta — Q8WXI9 (reviewed: Q8WXI9)

Alternative names: GATA zinc finger domain-containing protein 2B, p66/p68

All UniProt accessions (8): Q8WXI9, A0A0U1RR30, A0A0U1RR34, A0A0U1RRK3, A0A0U1RRM1, A0A1B0GVS4, A0A1B0GW07, A0A994J4D5

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional repressor. Acts as a component of the histone deacetylase NuRD complex which participates in the remodeling of chromatin. Enhances MBD2-mediated repression. Efficient repression requires the presence of GATAD2A. Targets MBD3 to discrete loci in the nucleus. May play a role in synapse development.

Subunit / interactions. Homooligomer. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with MBD2; this is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin. Interacts with MBD3. Component of the MeCP1 histone deacetylase complex. Interacts with histone tails, including that of histones H2A, H2B, H3 and H4. Interacts with ERCC6.

Subcellular location. Nucleus speckle. Nucleus. Chromosome.

Tissue specificity. Widely expressed.

Disease relevance. Gand syndrome (GAND) [MIM:615074] An autosomal dominant syndrome characterized by global developmental delay with motor delay, moderate to severely impaired intellectual development, and poor speech acquisition in most patients. Additional features include hypotonia, feeding difficulties in infancy, and dysmorphic features. More variable features may include seizures, cardiac abnormalities, and non-specific findings on brain imaging. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Both CR1 and CR2 regions are required for speckled nuclear localization.

RefSeq proteins (1): NP_065750* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000679	Znf_GATA	Domain
IPR013088	Znf_NHR/GATA	Homologous_superfamily
IPR032346	P66_CC	Domain
IPR040386	P66	Family

Pfam: PF00320, PF16563

UniProt features (33 total): modified residue 11, cross-link 10, region of interest 4, sequence variant 2, coiled-coil region 2, compositionally biased region 2, chain 1, zinc finger region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WXI9-F1	59.85	0.10

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (21): 17, 120, 122, 129, 134, 135, 208, 333, 338, 340, 486, 33, 66, 97, 147, 199, 281, 353, 454, 467 …

Function

Pathways and Gene Ontology

Reactome pathways

12 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 342 (showing top): PID_HDAC_CLASSI_PATHWAY, TGCACTT_MIR519C_MIR519B_MIR519A, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, ATGCAGT_MIR217, AGGCACT_MIR5153P, TGAGATT_MIR216, GOBP_STEM_CELL_DIFFERENTIATION, GOBP_REGULATION_OF_CELL_FATE_SPECIFICATION, GOBP_CELL_FATE_SPECIFICATION, CTTTGTA_MIR524, GOBP_CHROMATIN_REMODELING, GOBP_CELL_FATE_COMMITMENT, GOBP_REGULATION_OF_CELL_FATE_COMMITMENT, GOBP_REGULATION_OF_STEM_CELL_DIFFERENTIATION

GO Biological Process (7): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin remodeling (GO:0006338), regulation of cell fate specification (GO:0042659), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), regulation of stem cell differentiation (GO:2000736), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (5): zinc ion binding (GO:0008270), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), nucleosomal DNA binding (GO:0031492), metal ion binding (GO:0046872)

GO Cellular Component (8): chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), NuRD complex (GO:0016581), nuclear speck (GO:0016607), protein-containing complex (GO:0032991), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-11 pathways:

