ME2

Summary

ME2 (malic enzyme 2, HGNC:6984) is a protein-coding gene on chromosome 18q21.2, encoding NAD-dependent malic enzyme, mitochondrial (P23368). NAD-dependent mitochondrial malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate.

This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene.

Source: NCBI Gene 4200 — RefSeq curated summary.

At a glance

• Gene–disease (curated): inborn disorder of energy metabolism (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 97 total — 1 likely-pathogenic
• Druggable target: yes
• MANE Select transcript: NM_002396

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6984
Approved symbol	ME2
Name	malic enzyme 2
Location	18q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000082212
Ensembl biotype	protein_coding
OMIM	154270
Entrez	4200

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 13 protein_coding, 8 nonsense_mediated_decay, 4 retained_intron

ENST00000321341, ENST00000382927, ENST00000585680, ENST00000589330, ENST00000591925, ENST00000638410, ENST00000638768, ENST00000638937, ENST00000639115, ENST00000639255, ENST00000639398, ENST00000639612, ENST00000639663, ENST00000639665, ENST00000639688, ENST00000639850, ENST00000640530, ENST00000640965, ENST00000640967, ENST00000901565, ENST00000901566, ENST00000901567, ENST00000935531, ENST00000935532, ENST00000953407

RefSeq mRNA: 2 — MANE Select: NM_002396 NM_001168335, NM_002396

CCDS: CCDS11948, CCDS54187

Canonical transcript exons

ENST00000321341 — 16 exons

Exon	Start	End
ENSE00000950181	50924098	50924212
ENSE00000950182	50925756	50925898
ENSE00000950184	50939570	50939640
ENSE00000996845	50908063	50908196
ENSE00000996846	50912801	50912950
ENSE00001151634	50921074	50921187
ENSE00001151639	50920661	50920758
ENSE00001151654	50917347	50917508
ENSE00001151659	50916168	50916243
ENSE00001222938	50895809	50895928
ENSE00001605064	50947017	50954257
ENSE00003526712	50932258	50932360
ENSE00003547112	50918110	50918213
ENSE00003564587	50920456	50920565
ENSE00003645078	50940288	50940386
ENSE00003808655	50879118	50879308

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 98.23.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 45.5385 / max 937.1130, expressed in 1818 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
170265	38.6615	1815
170264	6.1964	1535
208557	0.6807	417

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
choroid plexus epithelium	UBERON:0003911	98.23	gold quality
jejunal mucosa	UBERON:0000399	97.53	gold quality
cardiac muscle of right atrium	UBERON:0003379	96.78	gold quality
colonic mucosa	UBERON:0000317	96.28	gold quality
myocardium	UBERON:0002349	96.27	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.18	gold quality
monocyte	CL:0000576	96.07	gold quality
duodenum	UBERON:0002114	96.03	gold quality
mononuclear cell	CL:0000842	95.98	gold quality
heart right ventricle	UBERON:0002080	95.89	gold quality
left ventricle myocardium	UBERON:0006566	95.83	gold quality
leukocyte	CL:0000738	95.77	gold quality
jejunum	UBERON:0002115	95.59	gold quality
rectum	UBERON:0001052	95.40	gold quality
trabecular bone tissue	UBERON:0002483	94.82	gold quality
buccal mucosa cell	CL:0002336	94.72	gold quality
ileal mucosa	UBERON:0000331	94.66	gold quality
mucosa of transverse colon	UBERON:0004991	94.59	gold quality
cardiac atrium	UBERON:0002081	94.05	gold quality
right atrium auricular region	UBERON:0006631	93.82	gold quality
vena cava	UBERON:0004087	93.69	gold quality
gluteal muscle	UBERON:0002000	93.62	gold quality
seminal vesicle	UBERON:0000998	93.61	gold quality
vermiform appendix	UBERON:0001154	93.58	gold quality
adrenal tissue	UBERON:0018303	93.53	gold quality
caecum	UBERON:0001153	93.51	gold quality
diaphragm	UBERON:0001103	93.44	gold quality
deltoid	UBERON:0001476	93.36	gold quality
cortical plate	UBERON:0005343	93.35	gold quality
bone marrow	UBERON:0002371	93.34	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.60
E-CURD-97	no	1131.43
E-GEOD-106540	no	198.25
E-MTAB-6524	no	119.45

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

109 targeting ME2, 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-3120-5P	100.00	65.56	965
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-9902	99.89	69.15	2250
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-944	99.82	70.85	3042
HSA-MIR-3180-5P	99.82	69.12	2422
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4659A-3P	99.80	72.62	4248

Literature-anchored findings (GeneRIF, showing 19)

• An ME2-centered nine-SNP haplotype, when present homozygously, increases the risk for IGE (odds ratio 6.1; 95% confidence interval 2.9-12.7) compared with any other genotype (PMID:15532013)
• Site directed mutagenesis was used to detrmine which amino acids in the active site of human mitochondrial NAD+-dependent malic enzyme are necessary for the inhibitory effects of ATP. (PMID:16171388)
• These findings provide a molecular rationale for the role of hS14 in TR-dependent transcriptional activation of the expression of specific genes. (PMID:17418816)
• Schizophrenic subjects are identified with mitochondrial genes involved in oxidative metabolism as showing consistently decreased expression, including ME2. (PMID:17638511)
• Single nucleotide polymorphism in ME2 gene is associated with acute lymphoblastic leukemia. (PMID:19066393)
• ME2 activity in Islets of Langerhans cells was measured by a spectrophotometric enzyme assay by utilizing the distinct kinetic properties. (PMID:19691144)
• Depletion of malic enzyme 2 induced erythroid differentiation in human erythroleukemia cells. (PMID:20824065)
• p53 represses the expression of the tricarboxylic-acid-cycle-associated malic enzymes ME1 and ME2 in human and mouse cells (PMID:23334421)
• Three SNP alleles in BRD2, Cx-36, and ME2 and microdeletions in 15q13.3, 15q11.2, and 16p13.11 also contribute risk to juvenile myclonic epilepsy. (PMID:23756480)
• Data indicate that malic enzyme 2 knockdown impacts phosphatidylinositol 3-kinases/proto-oncogene protein akt (PI3K/AKT) signaling. (PMID:24957098)
• ME2 might be an important factor in melanoma progression and a novel biomarker of invasion. (PMID:25202825)
• ME1/ME2 expression phenotype may have a potential to be a valuable marker for sebaceous differentiation in sebaceous lesions. (PMID:26381116)
• ME2 was involved in glioblastoma multiforme growth, invasion, migration, Reactive oxygen species and ATP production. (PMID:27166188)
• deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer (PMID:28099419)
• The chromosome 18q21 deletion in nearly one third of pancreatic adenocarcinomas eliminates not only the tumor suppressor SMAD4, but also neighboring genes with important cellular roles, such as ME2 (PMID:28174172)
• influences susceptibility to adolescent-onset genetic generalized epilepsy (PMID:30719716)
• Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma. (PMID:32564485)
• Malic enzyme 2 maintains protein stability of mutant p53 through 2-hydroxyglutarate. (PMID:35228743)
• SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration. (PMID:38007551)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	me2	ENSDARG00000100718
mus_musculus	Me2	ENSMUSG00000024556
rattus_norvegicus	Me2	ENSRNOG00000015582
drosophila_melanogaster	Men	FBGN0002719
drosophila_melanogaster	Menl-2	FBGN0029153
drosophila_melanogaster	Menl-1	FBGN0029154
drosophila_melanogaster	Men-b	FBGN0029155
drosophila_melanogaster	CG7848	FBGN0034127
caenorhabditis_elegans		WBGENE00012983

Paralogs (2): ME1 (ENSG00000065833), ME3 (ENSG00000151376)

Protein

Protein identifiers

NAD-dependent malic enzyme, mitochondrial — P23368 (reviewed: P23368)

Alternative names: Malic enzyme 2

All UniProt accessions (13): P23368, A0A1W2PPH1, A0A1W2PPY2, A0A1W2PQ37, A0A1W2PQF8, A0A1W2PQH3, A0A1W2PQH4, A0A1W2PQT3, A0A1W2PQY8, A0A1W2PR68, A0A1W2PRH1, A0A1W2PRS2, A0A1W2PRY9

UniProt curated annotations — full annotation on UniProt →

Function. NAD-dependent mitochondrial malic enzyme that catalyzes the oxidative decarboxylation of malate to pyruvate.

Subunit / interactions. Homotetramer.

Subcellular location. Mitochondrion matrix.

Activity regulation. Subject to allosteric activation by fumarate.

Cofactor. Divalent metal cations. Prefers magnesium or manganese.

Miscellaneous. This isoenzyme can also use NADP(+) but is more effective with NAD(+).

Similarity. Belongs to the malic enzymes family.

Isoforms (2)

UniProt ID	Names	Canonical?
P23368-1	1	yes
P23368-2	2

RefSeq proteins (2): NP_001161807, NP_002387* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001891	Malic_OxRdtase	Family
IPR012301	Malic_N_dom	Domain
IPR012302	Malic_NAD-bd	Domain
IPR015884	Malic_enzyme_CS	Conserved_site
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR037062	Malic_N_dom_sf	Homologous_superfamily
IPR046346	Aminoacid_DH-like_N_sf	Homologous_superfamily

Pfam: PF00390, PF03949

Enzyme classification (BRENDA):

• EC 1.1.1.38 — malate dehydrogenase (oxaloacetate-decarboxylating) (BRENDA: 31 organisms, 27 substrates, 60 inhibitors, 84 Km, 25 kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
L-MALATE	0.19–50	31
NAD+	0.004–17.2	28
NICOTINAMIDE CYTOSINE DINUCLEOTIDE	0.13–102	8
(S)-MALATE	0.42–15.6	5
NADH	0.025–1.4	5
OXALOACETATE	2.1–5	3
MN2+	0.12–0.32	2
NADP+	2.3	1
PYRUVATE	—	0

Catalyzed reactions (Rhea), 2 shown:

• (S)-malate + NAD(+) = pyruvate + CO2 + NADH (RHEA:12653)
• oxaloacetate + H(+) = pyruvate + CO2 (RHEA:15641)

UniProt features (86 total): helix 32, strand 18, binding site 13, turn 8, modified residue 5, active site 2, sequence variant 2, mutagenesis site 2, transit peptide 1, chain 1, splice variant 1, sequence conflict 1

Structure

Experimental structures (PDB)

18 structures.

PDB	Method	Resolution (Å)
9AYI	X-RAY DIFFRACTION	1.89
1PJ3	X-RAY DIFFRACTION	2.1
1QR6	X-RAY DIFFRACTION	2.1
1DO8	X-RAY DIFFRACTION	2.2
1GZ4	X-RAY DIFFRACTION	2.2
1GZ3	X-RAY DIFFRACTION	2.3
1PJ2	X-RAY DIFFRACTION	2.3
1PJ4	X-RAY DIFFRACTION	2.3
9MYF	X-RAY DIFFRACTION	2.45
7BSJ	X-RAY DIFFRACTION	2.48
7BSK	X-RAY DIFFRACTION	2.55
7BSL	X-RAY DIFFRACTION	2.55
1EFK	X-RAY DIFFRACTION	2.6
1EFL	X-RAY DIFFRACTION	2.6
7XDE	ELECTRON MICROSCOPY	2.72
7XDF	ELECTRON MICROSCOPY	2.72
7XDG	ELECTRON MICROSCOPY	2.84
1PJL	X-RAY DIFFRACTION	2.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P23368-F1	94.55	0.91

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 (2): 112 (proton donor); 183 (proton acceptor)

Ligand- & substrate-binding residues (13): 259; 279; 312; 314; 315; 421; 466; 67; 91; 165; 165; 255 …

Post-translational modifications (5): 156, 224, 240, 272, 346

Mutagenesis-validated functional residues (2):

Position	Phenotype
67	abolishes activation by fumarate.
91	abolishes activation by fumarate.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-70268	Pyruvate metabolism
R-HSA-9837999	Mitochondrial protein degradation
R-HSA-1428517	Aerobic respiration and respiratory electron transport
R-HSA-1430728	Metabolism
R-HSA-392499	Metabolism of proteins

