GATAD2A

Summary

GATAD2A (GATA zinc finger domain containing 2A, HGNC:29989) is a protein-coding gene on chromosome 19p13.11, encoding Transcriptional repressor p66-alpha (Q86YP4). Transcriptional repressor. It is a selective cancer dependency (DepMap: 25.2% of cell lines).

Enables protein-macromolecule adaptor activity. Involved in chromatin remodeling and negative regulation of DNA-templated transcription. Located in nucleoplasm. Part of NuRD complex.

Source: NCBI Gene 54815 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC)
• GWAS associations: 37
• Clinical variants (ClinVar): 132 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 25.2% of screened cell lines
• MANE Select transcript: NM_001384528

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29989
Approved symbol	GATAD2A
Name	GATA zinc finger domain containing 2A
Location	19p13.11
Locus type	gene with protein product
Status	Approved
Aliases	p66alpha
Ensembl gene	ENSG00000167491
Ensembl biotype	protein_coding
OMIM	614997
Entrez	54815

Gene structure

Transcript identifiers

Ensembl transcripts: 50 — 46 protein_coding, 2 nonsense_mediated_decay, 2 protein_coding_CDS_not_defined

ENST00000358713, ENST00000360315, ENST00000404158, ENST00000417582, ENST00000418032, ENST00000429242, ENST00000432704, ENST00000444839, ENST00000448576, ENST00000473184, ENST00000494516, ENST00000609040, ENST00000683918, ENST00000868304, ENST00000868305, ENST00000868306, ENST00000868307, ENST00000868308, ENST00000868309, ENST00000868310, ENST00000868311, ENST00000868312, ENST00000868313, ENST00000868314, ENST00000868315, ENST00000868316, ENST00000868317, ENST00000868318, ENST00000868319, ENST00000868320, ENST00000868321, ENST00000868322, ENST00000915056, ENST00000915057, ENST00000915058, ENST00000915059, ENST00000915060, ENST00000915061, ENST00000915062, ENST00000915063, ENST00000915064, ENST00000915065, ENST00000915066, ENST00000915067, ENST00000915068, ENST00000915069, ENST00000915070, ENST00000915071, ENST00000956365, ENST00000956366

RefSeq mRNA: 33 — MANE Select: NM_001384528 NM_001300946, NM_001359631, NM_001384511, NM_001384512, NM_001384513, NM_001384514, NM_001384515, NM_001384516, NM_001384517, NM_001384518, NM_001384519, NM_001384521, NM_001384522, NM_001384523, NM_001384524, NM_001384525, NM_001384526, NM_001384527, NM_001384528, NM_001384529, NM_001384530, NM_001384531, NM_001384532, NM_001384533, NM_001384534, NM_001384535, NM_001384536, NM_001384537, NM_001384538, NM_001384539, NM_001384540, NM_001384541, NM_017660

CCDS: CCDS12402, CCDS77270

Canonical transcript exons

ENST00000683918 — 12 exons

Exon	Start	End
ENSE00001050169	19494294	19494383
ENSE00001050174	19495754	19495885
ENSE00001284112	19501969	19502043
ENSE00001341504	19496052	19496219
ENSE00001681019	19492306	19492438
ENSE00001769622	19405675	19406019
ENSE00002278492	19465340	19465614
ENSE00003663693	19492581	19492712
ENSE00003691641	19498443	19498722
ENSE00003695743	19501118	19501416
ENSE00003696582	19502331	19502526
ENSE00003916222	19505344	19508932

Expression profiles

Bgee: expression breadth ubiquitous, 272 present calls, max score 98.59.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.0350 / max 391.1123, expressed in 1826 samples.

FANTOM5 promoters (12 alternative TSS)

Promoter ID	TPM avg	Samples expressed
174791	19.8142	1804
174786	14.5020	1801
174785	5.9025	1574
174788	3.9953	1618
174784	3.8250	1400
174790	2.7155	1410
174789	2.1824	1305
174783	1.5543	707
208742	0.2512	109
174787	0.1559	61