Category	Pathways
Regulation of endogenous retroelements	2
Chromatin modifying enzymes	1
Positive epigenetic regulation of rRNA expression	1
Regulation of TP53 Activity	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
SARS-CoV Infections	1
Transcriptional regulation of brown and beige adipocyte differentiation	1
CHD3, CHD4, CHD5 subfamily	1
NuRD complex assembly	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
DNA-templated transcription	3
regulation of DNA-templated transcription	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
chromatin organization	1
cell fate specification	1
regulation of cell fate commitment	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
regulation of cell differentiation	1
stem cell differentiation	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transition metal ion binding	1
DNA binding	1
binding	1
chromatin DNA binding	1
nucleosome binding	1
cation binding	1
chromosomal region	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
histone deacetylase complex	1
transcription regulator complex	1
CHD-type complex	1
nuclear ribonucleoprotein granule	1
cellular_component	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1342 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATAD2B	RBBP4	P31149	993
GATAD2B	RBBP7	Q16576	993
GATAD2B	HDAC1	Q13547	988
GATAD2B	HDAC2	Q92769	973
GATAD2B	CHD4	Q14839	970
GATAD2B	MTA2	O94776	964
GATAD2B	MTA1	Q13330	962
GATAD2B	CHD3	Q12873	937
GATAD2B	GATAD2A	Q86YP4	893
GATAD2B	MTA3	Q9BTC8	881
GATAD2B	CDK2AP1	O14519	798
GATAD2B	MBD2	Q9UBB5	734
GATAD2B	KDM1A	O60341	630
GATAD2B	SIN3A	Q96ST3	608
GATAD2B	SAP18	O00422	574

IntAct

265 interactions, top by confidence:

A	B	Type	Score
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
GATAD2B	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
MBD3	GATAD2B	psi-mi:“MI:0915”(physical association)	0.740
GATAD2B	MBD3	psi-mi:“MI:0915”(physical association)	0.740
HMG20A	KDM1A	psi-mi:“MI:0914”(association)	0.730
CHD4	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730
PRKAB2	GATAD2B	psi-mi:“MI:0915”(physical association)	0.670
GATAD2B	TRAF1	psi-mi:“MI:0915”(physical association)	0.670
GATAD2B	PRKAB2	psi-mi:“MI:0915”(physical association)	0.670
TRAF1	GATAD2B	psi-mi:“MI:0915”(physical association)	0.670
MAGEE1	MCC	psi-mi:“MI:0914”(association)	0.670
GATAD2B	MTA2	psi-mi:“MI:0914”(association)	0.640
QPRT	PIK3C2A	psi-mi:“MI:0914”(association)	0.640

BioGRID (476): GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), GATAD2B (Two-hybrid), CEP70 (Two-hybrid), USHBP1 (Two-hybrid), GATAD2B (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), GATAD2B (Affinity Capture-MS), GATAD2B (Reconstituted Complex)

ESM2 similar proteins: A0A0G2JTY4, A0JNC2, A2AQ25, E1BEQ5, O09000, O57539, O70305, O93602, P15336, P16951, P17544, P70365, P97305, Q00969, Q02930, Q12968, Q14157, Q15032, Q15596, Q15788, Q1LY51, Q4PJW2, Q4VCS5, Q5R9C9, Q5SFM8, Q5T5P2, Q5T6F2, Q61026, Q62415, Q6GP15, Q80TM6, Q80X50, Q86YP4, Q8CHY6, Q8IY63, Q8VCB2, Q8VHG2, Q8VHR5, Q8WXI9, Q91VX2

Diamond homologs: G5ED89, Q86YP4, Q8VHR5, Q8WXI9, Q8CHY6

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GATAD2B	“form complex”	“MBD2/NuRD complex”	binding
GATAD2B	“form complex”	“MBD3/NuRD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 167 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	10	31.5×	6e-11
Regulation of TP53 Activity through Acetylation	8	30.2×	9e-09
Interaction of NuRD complexes with transcription factors	20	21.0×	1e-18
Regulation of PTEN gene transcription	14	20.6×	8e-13
NuRD complex assembly	16	18.6×	6e-14
RNA Polymerase I Transcription Initiation	10	18.5×	9e-09
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	12	15.1×	2e-09
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	12	14.5×	3e-09

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	10	51.1×	6e-13
DNA methylation-dependent constitutive heterochromatin formation	5	18.1×	8e-04
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	5	13.4×	3e-03
circadian regulation of gene expression	7	10.9×	5e-04
chromatin remodeling	18	8.8×	7e-10
double-strand break repair	6	8.1×	7e-03
chromatin organization	11	7.3×	5e-05
protein import into nucleus	7	6.7×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