MSigDB gene sets: 181 (showing top): RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOBP_NADPPLUS_METABOLIC_PROCESS, CHIANG_LIVER_CANCER_SUBCLASS_UNANNOTATED_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, SHAFFER_IRF4_TARGETS_IN_ACTIVATED_B_LYMPHOCYTE, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, MODULE_528, MODULE_16, GOBP_MONOCARBOXYLIC_ACID_METABOLIC_PROCESS, SHIPP_DLBCL_CURED_VS_FATAL_DN, MODULE_503, GOBP_DICARBOXYLIC_ACID_METABOLIC_PROCESS, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS

GO Biological Process (2): malate metabolic process (GO:0006108), regulation of NADP metabolic process (GO:1902031)

GO Molecular Function (10): malic enzyme activity (GO:0004470), malate dehydrogenase (decarboxylating) (NAD+) activity (GO:0004471), malate dehydrogenase (decarboxylating) (NADP+) activity (GO:0004473), oxaloacetate decarboxylase activity (GO:0008948), electron transfer activity (GO:0009055), metal ion binding (GO:0046872), NAD binding (GO:0051287), catalytic activity (GO:0003824), oxidoreductase activity (GO:0016491), oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor (GO:0016616)

GO Cellular Component (2): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Aerobic respiration and respiratory electron transport	1
Metabolism of proteins	1
Metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
malic enzyme activity	2
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor	2
molecular_function	2
dicarboxylic acid metabolic process	1
NADP+ metabolic process	1
regulation of purine nucleotide metabolic process	1
malate dehydrogenase activity	1
carboxy-lyase activity	1
cation binding	1
adenyl nucleotide binding	1
catalytic activity	1
oxidoreductase activity, acting on CH-OH group of donors	1
cytoplasm	1
intracellular membrane-bounded organelle	1
mitochondrion	1
intracellular organelle lumen	1

Protein interactions and networks

STRING

1742 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ME2	JRK	O75564	825
ME2	LDHA	P00338	756
ME2	F13A1	P00488	669
ME2	MDH2	P40926	647
ME2	OPRM1	P35372	634
ME2	PCK2	Q16822	550
ME2	CS	O75390	549
ME2	CACNA1A	P78510	549
ME2	KCNQ3	O43525	538
ME2	FH	P07954	534
ME2	H6PD	O95479	526
ME2	PGD	P52209	524
ME2	POGK	Q9P215	517
ME2	PC	P11498	511
ME2	RPEL1	Q2QD12	496

IntAct

37 interactions, top by confidence:

A	B	Type	Score
HSPD1	NUDT19	psi-mi:“MI:0914”(association)	0.710
IFT25	IFT56	psi-mi:“MI:0914”(association)	0.690
	GNAT3	psi-mi:“MI:0915”(physical association)	0.400
SIRT4	VWA8	psi-mi:“MI:0914”(association)	0.350
HSCB	RBP5	psi-mi:“MI:0914”(association)	0.350
LRRK2		psi-mi:“MI:0914”(association)	0.350
TMEM184A	NRDC	psi-mi:“MI:0914”(association)	0.350
KDM4C	SMCHD1	psi-mi:“MI:0914”(association)	0.350
MYLK	ACOT7	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CAPZB	ENAH	psi-mi:“MI:0914”(association)	0.350
	GTPBP10	psi-mi:“MI:0914”(association)	0.350
VCP	SHTN1	psi-mi:“MI:0914”(association)	0.350
VCP	FAM171A2	psi-mi:“MI:0914”(association)	0.350
FECH	GTPBP10	psi-mi:“MI:0914”(association)	0.350
DDX28	UBA6	psi-mi:“MI:0914”(association)	0.350
GAB2	UBA6	psi-mi:“MI:0914”(association)	0.350
MRPL49	UBA6	psi-mi:“MI:0914”(association)	0.350
USP46	UBA6	psi-mi:“MI:0914”(association)	0.350
	EIF3F	psi-mi:“MI:0914”(association)	0.350
MRPL58		psi-mi:“MI:0914”(association)	0.350
	VWA8	psi-mi:“MI:2364”(proximity)	0.270
HSPD1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
MGST3	VWA8	psi-mi:“MI:2364”(proximity)	0.270
PDK1	VWA8	psi-mi:“MI:2364”(proximity)	0.270
TRMT61B	VWA8	psi-mi:“MI:2364”(proximity)	0.270

BioGRID (115): ME2 (Affinity Capture-MS), ME2 (Affinity Capture-MS), ME2 (Affinity Capture-MS), ME2 (Affinity Capture-RNA), ME2 (Affinity Capture-MS), ME2 (Proximity Label-MS), ME2 (Affinity Capture-MS), ME2 (Affinity Capture-MS), ME2 (Affinity Capture-MS), ME2 (Proximity Label-MS), ME2 (Proximity Label-MS), ME2 (Proximity Label-MS), ME2 (Proximity Label-MS), ME2 (Affinity Capture-MS), SHMT2 (Co-fractionation)

ESM2 similar proteins: A0A1D8PHA3, D5ANZ4, O13966, O14321, O31216, O59680, O74198, O94609, P07142, P07143, P08574, P0CY49, P16243, P19414, P20114, P22178, P23135, P23368, P25087, P27443, P30594, P30595, P36444, P37222, P51615, P54385, P81379, P87111, Q00988, Q02760, Q08822, Q11190, Q12166, Q12632, Q4QAU9, Q54D07, Q54KB7, Q54XM6, Q55C16, Q6BRB7

Diamond homologs: A0KHR8, A0KT69, A1JTY5, A1RNF8, A1S8W7, A3D0E1, A3QH80, A4SKE9, A4TKN8, A4WAJ3, A4Y3I1, A5F1Z0, A6V1V5, A6WSH0, A7FJK4, A7N025, A7ZLS1, A8AGN6, A8FZ49, A8GC31, A8H7G5, A9L2F4, A9MR05, A9MYU8, B0TRQ2, B1JPZ6, B1KFN0, B2JZJ5, B4ESY2, B4T5V6, B4TII8, B4TW15, B5F5W5, B5FHJ6, B5QTN6, B5RAB4, B5Z1T9, B7L7H9, B7UWK9, B8CQT6

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
ME2	“up-regulates quantity”	NADPH(4-)	“chemical modification”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	71
Likely benign	5
Benign	3

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
3390850	NM_002396.5(ME2):c.1379_1380del (p.Phe460fs)	Likely pathogenic

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

3814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
18:50908088:G:C	R45P	1.000
18:50920557:A:C	D279A	1.000
18:50920557:A:T	D279V	1.000
18:50895928:G:C	K36N	0.999
18:50895928:G:T	K36N	0.999
18:50908072:T:C	F40L	0.999
18:50908074:T:A	F40L	0.999
18:50908074:T:G	F40L	0.999
18:50917426:A:T	K183I	0.999
18:50920489:C:A	D256E	0.999
18:50920489:C:G	D256E	0.999
18:50920552:T:A	N277K	0.999
18:50920552:T:G	N277K	0.999
18:50920557:A:G	D279G	0.999
18:50920558:T:A	D279E	0.999
18:50920558:T:G	D279E	0.999
18:50925847:T:A	N421K	0.999
18:50925847:T:G	N421K	0.999
18:50932344:T:A	N467K	0.999
18:50932344:T:G	N467K	0.999
18:50932354:T:C	F471L	0.999
18:50932356:T:A	F471L	0.999
18:50932356:T:G	F471L	0.999
18:50908108:G:A	G52R	0.998
18:50908108:G:C	G52R	0.998
18:50908109:G:A	G52E	0.998
18:50912857:T:C	L100P	0.998
18:50917351:T:A	V158D	0.998
18:50917422:G:A	G182R	0.998
18:50917422:G:C	G182R	0.998

dbSNP variants (sampled 300 via entrez): RS1000032741 (18:50942019 A>T), RS1000073826 (18:50940655 G>A,C), RS1000101839 (18:50933016 C>G), RS1000125627 (18:50943091 A>G), RS1000193565 (18:50910852 TC>T), RS1000218525 (18:50912977 T>C), RS1000255347 (18:50948763 C>T), RS1000264885 (18:50899809 T>A,G), RS1000355387 (18:50906285 T>G), RS1000359320 (18:50953927 T>C,G), RS1000371307 (18:50910546 G>A,T), RS1000405265 (18:50940282 C>G,T), RS1000427586 (18:50906459 C>G,T), RS1000547901 (18:50942254 C>G,T), RS1000550532 (18:50902046 A>G)

Disease associations

OMIM: gene MIM:154270 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
inborn disorder of energy metabolism	Limited	Autosomal recessive
Tourette syndrome	No Known Disease Relationship	Unknown

Mondo (2): Tourette syndrome (MONDO:0007661), inborn disorder of energy metabolism (MONDO:0019243)

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST000894_5	Entorhinal cortical thickness	7.000000e-06
GCST009086_3	Pneumococcal meningitis	8.000000e-08
GCST009391_65	Metabolite levels	6.000000e-06
GCST90002382_487	Eosinophil percentage of white cells	4.000000e-09

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004840	cortical thickness
EFO:0010352	diacylglycerol 34:1 measurement
EFO:0007991	eosinophil percentage of leukocytes

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D005879	Tourette Syndrome	C10.228.140.079.898; C10.228.662.825.800; C10.574.500.850; C16.320.400.820; F03.625.992.850

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5291602 (SINGLE PROTEIN)

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

ChEMBL bioactivities

31 potent at pChembl≥5 of 31 total, top 31 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.48	Kd	32.97	nM	CHEMBL5653589
7.48	ED50	32.97	nM	CHEMBL5653589
6.82	IC50	150	nM	CHEMBL5279096
6.72	IC50	190	nM	CHEMBL5284469
6.70	IC50	200	nM	CHEMBL372408
6.70	IC50	200	nM	CHEMBL5267207
6.68	IC50	210	nM	CHEMBL5287773
6.66	IC50	220	nM	CHEMBL5278951
6.64	IC50	230	nM	CHEMBL5275653
6.57	IC50	270	nM	CHEMBL5289840
6.57	IC50	270	nM	CHEMBL5277536
6.46	IC50	350	nM	CHEMBL5284610
6.44	IC50	360	nM	CHEMBL5289950
6.41	IC50	390	nM	CHEMBL5279230
6.39	IC50	410	nM	CHEMBL5283020
6.38	IC50	420	nM	CHEMBL5218866
6.01	IC50	980	nM	CHEMBL5278596
5.96	IC50	1110	nM	CHEMBL5274945
5.89	IC50	1290	nM	CHEMBL5279589
5.86	IC50	1370	nM	CHEMBL5267542
5.80	IC50	1590	nM	CHEMBL5273550
5.79	IC50	1630	nM	CHEMBL5286488
5.78	IC50	1660	nM	CHEMBL5282439
5.77	IC50	1700	nM	CHEMBL5283717
5.76	IC50	1720	nM	CHEMBL5281297
5.71	IC50	1970	nM	CHEMBL5290463
5.60	IC50	2500	nM	CHEMBL5270965
5.58	IC50	2600	nM	CHEMBL5281258
5.55	IC50	2800	nM	CHEMBL5277143
5.55	IC50	2800	nM	CHEMBL5286064
5.41	IC50	3900	nM	CHEMBL5291081

PubChem BioAssay actives

30 with measured affinity, of 34 total; 30 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	2148740: Binding affinity to human ME2 incubated for 45 mins by Kinobead based pull down assay	kd	0.0330	uM
2-(4-chlorophenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1500	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-phenylethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.1900	uM
N-(2H-tetrazol-5-yl)-9,9a-dihydro-4aH-xanthene-9-carboxamide	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2000	uM
3-[4-(4-hydroxyphenyl)piperazin-1-yl]-1-phenylpyrrolidine-2,5-dione	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2000	uM
2-(4-fluorophenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]ethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2100	uM
4-(4-hydroxyphenyl)-N-phenylpiperazine-1-carboxamide	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2200	uM
(E)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-phenylprop-2-en-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2300	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-methyl-3-phenylbutan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2700	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-3-phenylpropan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.2700	uM
3-(4-butoxyphenyl)-1-[4-(4-hydroxyphenyl)piperazin-1-yl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3500	uM
2-[4-(4-hydroxyphenyl)piperazin-1-yl]-N-phenylacetamide	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3600	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-phenoxyethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.3900	uM
1-[4-(4-hydroxyphenyl)piperazin-1-yl]-2-[4-(trifluoromethyl)phenyl]ethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.4100	uM
2,5-dihydroxy-3,6-bis(4-methoxyphenyl)cyclohexa-2,5-diene-1,4-dione	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.4200	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-2-phenylethanone	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	0.9800	uM
3-(4-fluorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methylbutan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.1100	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-thiophen-2-ylpropan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.2900	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methyl-3-phenylbutan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.3700	uM
3-(4-chlorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.5900	uM
3-(1-benzothiophen-2-yl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.6300	uM
3-(4-fluorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.6600	uM
2-phenyl-N-(2H-tetrazol-5-yl)quinoline-4-carboxamide	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.7000	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-phenylpropan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.7200	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-(5-phenylthiophen-2-yl)propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	1.9700	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-(4-methoxyphenyl)propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	2.5000	uM
1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-[4-(2-methoxyethoxy)phenyl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	2.6000	uM
3-(4-chlorophenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]-3-methylbutan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	2.8000	uM
3-[(3-carboxy-2-hydroxynaphthalen-1-yl)methyl]-2-hydroxynaphthalene-1-carboxylic acid	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	2.8000	uM
3-(4-butoxyphenyl)-1-[4-(5-hydroxy-2-pyridinyl)piperazin-1-yl]propan-1-one	1922683: Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs without shaking by resorufin dye based fluorescence analysis	ic50	3.9000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	decreases expression, increases expression	2
Acetaminophen	decreases expression, increases expression	2
Nickel	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
bufotalin	decreases expression	1
alpha-pinene	affects cotreatment, increases expression, increases abundance	1
pyrogallol 1,3-dimethyl ether	affects cotreatment, increases expression	1
tris(2-butoxyethyl) phosphate	affects expression	1
methotrexate polyglutamate	affects abundance	1
beta-lapachone	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
perfluorooctanoic acid	increases expression	1
methacrylaldehyde	affects cotreatment, increases expression, increases abundance	1
beta-methylcholine	affects expression	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	decreases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acrolein	affects cotreatment, increases expression, increases abundance	1
Air Pollutants	increases expression, affects cotreatment, increases abundance	1
Atrazine	increases expression	1
Vehicle Emissions	increases abundance, decreases 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
CHEMBL5225648	Binding	Inhibition of His-tagged human recombinant full length ME2 using L-malate and beta-NAD+ as substrate preincubated with enzyme for 5 mins followed by beta-NAD+ challenge and incubated under shaking for 5 mins followed by incubation for 2 hrs	In the Quest for Potent and Selective Malic Enzyme 3 Inhibitors for the Treatment of Pancreatic Ductal Adenocarcinoma. — ACS Med Chem Lett

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1NS	Abcam K-562 ME2 KO	Cancer cell line	Female
CVCL_D2KD	Abcam Raji ME2 KO	Cancer cell line	Male
CVCL_SX70	HAP1 ME2 (-) 1	Cancer cell line	Male
CVCL_UQ94	Abcam Jurkat ME2 KO	Cancer cell line	Male
CVCL_XQ38	HAP1 ME2 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00152750	PHASE4	UNKNOWN	Study of Clonidine on Sleep Architecture in Children With Tourette’s Syndrome (TS) and Comorbid ADHD
NCT00226824	PHASE4	TERMINATED	Safety Study of Galantamine in Tic Disorders
NCT00241176	PHASE4	COMPLETED	Open Label Trial of Aripiprazole in Children and Adolescents With Tourette’s Disorder
NCT00370838	PHASE4	COMPLETED	Comparison of Keppra and Clonidine in the Treatment of Tics
NCT01018056	PHASE4	COMPLETED	Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
NCT01547000	PHASE4	COMPLETED	Guanfacine in Children With Tic Disorders
NCT03239210	PHASE4	COMPLETED	Effects of Ondansetron in Obsessive-compulsive and Tic Disorders
NCT00004376	PHASE3	COMPLETED	Phase III Randomized, Double-Blind, Placebo-Controlled Study of Guanfacine for Tourette Syndrome and Attention Deficit Hyperactivity Disorder
NCT00206323	PHASE3	COMPLETED	A Randomized, Placebo-controlled, Tourette Syndrome Study.
NCT00206336	PHASE3	COMPLETED	An Open-label Study to Determine the Efficacy and Safety of Topiramate in the Treatment of Tourette Syndrome.
NCT00478842	PHASE3	COMPLETED	Pallidal Stimulation and Gilles de la Tourette Syndrome
NCT00681863	PHASE3	TERMINATED	Open-label Extension Study of Pramipexole in the Treatment of Children and Adolescents With Tourette Syndrome
NCT01501695	PHASE3	COMPLETED	Phase III Study of 5LGr to Treat Tic Disorder
NCT03087201	PHASE3	COMPLETED	CANNAbinoids in the Treatment of TICS (CANNA-TICS)
NCT03487783	PHASE3	COMPLETED	Aripiprazole Oral Solution in the Treatment of Children and Adolescents With Tourette’s Syndrome
NCT03567291	PHASE3	TERMINATED	Evaluation of Safety and Tolerability of Long-term TEV-50717 (Deutetrabenazine) for Treatment of Tourette Syndrome in Children and Adolescents
NCT03571256	PHASE3	COMPLETED	A Study to Test if TEV-50717 is Effective in Relieving Tics Associated With Tourette Syndrome (TS)
NCT06021522	PHASE3	ACTIVE_NOT_RECRUITING	A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette’s Disorder
NCT00004393	PHASE2	COMPLETED	Phase II Double Blind Placebo Controlled Trial of Risperidone in Tourette Syndrome
NCT00004652	PHASE2	COMPLETED	Phase II Pilot Controlled Study of Short Vs Longer Term Pimozide (Orap) Therapy in Tourette Syndrome
NCT00231985	PHASE2	COMPLETED	Effectiveness of Behavior Therapy and Psychosocial Therapy for the Treatment of Tourette Syndrome and Chronic Tic Disorder
NCT00311909	PHASE2	COMPLETED	Thalamic Deep Brain Stimulation for Tourette Syndrome
NCT00529308	PHASE2	COMPLETED	Transcranial Magnetic Stimulation (TMS) for Individuals With Tourette’s Syndrome
NCT00558467	PHASE2	COMPLETED	Pramipexole Pilot Phase II Study in Children and Adolescents With Tourette Disorder According to DSM-IV Criteria
NCT01043549	PHASE2	TERMINATED	Repetitive Transcranial Magnetic Stimulation of the Posterior Parietal Cortex in Patients Suffering From Gilles de la Tourette Syndrome
NCT01133353	PHASE2	WITHDRAWN	A Study of the Effectiveness and Safety of Tetrabenazine MR in Pediatric Subjects With Tourette’s Syndrome
NCT01475383	PHASE2	WITHDRAWN	Study Evaluating The Safety And Efficacy Of PF-03654746 In Adult Subjects With Tourette’s Syndrome
NCT01647269	PHASE2	COMPLETED	A Trial of Bilateral Deep Brain Stimulation to the Globus Pallidus Internum in Tourette Syndrome
NCT01904773	PHASE2	COMPLETED	Safety, Tolerability, Pharmacokinetic, and Efficacy Study of AZD5213 in Adolescents With Tourette’s Disorder
NCT02102698	PHASE2	COMPLETED	Ecopipam Treatment of Tourette’s Syndrome in Subjects 7-17 Years
NCT02217007	PHASE2	WITHDRAWN	A Trial Evaluating the Efficacy, Safety, and Pharmacokinetics of SNC-102 in Subjects With Tourette Syndrome
NCT02247206	PHASE2	COMPLETED	VoIP Delivered Behavior Therapy for Tourette Syndrome
NCT02581865	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Adults With Tourette Syndrome
NCT02619084	PHASE2	COMPLETED	Subthalamic Stimulation in Tourette’s Syndrome
NCT02679079	PHASE2	COMPLETED	Safety and Efficacy Study of NBI-98854 in Children and Adolescents With Tourette Syndrome
NCT02879578	PHASE2	COMPLETED	Safety and Tolerability Study of NBI-98854 for the Treatment of Subjects With Tourette Syndrome
NCT03066193	PHASE2	COMPLETED	Efficacy of a Therapeutic Combination of Dronabinol and PEA for Tourette Syndrome
NCT03247244	PHASE2	TERMINATED	Safety and Efficacy of Cannabis in Tourette Syndrome
NCT03325010	PHASE2	COMPLETED	Safety, Tolerability, and Efficacy of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome
NCT03444038	PHASE2	COMPLETED	Open-Label Safety and Tolerability Study of NBI-98854 for the Treatment of Pediatric Subjects With Tourette Syndrome