TRIO

Summary

TRIO (trio Rho guanine nucleotide exchange factor, HGNC:12303) is a protein-coding gene on chromosome 5p15.2, encoding Triple functional domain protein (O75962). Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a large protein that functions as a GDP to GTP exchange factor. This protein promotes the reorganization of the actin cytoskeleton, thereby playing a role in cell migration and growth. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7204 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 13
• Clinical variants (ClinVar): 1,826 total — 77 pathogenic, 84 likely-pathogenic
• Phenotypes (HPO): 110
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_007118

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12303
Approved symbol	TRIO
Name	trio Rho guanine nucleotide exchange factor
Location	5p15.2
Locus type	gene with protein product
Status	Approved
Aliases	ARHGEF23
Ensembl gene	ENSG00000038382
Ensembl biotype	protein_coding
OMIM	601893
Entrez	7204

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 17 retained_intron, 6 protein_coding, 2 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay

ENST00000344135, ENST00000344204, ENST00000502490, ENST00000502816, ENST00000503399, ENST00000504606, ENST00000505971, ENST00000506611, ENST00000507714, ENST00000508283, ENST00000508343, ENST00000508717, ENST00000509354, ENST00000509967, ENST00000510281, ENST00000510757, ENST00000511019, ENST00000512070, ENST00000512303, ENST00000512979, ENST00000513206, ENST00000515144, ENST00000515710, ENST00000639876, ENST00000698541, ENST00000698542, ENST00000704488

RefSeq mRNA: 1 — MANE Select: NM_007118 NM_007118

CCDS: CCDS3883

Canonical transcript exons

ENST00000344204 — 57 exons

Exon	Start	End
ENSE00001133883	14290716	14291228
ENSE00001188272	14487464	14488260
ENSE00001856401	14507880	14510204
ENSE00003462730	14481234	14481284
ENSE00003469275	14397043	14397154
ENSE00003470931	14482582	14482773
ENSE00003480113	14374229	14374343
ENSE00003481508	14381130	14381252
ENSE00003491199	14330778	14330900
ENSE00003496763	14504393	14504593
ENSE00003498871	14270825	14270899
ENSE00003500387	14476894	14476963
ENSE00003502169	14280322	14280436
ENSE00003508109	14293012	14293134
ENSE00003510932	14390231	14390300
ENSE00003512817	14364650	14364816
ENSE00003518368	14378012	14378127
ENSE00003524609	14369374	14369523
ENSE00003531013	14316513	14316743
ENSE00003535076	14389289	14389398
ENSE00003539940	14479261	14479350
ENSE00003540874	14471318	14471466
ENSE00003542515	14336536	14336727
ENSE00003547020	14387438	14387632
ENSE00003547053	14390901	14390990
ENSE00003552147	14368708	14368899
ENSE00003552478	14398880	14399070
ENSE00003557289	14498519	14498640
ENSE00003560098	14507122	14507260
ENSE00003578982	14363732	14363927
ENSE00003581235	14387732	14387847
ENSE00003583652	14462755	14462925
ENSE00003606396	14465545	14465640
ENSE00003607061	14359357	14359531
ENSE00003615347	14492567	14492814
ENSE00003616056	14473994	14474097
ENSE00003628913	14502579	14502657
ENSE00003631714	14485069	14485246
ENSE00003632566	14297072	14297263
ENSE00003638477	14419778	14420021
ENSE00003638646	14358178	14358347
ENSE00003642276	14498089	14498251
ENSE00003648815	14394038	14394130
ENSE00003653976	14479919	14480011
ENSE00003654359	14405848	14405990
ENSE00003670457	14406573	14406672
ENSE00003679470	14400963	14401064
ENSE00003680696	14304461	14304592
ENSE00003680783	14366860	14366979
ENSE00003683473	14461019	14461311
ENSE00003684370	14481541	14481618
ENSE00003687430	14388613	14388679
ENSE00003687532	14472592	14472658
ENSE00003688338	14286871	14287063
ENSE00003689677	14497847	14497874
ENSE00003691144	14496879	14497017
ENSE00003973958	14143342	14143882

Expression profiles

Bgee: expression breadth ubiquitous, 279 present calls, max score 98.52.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 36.2926 / max 1065.9772, expressed in 1738 samples.

FANTOM5 promoters (23 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55747	17.7379	1690
55745	8.5857	1652
55807	2.5500	609
55808	1.4160	383
55806	0.8769	392
55803	0.7061	249
55746	0.6734	412
55753	0.6717	399
55805	0.5787	266
55751	0.5201	295

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	98.52	gold quality
cortical plate	UBERON:0005343	98.51	gold quality
stromal cell of endometrium	CL:0002255	97.84	gold quality
mucosa of stomach	UBERON:0001199	97.46	gold quality
ganglionic eminence	UBERON:0004023	97.26	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.14	gold quality
cerebellar hemisphere	UBERON:0002245	96.99	gold quality
tibial nerve	UBERON:0001323	96.96	gold quality
right ovary	UBERON:0002118	96.94	gold quality
cerebellar cortex	UBERON:0002129	96.87	gold quality
left ovary	UBERON:0002119	96.59	gold quality
calcaneal tendon	UBERON:0003701	96.16	gold quality
cerebellum	UBERON:0002037	96.09	gold quality
colonic epithelium	UBERON:0000397	95.96	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.96	gold quality
adrenal tissue	UBERON:0018303	95.85	gold quality
right frontal lobe	UBERON:0002810	95.77	gold quality
body of uterus	UBERON:0009853	95.77	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.76	gold quality
lower esophagus	UBERON:0013473	95.72	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.42	gold quality
ventricular zone	UBERON:0003053	95.29	gold quality
metanephros cortex	UBERON:0010533	95.12	gold quality
ascending aorta	UBERON:0001496	95.08	gold quality
thoracic aorta	UBERON:0001515	95.07	gold quality
transverse colon	UBERON:0001157	94.88	gold quality
descending thoracic aorta	UBERON:0002345	94.86	gold quality
ovary	UBERON:0000992	94.43	gold quality
aorta	UBERON:0000947	94.32	gold quality
left coronary artery	UBERON:0001626	94.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.88

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): PITX2

miRNA regulators (miRDB)

186 targeting TRIO, 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-5692A	100.00	74.40	6850
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-32-5P	99.98	75.21	1964
HSA-MIR-363-3P	99.98	74.72	1821
HSA-MIR-367-3P	99.98	74.83	1819

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 39)

• present the x-ray structure refined to 1.7-A resolution and effect on signaling pathway by PI 3-kinase (PMID:15199069)
• TRIO amplification is associated with invasive tumor growth and rapid tumor cell proliferation in bladder neoplasms. (PMID:15215162)
• Expression of Tgat in NIH3T3 resulted in the loss of contact inhibition, increase of saturation density, anchorage-independent growth, tumorigenicity in nude mice, and increased invasiveness. (PMID:15308664)
• We have identified neuronal specific isoforms of Trio which could be essential for Trio function in neuronal morphology. (PMID:16033331)
• TRIO represents a candidate target of 5p amplifications in soft tissue sarcomas and might play a crucial role during the progression of this disease. (PMID:16752383)
• Results support a general role for DH-associated PH domains of TRIO in engaging Rho GTPases directly for efficient guanine nucleotide exchange. (PMID:17391702)
• Galphaq directly activates p63RhoGEF and Trio via a conserved extension of the Dbl homology-associated pleckstrin homology domain (PMID:17606614)
• Data show that Trio, Ect2, and Vav3 are expressed at higher levels in glioblastoma versus low-grade glioma, and are involved in tumor cell migration and invasion. (PMID:19008376)
• GEF Trio is responsible for lamellipodia formation through its N-terminal DH-PH domain in a Rac1-dependent manner during fibronectin-mediated spreading and migration. (PMID:22238672)
• We conclude that Trio promotes leukocyte transendothelial migration by inducing endothelial docking structure formation in a filamin-dependent manner through the activation of Rac1 and RhoG. (PMID:22696684)
• Trio, is essential for activating Rho- and Rac-regulated signaling pathways acting on JNK and p38. (PMID:23177739)
• Describe here an invadopodia disassembly model, where a signalling axis involving TrioGEF, Rac1, Pak1, and phosphorylation of cortactin, causes invadopodia dissolution. (PMID:24859002)
• TRIO is an EB1 dependent MT plus end tracking protein, and forms a complex with NAV1 at growing MT ends, which regulates TRIO-mediated Rac1 activation and neurite outgrowth. (PMID:25065758)
• The +TIP Navigator 1 (NAV1) is important for neurite outgrowth and interacts and colocalizes with TRIO, a Rho guanine nucleotide exchange factor that enables neurite outgrowth by activating the Rho GTPases Rac1 and RhoG. (PMID:25065758)
• TRIO controls Rac1 activation in dividing cells which counteracts MgcRacGAP function in cytokinesis. (PMID:25355950)
• Aberrant expression of TRIO might play an important role in hepatocellular carcinoma (HCC) through promoting cell proliferation and invasion, and TRIO may be a novel therapeutic target for the treatment of HCC (PMID:25851347)
• our data show the importance of spatio-temporal regulation of the actin cytoskeleton through Trio and Rac1 at VE-cadherin-based cell-cell junctions in the maintenance of the endothelial barrier. (PMID:26116572)
• Strong statistical evidence for a causal role of TRIO in neurodevelopmental and neuropsychiatric disorders. (PMID:26235986)
• TRIO loss of function is associated with mild intellectual disability and affects dendritic branching and synapse function. (PMID:26721934)
• A recurrent rearrangement involving TRIO with various partners was identified in 5.1% of non-translocation-related sarcoma cases. TRIO translocations are either intrachromosomal with TERT or interchromosomal with LINC01504 or ZNF558. All translocations led to a truncated TRIO protein either directly or indirectly by alternative splicing. TRIO rearrangement is associated with a modified transcriptomic program. (PMID:27528700)
• The findings provide a mechanism for the presynaptic targeting of Trio and support a model in which Piccolo and Bassoon play a role in regulating neurotransmission through interactions with proteins, including Trio, that modulate the dynamic assembly of F-actin during cycles of synaptic vesicle exo- and endocytosis. (PMID:27907191)
• study found TRIO somatic frameshift mutations in gastric cancers (GCs) and colorectal cancers (CRCs) with MSI-H, but not in CRCs and GCs with MSS (p < 0.001); all of the mutations were deletion or duplication mutations in the repeats that would cause premature stops (PMID:28224356)
• Study identifies a large cluster of de novo mutations in the GEF1 domain of Trio in whole-exome sequencing data from individuals with autism spectrum disorder. (PMID:28928363)
• Genetic damage to both TGEF domains altered TRIO catalytic activity, decreasing TGEF1 activity and increasing TGEF2 activity. (PMID:28973398)
• Results revealed that TRIO high expression levels in cervical cancer were correlated with lymph node metastasis. Its inhibition significantly decreased the migration and invasion abilities of cervical cancer cells through the RhoA/ROCK signaling pathway. (PMID:29207149)
• Trio plays a role in activating Rac1 in podocytes both in basal conditions and when stimulated with TGFbeta1. We speculate that Trio may have dual roles; it may play important roles in podocyte development but it may also regulate pathological Rac1 hyperactivation in the context of TGFbeta1-mediated podocyte injury and glomerulosclerosis. (PMID:29415466)
• results highlight a role for the C-terminal 15 amino acids in the membrane association of TGAT and the subsequent activation of RhoA and actin polymerization by TGAT (PMID:29879899)
• Synaptic Kalirin-7 and Trio Interactomes Reveal a GEF Protein-Dependent Neuroligin-1 Mechanism of Action. (PMID:31801062)
• demonstrates distinct clinical and molecular disorders clustering in the GEFD1 and seventh spectrin repeat domains and highlights the importance of tight control of TRIO-RAC1 signaling in neuronal development (PMID:32109419)
• Genetics of physiological dysregulation: findings from the long life family study using joint models. (PMID:32235003)
• The Rho guanine nucleotide exchange factor Trio is required for neural crest cell migration and interacts with Dishevelled. (PMID:32366678)
• Novel loss-of-function variants in TRIO are associated with neurodevelopmental disorder: case report. (PMID:33167890)
• Complex interactions between the angiotensin II type 1 receptor, the epidermal growth factor receptor and TRIO-dependent signaling partners. (PMID:33741329)
• More evidence on TRIO missense mutations in the spectrin repeat domain causing severe developmental delay and recognizable facial dysmorphism with macrocephaly. (PMID:34013494)
• Rho-GEF Trio regulates osteosarcoma progression and osteogenic differentiation through Rac1 and RhoA. (PMID:34893584)
• Structural/functional studies of Trio provide insights into its configuration and show that conserved linker elements enhance its activity for Rac1. (PMID:35779635)
• Autoinhibition of the GEF activity of cytoskeletal regulatory protein Trio is disrupted in neurodevelopmental disorder-related genetic variants. (PMID:35963430)
• Pathogenic TRIO variants associated with neurodevelopmental disorders perturb the molecular regulation of TRIO and axon pathfinding in vivo. (PMID:36717740)
• Detection of autism spectrum disorder-related pathogenic trio variants by a novel structure-based approach. (PMID:38566250)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	trioa	ENSDARG00000019426
mus_musculus	Trio	ENSMUSG00000022263
rattus_norvegicus	Trio	ENSRNOG00000012148

Paralogs (22): MCF2L2 (ENSG00000053524), PLEKHG2 (ENSG00000090924), MCF2 (ENSG00000101977), ARHGEF7 (ENSG00000102606), PLEKHG1 (ENSG00000120278), MCF2L (ENSG00000126217), ARHGEF6 (ENSG00000129675), ARHGEF9 (ENSG00000131089), VAV3 (ENSG00000134215), VAV1 (ENSG00000141968), TIAM2 (ENSG00000146426), KIAA1755 (ENSG00000149633), PLEKHG4B (ENSG00000153404), TIAM1 (ENSG00000156299), KALRN (ENSG00000160145), VAV2 (ENSG00000160293), ARHGEF40 (ENSG00000165801), SPATA13 (ENSG00000182957), SESTD1 (ENSG00000187231), PLEKHN1 (ENSG00000187583), PLEKHG4 (ENSG00000196155), ARHGEF25 (ENSG00000240771)

Protein

Protein identifiers

Triple functional domain protein — O75962 (reviewed: O75962)

Alternative names: PTPRF-interacting protein

All UniProt accessions (8): A0A1W2PRD7, A0A8V8TLX5, A0A8V8TNC6, A0A994J7G8, O75962, E7EPJ7, E7EWP2, F5H228

UniProt curated annotations — full annotation on UniProt →

Function. Guanine nucleotide exchange factor (GEF) for RHOA and RAC1 GTPases. Involved in coordinating actin remodeling, which is necessary for cell migration and growth. Plays a key role in the regulation of neurite outgrowth and lamellipodia formation. In developing hippocampal neurons, limits dendrite formation, without affecting the establishment of axon polarity. Once dendrites are formed, involved in the control of synaptic function by regulating the endocytosis of AMPA-selective glutamate receptors (AMPARs) at CA1 excitatory synapses. May act as a regulator of adipogenesis.

Subunit / interactions. Interacts with CARMIL1. Interacts with PTPRF/LAR. Interacts with ANKRD26. Interacts with Bassoon/BSN and Piccolo/PCLO. Interacts with the cytoplasmic region of the heterodimer formed by NGFR and SORCS2. ProNGF binding mediates dissociation of TRIO from the receptor complex.

Subcellular location. Cytoplasm. Cell projection.

Tissue specificity. Widely expressed, with highest levels in heart, skeletal muscle, and brain.

Post-translational modifications. Phosphorylated on serine residue(s).

Disease relevance. Intellectual developmental disorder, autosomal dominant 44, with microcephaly (MRD44) [MIM:617061] A disorder characterized by developmental delay, variable intellectual disability, distinctive facial features, and abnormalities of the fingers. Most patients also have microcephaly. The disease may be caused by variants affecting the gene represented in this entry. Intellectual developmental disorder, autosomal dominant 63, with macrocephaly (MRD63) [MIM:618825] An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD63 is characterized by moderate to severe impaired intellectual development with poor or absent speech, global developmental delay, and variable behavioral abnormalities. Variable dysmorphic features are preset in half of the patients. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The N-terminal DBL/GEF domain specifically catalyzes nucleotide exchange for RAC1, leading to the activation of Jun kinase and the production of membrane ruffles. The second DBL/GEF domain is an exchange factor for rhoa and induces the formation of stress fibers.

Similarity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family.

Isoforms (5)

UniProt ID	Names	Canonical?
O75962-1	1	yes
O75962-2	2
O75962-3	3
O75962-4	4
O75962-5	5

RefSeq proteins (1): NP_009049* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000219	DH_dom	Domain
IPR000719	Prot_kinase_dom	Domain
IPR001251	CRAL-TRIO_dom	Domain
IPR001452	SH3_domain	Domain
IPR001849	PH_domain	Domain
IPR002017	Spectrin_repeat	Repeat
IPR003598	Ig_sub2	Domain
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR011993	PH-like_dom_sf	Homologous_superfamily
IPR013098	Ig_I-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR018159	Spectrin/alpha-actinin	Repeat
IPR028570	Kalirin_TRIO_SH3_1	Domain
IPR035899	DBL_dom_sf	Homologous_superfamily
IPR036028	SH3-like_dom_sf	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR036865	CRAL-TRIO_dom_sf	Homologous_superfamily
IPR047053	Kalirin_TRIO_SH3_2	Domain
IPR047054	Kalirin_TRIO_PH_1	Domain
IPR051336	RhoGEF_Guanine_NuclExch_SF	Family
IPR055251	SOS1_NGEF_PH	Domain
IPR058918	KALRN/TRIO-like_spectrin	Domain

Pfam: PF00018, PF00069, PF00435, PF00621, PF07679, PF13716, PF16609, PF22697, PF23323, PF23587

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (149 total): helix 31, sequence variant 28, strand 16, compositionally biased region 13, mutagenesis site 12, domain 9, turn 8, modified residue 8, splice variant 7, region of interest 5, repeat 4, sequence conflict 3, binding site 2, chain 1, active site 1, disulfide bond 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
1NTY	X-RAY DIFFRACTION	1.7
2NZ8	X-RAY DIFFRACTION	2
6D8Z	X-RAY DIFFRACTION	2.65
7SJ4	ELECTRON MICROSCOPY	2.86

Predicted structure (AlphaFold)

No AlphaFold model available for O75962 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

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

Catalytic / active sites (1): 2915

Ligand- & substrate-binding residues (2): 2802–2810; 2825

Post-translational modifications (8): 1627, 1632, 1633, 1824, 2282, 2455, 2459, 2631

Disulfide bonds (1): 2696–2759

Mutagenesis-validated functional residues (12):

Position	Phenotype
1299	50% decrease in nucleotide exchange activity.
1303	40% decrease in nucleotide exchange activity.
1389	no change in nucleotide exchange activity.
1426	90% decrease in nucleotide exchange activity.
1427	80% decrease in nucleotide exchange activity.
1428	80% decrease in nucleotide exchange activity.
1430	80% decrease in nucleotide exchange activity.
1431	loss of nucleotide exchange activity.
1434	40% decrease in nucleotide exchange activity.
1437	no change in nucleotide exchange activity.
1438	30% decrease in nucleotide exchange activity.
2917	expected to disrupt kinase activity. causes reorganization of the actin cytoskeleton in the absence of ngf.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-193648	NRAGE signals death through JNK
R-HSA-416476	G alpha (q) signalling events
R-HSA-416482	G alpha (12/13) signalling events
R-HSA-418885	DCC mediated attractive signaling
R-HSA-8980692	RHOA GTPase cycle
R-HSA-9013148	CDC42 GTPase cycle
R-HSA-9013149	RAC1 GTPase cycle
R-HSA-9013404	RAC2 GTPase cycle
R-HSA-9013408	RHOG GTPase cycle
R-HSA-9013409	RHOJ GTPase cycle
R-HSA-9013423	RAC3 GTPase cycle

MSigDB gene sets: 0 (showing top):

GO Biological Process (7): cell surface receptor protein tyrosine phosphatase signaling pathway (GO:0007185), axon guidance (GO:0007411), negative regulation of fat cell differentiation (GO:0045599), neuron projection morphogenesis (GO:0048812), regulation of small GTPase mediated signal transduction (GO:0051056), postsynaptic modulation of chemical synaptic transmission (GO:0099170), protein phosphorylation (GO:0006468)

GO Molecular Function (9): protein serine/threonine kinase activity (GO:0004674), guanyl-nucleotide exchange factor activity (GO:0005085), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (7): cytoplasm (GO:0005737), cytosol (GO:0005829), extrinsic component of membrane (GO:0019898), cell projection (GO:0042995), presynaptic active zone (GO:0048786), postsynapse (GO:0098794), glutamatergic synapse (GO:0098978)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
RHO GTPase cycle	7
GPCR downstream signalling	2
Cell death signalling via NRAGE, NRIF and NADE	1
Netrin-1 signaling	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	6
protein kinase activity	2
synapse	2
enzyme-linked receptor protein signaling pathway	1
axonogenesis	1
neuron projection guidance	1
fat cell differentiation	1
negative regulation of cell differentiation	1
regulation of fat cell differentiation	1
neuron projection development	1
plasma membrane bounded cell projection morphogenesis	1
small GTPase-mediated signal transduction	1
regulation of intracellular signal transduction	1
modulation of chemical synaptic transmission	1
postsynapse	1
phosphorylation	1
protein modification process	1
GTP binding	1
GDP binding	1
GTPase regulator activity	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
intracellular anatomical structure	1
cytoplasm	1
membrane	1
presynapse	1

Protein interactions and networks

STRING

2685 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TRIO	CDC42	P21181	572
TRIO	GGCT	O75223	514
TRIO	RABIF	P47224	494
TRIO	PPFIBP2	Q8ND30	480
TRIO	RHOG	P35238	447
TRIO	RHOA	P06749	438
TRIO	PTPRF	P10586	428
TRIO	ITGA10	O75578	414
TRIO	RAC1	P15154	410
TRIO	OPHN1	O60890	385
TRIO	GGTLC3	B5MD39	375
TRIO	ARHGEF1	Q92888	371
TRIO	TMEM9B	Q9NQ34	369
TRIO	EFNB3	Q15768	361
TRIO	GALP	Q9UBC7	355

IntAct

72 interactions, top by confidence:

A	B	Type	Score
LMO1	ZBTB43	psi-mi:“MI:0914”(association)	0.830
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
LMO3	ZBTB43	psi-mi:“MI:0914”(association)	0.550
ZNF785	TRIO	psi-mi:“MI:0914”(association)	0.530
TRIO		psi-mi:“MI:0915”(physical association)	0.490
	TRIO	psi-mi:“MI:0915”(physical association)	0.490
Nlgn1	TRIO	psi-mi:“MI:0915”(physical association)	0.400
TRIO	PALS2	psi-mi:“MI:0915”(physical association)	0.400
Stmn1	FXR1	psi-mi:“MI:0914”(association)	0.350
ZSCAN26	TDG	psi-mi:“MI:0914”(association)	0.350
MYC	TARS3	psi-mi:“MI:0914”(association)	0.350
Prdx1	TRIO	psi-mi:“MI:0914”(association)	0.350
		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
ZNF785	CASK	psi-mi:“MI:0914”(association)	0.350
ZNF232	ZNF197	psi-mi:“MI:0914”(association)	0.350
TRIO	Ppfibp1	psi-mi:“MI:0914”(association)	0.350
Dock10	TRIO	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
SYNGAP1	POM121C	psi-mi:“MI:0914”(association)	0.350
MAPRE1	SCAMP1	psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350

BioGRID (135): TRIO (Affinity Capture-MS), CFAP45 (Co-fractionation), PPM1F (Co-fractionation), RPE (Co-fractionation), SSU72 (Co-fractionation), TRIO (Co-fractionation), TRIO (Proximity Label-MS), TRIO (Affinity Capture-MS), TRIO (Affinity Capture-MS), TRIO (Affinity Capture-MS), TRIO (Affinity Capture-MS), TRIO (Two-hybrid), TRIO (Proximity Label-MS), TRIO (Proximity Label-MS), TRIO (Proximity Label-MS)

ESM2 similar proteins: A0A8M2BID5, A0A8M9PQ61, A1Z7A6, D3ZHV2, E9Q557, F1LMV6, F1M0Z1, G3V7L1, O43150, O60229, O60437, O75962, O97592, O97902, P0CE94, P0CE95, P10911, P11530, P11531, P11532, P11533, P15924, P30427, P33175, P46939, Q03001, Q0KL02, Q15149, Q1AAU6, Q1LUA6, Q5GN48, Q6ZWR6, Q7SIG6, Q8CIS0, Q8NF91, Q8WXH0, Q91ZU6, Q92817, Q95RG8, Q9BXL7

Diamond homologs: A1L390, F1M0Z1, O43307, O75962, P91620, P91621, Q0KL02, Q13009, Q1ZXH8, Q3UTH8, Q4VAC9, Q58DL7, Q58EX7, Q5DU57, Q5RDK0, Q60610, Q6KAU7, Q6P720, Q6ZPF3, Q7TNR9, Q96N96, Q9H7P9, Q9NR80, Q9QX73, Q9ULL1, A2ASS6, A2CG49, A4IFM7, A8C984, A8X6H4, E9PT87, O02827, O14936, O43293, O44997, O49717, O54784, O60229, O70589, O80673

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
TRIO	“up-regulates activity”	RAC1	“guanine nucleotide exchange factor”
CDK5	“up-regulates activity”	TRIO	phosphorylation
TRIO	“up-regulates quantity”	DCC	binding
PTK2	“up-regulates activity”	TRIO	phosphorylation
FYN	“up-regulates activity”	TRIO	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1826 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	77
Likely pathogenic	84
Uncertain significance	948
Likely benign	395
Benign	173

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1076946	NM_007118.4(TRIO):c.7762_7763del (p.Met2588fs)	Pathogenic
1202305	NM_007118.4(TRIO):c.2119C>T (p.Gln707Ter)	Pathogenic
1212084	NM_007118.4(TRIO):c.6556_6557del (p.Arg2186fs)	Pathogenic
1212128	NM_007118.4(TRIO):c.77C>A (p.Ser26Ter)	Pathogenic
1254169	NM_007118.4(TRIO):c.4112A>G (p.His1371Arg)	Pathogenic
1334359	NM_007118.4(TRIO):c.3415C>T (p.Gln1139Ter)	Pathogenic
1683784	NM_007118.4(TRIO):c.838C>T (p.Gln280Ter)	Pathogenic
1693017	NM_007118.4(TRIO):c.3223A>G (p.Thr1075Ala)	Pathogenic
1707513	NM_007118.4(TRIO):c.5491_5496+12del	Pathogenic
1804429	NM_007118.4(TRIO):c.163C>T (p.Arg55Ter)	Pathogenic
1804592	NM_007118.4(TRIO):c.4295A>G (p.Tyr1432Cys)	Pathogenic
2032667	NM_007118.4(TRIO):c.7418_7419insA (p.Phe2473fs)	Pathogenic
2098259	NM_007118.4(TRIO):c.3256A>G (p.Lys1086Glu)	Pathogenic
2497879	NM_007118.4(TRIO):c.2842C>T (p.Arg948Ter)	Pathogenic
2501980	NM_007118.4(TRIO):c.4504C>T (p.Arg1502Ter)	Pathogenic
253080	NM_007118.4(TRIO):c.4128G>A (p.Trp1376Ter)	Pathogenic
253081	NM_007118.4(TRIO):c.3752del (p.Asp1251fs)	Pathogenic
253082	NM_007118.4(TRIO):c.649A>T (p.Arg217Ter)	Pathogenic
253083	NM_007118.4(TRIO):c.4466del (p.Gln1489fs)	Pathogenic
253085	NM_007118.4(TRIO):c.4381C>A (p.Pro1461Thr)	Pathogenic
253086	NM_007118.4(TRIO):c.3239A>T (p.Asn1080Ile)	Pathogenic
2581763	NM_007118.4(TRIO):c.3826C>T (p.Arg1276Ter)	Pathogenic
3182879	NM_007118.4(TRIO):c.7353_7354insCCAAGCCCCGGGCC (p.Gly2452fs)	Pathogenic
3236236	NM_007118.4(TRIO):c.7048_7051del (p.Pro2350fs)	Pathogenic
3343386	NM_007118.4(TRIO):c.8364G>A (p.Trp2788Ter)	Pathogenic
3343394	NM_007118.4(TRIO):c.4614+1G>T	Pathogenic
3343416	NM_007118.4(TRIO):c.1362del (p.Glu455fs)	Pathogenic
3343875	NM_007118.4(TRIO):c.6400del (p.Val2134fs)	Pathogenic
3366985	NM_007118.4(TRIO):c.4231C>T (p.Arg1411Ter)	Pathogenic
3377102	NM_007118.4(TRIO):c.2046+1G>A	Pathogenic

SpliceAI

10878 predictions. Top by Δscore:

Variant	Effect	Δscore
5:14270815:T:TA	acceptor_gain	1.0000
5:14270819:TTTCA:T	acceptor_loss	1.0000
5:14270820:TTCA:T	acceptor_loss	1.0000
5:14270821:TCA:T	acceptor_loss	1.0000
5:14270822:CAG:C	acceptor_loss	1.0000
5:14270823:A:AG	acceptor_gain	1.0000
5:14270823:A:C	acceptor_loss	1.0000
5:14270823:AG:A	acceptor_gain	1.0000
5:14270824:G:GA	acceptor_loss	1.0000
5:14270824:G:GG	acceptor_gain	1.0000
5:14270824:GG:G	acceptor_gain	1.0000
5:14270824:GGGT:G	acceptor_gain	1.0000
5:14270895:TTCAG:T	donor_loss	1.0000
5:14270896:TCAGG:T	donor_loss	1.0000
5:14270897:CAGG:C	donor_loss	1.0000
5:14270898:AGGT:A	donor_loss	1.0000
5:14270899:GGTAA:G	donor_loss	1.0000
5:14270901:T:A	donor_loss	1.0000
5:14280316:TTTTA:T	acceptor_loss	1.0000
5:14280317:TTTAG:T	acceptor_loss	1.0000
5:14280318:TTAG:T	acceptor_loss	1.0000
5:14280319:TAGGT:T	acceptor_loss	1.0000
5:14280321:GGT:G	acceptor_gain	1.0000
5:14280435:AG:A	donor_gain	1.0000
5:14280435:AGGTA:A	donor_loss	1.0000
5:14280436:GG:G	donor_gain	1.0000
5:14280436:GGT:G	donor_loss	1.0000
5:14280437:G:GG	donor_gain	1.0000
5:14280438:T:A	donor_loss	1.0000
5:14286866:TGCA:T	acceptor_loss	1.0000

AlphaMissense

20540 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:14270888:C:A	A74E	1.000
5:14280352:T:C	L88S	1.000
5:14280409:T:C	L107P	1.000
5:14280421:T:C	L111P	1.000
5:14286908:G:C	D129H	1.000
5:14286915:G:C	R131P	1.000
5:14286926:T:A	W135R	1.000
5:14286926:T:C	W135R	1.000
5:14286928:G:C	W135C	1.000
5:14286928:G:T	W135C	1.000
5:14286938:A:G	K139E	1.000
5:14286940:G:C	K139N	1.000
5:14286940:G:T	K139N	1.000
5:14286948:T:C	L142P	1.000
5:14286957:T:C	L145P	1.000
5:14286990:C:A	A156D	1.000
5:14286993:T:C	L157P	1.000
5:14286996:T:A	I158N	1.000
5:14286996:T:G	I158S	1.000
5:14286999:T:A	I159N	1.000
5:14287001:A:G	K160E	1.000
5:14287003:G:C	K160N	1.000
5:14287003:G:T	K160N	1.000
5:14287013:T:C	F164L	1.000
5:14287014:T:C	F164S	1.000
5:14287014:T:G	F164C	1.000
5:14287015:C:A	F164L	1.000
5:14287015:C:G	F164L	1.000
5:14287016:T:A	W165R	1.000
5:14287016:T:C	W165R	1.000

dbSNP variants (sampled 300 via entrez): RS1000001991 (5:14234320 C>T), RS1000004838 (5:14392700 G>T), RS1000011968 (5:14465158 A>G), RS1000022867 (5:14187321 G>A), RS1000037813 (5:14503639 C>T), RS1000044488 (5:14149411 CACTT>C), RS1000046378 (5:14272701 G>A,T), RS1000046588 (5:14395054 T>A), RS1000057467 (5:14267238 C>T), RS1000075504 (5:14161543 C>A,T), RS1000089029 (5:14495495 G>A,T), RS1000089591 (5:14186309 A>G), RS1000099444 (5:14366107 C>T), RS1000111592 (5:14200342 C>G), RS1000115060 (5:14349747 CAG>C)

Disease associations

OMIM: gene MIM:601893 | disease phenotypes: MIM:617061, MIM:618825, MIM:610805, MIM:609823, MIM:616579

GenCC curated gene-disease

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	Autosomal dominant
micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome	Strong	Autosomal dominant
intellectual developmental disorder, autosomal dominant 63, with macrocephaly	Strong	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (11): micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome (MONDO:0014892), intellectual developmental disorder, autosomal dominant 63, with macrocephaly (MONDO:0032939), hereditary ataxia (MONDO:0100309), congenital anomaly of kidney and urinary tract (MONDO:0019719), neurodevelopmental disorder (MONDO:0700092), intellectual disability (MONDO:0001071), autism spectrum disorder (MONDO:0005258), autosomal recessive nonsyndromic hearing loss 28 (MONDO:0012355), syndromic intellectual disability (MONDO:0000508), intellectual disability, autosomal dominant 40 (MONDO:0014699), microcephaly (MONDO:0001149)

Orphanet (8): Micrognathia-recurrent infections-behavioral abnormalities-mild intellectual disability syndrome (Orphanet:476126), Hereditary ataxia (Orphanet:183518), Renal or urinary tract malformation (Orphanet:93545), Rare autosomal recessive non-syndromic sensorineural deafness type DFNB (Orphanet:90636), Rare genetic syndromic intellectual disability (Orphanet:183763), CHAMP1-related intellectual disability-facial dysmorphism-behavioral abnormalities syndrome (Orphanet:692193), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

110 total (30 of 110 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000020	Urinary incontinence
HP:0000154	Wide mouth
HP:0000164	Abnormality of the dentition
HP:0000218	High palate
HP:0000219	Thin upper lip vermilion
HP:0000252	Microcephaly
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000331	Short chin
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000396	Overfolded helix
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000426	Prominent nasal bridge
HP:0000430	Underdeveloped nasal alae
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000574	Thick eyebrow
HP:0000582	Upslanted palpebral fissure

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST002074_5	Paclitaxel-induced neuropathy	4.000000e-06
GCST002179_3	Adverse response to chemotherapy in breast cancer (alopecia) (paclitaxel)	6.000000e-07
GCST002709_20	Electroencephalogram traits	6.000000e-06
GCST005547_6	Major depressive disorder	3.000000e-07
GCST007202_13	High density lipoprotein cholesterol levels	3.000000e-07
GCST007356_4	Antidepressant treatment resistance (number of drugs prescribed)	5.000000e-07
GCST007995_21	Asthma (childhood onset)	9.000000e-16
GCST008151_56	Waist circumference	8.000000e-06
GCST008160_15	Waist circumference	8.000000e-06
GCST008759_48	Intake of total sugars	4.000000e-06
GCST009798_56	Asthma	5.000000e-13
GCST010279_1	Physiological dysregulation (Mahalanobis distance)	7.000000e-09
GCST012071_10	Response to selenium supplementation (change in plasma selenium concentration)	9.000000e-06

EFO canonical traits (10, from GWAS)

EFO ID	Trait name
EFO:0004357	electroencephalogram measurement
EFO:0006873	theta wave measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0010158	sugar consumption measurement
EFO:0003892	pulmonary function measurement
EFO:0004312	vital capacity
EFO:0004503	hematological measurement
EFO:0004732	lipoprotein measurement
EFO:0006941	grip strength measurement
EFO:0600021	response to dietary selenium supplementation

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D008831	Microcephaly	C05.660.207.620; C10.500.507.400.500; C16.131.621.207.620; C16.131.666.507.400.500
D065886	Neurodevelopmental Disorders	F03.625
C566906	Cakut (supp.)
C565218	Deafness, Autosomal Recessive 28 (supp.)
C531684	Hereditary spinal ataxia (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523153 (SINGLE PROTEIN)

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Trio family

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression, increases methylation	6
Estradiol	affects expression, affects cotreatment, increases expression, decreases expression	5
methylmercuric chloride	increases expression	3
Cadmium Chloride	increases expression	3
bisphenol A	increases methylation, affects cotreatment, decreases expression	2
trichostatin A	increases expression	2
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, affects methylation	2
Ozone	affects cotreatment, increases expression, increases oxidation, increases abundance	2
Parathion	affects cotreatment, decreases reaction, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Tobacco Smoke Pollution	decreases methylation, increases expression	2
Tretinoin	decreases expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
arsenite	decreases reaction, affects binding	1
sodium arsenite	increases expression	1
nickel chloride	increases expression	1
ethylene dichloride	increases expression	1
benzo(e)pyrene	affects methylation	1
aflatoxin B2	affects methylation	1
coumarin	increases phosphorylation	1
beta-methylcholine	affects expression	1
tamibarotene	affects expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4419749	Binding	Binding affinity to GST-tagged human TrioN RhoGEF (1284 to 1711 residues) by microscale thermophoresis analysis	Small-molecule inhibitors targeting g-protein-coupled rho guanine nucleotide exchange factors

Cellosaurus cell lines

4 cell lines: 2 cancer cell line, 1 finite cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2TV	GM27899	Finite cell line	Male
CVCL_B3K3	Abcam HEK293T TRIO KO	Transformed cell line	Female
CVCL_KU14	HeLa SilenciX TRIO	Cancer cell line	Female
CVCL_TU63	HAP1 TRIO (-)	Cancer cell line	Male

Clinical trials (associated diseases)

299 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
NCT00202397	PHASE2	COMPLETED	Effect of Riluzole as a Symptomatic Approach in Patients With Chronic Cerebellar Ataxia
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
NCT04115345	PHASE1	COMPLETED	A Study of a Renal Autologous Cell Therapy (REACT) in Patients With Chronic Kidney Disease (CKD) From Congenital Anomalies of the Kidney and Urinary Tract (CAKUT).
NCT05694169	PHASE1	TERMINATED	A Study of Participants With Chronic Kidney Disease Previously Treated With REACT
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)
NCT01360164	PHASE1/PHASE2	UNKNOWN	Safety and Efficacy of Umbilical Cord Mesenchymal Stem Cell Therapy for Patients With Hereditary Ataxia
NCT00004306	Not specified	COMPLETED	Clinical and Molecular Correlations in Spinocerebellar Ataxia Type 10 (SCA10)
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT04750850	Not specified	COMPLETED	Core Stability Exercises and Hereditary Ataxia
NCT05160870	Not specified	UNKNOWN	Genotype-phenotype Correlation and Pathogenic Mechanism in Hereditary Ataxia
NCT05160883	Not specified	UNKNOWN	Neuroimaging Changes in Hereditary Ataxia
NCT06034886	Not specified	AVAILABLE	Expanded Access Protocol of Troriluzole in Patients With Spinocerebellar Ataxia (SCA)
NCT06152133	Not specified	COMPLETED	Telerehabilitation, Core Stability Exercises and Hereditary Ataxia (TRCore-ataxia)
NCT06267222	Not specified	ENROLLING_BY_INVITATION	Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
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