678 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	82
Likely pathogenic	28
Uncertain significance	277
Likely benign	208
Benign	33

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1012542	NM_020699.4(GATAD2B):c.185_186del (p.Glu62fs)	Pathogenic
1183040	NM_020699.4(GATAD2B):c.1321T>C (p.Cys441Arg)	Pathogenic
1320103	NM_020699.4(GATAD2B):c.777_778del (p.Met259fs)	Pathogenic
1358786	NM_020699.4(GATAD2B):c.487C>T (p.Gln163Ter)	Pathogenic
1453672	NM_020699.4(GATAD2B):c.653del (p.Gly218fs)	Pathogenic
1684116	NM_020699.4(GATAD2B):c.820C>T (p.Gln274Ter)	Pathogenic
1702719	NM_020699.4(GATAD2B):c.182_183del (p.His61fs)	Pathogenic
1707715	NC_000001.10:g.(?153753742)(153791156_?)del	Pathogenic
211069	NM_020699.4(GATAD2B):c.981del (p.Thr328fs)	Pathogenic
2227242	NM_020699.4(GATAD2B):c.229G>T (p.Glu77Ter)	Pathogenic
2242008	NM_020699.4(GATAD2B):c.818dup (p.Gln274fs)	Pathogenic
2300447	NM_020699.4(GATAD2B):c.453dup (p.Glu152fs)	Pathogenic
2429332	NM_020699.4(GATAD2B):c.117_127del (p.Met40fs)	Pathogenic
2446013	NM_020699.4(GATAD2B):c.1043C>G (p.Ser348Ter)	Pathogenic
2626894	NM_020699.4(GATAD2B):c.466-1G>C	Pathogenic
2695159	NM_020699.4(GATAD2B):c.646del (p.His216fs)	Pathogenic
280108	NM_020699.4(GATAD2B):c.1217-2A>G	Pathogenic
280149	NM_020699.4(GATAD2B):c.335+2T>G	Pathogenic
280408	NM_020699.4(GATAD2B):c.346C>T (p.Arg116Ter)	Pathogenic
280788	NM_020699.4(GATAD2B):c.335+1G>T	Pathogenic
2838955	NM_020699.4(GATAD2B):c.1378del (p.Arg460fs)	Pathogenic
2839266	NM_020699.4(GATAD2B):c.1404_1408dup (p.Gln470fs)	Pathogenic
2864432	NM_020699.4(GATAD2B):c.199C>T (p.Gln67Ter)	Pathogenic
3254776	NM_020699.4(GATAD2B):c.251_257del (p.Arg84fs)	Pathogenic
3280870	NM_020699.4(GATAD2B):c.727C>T (p.Gln243Ter)	Pathogenic
3381764	NM_020699.4(GATAD2B):c.653_654dup (p.Gln219fs)	Pathogenic
3519121	NM_020699.4(GATAD2B):c.1091del (p.Leu364fs)	Pathogenic
3650576	NM_020699.4(GATAD2B):c.892dup (p.Tyr298fs)	Pathogenic
3650669	NM_020699.4(GATAD2B):c.1085del (p.Lys362fs)	Pathogenic
3652338	NM_020699.4(GATAD2B):c.528_539del (p.Glu177_Leu180del)	Pathogenic

SpliceAI

2485 predictions. Top by Δscore:

Variant	Effect	Δscore
1:153812016:CCTTA:C	donor_loss	1.0000
1:153812017:CTTA:C	donor_loss	1.0000
1:153812018:TTA:T	donor_loss	1.0000
1:153812019:TA:T	donor_loss	1.0000
1:153812020:A:AC	donor_gain	1.0000
1:153812020:ACCTG:A	donor_gain	1.0000
1:153812021:C:CC	donor_gain	1.0000
1:153812021:CCTG:C	donor_gain	1.0000
1:153812021:CCTGC:C	donor_gain	1.0000
1:153812129:TTTC:T	acceptor_gain	1.0000
1:153812130:TTC:T	acceptor_gain	1.0000
1:153812132:CCTG:C	acceptor_loss	1.0000
1:153812133:CTGTT:C	acceptor_loss	1.0000
1:153812134:T:A	acceptor_loss	1.0000
1:153813244:TCTTA:T	donor_loss	1.0000
1:153813245:CTTA:C	donor_loss	1.0000
1:153813246:TTA:T	donor_loss	1.0000
1:153813247:TAC:T	donor_loss	1.0000
1:153813248:ACCTG:A	donor_loss	1.0000
1:153813249:C:A	donor_loss	1.0000
1:153816269:TTACC:T	donor_loss	1.0000
1:153816270:TA:T	donor_loss	1.0000
1:153816271:A:C	donor_loss	1.0000
1:153816586:CTG:C	acceptor_gain	1.0000
1:153817366:TCTTA:T	donor_loss	1.0000
1:153817367:CTTA:C	donor_loss	1.0000
1:153817368:TTAC:T	donor_loss	1.0000
1:153817369:TA:T	donor_loss	1.0000
1:153817370:A:AC	donor_gain	1.0000
1:153817370:A:T	donor_loss	1.0000

AlphaMissense

3872 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:153810220:A:C	I580S	1.000
1:153810220:A:G	I580T	1.000
1:153810220:A:T	I580N	1.000
1:153810226:T:A	D578V	1.000
1:153810229:A:G	L577S	1.000
1:153810232:A:G	L576P	1.000
1:153810232:A:T	L576H	1.000
1:153810235:T:C	Y575C	1.000
1:153810236:A:G	Y575H	1.000
1:153810241:C:G	R573P	1.000
1:153810242:G:A	R573C	1.000
1:153810242:G:T	R573S	1.000
1:153812128:A:C	I475S	1.000
1:153813251:T:G	Q473P	1.000
1:153813253:T:A	E472D	1.000
1:153813253:T:G	E472D	1.000
1:153813254:T:A	E472V	1.000
1:153813255:C:T	E472K	1.000
1:153813257:T:G	Q471P	1.000
1:153813260:T:G	Q470P	1.000
1:153813263:A:G	L469P	1.000
1:153813263:A:T	L469Q	1.000
1:153813266:G:T	A468D	1.000
1:153813267:C:G	A468P	1.000
1:153813268:T:A	K467N	1.000
1:153813268:T:G	K467N	1.000
1:153813269:T:A	K467I	1.000
1:153813270:T:C	K467E	1.000
1:153813272:A:T	V466E	1.000
1:153813274:A:C	F465L	1.000

dbSNP variants (sampled 300 via entrez): RS1000008109 (1:153837980 T>C), RS1000082705 (1:153874246 A>G), RS1000085540 (1:153914448 C>T), RS1000122103 (1:153900067 T>C), RS1000143751 (1:153919857 T>C), RS1000159950 (1:153872723 G>A,C,T), RS1000183549 (1:153868494 A>G), RS1000221178 (1:153914827 G>A,C), RS1000268683 (1:153824498 G>C), RS1000276711 (1:153818410 G>A), RS1000306473 (1:153829758 T>C), RS1000330491 (1:153917395 A>C,G), RS1000357054 (1:153821426 T>A,C), RS1000367386 (1:153862999 T>C,G), RS1000411860 (1:153819136 G>A)

Disease associations

OMIM: gene MIM:614998 | disease phenotypes: MIM:615074

GenCC curated gene-disease

Disease	Classification	Inheritance
severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome	Definitive	AD

Mondo (3): severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (MONDO:0014034), autism spectrum disorder (MONDO:0005258), intellectual disability (MONDO:0001071)

Orphanet (3): Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome (Orphanet:363686), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

56 total (30 of 56 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000047	Hypospadias
HP:0000154	Wide mouth
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000273	Facial grimacing
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000337	Broad forehead
HP:0000347	Micrognathia
HP:0000431	Wide nasal bridge
HP:0000455	Broad nasal tip
HP:0000483	Astigmatism
HP:0000484	Hyperopic astigmatism
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000540	Hypermetropia
HP:0000581	Blepharophimosis
HP:0000582	Upslanted palpebral fissure
HP:0000609	Optic nerve hypoplasia
HP:0000629	Periorbital fullness
HP:0000637	Long palpebral fissure
HP:0000729	Autistic behavior
HP:0000742	Self-mutilation
HP:0000744	Low frustration tolerance
HP:0000748	Inappropriate laughter
HP:0000752	Hyperactivity
HP:0001263	Global developmental delay
HP:0001319	Neonatal hypotonia

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST001640_13	Lentiform nucleus volume	3.000000e-06
GCST003795_1	Age at first birth	6.000000e-10
GCST003796_1	Number of children ever born	2.000000e-08
GCST005751_3	Empathy quotient	3.000000e-07
GCST006044_1	Age at first birth	3.000000e-07
GCST006045_3	Age at first birth	5.000000e-06
GCST006047_1	Number of children ever born	8.000000e-06
GCST006269_821	General cognitive ability	1.000000e-08
GCST007576_218	Chronotype	2.000000e-09
GCST008839_316	Height	5.000000e-14
GCST010136_18	Fruit consumption	3.000000e-08
GCST010137_3	Cooked vegetable consumption	3.000000e-09
GCST010138_14	Raw vegetable consumption	5.000000e-11
GCST010142_60	Fish- and plant-related diet	4.000000e-09
GCST010142_92	Fish- and plant-related diet	6.000000e-14
GCST010696_22	Cortical thickness (min-P)	4.000000e-10
GCST010697_50	Cortical surface area (min-P)	1.000000e-12
GCST010698_81	Subcortical volume (min-P)	1.000000e-23
GCST010699_7	Brain morphology (min-P)	1.000000e-10
GCST010700_11	Cortical thickness (MOSTest)	4.000000e-13
GCST010701_73	Cortical surface area (MOSTest)	4.000000e-09
GCST010702_45	Subcortical volume (MOSTest)	4.000000e-10
GCST010703_276	Brain morphology (MOSTest)	2.000000e-15
GCST90000047_17	Age at first sexual intercourse	3.000000e-10

EFO canonical traits (9, from GWAS)

EFO ID	Trait name
EFO:0009101	age at first birth measurement
EFO:0009102	number of children ever born measurement
EFO:0009183	empathy measurement
EFO:0004337	intelligence
EFO:0008328	chronotype measurement
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009749	age at first sexual intercourse measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725181 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

3 potent at pChembl≥5 of 3 total, top 3 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.52	Kd	3.012	nM	CHEMBL5653589
8.52	ED50	3.012	nM	CHEMBL5653589
5.26	IC50	5530	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148420: Binding affinity to human GATAD2B incubated for 45 mins by Kinobead based pull down assay	kd	0.0030	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178649: Inhibition of GATAD2B (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	5.5300	uM

CTD chemical–gene interactions

36 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression	7
trichostatin A	decreases expression, affects cotreatment	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment, increases expression	2
Benzo(a)pyrene	affects methylation, decreases methylation	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
GSK-J4	increases expression	1
FR900359	increases phosphorylation	1
TAK-243	affects sumoylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
cobaltous chloride	increases expression	1
dorsomorphin	decreases expression, affects cotreatment	1
LDN 193189	increases expression, affects cotreatment	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Acetaminophen	increases expression	1
Atrazine	increases expression	1
Benztropine	affects cotreatment, decreases expression	1
Cadmium	decreases expression, increases abundance	1
Caffeine	affects phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Carbamazepine	affects expression	1
Cisplatin	decreases expression	1
Cuprizone	affects cotreatment, decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Ivermectin	decreases expression	1
Lead	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651462	Binding	Binding affinity to human GATAD2B incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

3 cell lines: 2 embryonic stem cell, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A0VU	WAe001-A-73	Embryonic stem cell	Male
CVCL_A0VV	WAe001-A-74	Embryonic stem cell	Male
CVCL_D3AA	GM28225	Transformed cell line	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder