PPP2R1A

Summary

PPP2R1A (protein phosphatase 2 scaffold subunit Aalpha, HGNC:9302) is a protein-coding gene on chromosome 19q13.41, encoding Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform (P30153). The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. It is a selective cancer dependency (DepMap: 85.1% of cell lines).

This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A. Alternatively spliced transcript variants have been described.

Source: NCBI Gene 5518 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Definitive, ClinGen) — +1 more curated relationship
• Clinical variants (ClinVar): 603 total — 5 pathogenic, 7 likely-pathogenic
• Phenotypes (HPO): 50
• Druggable target: yes
• Cancer driver (intOGen): activating (oncogene-like) across 8 cancer types
• Cancer dependency (DepMap): dependent in 85.1% of screened cell lines
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_014225

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9302
Approved symbol	PPP2R1A
Name	protein phosphatase 2 scaffold subunit Aalpha
Location	19q13.41
Locus type	gene with protein product
Status	Approved
Aliases	PR65A, PP2A-Aalpha, PP2AA
Ensembl gene	ENSG00000105568
Ensembl biotype	protein_coding
OMIM	605983
Entrez	5518

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 22 protein_coding, 5 retained_intron, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000322088, ENST00000391791, ENST00000454220, ENST00000462047, ENST00000462990, ENST00000468280, ENST00000473455, ENST00000473820, ENST00000477989, ENST00000490868, ENST00000495876, ENST00000703395, ENST00000703396, ENST00000703397, ENST00000703398, ENST00000703399, ENST00000703400, ENST00000703401, ENST00000703402, ENST00000703421, ENST00000703422, ENST00000703423, ENST00000861169, ENST00000861170, ENST00000861171, ENST00000925659, ENST00000925660, ENST00000925661, ENST00000925662, ENST00000960953, ENST00000960954, ENST00000960955, ENST00000960956, ENST00000960957

RefSeq mRNA: 2 — MANE Select: NM_014225 NM_001363656, NM_014225

CCDS: CCDS12849, CCDS86798

Canonical transcript exons

ENST00000322088 — 15 exons

Exon	Start	End
ENSE00003007954	52220979	52221133
ENSE00003013963	52222099	52222241
ENSE00003051100	52219691	52219864
ENSE00003122425	52225717	52225808
ENSE00003152777	52220189	52220249
ENSE00003511789	52216529	52216663
ENSE00003529716	52216004	52216074
ENSE00003532732	52215779	52215893
ENSE00003539861	52212955	52213110
ENSE00003988881	52225965	52229518
ENSE00003988895	52211260	52211492
ENSE00003988899	52205963	52206063
ENSE00003988938	52201944	52202034
ENSE00003988942	52212686	52212833
ENSE00003988943	52190052	52190174

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 99.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 171.3647 / max 667.8498, expressed in 1828 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
177287	170.3273	1828
177292	0.6755	412
177290	0.3494	150
177288	0.0125	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	99.51	gold quality
adrenal tissue	UBERON:0018303	99.36	gold quality
apex of heart	UBERON:0002098	99.33	gold quality
ganglionic eminence	UBERON:0004023	99.30	gold quality
right frontal lobe	UBERON:0002810	99.22	gold quality
right hemisphere of cerebellum	UBERON:0014890	99.22	gold quality
cerebellar hemisphere	UBERON:0002245	99.19	gold quality
cerebellar cortex	UBERON:0002129	99.18	gold quality
ventricular zone	UBERON:0003053	99.12	gold quality
right adrenal gland cortex	UBERON:0035827	99.12	gold quality
prefrontal cortex	UBERON:0000451	99.11	gold quality
right adrenal gland	UBERON:0001233	99.08	gold quality
lower esophagus mucosa	UBERON:0035834	99.05	gold quality
cingulate cortex	UBERON:0003027	99.03	gold quality
right atrium auricular region	UBERON:0006631	99.02	gold quality
anterior cingulate cortex	UBERON:0009835	99.01	gold quality
left adrenal gland cortex	UBERON:0035825	99.01	gold quality
left adrenal gland	UBERON:0001234	99.00	gold quality
right uterine tube	UBERON:0001302	99.00	gold quality
nucleus accumbens	UBERON:0001882	98.99	gold quality
caudate nucleus	UBERON:0001873	98.91	gold quality
adrenal gland	UBERON:0002369	98.88	gold quality
amygdala	UBERON:0001876	98.84	gold quality
left ovary	UBERON:0002119	98.84	gold quality
metanephros cortex	UBERON:0010533	98.82	gold quality
cardiac atrium	UBERON:0002081	98.81	gold quality
cerebellum	UBERON:0002037	98.80	gold quality
heart left ventricle	UBERON:0002084	98.80	gold quality
stromal cell of endometrium	CL:0002255	98.73	gold quality
adrenal cortex	UBERON:0001235	98.73	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-10	yes	36.31
E-MTAB-7303	no	1783.54
E-MTAB-2983	no	1613.47
E-MTAB-7052	no	284.33
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): NFKB, SP1, SP3, TFAP2A, YY1

miRNA regulators (miRDB)

68 targeting PPP2R1A, 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-8485	100.00	77.57	4731
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-3689D	100.00	66.14	1181
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-4731-5P	99.89	67.23	2537
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-548D-3P	99.87	70.67	4362
HSA-MIR-548BB-3P	99.86	70.58	4354
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-548AC	99.84	70.77	4351
HSA-MIR-548H-3P	99.84	70.80	4349
HSA-MIR-548Z	99.84	70.80	4349

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map DepMap (CRISPR cell-line fitness): dependent in 85.1% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• PP2A-A has a role in the failure of beta1 integrin dephosphorylation at threonines 788 and 789 in tumor cell lines (PMID:14532964)
• PP2A-mediated dephosphorylation of BCL-2 is required to protect BCL-2 from proteasome-dependent degradation, affecting resistance to ER stress (PMID:16717086)
• dysfunction of E-cadherin due to its endocytosis may occur in some proportion of human breast carcinomas in which the PP2A-A protein is lost or significantly reduced (PMID:16930554)
• Claspin may be one of the phosphoproteins through which PP2A(Aalpha/Cbeta) affects Chk1 phosphorylation when ATR is activated by human immunodeficiency virus-1 Vpr. (PMID:17210576)
• protein phosphatase 2a recruitment to I-kappaB kinase gamma/NF-kappaB essential modulator is regulated by heptad repeats, which are targeted by HTLV-I tax (PMID:17314097)
• The results of these experiments indicate that the HSF2 region comprising amino acids 343-363 is important for A subunit interaction. (PMID:17688198)
• PP2A-A alpha transcriptional regulation is mediated by multiple factors including AP-2alpha, CREB, ETS-1, and SP-1 (PMID:19750005)
• Data show that DSB promote PP2A to associate with Ku 70 and Ku 86. (PMID:19794960)
• Data show that upon hypoxia, the TGF-beta-induced phosphorylation of Smad3 was inhibited, although Smad2 remained phosphorylated, and Smad3 was dephosphorylated by PP2A. (PMID:19951945)
• Results demonstrate that PP2A-B55alpha and importin-beta1 cooperate in the regulation of postmitotic assembly mechanisms in human cells. (PMID:20711181)
• genes mutated in ovarian clear cell carcinoma(OCCC);data suggest PPP2R1A functions as an oncogene and ARID1A as tumor-suppressor gene; in 42 OCCCs, 7% had mutations in PPP2R1A and 57% in ARID1A; suggests aberrant chromatin remodeling contributes to OCCC (PMID:20826764)
• PP2A-mediated dephosphorylation of Carma1 is a critical step to limit T-cell activation and effector cytokine production. (PMID:21157432)
• identified somatic missense mutations in 40.8% of high-grade serous endometrial tumours and 5% of endometrial endometrioid carcinomas; mutations identified in ovarian tumours at lower frequencies;no mutations found in high- or low-grade serous carcinoma (PMID:21381030)
• PPP2R1A somatic mutations occur in certain types of uterine and ovarian neoplastic lesions, especially uterine serous carcinomas (PMID:21435433)
• the frequent mutation of PPP2R1A in the serous type of uterine cancer, a low frequency of mutation in endometrioid endometrial cancer and absence of mutation in uterine carcinosarcoma. (PMID:21882256)
• Our findings suggest that functional genetic variants in the proximal promoter of the PP2A-Aalpha gene and their haplotypes are critical in the regulation of transcriptional activation. (PMID:21889517)
• This study indicates that the PPP2R1A mutation occurs at a lower frequency compared to other gynecological malignancies, irrespective of the histological subtype (PMID:23267135)
• gene transcription of PPP2R1A regulated by the polymorphism and methylation in the promoter region (PMID:23555712)
• For PPP2R1A, a heterozygous, somatic mutation (c.771G>T, p.W257C) was identified in 1 out of 37 patients (2.7%) with primary ovarian endometrioid carcinoma. (PMID:23588898)
• Partial unfolding of PR65/A impacts catalysis by altering the proximity of bound catalytic subunit and substrate. (PMID:24120762)
• The two functional variants in PPP2R1A and PPP2R5E and their combinations are associated with lung cancer risk in the Chinese. (PMID:24204789)
• PR65A phosphorylation regulates PP2A complex signaling. (PMID:24465463)
• Our results suggest that IH-induced ROS generation increases PP2A activation and subsequently downregulates ERK1/2 activation, which results in inhibition of PC12 cell proliferation through G0/G1 phase arrest and NGF-induced neuronal differentiation. (PMID:24885237)
• Results demonstrated that the promotive effect of eEF-2K on glycolysis resulted from the kinase-mediated restriction of synthesis of the protein phosphatase 2A-A (PP2A-A). (PMID:27181208)
• Total PP2A activity and PPP2R1A-associated PP2Ac activity were significantly increased in cells overexpressing PPP2R1A-WT. In addition, overexpression of PPP2R1A-WT increased cell proliferation in vitro and tumor growth in vivo (PMID:27272709)
• PPP2R1A mutation is associated with endometrial carcinoma progression and abdominopelvic metastasis. (PMID:27348297)
• PPP2R1A mutations occur in a subset of gastrointestinal stromal tumors and are associated with a high malignant potential that leads to decreased disease-free survival and overall survival (PMID:27469332)
• PPP2R1A mutations affect PP2A function and oncogenic signaling, illuminating the genetic basis for serous EC development. (PMID:27485451)
• RAB9 competes with the catalytic subunit PPP2CA in binding to PPP2R1A. This competitive association has an important role in controlling the PP2A catalytic activity. (PMID:27611305)
• PP2A controls mitotic exit through EG5 dephosphorylation. (PMID:28487562)
• In addition, 6 other cancer-associated genes (BRAF, NRAS, HRAS, ERK1, ERK2 and PTEN) were also analyzed. In total, four somatic mutations were identified in three out of 101 ovarian endometriotic lesions (4%, 4/101), including a KRAS p.G12V, a PPP2R1A p.S256F and two ARID1A nonsense mutations (p.Q403* and p.G1926*); while no mutations were identified in the remaining 7 genes (BRAF, NRAS, HRAS, ERK1, ERK2, PTEN and PIK3CA) (PMID:29547736)
• Association of the rs10406151 C variant with AD risk appears to involve brain PPP2R1A gene expression alterations. (PMID:31349112)
• R183W mutant of PPP2R1A, the gene encoding the PP2A Aalpha scaffolding subunit, failed to suppress tumor growth in vivo through activation of the MAPK pathway in RAS-mutant transformed cells. Cells expressing R183W were less sensitive to MEK inhibitors. Results demonstrate that the R183W mutation in PPP2R1A potentiates oncogenic signaling and reduces drug sensitivity of RAS-mutant cells to MEK inhibitors. (PMID:31541192)
• Phosphoproteome and drug-response effects mediated by the three protein phosphatase 2A inhibitor proteins CIP2A, SET, and PME-1. (PMID:32071079)
• The broad phenotypic spectrum of PPP2R1A-related neurodevelopmental disorders correlates with the degree of biochemical dysfunction. (PMID:33106617)
• Targeting Ribonucleotide Reductase Induces Synthetic Lethality in PP2A-Deficient Uterine Serous Carcinoma. (PMID:34921012)
• Chk1 Inhibition Ameliorates Alzheimer’s Disease Pathogenesis and Cognitive Dysfunction Through CIP2A/PP2A Signaling. (PMID:35286657)
• PPP2R1A neurodevelopmental disorder is associated with congenital heart defects. (PMID:36209351)
• Novel Variants of PPP2R1A in Catalytic Subunit Binding Domain and Genotype-Phenotype Analysis in Neurodevelopmentally Delayed Patients. (PMID:37761890)
• The PPP2R1A cancer hotspot mutant p.R183W increases clofarabine resistance in uterine serous carcinoma cells by a gain-of-function mechanism. (PMID:38888850)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Ppp2r1a	ENSMUSG00000007564
rattus_norvegicus	Ppp2r1a	ENSRNOG00000011282
drosophila_melanogaster	Pp2A-29B	FBGN0260439

Paralogs (2): PPP2R1B (ENSG00000137713), PPP4R1 (ENSG00000154845)

Protein

Protein identifiers

Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform — P30153 (reviewed: P30153)

Alternative names: Medium tumor antigen-associated 61 kDa protein, PP2A subunit A isoform PR65-alpha, PP2A subunit A isoform R1-alpha

All UniProt accessions (10): P30153, A0A994J3H1, A0A994J3N8, A0A994J6A3, A8K7B7, B3KQV6, C9J9C1, E9PH38, M0QXG4, M0R0K6

UniProt curated annotations — full annotation on UniProt →

Function. The PR65 subunit of protein phosphatase 2A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. Upon interaction with GNA12 promotes dephosphorylation of microtubule associated protein TAU/MAPT. Required for proper chromosome segregation and for centromeric localization of SGO1 in mitosis. Together with RACK1 adapter, mediates dephosphorylation of AKT1 at ‘Ser-473’, preventing AKT1 activation and AKT-mTOR signaling pathway. Dephosphorylation of AKT1 is essential for regulatory T-cells (Treg) homeostasis and stability. Part of the striatin-interacting phosphatase and kinase (STRIPAK) complexes. STRIPAK complexes have critical roles in protein (de)phosphorylation and are regulators of multiple signaling pathways including Hippo, MAPK, nuclear receptor and cytoskeleton remodeling. Different types of STRIPAK complexes are involved in a variety of biological processes such as cell growth, differentiation, apoptosis, metabolism and immune regulation. Key mediator of a quality checkpoint during transcription elongation as part of the Integrator-PP2A (INTAC) complex. The INTAC complex drives premature transcription termination of transcripts that are unfavorably configured for transcriptional elongation: within the INTAC complex, acts as a scaffolding subunit for PPP2CA, which catalyzes dephosphorylation of the C-terminal domain (CTD) of Pol II subunit POLR2A/RPB1 and SUPT5H/SPT5, thereby preventing transcriptional elongation. Regulates the recruitment of the SKA complex to kinetochores.

Subunit / interactions. PP2A consists of a common heterodimeric core enzyme, composed of PPP2CA a 36 kDa catalytic subunit (subunit C) and PPP2R1A a 65 kDa constant regulatory subunit (PR65 or subunit A), that associates with a variety of regulatory subunits. Proteins that associate with the core dimer include three families of regulatory subunits B (the R2/B/PR55/B55, R3/B’’/PR72/PR130/PR59 and R5/B’/B56 families), the 48 kDa variable regulatory subunit, viral proteins, and cell signaling molecules. Found in a complex with at least ARL2, PPP2CB, PPP2R1A, PPP2R2A, PPP2R5E and TBCD. Interacts with the PP2A C catalytic subunit PPP2CA. Interacts with the PP2A B subunit PPP2R2A. Interacts with the PP2A B subunit PPP2R5D. Interacts with FOXO1; the interaction dephosphorylates FOXO1 on AKT-mediated phosphorylation sites. Interacts with IPO9. Interacts with TP53 and SGO1. Interacts with PLA2G16; this interaction might decrease PP2A activity. Interacts with CTTNBP2NL. Interacts with GNA12; the interaction promotes protein phosphatase 2A activation causing dephosphorylation of MAPT. Interacts with CIP2A; this interaction stabilizes CIP2A. Interacts with PABIR1/FAM122A. Interacts with ADCY8; antagonizes interaction between ADCY8 and calmodulin. Interacts with CRTC3 (when phosphorylated at ‘Ser-391’). Interacts with SPRY2. Part of the core of STRIPAK complexes composed of PP2A catalytic and scaffolding subunits, the striatins (PP2A regulatory subunits), the striatin-associated proteins MOB4, STRIP1 and STRIP2, PDCD10 and members of the STE20 kinases, such as STK24 and STK26. Component of the Integrator-PP2A (INTAC) complex, composed of the Integrator core complex and protein phosphatase 2A subunits PPP2CA and PPP2R1A. (Microbial infection) Interacts with JC virus small t antigen; this interaction inhibits PPP2R1A activity.

Subcellular location. Cytoplasm. Nucleus. Chromosome. Centromere. Lateral cell membrane. Cell projection. Dendrite.

Disease relevance. Houge-Janssens syndrome 2 (HJS2) [MIM:616362] An autosomal dominant disorder characterized by global developmental delay, hypotonia, variably impaired intellectual development, poor speech, and dysmorphic facial features. Some patients may develop seizures. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. Each HEAT repeat appears to consist of two alpha helices joined by a hydrophilic region, the intrarepeat loop. The repeat units may be arranged laterally to form a rod-like structure.

Similarity. Belongs to the phosphatase 2A regulatory subunit A family.

RefSeq proteins (2): NP_001350585, NP_055040* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000357	HEAT	Repeat
IPR011989	ARM-like	Homologous_superfamily
IPR016024	ARM-type_fold	Homologous_superfamily
IPR021133	HEAT_type_2	Repeat
IPR051023	PP2A_Regulatory_Subunit_A	Family
IPR054573	PP2A/SF3B1-like_HEAT	Domain
IPR055231	PIK3R4-like_middle	Domain

Pfam: PF02985, PF13646, PF22646, PF22956

UniProt features (102 total): helix 53, repeat 15, strand 9, sequence variant 8, turn 5, region of interest 4, sequence conflict 4, modified residue 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

41 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
1B3U	X-RAY DIFFRACTION	2.3
4I5L	X-RAY DIFFRACTION	2.43
8TWE	ELECTRON MICROSCOPY	2.55
2IE4	X-RAY DIFFRACTION	2.6
9C6B	ELECTRON MICROSCOPY	2.6
8TWI	ELECTRON MICROSCOPY	2.69
8U1X	ELECTRON MICROSCOPY	2.7
9C7T	ELECTRON MICROSCOPY	2.7
8TTB	ELECTRON MICROSCOPY	2.77
8SO0	ELECTRON MICROSCOPY	2.8
2IE3	X-RAY DIFFRACTION	2.8
3C5W	X-RAY DIFFRACTION	2.8
4I5N	X-RAY DIFFRACTION	2.8
4LAC	X-RAY DIFFRACTION	2.82
3DW8	X-RAY DIFFRACTION	2.85
3K7V	X-RAY DIFFRACTION	2.85
3K7W	X-RAY DIFFRACTION	2.96
8RC4	ELECTRON MICROSCOPY	3.1
8UWB	X-RAY DIFFRACTION	3.15
9MZW	ELECTRON MICROSCOPY	3.16
8UO5	ELECTRON MICROSCOPY	3.27
2NPP	X-RAY DIFFRACTION	3.3
2PKG	X-RAY DIFFRACTION	3.3
7K36	ELECTRON MICROSCOPY	3.3
8U89	ELECTRON MICROSCOPY	3.3
6IUR	X-RAY DIFFRACTION	3.33
7SOY	ELECTRON MICROSCOPY	3.4
9MIP	ELECTRON MICROSCOPY	3.4
7CUN	ELECTRON MICROSCOPY	3.5
9N0Z	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30153-F1	95.09	0.92

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 (2): 2, 280

Function

Pathways and Gene Ontology

Reactome pathways

145 pathways

ID	Pathway
R-HSA-113501	Inhibition of replication initiation of damaged DNA by RB1/E2F1
R-HSA-1295596	Spry regulation of FGF signaling
R-HSA-141444	Amplification of signal from unattached kinetochores via a MAD2 inhibitory signal
R-HSA-163767	PP2A-mediated dephosphorylation of key metabolic factors
R-HSA-180024	DARPP-32 events
R-HSA-195253	Degradation of beta-catenin by the destruction complex
R-HSA-196299	Beta-catenin phosphorylation cascade
R-HSA-198753	ERK/MAPK targets
R-HSA-202670	ERKs are inactivated
R-HSA-2465910	MASTL Facilitates Mitotic Progression
R-HSA-2467813	Separation of Sister Chromatids
R-HSA-2500257	Resolution of Sister Chromatid Cohesion
R-HSA-2565942	Regulation of PLK1 Activity at G2/M Transition
R-HSA-2995383	Initiation of Nuclear Envelope (NE) Reformation
R-HSA-380259	Loss of Nlp from mitotic centrosomes
R-HSA-380270	Recruitment of mitotic centrosome proteins and complexes
R-HSA-380284	Loss of proteins required for interphase microtubule organization from the centrosome
R-HSA-380320	Recruitment of NuMA to mitotic centrosomes
R-HSA-389356	Co-stimulation by CD28
R-HSA-389513	Co-inhibition by CTLA4
R-HSA-432142	Platelet sensitization by LDL
R-HSA-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-5339716	Signaling by GSK3beta mutants
R-HSA-5358747	CTNNB1 S33 mutants aren’t phosphorylated
R-HSA-5358749	CTNNB1 S37 mutants aren’t phosphorylated
R-HSA-5358751	CTNNB1 S45 mutants aren’t phosphorylated
R-HSA-5358752	CTNNB1 T41 mutants aren’t phosphorylated
R-HSA-5467337	APC truncation mutants have impaired AXIN binding
R-HSA-5467340	AXIN missense mutants destabilize the destruction complex
R-HSA-5467348	Truncations of AMER1 destabilize the destruction complex

MSigDB gene sets: 519 (showing top): MORF_MTA1, GOBP_MEIOTIC_CHROMOSOME_SEGREGATION, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_INHIBITION_OF_REPLICATION_INITIATION_OF_DAMAGED_DNA_BY_RB1_E2F1, REACTOME_INNATE_IMMUNE_SYSTEM, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, ENK_UV_RESPONSE_KERATINOCYTE_UP, DAZARD_UV_RESPONSE_CLUSTER_G4, REACTOME_SIGNALING_BY_FGFR, GOBP_T_CELL_HOMEOSTASIS, MORF_UBE2I, GOBP_LYMPHOCYTE_HOMEOSTASIS, GOBP_GROWTH

GO Biological Process (18): chromosome segregation (GO:0007059), female meiotic nuclear division (GO:0007143), negative regulation of hippo signaling (GO:0035331), intracellular signal transduction (GO:0035556), regulation of growth (GO:0040008), T cell homeostasis (GO:0043029), regulation of cell differentiation (GO:0045595), spindle assembly (GO:0051225), meiotic spindle elongation (GO:0051232), mitotic sister chromatid separation (GO:0051306), meiotic sister chromatid cohesion, centromeric (GO:0051754), negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction (GO:0051898), protein-containing complex assembly (GO:0065003), RNA polymerase II transcription initiation surveillance (GO:0160240), regulation of meiotic cell cycle process involved in oocyte maturation (GO:1903538), positive regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001241), transcription by RNA polymerase II (GO:0006366), transcription elongation by RNA polymerase II (GO:0006368)

GO Molecular Function (5): protein serine/threonine phosphatase activity (GO:0004722), protein phosphatase regulator activity (GO:0019888), protein heterodimerization activity (GO:0046982), protein antigen binding (GO:1990405), protein binding (GO:0005515)

GO Cellular Component (21): protein phosphatase type 2A complex (GO:0000159), chromosome, centromeric region (GO:0000775), chromatin (GO:0000785), nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), cytosol (GO:0005829), microtubule cytoskeleton (GO:0015630), membrane (GO:0016020), lateral plasma membrane (GO:0016328), dendrite (GO:0030425), neuron projection (GO:0043005), neuronal cell body (GO:0043025), extracellular exosome (GO:0070062), FAR/SIN/STRIPAK complex (GO:0090443), glutamatergic synapse (GO:0098978), INTAC complex (GO:0160232), chromosome (GO:0005694), plasma membrane (GO:0005886), cell projection (GO:0042995), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-21 pathways:

Category	Pathways
Mitotic Prometaphase	2
Centrosome maturation	2
Regulation of T cell activation by CD28 family	2
E2F mediated regulation of DNA replication	1
Negative regulation of FGFR1 signaling	1
Negative regulation of FGFR2 signaling	1
Negative regulation of FGFR3 signaling	1
Negative regulation of FGFR4 signaling	1
Amplification of signal from the kinetochores	1
Integration of energy metabolism	1
Opioid Signalling	1
Signaling by WNT	1
Degradation of beta-catenin by the destruction complex	1
Nuclear Events (kinase and transcription factor activation)	1
MAPK targets/ Nuclear events mediated by MAP kinases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
meiotic cell cycle	2
negative regulation of intracellular signal transduction	2
intracellular anatomical structure	2
phosphoprotein phosphatase activity	2
intracellular membrane-bounded organelle	2
cytoplasm	2
cell cycle process	1
female gamete generation	1
meiotic nuclear division	1
hippo signaling	1
regulation of hippo signaling	1
signal transduction	1
growth	1
regulation of biological process	1
lymphocyte homeostasis	1
cell differentiation	1
regulation of developmental process	1
regulation of cellular process	1
spindle organization	1
chromosome segregation	1
membraneless organelle assembly	1
meiotic spindle organization	1
meiotic chromosome segregation	1
spindle elongation	1
meiotic cell cycle process	1
mitotic sister chromatid segregation	1
chromosome separation	1
mitotic cell cycle process	1
meiotic sister chromatid cohesion	1
centromeric sister chromatid cohesion	1
phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction	1
cellular component assembly	1
protein-containing complex organization	1
transcription initiation at RNA polymerase II promoter	1
nuclear RNA surveillance	1
regulation of cell cycle process	1
meiotic cell cycle process involved in oocyte maturation	1
regulation of reproductive process	1

Protein interactions and networks

STRING

3046 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PPP2R1A	PPP2CA	P05323	999
PPP2R1A	PPP2CB	P11082	993
PPP2R1A	PPP2R2A	P50409	987
PPP2R1A	STRN	O43815	981
PPP2R1A	PPP2R5C	Q13362	955
PPP2R1A	MOB4	Q9Y3A3	949
PPP2R1A	STRIP1	Q5VSL9	939
PPP2R1A	ARID1A	O14497	911
PPP2R1A	PPP2R5A	Q15172	908
PPP2R1A	PTPA	Q15257	899
PPP2R1A	PPME1	Q9Y570	896
PPP2R1A	PPP2R2D	Q66LE6	880
PPP2R1A	STRIP2	Q9ULQ0	876
PPP2R1A	PPP2R3A	Q06190	875
PPP2R1A	PPP2R5D	Q14738	872

IntAct

570 interactions, top by confidence:

A	B	Type	Score
PPP2R1A	PPP2CA	psi-mi:“MI:0407”(direct interaction)	0.990
PPP2R1A	PPP2CA	psi-mi:“MI:0915”(physical association)	0.990
PPP2CA	PPP2R1A	psi-mi:“MI:0915”(physical association)	0.990
PPP2CA	PPP2R1A	psi-mi:“MI:0407”(direct interaction)	0.990
PPP2R1A	PPP2CA	psi-mi:“MI:0414”(enzymatic reaction)	0.990
PPP2R1A	PPP2CA	psi-mi:“MI:0914”(association)	0.990
PPP2R2A	PPP2R1A	psi-mi:“MI:2364”(proximity)	0.970
PPP2R1A	PPP2R2A	psi-mi:“MI:0915”(physical association)	0.970
PPP2R1A	PPP2R2A	psi-mi:“MI:0914”(association)	0.970
PPME1	PPP2R1A	psi-mi:“MI:0914”(association)	0.950
PPP2R1A	STRN	psi-mi:“MI:0914”(association)	0.880

BioGRID (1198): CSDC2 (Two-hybrid), PPP2R1A (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), PPP2R1A (Affinity Capture-MS), PPP2R1A (Affinity Capture-Western), PPP2R1A (Affinity Capture-Western), DAPK1 (Biochemical Activity), PPP2R1A (Affinity Capture-Western), PPP2R1A (Reconstituted Complex), PPP2R1A (Two-hybrid), PPP2R1A (Two-hybrid), PPP2R5D (Two-hybrid), PPP2R5E (Two-hybrid), RORC (Two-hybrid), PPP2R1A (Affinity Capture-MS)

ESM2 similar proteins: A2VE21, A7MBJ5, D4ABY2, O00410, O60100, O60518, O81742, P30153, P30154, P31383, P36179, P36875, P53620, P54612, P54613, P97536, Q04173, Q09543, Q0P5A6, Q16401, Q29AE5, Q32PI5, Q38845, Q38950, Q38951, Q4AEF8, Q4QQT4, Q54QR9, Q5IFJ8, Q5R6L5, Q66JI9, Q6DKD7, Q6ZQ38, Q76MZ3, Q7TNP2, Q86VP6, Q8BIV3, Q8BJY1, Q8BKC5, Q8H852

Diamond homologs: P30153, P30154, P31383, P36179, P54612, P54613, Q09543, Q32PI5, Q38845, Q38950, Q38951, Q4QQT4, Q54QR9, Q76MZ3, Q7TNP2, Q9UT08

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
PPP2R1A	down-regulates	MAPT	dephosphorylation
PPP2R1A	up-regulates	PPP2CA	binding
PPP2R1A	up-regulates	PPP2CB	binding
PPP2R1A	up-regulates	SGO1	binding
PPP2R1A	“form complex”	PP2CA_R1A_R2A	binding
PPP2R1A	“form complex”	PP2Ca_R1A_Bd	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 171 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
Signaling by GSK3beta mutants	7	50.8×	3e-09
CTNNB1 S33 mutants aren’t phosphorylated	7	50.8×	3e-09
CTNNB1 S37 mutants aren’t phosphorylated	7	50.8×	3e-09
CTNNB1 S45 mutants aren’t phosphorylated	7	50.8×	3e-09
CTNNB1 T41 mutants aren’t phosphorylated	7	50.8×	3e-09
Beta-catenin phosphorylation cascade	7	44.8×	7e-09
Platelet sensitization by LDL	6	38.4×	3e-07
ERK/MAPK targets	5	32.0×	7e-06

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 8 cancer types — ACYC, COADREAD, OVT, SCLC, UCEC, UCS, UM, WDTC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	7
Uncertain significance	191
Likely benign	302
Benign	29

Top pathogenic / likely-pathogenic (12)

Variant ID	HGVS	Classification
1204633	NM_014225.6(PPP2R1A):c.538A>G (p.Met180Val)	Pathogenic
1297557	NM_014225.6(PPP2R1A):c.658G>A (p.Val220Met)	Pathogenic
190313	NM_014225.6(PPP2R1A):c.536C>T (p.Pro179Leu)	Pathogenic
2504579	NM_014225.6(PPP2R1A):c.843dup (p.Asp282fs)	Pathogenic
4537882	NM_014225.6(PPP2R1A):c.533C>A (p.Thr178Asn)	Pathogenic
1064777	NM_014225.6(PPP2R1A):c.522C>G (p.Cys174Trp)	Likely pathogenic
1098340	NM_014225.6(PPP2R1A):c.539T>G (p.Met180Arg)	Likely pathogenic
2430276	NM_014225.6(PPP2R1A):c.532A>G (p.Thr178Ala)	Likely pathogenic
2498148	NM_014225.6(PPP2R1A):c.96C>G (p.Ile32Met)	Likely pathogenic
2504581	NM_014225.6(PPP2R1A):c.1493G>T (p.Arg498Leu)	Likely pathogenic
3236825	NM_014225.6(PPP2R1A):c.400C>T (p.Arg134Trp)	Likely pathogenic
985103	NM_014225.6(PPP2R1A):c.548G>C (p.Arg183Pro)	Likely pathogenic

SpliceAI

2053 predictions. Top by Δscore:

Variant	Effect	Δscore
19:52171332:TTA:T	donor_loss	1.0000
19:52171333:TA:T	donor_loss	1.0000
19:52171334:A:AC	donor_gain	1.0000
19:52171335:C:CT	donor_gain	1.0000
19:52171335:CTTG:C	donor_gain	1.0000
19:52190166:G:GT	donor_gain	1.0000
19:52190183:GC:G	donor_gain	1.0000
19:52201930:T:A	acceptor_gain	1.0000
19:52201939:A:AG	acceptor_gain	1.0000
19:52201940:T:G	acceptor_gain	1.0000
19:52201940:TTA:T	acceptor_loss	1.0000
19:52201941:TAG:T	acceptor_loss	1.0000
19:52201942:A:AG	acceptor_gain	1.0000
19:52201942:A:G	acceptor_loss	1.0000
19:52201943:G:GT	acceptor_gain	1.0000
19:52201943:GC:G	acceptor_gain	1.0000
19:52201943:GCT:G	acceptor_gain	1.0000
19:52201943:GCTT:G	acceptor_gain	1.0000
19:52201943:GCTTC:G	acceptor_gain	1.0000
19:52211258:A:AG	acceptor_gain	1.0000
19:52211259:G:GG	acceptor_gain	1.0000
19:52211259:GCC:G	acceptor_gain	1.0000
19:52211489:GACA:G	donor_gain	1.0000
19:52211490:ACA:A	donor_gain	1.0000
19:52211493:G:GG	donor_gain	1.0000
19:52212829:AGCAG:A	donor_gain	1.0000
19:52212830:GCAG:G	donor_gain	1.0000
19:52212830:GCAGG:G	donor_gain	1.0000
19:52212831:CAG:C	donor_gain	1.0000
19:52212831:CAGG:C	donor_loss	1.0000

AlphaMissense

3817 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:52190131:C:A	P12H	1.000
19:52190134:T:A	I13N	1.000
19:52190134:T:G	I13S	1.000
19:52190136:G:C	A14P	1.000
19:52190137:C:A	A14E	1.000
19:52190143:T:A	L16H	1.000
19:52190143:T:C	L16P	1.000
19:52190143:T:G	L16R	1.000
19:52190146:T:A	I17K	1.000
19:52190148:G:C	D18H	1.000
19:52190149:A:T	D18V	1.000
19:52190151:G:A	E19K	1.000
19:52190152:A:T	E19V	1.000
19:52190155:T:A	L20H	1.000
19:52190155:T:C	L20P	1.000
19:52190155:T:G	L20R	1.000
19:52190157:C:A	R21S	1.000
19:52190158:G:C	R21P	1.000
19:52190166:G:C	D24H	1.000
19:52201945:T:C	L27P	1.000
19:52201947:C:A	R28S	1.000
19:52201947:C:T	R28C	1.000
19:52201948:G:C	R28P	1.000
19:52201951:T:A	L29H	1.000
19:52201951:T:C	L29P	1.000
19:52201956:A:C	S31R	1.000
19:52201957:G:T	S31I	1.000
19:52201958:C:A	S31R	1.000
19:52201958:C:G	S31R	1.000
19:52201960:T:A	I32N	1.000

dbSNP variants (sampled 300 via entrez): RS1000055510 (19:52193018 C>A,G,T), RS1000144412 (19:52200295 G>A), RS1000261809 (19:52221419 T>G), RS1000325355 (19:52194877 A>G), RS1000337722 (19:52195348 A>G), RS1000370471 (19:52195052 G>A), RS1000387929 (19:52190031 G>A,C,T), RS1000440373 (19:52189741 C>T), RS1000496502 (19:52216548 A>G), RS1000672898 (19:52196522 T>C), RS1000714455 (19:52190042 C>CA,CG,CT), RS1000771315 (19:52190483 G>C), RS1000783313 (19:52228285 A>T), RS1000925695 (19:52205834 A>G), RS1000972114 (19:52216452 A>C)

Disease associations

OMIM: gene MIM:605983 | disease phenotypes: MIM:616362

GenCC curated gene-disease

Disease	Classification	Inheritance
Houge-Janssens syndrome 2	Definitive	Autosomal dominant
complex neurodevelopmental disorder	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
complex neurodevelopmental disorder	Definitive	AD

Mondo (5): Houge-Janssens syndrome 2 (MONDO:0014605), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), complex neurodevelopmental disorder (MONDO:0100038)

Orphanet (3): Microcephaly-corpus callosum hypoplasia-intellectual disability-facial dysmorphism syndrome (Orphanet:457284), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

50 total (30 of 50 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000122	Unilateral renal agenesis
HP:0000151	Aplasia of the uterus
HP:0000194	Open mouth
HP:0000238	Hydrocephalus
HP:0000252	Microcephaly
HP:0000297	Facial hypotonia
HP:0000316	Hypertelorism
HP:0000324	Facial asymmetry
HP:0000463	Anteverted nares
HP:0000478	Abnormality of the eye
HP:0000494	Downslanted palpebral fissures
HP:0000505	Visual impairment
HP:0000609	Optic nerve hypoplasia
HP:0000752	Hyperactivity
HP:0000767	Pectus excavatum
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001344	Absent speech
HP:0001357	Plagiocephaly
HP:0001382	Joint hypermobility
HP:0001385	Hip dysplasia
HP:0002066	Gait ataxia
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002188	Delayed CNS myelination

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724747 (SINGLE PROTEIN)

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

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.70	Kd	2003	nM	CHEMBL3752910
5.70	ED50	2003	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 10 total; 1 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-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149053: Binding affinity to human PPP2R1A incubated for 45 mins by Kinobead based pull down assay	kd	2.0028	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cyanoginosin LR	affects binding, decreases reaction, decreases expression, increases expression	3
sodium arsenite	affects reaction, decreases phosphorylation, increases expression	2
Arsenic	affects expression, decreases expression, increases abundance	2
Camptothecin	affects localization, decreases response to substance	2
Smoke	decreases expression, increases abundance, increases expression	2
Tobacco Smoke Pollution	affects reaction, increases expression, affects expression	2
Aflatoxin B1	increases methylation	2
Cadmium Chloride	decreases response to substance, decreases reaction, increases abundance, increases palmitoylation	2
FR900359	increases phosphorylation	1
bisphenol F	increases expression	1
bisphenol A	decreases expression	1
pyrogallol 1,3-dimethyl ether	affects localization, decreases expression, affects cotreatment	1
decabromobiphenyl ether	decreases expression	1
cobaltous chloride	decreases expression	1
2-bromopalmitate	increases palmitoylation, decreases reaction, increases abundance	1
sulindac sulfide	decreases expression	1
butylidenephthalide	increases expression	1
nickel sulfate	increases expression	1
cupric oxide	increases expression	1
arsenic trichloride	decreases expression, increases abundance	1
microcystin RR	increases expression	1
di-n-butylphosphoric acid	affects expression	1
aspartyl-glutamyl-valyl-aspartal	decreases activity, decreases degradation	1
fenpyroximate	decreases expression	1
nutlin 3	affects cotreatment, increases secretion	1
ICG 001	decreases expression	1
bisphenol B	increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
bisphenol S	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
CHEMBL5652095	Binding	Binding affinity to human PPP2R1A 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

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D716	ACI-158	Cancer cell line	Female
CVCL_D717	ACI-89	Cancer cell line	Female

Clinical trials (associated diseases)

301 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,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
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
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
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
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
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
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06310681	Not specified	COMPLETED	Pilot Testing of a Co-adapted Group Programme for Parents/Carers of Children With Complex Neurodisability
NCT07303049	Not specified	NOT_YET_RECRUITING	Cognitive Benefit of Intensive Rehabilitation Using Rhythmic Music Training in Children With Complex Neurodevelopmental Disorder
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