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	98.59	gold quality
tendon of biceps brachii	UBERON:0008188	96.80	gold quality
ileal mucosa	UBERON:0000331	95.33	gold quality
blood	UBERON:0000178	94.47	gold quality
bone marrow cell	CL:0002092	93.53	gold quality
secondary oocyte	CL:0000655	92.92	gold quality
upper arm skin	UBERON:0004263	92.91	gold quality
right testis	UBERON:0004534	92.72	gold quality
granulocyte	CL:0000094	92.65	gold quality
oocyte	CL:0000023	92.63	gold quality
left testis	UBERON:0004533	92.46	gold quality
testis	UBERON:0000473	92.25	gold quality
sural nerve	UBERON:0015488	91.90	gold quality
skin of leg	UBERON:0001511	91.88	gold quality
skin of abdomen	UBERON:0001416	91.53	gold quality
oviduct epithelium	UBERON:0004804	91.51	gold quality
mucosa of sigmoid colon	UBERON:0004993	91.50	gold quality
sperm	CL:0000019	91.49	silver quality
stromal cell of endometrium	CL:0002255	91.42	gold quality
zone of skin	UBERON:0000014	91.24	gold quality
male germ cell	CL:0000015	91.20	silver quality
leukocyte	CL:0000738	90.98	gold quality
medial globus pallidus	UBERON:0002477	90.78	gold quality
mononuclear cell	CL:0000842	90.74	gold quality
monocyte	CL:0000576	90.73	gold quality
colonic epithelium	UBERON:0000397	90.69	gold quality
tendon	UBERON:0000043	90.67	gold quality
colonic mucosa	UBERON:0000317	90.52	gold quality
duodenum	UBERON:0002114	90.29	gold quality
vermiform appendix	UBERON:0001154	90.24	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NR1I2

miRNA regulators (miRDB)

147 targeting GATAD2A, 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-3613-3P	100.00	76.36	7965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-185-3P	99.95	67.01	1743
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 25.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 11)

• These factors lead to a binding affinity hierarchy of p66alpha for the different MBD2 homologues (MBD2 approximately MBD3 > MBD3L1 approximately MBD3L2). (PMID:23239876)
• The MYND domain of ZMYND8 directly interacts with PPPLPhi motifs in the NuRD subunit GATAD2A. (PMID:27732854)
• Results showed that suppression of GATAD2A attenuated thyroid cancer cell proliferation and colony formation and promoted apoptosis suggesting it as an essential factor in thyroid cancer cell pathogenesis. (PMID:28260108)
• circ-GATAD2A promotes the replication of H1N1 by inhibiting autophagy. (PMID:30955816)
• This study unveils a novel biomarker panel consisting of the hsa_circ_0058124/NOTCH3/GATAD2A axis which is critical for papillary thyroid cancer (PTC) tumorigenesis and invasiveness and may represent a novel therapeutic target for intervening in PTC progression. (PMID:31324198)
• A shared genetic contribution to breast cancer and schizophrenia. (PMID:32934226)
• Germinal GLT8D1, GATAD2A and SLC25A39 mutations in a patient with a glomangiopericytal tumor and five different sarcomas over a 10-year period. (PMID:33963205)
• GATA zinc finger domain-containing protein 2A (GATAD2A) deficiency reactivates fetal haemoglobin in patients with beta-thalassaemia through impaired formation of methyl-binding domain protein 2 (MBD2)-containing nucleosome remodelling and deacetylation (NuRD) complex. (PMID:33997955)
• p66alpha Suppresses Breast Cancer Cell Growth and Migration by Acting as Co-Activator of p53. (PMID:34944103)
• lncKRT16P6 promotes tongue squamous cell carcinoma progression by sponging miR3180 and regulating GATAD2A expression. (PMID:35904180)
• De novo variants in GATAD2A in individuals with a neurodevelopmental disorder: GATAD2A-related neurodevelopmental disorder. (PMID:37181331)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gatad2ab	ENSDARG00000006192
mus_musculus	Gatad2a	ENSMUSG00000036180
rattus_norvegicus	Gatad2a	ENSRNOG00000022173
drosophila_melanogaster	simj	FBGN0010762
caenorhabditis_elegans	dcp-66	WBGENE00000938

Paralogs (1): GATAD2B (ENSG00000143614)

Protein

Protein identifiers

Transcriptional repressor p66-alpha — Q86YP4 (reviewed: Q86YP4)

Alternative names: GATA zinc finger domain-containing protein 2A

All UniProt accessions (8): C9JGN4, C9JJK9, C9JMI3, C9JVY3, Q86YP4, H7C3H1, V9GY85, V9GYX5

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 GATAD2B.

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. Component of the MeCP1 histone deacetylase complex. Interacts with CDK2AP1. Interacts with CHD4. Interacts with ERCC6. Interacts with HDAC1. Interacts with HDAC2. Interacts with MBD2; this interaction is required for the enhancement of MBD2-mediated repression and for targeting to the chromatin. Interacts with MBD3. Interacts with MTA2. Interacts with ZMYND8. Interacts with histone tails, including that of histones H2A, H2B, H3 and H4, the interaction is reduced by histone acetylation.

Subcellular location. Nucleus speckle. Nucleus. Chromosome.

Tissue specificity. Ubiquitous, both in fetal and adult tissues.

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

Isoforms (3)

UniProt ID	Names	Canonical?
Q86YP4-1	1	yes
Q86YP4-2	2
Q86YP4-3	3

RefSeq proteins (33): NP_001287875, NP_001346560, NP_001371440, NP_001371441, NP_001371442, NP_001371443, NP_001371444, NP_001371445, NP_001371446, NP_001371447, NP_001371448, NP_001371450, NP_001371451, NP_001371452, NP_001371453, NP_001371454, NP_001371455, NP_001371456, NP_001371457, NP_001371458, NP_001371459, NP_001371460, NP_001371461, NP_001371462, NP_001371463, NP_001371464, NP_001371465, NP_001371466, NP_001371467, NP_001371468, NP_001371469, NP_001371470, NP_060130 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000679	Znf_GATA	Domain
IPR032346	P66_CC	Domain
IPR040386	P66	Family

Pfam: PF00320, PF16563

UniProt features (55 total): modified residue 23, cross-link 9, region of interest 7, compositionally biased region 6, splice variant 2, sequence variant 2, chain 1, zinc finger region 1, mutagenesis site 1, sequence conflict 1, helix 1, coiled-coil region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2L2L	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q86YP4-F1	57.54	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 (32): 20, 49, 100, 107, 113, 114, 137, 189, 225, 249, 258, 273, 275, 285, 340, 343, 512, 539, 539, 546 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
149	disruption of mbd2-binding, loss of enhancement of mbd2-mediated repression and loss of speckled nuclear localization.

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: 227 (showing top): PID_HDAC_CLASSI_PATHWAY, TONKS_TARGETS_OF_RUNX1_RUNX1T1_FUSION_MONOCYTE_UP, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, CACCAGC_MIR138, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, MODULE_195, BYSTRYKH_HEMATOPOIESIS_STEM_CELL_AND_BRAIN_QTL_CIS, MODULE_206, BENPORATH_ES_CORE_NINE_CORRELATED, MODULE_147, FISCHER_DREAM_TARGETS, GOBP_STEM_CELL_DIFFERENTIATION, VANTVEER_BREAST_CANCER_ESR1_DN

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), protein-macromolecule adaptor activity (GO:0030674), sequence-specific DNA binding (GO:0043565), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), NuRD complex (GO:0016581), nuclear speck (GO:0016607), 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
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
protein binding	1
molecular adaptor activity	1
DNA binding	1
binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
histone deacetylase complex	1
transcription regulator complex	1
CHD-type complex	1
nuclear ribonucleoprotein granule	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1964 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GATAD2A	RBBP4	P31149	996
GATAD2A	CHD3	Q12873	995
GATAD2A	MTA1	Q13330	993
GATAD2A	HDAC1	Q13547	993
GATAD2A	RBBP7	Q16576	993
GATAD2A	CHD4	Q14839	987
GATAD2A	HDAC2	Q92769	986
GATAD2A	MTA2	O94776	983
GATAD2A	CDK2AP1	O14519	957
GATAD2A	MTA3	Q9BTC8	913
GATAD2A	GATAD2B	Q8WXI9	893
GATAD2A	MBD2	Q9UBB5	791
GATAD2A	ZMYND8	Q9ULU4	709
GATAD2A	KDM1A	O60341	658
GATAD2A	MECP2	P51608	572

IntAct

169 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
MBD2	GATAD2A	psi-mi:“MI:0407”(direct interaction)	0.880
GATAD2A	MBD2	psi-mi:“MI:0915”(physical association)	0.880
MBD2	GATAD2A	psi-mi:“MI:0915”(physical association)	0.880
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
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
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
GATAD2A	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
CDK2AP1	MTA2	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
MBD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.730
GATAD2A	MBD3L1	psi-mi:“MI:0915”(physical association)	0.670
ZNF219	CDK2AP1	psi-mi:“MI:0914”(association)	0.640
KPNA1	TCERG1	psi-mi:“MI:0914”(association)	0.640
CHD4	MTA2	psi-mi:“MI:0914”(association)	0.630

BioGRID (393): KRT40 (Two-hybrid), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), GATAD2A (Affinity Capture-MS), CHD3 (Co-fractionation), GATAD2A (Co-fractionation), GATAD2A (Co-fractionation), GATAD2A (Co-fractionation), MBD2 (Co-fractionation)

ESM2 similar proteins: A0A087WPF7, A0A0R4IBL7, O09000, O54972, O70305, O75081, O75376, P15806, P15881, P15884, P15923, P21677, P30985, P51514, P98180, Q05AQ8, Q14157, Q14687, Q1LY51, Q2VPM4, Q3U3C9, Q4KKX4, Q4VCS5, Q566L4, Q5F3B1, Q5SFM8, Q5T6F2, Q60722, Q60974, Q61286, Q62655, Q6DIH5, Q7ZWN6, Q7ZXS3, Q80X50, Q86YP4, Q8BZ47, Q8CHY6, Q8IXK0, Q8VHG2

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

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
GATAD2A	“form complex”	“MBD2/NuRD complex”	binding
GATAD2A	“form complex”	“MBD3/NuRD complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 153 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	34.0×	2e-11
Regulation of TP53 Activity through Acetylation	8	32.6×	5e-09
Regulation of PTEN gene transcription	16	25.5×	3e-16
RNA Polymerase I Transcription Initiation	11	22.0×	2e-10
Notch-HLH transcription pathway	6	21.9×	1e-05
NuRD complex assembly	17	21.4×	4e-16
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	16	20.9×	4e-15
Interaction of NuRD complexes with transcription factors	18	20.4×	2e-16

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	10	56.7×	1e-13
NLS-bearing protein import into nucleus	5	29.7×	5e-05
DNA methylation-dependent constitutive heterochromatin formation	7	28.2×	6e-07
negative regulation of proteasomal ubiquitin-dependent protein catabolic process	6	17.8×	8e-05
chromatin remodeling	17	9.2×	1e-09
double-strand break repair	6	9.0×	3e-03
chromatin organization	12	8.8×	2e-06
circadian regulation of gene expression	5	8.7×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	107
Likely benign	8
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
1705819	NM_001384528.1(GATAD2A):c.1880del (p.Ile627fs)	Likely pathogenic

SpliceAI

3701 predictions. Top by Δscore:

Variant	Effect	Δscore
19:19465338:A:G	acceptor_gain	1.0000
19:19492304:A:AG	acceptor_gain	1.0000
19:19492305:G:GG	acceptor_gain	1.0000
19:19492305:GT:G	acceptor_gain	1.0000
19:19492436:ATGG:A	donor_loss	1.0000
19:19492437:TGGTG:T	donor_loss	1.0000
19:19492439:G:GG	donor_gain	1.0000
19:19492440:T:A	donor_loss	1.0000
19:19492570:C:A	acceptor_gain	1.0000
19:19492578:CA:C	acceptor_loss	1.0000
19:19492579:A:AG	acceptor_gain	1.0000
19:19492579:AG:A	acceptor_loss	1.0000
19:19492580:G:GC	acceptor_gain	1.0000
19:19492580:GA:G	acceptor_gain	1.0000
19:19492580:GAA:G	acceptor_gain	1.0000
19:19492580:GAAA:G	acceptor_gain	1.0000
19:19492580:GAAAA:G	acceptor_gain	1.0000
19:19492695:G:GT	donor_gain	1.0000
19:19492709:GAAG:G	donor_gain	1.0000
19:19492711:AGGTG:A	donor_loss	1.0000
19:19492713:G:GA	donor_loss	1.0000
19:19492714:T:A	donor_loss	1.0000
19:19496042:A:AG	acceptor_gain	1.0000
19:19496043:C:G	acceptor_gain	1.0000
19:19496048:ACAG:A	acceptor_loss	1.0000
19:19496049:CAG:C	acceptor_loss	1.0000
19:19496050:A:AG	acceptor_gain	1.0000
19:19496050:AGCA:A	acceptor_loss	1.0000
19:19496051:G:GC	acceptor_gain	1.0000
19:19496051:GC:G	acceptor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000045565 (19:19455006 G>A), RS1000056077 (19:19394001 C>T), RS1000076707 (19:19451908 C>T), RS1000078227 (19:19486038 A>T), RS1000080789 (19:19404953 T>G), RS1000142064 (19:19442916 C>G), RS1000146489 (19:19505257 G>A,T), RS1000215401 (19:19463947 C>T), RS1000223227 (19:19500748 G>A,T), RS1000231894 (19:19399736 G>A), RS1000237 (19:19407507 T>A), RS1000238036 (19:19444480 GGT>G), RS1000259452 (19:19485547 G>A), RS1000278514 (19:19500493 C>T), RS1000280236 (19:19449467 T>C)

Disease associations

OMIM: gene MIM:614997 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

37 associations (top):

Study	Trait	p-value
GCST002149_11	Schizophrenia	3.000000e-09
GCST002539_89	Schizophrenia	4.000000e-10
GCST002647_163	Height	9.000000e-14
GCST003486_10	Response to fenofibrate (LDL cholesterol levels)	2.000000e-08
GCST004894_26	Type 2 diabetes	9.000000e-13
GCST004894_84	Type 2 diabetes	4.000000e-09
GCST004988_641	Breast cancer	6.000000e-12
GCST005308_7	Nonalcoholic fatty liver disease	2.000000e-08
GCST006100_5	Strenuous sports or other exercises	3.000000e-09
GCST006291_84	Spherical equivalent or myopia (age of diagnosis)	1.000000e-09
GCST006803_88	Schizophrenia	7.000000e-12
GCST006804_31	Red cell distribution width	2.000000e-15
GCST007269_137	Pulse pressure	9.000000e-09
GCST007294_16	Body fat distribution (trunk fat ratio)	2.000000e-07
GCST007294_35	Body fat distribution (trunk fat ratio)	1.000000e-10
GCST007295_166	Body fat distribution (leg fat ratio)	2.000000e-11
GCST007295_22	Body fat distribution (leg fat ratio)	3.000000e-07
GCST008103_10	Bipolar disorder	1.000000e-09
GCST008115_2	Bipolar I disorder	3.000000e-09
GCST008116_4	Bipolar II disorder	4.000000e-06
GCST008839_602	Height	2.000000e-13
GCST010002_52	Refractive error	4.000000e-29
GCST010703_335	Brain morphology (MOSTest)	3.000000e-10
GCST010797_18	Breast cancer, ovarian cancer or prostate cancer (pleiotropy)	1.000000e-10
GCST010989_290	Body size at age 10	1.000000e-09
GCST011639_10	Cirrhosis (alcohol related)	1.000000e-06
GCST011639_11	Cirrhosis (alcohol related)	3.000000e-09
GCST012020_58	Serum metabolite levels	2.000000e-11
GCST90000025_561	Appendicular lean mass	4.000000e-24
GCST90002385_507	High light scatter reticulocyte count	2.000000e-11

EFO canonical traits (15, from GWAS)

EFO ID	Trait name
EFO:0007804	LDL cholesterol change measurement
EFO:0008002	physical activity measurement
EFO:0004847	age at onset
EFO:0009188	Red cell distribution width
EFO:0005763	pulse pressure measurement
EFO:0004341	body fat distribution
EFO:0009963	bipolar I disorder
EFO:0009964	bipolar II disorder
EFO:0004346	neuroimaging measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004980	appendicular lean mass
EFO:0007986	reticulocyte count
EFO:0007985	platelet crit
EFO:0004309	platelet count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725025 (SINGLE PROTEIN)

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

ChEMBL bioactivities

4 potent at pChembl≥5 of 4 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.39	Kd	41.04	nM	CHEMBL5653589
7.39	ED50	41.04	nM	CHEMBL5653589
5.46	Kd	3459	nM	CHEMBL3752910
5.46	ED50	3459	nM	CHEMBL3752910

PubChem BioAssay actives

2 with measured affinity, of 10 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	2148419: Binding affinity to human GATAD2A incubated for 45 mins by Kinobead based pull down assay	kd	0.0410	uM
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148419: Binding affinity to human GATAD2A incubated for 45 mins by Kinobead based pull down assay	kd	3.4585	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression, affects cotreatment	3
Estradiol	affects expression, increases expression	3
bisphenol A	increases methylation, decreases expression, decreases methylation, affects cotreatment	2
Acetaminophen	decreases expression, increases expression	2
Benzo(a)pyrene	affects methylation, decreases expression	2
Aflatoxin B1	increases methylation	2
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
perfluorooctanoic acid	decreases expression	1
benzo(e)pyrene	increases methylation	1
cupric chloride	increases expression	1
coumarin	increases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
perfluoro-n-nonanoic acid	decreases expression	1
2-palmitoylglycerol	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	increases methylation	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Air Pollutants	affects expression, increases abundance	1
Vehicle Emissions	increases abundance, increases 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
CHEMBL5651461	Binding	Binding affinity to human GATAD2A 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice