GCH1

Summary

GCH1 (GTP cyclohydrolase 1, HGNC:4193) is a protein-coding gene on chromosome 14q22.2, encoding GTP cyclohydrolase 1 (P30793). Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). It is haploinsufficient (ClinGen: sufficient evidence).

This gene encodes a member of the GTP cyclohydrolase family. The encoded protein is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis, catalyzing the conversion of GTP into 7,8-dihydroneopterin triphosphate. BH4 is an essential cofactor required by aromatic amino acid hydroxylases as well as nitric oxide synthases. Mutations in this gene are associated with malignant hyperphenylalaninemia and dopa-responsive dystonia. Several alternatively spliced transcript variants encoding different isoforms have been described; however, not all variants give rise to a functional enzyme.

Source: NCBI Gene 2643 — RefSeq curated summary.

At a glance

• Gene–disease (curated): GTP cyclohydrolase I deficiency (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 14
• Clinical variants (ClinVar): 635 total — 87 pathogenic, 30 likely-pathogenic
• Phenotypes (HPO): 75
• Dosage sensitivity (ClinGen): haploinsufficiency sufficient evidence, triplosensitivity no evidence
• MANE Select transcript: NM_000161

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4193
Approved symbol	GCH1
Name	GTP cyclohydrolase 1
Location	14q22.2
Locus type	gene with protein product
Status	Approved
Aliases	GTPCH1, DYT5a
Ensembl gene	ENSG00000131979
Ensembl biotype	protein_coding
OMIM	600225
Entrez	2643

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000254299, ENST00000395514, ENST00000395521, ENST00000491895, ENST00000536224, ENST00000543643, ENST00000902570, ENST00000902573

RefSeq mRNA: 6 — MANE Select: NM_000161 NM_000161, NM_001024024, NM_001024070, NM_001024071, NM_001424104, NM_001424105

CCDS: CCDS41954, CCDS45110, CCDS9720

Canonical transcript exons

ENST00000491895 — 6 exons

Exon	Start	End
ENSE00001904587	54842017	54844143
ENSE00001934058	54902321	54902826
ENSE00003472475	54845768	54845852
ENSE00003479076	54847099	54847130
ENSE00003652018	54859681	54859736
ENSE00003662835	54865327	54865436

Expression profiles

Bgee: expression breadth ubiquitous, 275 present calls, max score 99.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.0332 / max 1810.1230, expressed in 1536 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
143343	22.3980	1505
143341	0.5551	191
143340	0.4583	125
143339	0.3464	144
143342	0.2755	130

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	99.90	gold quality
oocyte	CL:0000023	99.74	gold quality
type B pancreatic cell	CL:0000169	98.86	gold quality
jejunal mucosa	UBERON:0000399	97.27	gold quality
nephron tubule	UBERON:0001231	96.78	gold quality
cartilage tissue	UBERON:0002418	96.45	gold quality
palpebral conjunctiva	UBERON:0001812	96.36	gold quality
mononuclear cell	CL:0000842	96.22	gold quality
monocyte	CL:0000576	96.18	gold quality
islet of Langerhans	UBERON:0000006	96.14	gold quality
leukocyte	CL:0000738	96.00	gold quality
eye	UBERON:0000970	95.59	gold quality
epithelium of nasopharynx	UBERON:0001951	95.35	gold quality
nasopharynx	UBERON:0001728	95.33	gold quality
right lobe of liver	UBERON:0001114	95.01	gold quality
mucosa of sigmoid colon	UBERON:0004993	94.97	gold quality
liver	UBERON:0002107	94.67	gold quality
colonic mucosa	UBERON:0000317	94.29	gold quality
renal glomerulus	UBERON:0000074	94.20	gold quality
metanephric glomerulus	UBERON:0004736	93.90	gold quality
esophagus squamous epithelium	UBERON:0006920	93.90	gold quality
kidney epithelium	UBERON:0004819	93.66	gold quality
pigmented layer of retina	UBERON:0001782	92.82	gold quality
granulocyte	CL:0000094	92.81	gold quality
buccal mucosa cell	CL:0002336	91.31	gold quality
epithelium of esophagus	UBERON:0001976	90.81	gold quality
duodenum	UBERON:0002114	90.37	gold quality
tibia	UBERON:0000979	90.01	gold quality
squamous epithelium	UBERON:0006914	89.70	gold quality
gingival epithelium	UBERON:0001949	89.29	gold quality

Single-cell (SCXA)

Detected in 7 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-MTAB-5061	yes	396.98
E-MTAB-7037	yes	73.18
E-ANND-3	yes	12.97
E-GEOD-83139	yes	10.44
E-MTAB-3929	no	146.07
E-ENAD-27	no	7.44
E-GEOD-125970	no	3.27

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF2, CEBPB, CREB1, CRP, CTF1, ESR1, ESR2, FEV, IFNG, IL1B, IL6, IRF6, JUN, NFYA, NFYB, NFYC, NGF, NR3C1, NR4A1, NR4A2, SP1, SP3

miRNA regulators (miRDB)

107 targeting GCH1, 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-3064-3P	100.00	70.09	1254
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-548AE-3P	99.93	72.66	4867

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 40)

• kinetic studies with GFRP (PMID:11580249)
• A kindred is reported in which GTP-CH deficiency presents as a dopa-responsive myoclonus-dystonia syndrome, documented as a missense mutation in exon 6 of GTP-CH1 gene (K224R). (PMID:12391354)
• GTP cyclohydrolase I is alternatively spliced in mononuclear cells (PMID:12821132)
• Gene transfer of human GTPCH I restored arterial GTPCH I activity and BH4 levels, resulting in reduced O2- and improved endothelium-dependent relaxation and basal NO release in DOCA-salt hypertensive rats (PMID:12925450)
• Genetic transfer into rabbit vascular endothelium in vivo increases intracellular concentration of tetrahydrobiopterin. (PMID:14551046)
• GTPCH1 induction in endothelial cells is stimulated by cytokines and mediated by Stat1/3, Jak2 and NF-kappaB. (PMID:15604419)
• We tested 23 individuals with dopamine-resistant dystonia for the different GCH1 mutation types by conventional and quantitative PCR analyses and found mutations, including two large exon deletions, in 87%. (PMID:15753436)
• A new mutation (Thr106Ile) of the GTP cyclohydrolase 1 gene associated with DYT5 dystonia (Segawa disease). (PMID:15852365)
• Results suggest that variants within GCHI may contribute to bipolar disorder in the Irish population. (PMID:15909293)
• GTP cyclohydrolase I gene transcription is regulated by basic region leucine zipper transcription factors (PMID:16149046)
• Dopa-responsive dystonia and early-onset Parkinson’s disease in a patient revealed a mutation in the GTP cyclohydrolase I gene (GCH1). (PMID:16267845)
• Aha1 may recruit GCH1 into the endothelial nitric oxide synthase/heat shock protein (eNOS/Hsp90) complex to support changes in endothelial nitric oxide production through the local synthesis of BH4. (PMID:16696853)
• Data show that the detection of GCH I mutations is helpful in early diagnosis of non-typical cases of dopa-responsive dystonia. (PMID:17044972)
• Utility of multiple ligation-dependent probe amplificatino for deletion analysis of GCH1 in dopa-responsive dystnoia. (PMID:17111153)
• A novel mutation(H210Q) in GCH-1 gene in a case of dopa-responsive dystonia. (PMID:17410324)
• a new heterozygotic point mutation 151(G–>A) in GCH1 gene in Chinese sporadic patients with DRD (PMID:17557242)
• NO secretion traits are heritable, displaying joint genetic determination with autonomic activity by functional polymorphism at GCH1 (PMID:17717598)
• A large genomic deletion in GCH1 is sufficient to explain neurologic symptoms in the majority of Swiss family members with dopa-responsive dystonia. (PMID:17804835)
• This study rules out the previously reported DYT14 locus as a cause of dopa-responsive dystonia, since a novel multiexonic deletion has been identified in GTP cyclohydrolase I (GCH1). (PMID:17804835)
• We found a GCH1 point mutation in 27 patients of group 1 (54%) and in four patients of group 2 (5%). Of these, nine single and one double mutation have not been described before. GCH1 deletions were detected in four patients. (PMID:17898029)
• This study identified three mutations; two affected siblings carried a novel T209P mutation and two siblings from another family were compound heterozygous carriers of Met211Val and Lys224Arg mutations. (PMID:18044725)
• Sequencing of exons 1-6 of the GCH1 gene revealed a heterozygous deletion of two guanines at positions 64 and 65 and an insertion of 4 bases (AACC). (PMID:18202219)
• a unique presentation of autosomal recessive (AR) GTP cyclohydrolase I (GTPCH) deficiency, with severe CNS involvement but without hyperphenylalaninemia (PMID:18276179)
• male toddler with dopa-responsive dystonia caused by an autosomal-dominant GCH1 mutation found in three other family members (PMID:18358407)
• This study verifies previous results that decreased GCH1 function or inducibility as a result of genetic polymorphisms protects against pain, supporting specific functions of BH4 in relation to particular aspects of pain. (PMID:18374612)
• This study reports two Korean children affected with dopa-responsive dystonia caused by a novel missense mutation of the guanosine triphosphate cyclohydrolase I gene. One child exhibits a novel sporadic mutation(THR186ILE) (PMID:18410856)
• there is a common clinically relevant GCH1 genetics that is so far known to be related to unfavorable changes of endothelial function and a reduced risk for chronic pain. (PMID:18515178)
• identified novel mutations in dopa-responsive dystonia are Leu91Val, Pro95Leu, Val204Gly and 628delC in GCH-1 gene (PMID:18554280)
• haplotype has a striking effect on enzymatic coupling of eNOS as well as vascular O2 production and nitric oxide bioavailability in patients with coronary artery disease (PMID:18598896)
• Study identified the mutation at the GCH1 gene, IVS5+3insT, as the cause of Dopa-responsive dystonia in a Brazilian family (PMID:18752196)
• These findings highlight the importance of MCP-1/CCR2 signaling in the response to vascular injury and identify novel pathways linking endothelial BH4 to inflammation and vascular remodeling. (PMID:18824773)
• Quantitative analysis of cellular tetrahydrobiopterin versus superoxide production between GCH/eNOS-LOW and GCH/eNOS-HIGH cells revealed a striking linear relationship between eNOS protein and cellular BH4 stoichiometry (PMID:19011239)
• The GCH1 pain-protective haplotype does not have a significant effect on pain patterns or severity in recurrent acute pancreatitis or chronic pancreatitis (PMID:19014702)
• We conclude that SNPs of the GCH1 gene may profoundly affect the ratings of pain induced by capsaicin. (PMID:19081190)
• 6BH(4) de novo synthesis is controlled by H(2)O(2) in a concentration-dependent manner, but H(2)O(2)-mediated oxidation does not affect the functionality of the GTPCHI/GFRP complex. (PMID:19101819)
• GTPCH I is targeted to caveolae microdomains in vascular endothelial cells, and tetrahydrobiopterin production occurs in proximity to endothelial NO synthase. The regulation of GTPCH I activity involves the caveolar coat protein, caveolin-1. (PMID:19104007)
• genetic confirmation of the diagnosis of dopa-responsive dystonia,GCH-I mutation in dopa-responsive dystonia can be successfully managed using low doses of levodopa over a long period of time (PMID:19195260)
• Autosomal dominant GTP cyclohydrolase I (AD GCH 1) deficiency (Segawa disease) is an autosomal dominant dopa responsive dystonia caused by heterozygous mutation of the GCH 1 gene located on 14q22.1-q22.2. (PMID:19292934)
• In this study, using MALDI-TOF/MS,etc. several proteins were identified by coimmunoprecipitation with GTP cyclohydrolase 1. Findings provide a first glimpse into the mechanisms regulating GCH1 activation by cytokines in normal adult human astrocytes. (PMID:19294699)
• A detailed clinical evaluation of 34 patients with confirmed mutations in the GCH1 gene is presented (PMID:19332422)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	gch1	ENSDARG00000070453
mus_musculus	Gch1	ENSMUSG00000037580
rattus_norvegicus	Gch1	ENSRNOG00000011039
drosophila_melanogaster	Pu	FBGN0003162
caenorhabditis_elegans		WBGENE00000298

Protein

Protein identifiers

GTP cyclohydrolase 1 — P30793 (reviewed: P30793)

Alternative names: GTP cyclohydrolase I

All UniProt accessions (1): P30793

UniProt curated annotations — full annotation on UniProt →

Function. Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.

Subunit / interactions. Toroid-shaped homodecamer, composed of a dimer of pentamers. The inactive isoforms also form decamers and may possibly be incorporated into GCH1 heterodecamers, decreasing enzyme stability and activity. Interacts with AHSA1 and GCHFR/GFRP.

Subcellular location. Cytoplasm. Nucleus.

Tissue specificity. In epidermis, expressed predominantly in basal undifferentiated keratinocytes and in some but not all melanocytes (at protein level).

Post-translational modifications. Phosphorylated by casein kinase II at Ser-81 in HAECs during oscillatory shear stress; phosphorylation at Ser-81 results in increased enzyme activity.

Disease relevance. Hyperphenylalaninemia, BH4-deficient, B (HPABH4B) [MIM:233910] A disease characterized by malignant hyperphenylalaninemia due to tetrahydrobiopterin deficiency, and defective neurotransmission due to depletion of the neurotransmitters dopamine and serotonin. The principal symptoms include: psychomotor retardation, tonicity disorders, convulsions, drowsiness, irritability, abnormal movements, hyperthermia, hypersalivation, and difficulty swallowing. Some patients may present a phenotype of intermediate severity between severe hyperphenylalaninemia and mild dystonia. In this intermediate phenotype, there is marked motor delay, but no intellectual disability and only minimal, if any, hyperphenylalaninemia. The disease is caused by variants affecting the gene represented in this entry. Dystonia, dopa-responsive (DRD) [MIM:128230] A form of dystonia that responds to L-DOPA treatment without side effects. Dystonia is defined by the presence of sustained involuntary muscle contractions, often leading to abnormal postures. DRD typically presents in childhood with walking problems due to dystonia of the lower limbs and worsening of the dystonia towards the evening. It is characterized by postural and motor disturbances showing marked diurnal fluctuation. Torsion of the trunk is unusual. Symptoms are alleviated after sleep and aggravated by fatigue and exercise. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. GTP shows a positive allosteric effect, and tetrahydrobiopterin inhibits the enzyme activity. Zinc is required for catalytic activity. Inhibited by Mg(2+).

Induction. Up-regulated by IFNG/IFN-gamma, TNF, IL1B/interleukin-1 beta, bacterial lipopolysaccharides (LPS) and phenylalanine, and down-regulated by dibutyryl-cAMP, iloprost and 8-bromo-cGMP in HUVEC cells. Up-regulation of GCH1 expression, in turn, stimulates production of tetrahydrobiopterin, with subsequent elevation of endothelial nitric oxide synthase activity. Cytokine-induced GCH1 up-regulation in HUVECs in response to TNF and IFNG/IFN-gamma involves cooperative activation of both the NF-kappa-B and JAK2/STAT pathways. Also up-regulated by hydrogen peroxide in human aorta endothelial cells (HAECs).

Pathway. Cofactor biosynthesis; 7,8-dihydroneopterin triphosphate biosynthesis; 7,8-dihydroneopterin triphosphate from GTP: step 1/1.

Similarity. Belongs to the GTP cyclohydrolase I family.

Isoforms (4)

UniProt ID	Names	Canonical?
P30793-1	GCH-1	yes
P30793-2	GCH-2
P30793-3	GCH-3
P30793-4	GCH-4

RefSeq proteins (6): NP_000152, NP_001019195, NP_001019241, NP_001019242, NP_001411033, NP_001411034 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001474	GTP_CycHdrlase_I	Family
IPR018234	GTP_CycHdrlase_I_CS	Conserved_site
IPR020602	GTP_CycHdrlase_I_dom	Domain
IPR043133	GTP-CH-I_C/QueF	Homologous_superfamily
IPR043134	GTP-CH-I_N	Homologous_superfamily

Pfam: PF01227

Enzyme classification (BRENDA):

• EC 3.5.4.16 — GTP cyclohydrolase I (BRENDA: 28 organisms, 49 substrates, 111 inhibitors, 23 Km, 5 kcat entries)

Substrate kinetics (BRENDA)

2 substrates with measured Km, best-characterized 2. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
GTP	0.004–980	15
GDP	0.0143	1

Catalyzed reactions (Rhea), 1 shown:

• GTP + H2O = 7,8-dihydroneopterin 3’-triphosphate + formate + H(+) (RHEA:17473)

UniProt features (79 total): sequence variant 42, helix 10, strand 8, splice variant 5, binding site 3, turn 3, compositionally biased region 2, sequence conflict 2, modified residue 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

11 structures.

PDB	Method	Resolution (Å)
7ALC	X-RAY DIFFRACTION	1.73
7ALA	X-RAY DIFFRACTION	1.85
7ALB	X-RAY DIFFRACTION	1.98
7ALQ	X-RAY DIFFRACTION	2.21
6Z86	X-RAY DIFFRACTION	2.21
6Z89	X-RAY DIFFRACTION	2.37
6Z87	X-RAY DIFFRACTION	2.56
6Z88	X-RAY DIFFRACTION	2.69
6Z85	ELECTRON MICROSCOPY	2.9
6Z80	ELECTRON MICROSCOPY	3
1FB1	X-RAY DIFFRACTION	3.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P30793-F1	86.89	0.74

Functional residue map

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

Ligand- & substrate-binding residues (3): 141; 144; 212

Post-translational modifications (2): 60, 81

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation

MSigDB gene sets: 673 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_DN, GSE45365_NK_CELL_VS_CD11B_DC_DN, GOBP_PHENOL_CONTAINING_COMPOUND_METABOLIC_PROCESS, ELVIDGE_HYPOXIA_DN, GOBP_PHENOL_CONTAINING_COMPOUND_BIOSYNTHETIC_PROCESS, GOBP_REGULATION_OF_BLOOD_PRESSURE, GOBP_CIRCULATORY_SYSTEM_PROCESS, GOBP_RESPONSE_TO_PEPTIDE, MODULE_45, GOBP_POLYOL_METABOLIC_PROCESS, GAUSSMANN_MLL_AF4_FUSION_TARGETS_G_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, GOBP_SUPEROXIDE_METABOLIC_PROCESS

GO Biological Process (17): tetrahydrobiopterin biosynthetic process (GO:0006729), nitric oxide biosynthetic process (GO:0006809), regulation of blood pressure (GO:0008217), positive regulation of heart rate (GO:0010460), regulation of lung blood pressure (GO:0014916), response to lipopolysaccharide (GO:0032496), response to type II interferon (GO:0034341), response to tumor necrosis factor (GO:0034612), dopamine biosynthetic process (GO:0042416), pteridine-containing compound biosynthetic process (GO:0042559), tetrahydrofolate biosynthetic process (GO:0046654), response to pain (GO:0048265), neuromuscular process controlling posture (GO:0050884), positive regulation of nitric-oxide synthase activity (GO:0051000), regulation of removal of superoxide radicals (GO:2000121), pteridine-containing compound metabolic process (GO:0042558), tetrahydrobiopterin metabolic process (GO:0046146)

GO Molecular Function (12): GTPase activity (GO:0003924), GTP cyclohydrolase I activity (GO:0003934), GTP binding (GO:0005525), zinc ion binding (GO:0008270), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), mitogen-activated protein kinase binding (GO:0051019), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), cytoplasmic vesicle (GO:0031410), nuclear membrane (GO:0031965), protein-containing complex (GO:0032991), neuron projection terminus (GO:0044306)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of cofactors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
biosynthetic process	2
response to cytokine	2
pteridine-containing compound metabolic process	2
cytoplasm	2
diol biosynthetic process	1
pteridine-containing compound biosynthetic process	1
tetrahydrobiopterin metabolic process	1
nitric oxide metabolic process	1
blood circulation	1
regulation of biological quality	1
regulation of heart rate	1
positive regulation of heart contraction	1
regulation of blood pressure	1
response to molecule of bacterial origin	1
response to lipid	1
response to oxygen-containing compound	1
innate immune response	1
dopamine metabolic process	1
catecholamine biosynthetic process	1
folic acid-containing compound biosynthetic process	1
tetrahydrofolate metabolic process	1
multicellular organismal response to stress	1
musculoskeletal movement	1
neuromuscular process	1
nitric-oxide synthase activity	1
regulation of nitric-oxide synthase activity	1
positive regulation of oxidoreductase activity	1
removal of superoxide radicals	1
regulation of superoxide metabolic process	1
regulation of cellular response to oxidative stress	1
regulation of response to reactive oxygen species	1
metabolic process	1
diol metabolic process	1
ribonucleoside triphosphate phosphatase activity	1
GTP cyclohydrolase activity	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
protein binding	1

Protein interactions and networks

STRING

2007 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
GCH1	TH	P07101	915
GCH1	QDPR	P09417	864
GCH1	SPR	P35270	859
GCH1	PCBD1	P61457	841
GCH1	SGCE	O43556	835
GCH1	GCHFR	P30047	821
GCH1	TOR1A	O14656	793
GCH1	DHFR	P00374	726
GCH1	DHFR2	Q86XF0	722
GCH1	DDC	P20711	718
GCH1	PTS	Q03393	711
GCH1	PAH	P00439	688
GCH1	TPH1	P17752	680
GCH1	PNP	P00491	668
GCH1	THAP1	Q9NVV9	656

IntAct

33 interactions, top by confidence:

A	B	Type	Score
OSBPL9	VAPB	psi-mi:“MI:0914”(association)	0.790
GCH1	YWHAZ	psi-mi:“MI:0915”(physical association)	0.600
YWHAZ	GCH1	psi-mi:“MI:0403”(colocalization)	0.600
TNPO2	GCH1	psi-mi:“MI:0915”(physical association)	0.560
GCH1	TNPO3	psi-mi:“MI:0915”(physical association)	0.560
GCH1	AHSA1	psi-mi:“MI:0915”(physical association)	0.510
AHSA1	GCH1	psi-mi:“MI:0915”(physical association)	0.510
GCH1	RPS12	psi-mi:“MI:0915”(physical association)	0.400
GCH1	GIT2	psi-mi:“MI:0915”(physical association)	0.370
CDC37	GCH1	psi-mi:“MI:0915”(physical association)	0.370
GCH1	SH3GL2	psi-mi:“MI:0915”(physical association)	0.370
GCH1	HSPA8	psi-mi:“MI:0915”(physical association)	0.370
RAB26	GCH1	psi-mi:“MI:0915”(physical association)	0.370
CNRIP1	GCH1	psi-mi:“MI:0915”(physical association)	0.370
RLF	GCH1	psi-mi:“MI:0915”(physical association)	0.370
SP3	GCH1	psi-mi:“MI:0915”(physical association)	0.370
GCH1	SP3	psi-mi:“MI:0915”(physical association)	0.370
GCH1	GCH1	psi-mi:“MI:0915”(physical association)	0.370
GCH1	GCHFR	psi-mi:“MI:0915”(physical association)	0.370
GCH1	SECTM1	psi-mi:“MI:0914”(association)	0.350
GCH1	ARHGAP42	psi-mi:“MI:0914”(association)	0.350
TNPO2	GCH1	psi-mi:“MI:0915”(physical association)	0.000
TNPO3	GCH1	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (83): ARMC8 (Affinity Capture-MS), EIF4G1 (Affinity Capture-MS), GID4 (Affinity Capture-MS), GID8 (Affinity Capture-MS), MAEA (Affinity Capture-MS), MID1IP1 (Affinity Capture-MS), PLOD2 (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), RANBP9 (Affinity Capture-MS), RMND5A (Affinity Capture-MS), RRM1 (Affinity Capture-MS), SECTM1 (Affinity Capture-MS), SNX9 (Affinity Capture-MS), SQSTM1 (Affinity Capture-MS), TCEB2 (Affinity Capture-MS)

ESM2 similar proteins: A0A0E2IV13, A2SQD1, A4TKV8, A7FJS2, A8FWJ5, A8ZZ65, A9R2N5, B1JQQ0, B1VB70, B2JYU0, D0KZ73, D0LHE3, K9Y6N7, K9Y7V9, O30709, O83405, O87689, P0A328, P0A329, P0A330, P22288, P23656, P30793, P45690, P46205, P63746, P63747, P63748, P72760, P73406, P73407, P76540, Q05915, Q1CA21, Q1CGL4, Q2NU68, Q31QW7, Q31RK2, Q31RK3, Q55550

Diamond homologs: A0Q2L7, A1VXS2, A4J5D0, A4SF37, A5D2D8, A5N6S3, A6LFE8, A7GW42, A7H1R1, A7ZB36, A8AZD8, A8FJZ5, A9KFF3, A9NDB3, B0K5C1, B0KCE5, B0S1R1, B0S8X8, B0SRX6, B1HTA3, B2J1L7, B2RIJ1, B2UU76, B2V9P4, B5Z7T2, B6JME9, B9E092, B9KDZ8, C0QPU5, C1DHG2, C5BL73, O13774, O61573, O66603, P22288, P30793, P48596, P50141, P51594, P51599

SIGNOR signaling

19 interactions.

A	Effect	B	Mechanism
GCHFR	“down-regulates activity”	GCH1	binding
“UVB radiation”	up-regulates	GCH1
TNF	“up-regulates activity”	GCH1
AHSA1	“up-regulates activity”	GCH1	binding
CRP	“down-regulates activity”	GCH1
CRP	“down-regulates quantity by repression”	GCH1	“transcriptional regulation”
CTF1	“down-regulates quantity by repression”	GCH1	“transcriptional regulation”
IL6	“down-regulates quantity by repression”	GCH1	“transcriptional regulation”
GDNF	“up-regulates activity”	GCH1
HSPB1	“up-regulates quantity by stabilization”	GCH1	binding
IFNG	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
IL1B	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
JUN	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
ATF2	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
CREB1	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NFYA	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NFYB	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NFYC	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”
NGF	“up-regulates quantity by expression”	GCH1	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	87
Likely pathogenic	30
Uncertain significance	247
Likely benign	179
Benign	30

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070262	NC_000014.8:g.(?55313807)(55313858_?)del	Pathogenic
1070263	NC_000014.8:g.(?55332039)(55369387_?)del	Pathogenic
1070688	NM_000161.3(GCH1):c.158G>A (p.Trp53Ter)	Pathogenic
1298582	NM_000161.3(GCH1):c.220_223dup (p.Tyr75fs)	Pathogenic
1334460	NM_000161.3(GCH1):c.728dup (p.Phe244fs)	Pathogenic
1354621	NM_000161.3(GCH1):c.109G>T (p.Glu37Ter)	Pathogenic
1419261	NM_000161.3(GCH1):c.212del (p.Leu71fs)	Pathogenic
1432028	NM_000161.3(GCH1):c.724G>T (p.Glu242Ter)	Pathogenic
1452723	NM_000161.3(GCH1):c.1A>C (p.Met1Leu)	Pathogenic
1454629	NC_000014.8:g.(?55312466)(55313868_?)del	Pathogenic
1454630	NC_000014.8:g.(?55310735)(55313868_?)del	Pathogenic
1455907	NM_000161.3(GCH1):c.453+2T>G	Pathogenic
1457490	NM_000161.3(GCH1):c.395_396del (p.Val132fs)	Pathogenic
1460271	NC_000014.8:g.(?55369019)(55369381_?)del	Pathogenic
1685843	NM_000161.3(GCH1):c.601G>T (p.Gly201Ter)	Pathogenic
1685844	NM_000161.3(GCH1):c.510-1G>T	Pathogenic
1803977	NM_000161.3(GCH1):c.287G>A (p.Trp96Ter)	Pathogenic
2135414	NM_000161.3(GCH1):c.185del (p.Glu62fs)	Pathogenic
2135615	NM_000161.3(GCH1):c.49del (p.Arg17fs)	Pathogenic
2135851	NM_000161.3(GCH1):c.626+2T>C	Pathogenic
2137592	NM_000161.3(GCH1):c.233del (p.Ile78fs)	Pathogenic
2422499	NC_000014.8:g.(?55310735)(55326474_?)del	Pathogenic
2444362	NM_000161.3(GCH1):c.544C>T (p.Gln182Ter)	Pathogenic
2578718	NM_000161.3(GCH1):c.505del (p.Ala169fs)	Pathogenic
280517	NM_000161.3(GCH1):c.159G>A (p.Trp53Ter)	Pathogenic
2925514	NM_000161.3(GCH1):c.751T>C (p.Ter251Arg)	Pathogenic
2925519	NM_000161.3(GCH1):c.453+1G>A	Pathogenic
2947428	NM_000161.3(GCH1):c.307C>T (p.Gln103Ter)	Pathogenic
2953555	NM_000161.3(GCH1):c.601G>C (p.Gly201Arg)	Pathogenic
3243958	NC_000014.8:g.(?55310735)(55369403_?)del	Pathogenic

SpliceAI

1863 predictions. Top by Δscore:

Variant	Effect	Δscore
14:54844000:CACA:C	donor_gain	1.0000
14:54844002:CACA:C	donor_gain	1.0000
14:54844004:CA:C	donor_gain	1.0000
14:54844005:A:AC	donor_gain	1.0000
14:54844006:C:CC	donor_gain	1.0000
14:54844019:AGCT:A	donor_gain	1.0000
14:54844020:G:C	donor_gain	1.0000
14:54844045:T:TA	donor_gain	1.0000
14:54844046:C:A	donor_gain	1.0000
14:54865320:ACCTT:A	donor_loss	1.0000
14:54865321:CCTTA:C	donor_loss	1.0000
14:54865323:TTAC:T	donor_loss	1.0000
14:54865324:TACCT:T	donor_loss	1.0000
14:54865325:A:AG	donor_loss	1.0000
14:54865326:C:CA	donor_loss	1.0000
14:54865434:CAT:C	acceptor_gain	1.0000
14:54865435:ATC:A	acceptor_loss	1.0000
14:54865437:CTGA:C	acceptor_loss	1.0000
14:54902319:ACCTG:A	donor_loss	1.0000
14:54902320:C:CT	donor_loss	1.0000
14:54843970:C:CT	donor_gain	0.9900
14:54843971:T:TT	donor_gain	0.9900
14:54843999:A:AC	donor_gain	0.9900
14:54844000:C:CC	donor_gain	0.9900
14:54844000:CA:C	donor_gain	0.9900
14:54844139:TGTGT:T	acceptor_gain	0.9900
14:54844144:C:CC	acceptor_gain	0.9900
14:54845766:A:AC	donor_gain	0.9900
14:54845767:C:CC	donor_gain	0.9900
14:54845767:CGTTG:C	donor_gain	0.9900

AlphaMissense

1645 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:54844039:A:G	F244S	1.000
14:54844134:A:C	C212W	1.000
14:54844135:C:A	C212F	1.000
14:54844135:C:T	C212Y	1.000
14:54844136:A:G	C212R	1.000
14:54844142:G:C	H210D	1.000
14:54845772:C:G	A208P	1.000
14:54845786:C:T	G203E	1.000
14:54845792:C:T	G201E	1.000
14:54845825:G:T	A190D	1.000
14:54845826:C:G	A190P	1.000
14:54845840:A:G	L185P	1.000
14:54845848:C:A	Q182H	1.000
14:54845848:C:G	Q182H	1.000
14:54847110:C:A	R177I	1.000
14:54859681:C:A	R170M	1.000
14:54859689:T:A	K167N	1.000
14:54859689:T:G	K167N	1.000
14:54859690:T:A	K167I	1.000
14:54859693:C:A	S166I	1.000
14:54859699:C:T	G164D	1.000
14:54859726:C:T	G155D	1.000
14:54859729:A:T	I154N	1.000
14:54865331:C:T	G150E	1.000
14:54865343:A:T	V146D	1.000
14:54865348:G:C	H144Q	1.000
14:54865348:G:T	H144Q	1.000
14:54865350:G:C	H144D	1.000
14:54865350:G:T	H144N	1.000
14:54865351:A:C	H143Q	1.000

dbSNP variants (sampled 300 via entrez): RS1000118322 (14:54870436 C>T), RS1000135249 (14:54861867 C>A), RS1000158059 (14:54893931 C>T), RS1000376189 (14:54848358 A>G), RS1000387623 (14:54878938 T>C), RS1000389322 (14:54858852 A>G), RS1000426561 (14:54894222 C>T), RS1000445910 (14:54901119 G>A), RS1000461727 (14:54866566 T>C), RS1000525680 (14:54871528 C>T), RS1000584088 (14:54903919 G>A,C), RS1000670915 (14:54866368 A>G), RS1000737204 (14:54864766 G>A), RS1000749108 (14:54871249 G>C), RS1000803221 (14:54865324 T>C)

Disease associations

OMIM: gene MIM:600225 | disease phenotypes: MIM:128230, MIM:233910, MIM:261640

GenCC curated gene-disease

Disease	Classification	Inheritance
dystonia 5	Definitive	Autosomal dominant
GTP cyclohydrolase I deficiency with hyperphenylalaninemia	Definitive	Autosomal recessive
GTP cyclohydrolase I deficiency	Definitive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
GTP cyclohydrolase I deficiency	Definitive	SD

Mondo (9): dystonia 5 (MONDO:0007495), GTP cyclohydrolase I deficiency (MONDO:0100184), GTP cyclohydrolase I deficiency with hyperphenylalaninemia (MONDO:0100186), hyperphenylalaninemia due to tetrahydrobiopterin deficiency (MONDO:0016543), intellectual disability (MONDO:0001071), dopa-responsive dystonia (MONDO:0016812), dystonic disorder (MONDO:0003441), BH4-deficient hyperphenylalaninemia A (MONDO:0009863), dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive (MONDO:0100098)

Orphanet (6): Autosomal dominant dopa-responsive dystonia (Orphanet:98808), GTP cyclohydrolase I deficiency (Orphanet:2102), Hyperphenylalaninemia due to tetrahydrobiopterin deficiency (Orphanet:238583), Dopa-responsive dystonia (Orphanet:255), 6-pyruvoyl-tetrahydropterin synthase deficiency (Orphanet:13), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

75 total (30 of 75 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000365	Hearing impairment
HP:0000473	Torticollis
HP:0000496	Abnormality of eye movement
HP:0000666	Horizontal nystagmus
HP:0000716	Depression
HP:0000722	Compulsive behaviors
HP:0000737	Irritability
HP:0000739	Anxiety
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001254	Lethargy
HP:0001257	Spasticity
HP:0001260	Dysarthria
HP:0001263	Global developmental delay
HP:0001266	Choreoathetosis
HP:0001290	Generalized hypotonia
HP:0001300	Parkinsonism
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001370	Rheumatoid arthritis
HP:0001761	Pes cavus
HP:0001762	Talipes equinovarus

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST001454_11	Rheumatoid arthritis	2.000000e-06
GCST001762_867	Obesity-related traits	1.000000e-06
GCST001762_928	Obesity-related traits	6.000000e-08
GCST002544_1	Parkinson’s disease	6.000000e-11
GCST002927_23	Mercury levels	5.000000e-06
GCST003542_167	Night sleep phenotypes	2.000000e-06
GCST003984_6	Parkinson’s disease	9.000000e-15
GCST004902_7	Parkinson’s disease	4.000000e-16
GCST007576_130	Chronotype	7.000000e-09
GCST009325_16	Parkinson’s disease or first degree relation to individual with Parkinson’s disease	2.000000e-16
GCST010991_42	Parkinson’s disease	1.000000e-10
GCST012020_194	Serum metabolite levels	5.000000e-15
GCST012020_335	Serum metabolite levels	7.000000e-48
GCST012021_119	Serum metabolite levels	5.000000e-15

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005116	urinary metabolite measurement
EFO:0008328	chronotype measurement

MeSH disease descriptors (4)

Descriptor	Name	Tree numbers
D020821	Dystonic Disorders	C10.228.662.300
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
C535325	6-pyruvoyl-tetrahydropterin synthase deficiency (supp.)
C538007	Dystonia, Dopa-responsive (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB variants

3 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs752688	GCH1		0.00	0
rs4411417	GCH1		0.00	0
rs3783641	GCH1		0.00	0

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	9
Air Pollutants	affects cotreatment, affects expression, increases abundance, increases expression, decreases expression	4
Estradiol	affects expression, affects binding, increases expression, affects cotreatment, decreases expression	4
sodium arsenite	affects cotreatment, decreases expression, increases abundance, increases expression	3
(+)-JQ1 compound	increases expression	3
Particulate Matter	decreases expression, increases abundance, increases expression	3
sapropterin	decreases abundance, decreases reaction, increases chemical synthesis	2
methylmercuric chloride	increases expression, decreases expression	2
Decitabine	increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Cisplatin	affects cotreatment, increases expression, decreases expression	2
Ethyl Methanesulfonate	decreases expression, increases expression	2
Methyl Methanesulfonate	decreases expression, increases expression	2
Tretinoin	increases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
alpha-pinene	increases abundance, affects cotreatment, affects expression	1
bisphenol A	decreases expression	1
VX-agent	increases expression	1
trichostatin A	increases expression	1
butyraldehyde	increases expression	1
methacrylaldehyde	affects cotreatment, affects expression, increases abundance	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
beta-methylcholine	affects expression	1
GW 501516	decreases expression, decreases reaction	1
pyrazolanthrone	decreases reaction, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’,5-brominated diphenyl ether	increases expression	1
nutlin 3	affects cotreatment, increases expression	1

Cellosaurus cell lines

10 cell lines: 6 induced pluripotent stem cell, 4 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1FE	Abcam A-549 GCH1 KO 1	Cancer cell line	Male
CVCL_B2MY	Abcam A-549 GCH1 KO 2	Cancer cell line	Male
CVCL_E4SZ	KOLF2.1J GCH1 G201E SNV/SNV	Induced pluripotent stem cell	Male
CVCL_E4T0	KOLF2.1J GCH1 G201E SNV/WT	Induced pluripotent stem cell	Male
CVCL_E4T1	KOLF2.1J GCH1 1.5kbdel DEL/DEL	Induced pluripotent stem cell	Male
CVCL_QX40	DHMCi002-A	Induced pluripotent stem cell	Female
CVCL_QX84	CIRAi001-A	Induced pluripotent stem cell	Male
CVCL_SP81	HAP1 GCH1 (-) 1	Cancer cell line	Male
CVCL_SP82	HAP1 GCH1 (-) 2	Cancer cell line	Male
CVCL_UM02	DHMCi002-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
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
NCT00142259	PHASE4	UNKNOWN	Efficacy and Safety of DBS of the GPi in Patients With Primary Generalized and Segmental Dystonia
NCT00950196	PHASE4	COMPLETED	Amantadine for Improving Neurologic Symptoms in Ataxia-Telangiectasia
NCT00998660	PHASE4	COMPLETED	RECHARGE Sub-Study to the Implantable Systems Performance Registry (ISPR)
NCT02263417	PHASE4	COMPLETED	A Randomized Controlled Trail Comparing Subthalamic and Pallidal Deep Brain Stimulation for Dystonia
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
NCT00169403	PHASE3	UNKNOWN	Pallidal Stimulation in Patients With Idiopathic Generalised Dystonia
NCT03232320	PHASE3	COMPLETED	Meditoxin® Treatment in Patients With Cervical Dystonia
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
NCT00001784	PHASE2	COMPLETED	Mexiletine for the Treatment of Focal Dystonia
NCT00105430	PHASE2	COMPLETED	Deep Brain Stimulation for Cervical Dystonia
NCT00106782	PHASE2	COMPLETED	Transcranial Electrical Polarization to Treat Focal Hand Dystonia
NCT00122044	PHASE2	COMPLETED	Childhood Hypertonia of Central Origin: A Trial of Anticholinergic Treatment Effects
NCT00169338	PHASE2	COMPLETED	Pallidal Stimulation in Patients With Post-anoxic and Idiopathic Dystonia
NCT00331669	PHASE2	UNKNOWN	Efficacy and Safety of Deep Brain Stimulation (DBS) of the Pallidal (GPi) in Patients With Tardive Dystonia
NCT02107261	PHASE2	COMPLETED	Incobotulinum Toxin A (Xeomin®) As A Treatment For Focal Task-Specific Dystonia Of The Musician’s Hand
NCT02470325	PHASE2	UNKNOWN	The Effects of Cannabis on Dystonia and Spasticity on Pediatric Patients
NCT05027997	PHASE2	COMPLETED	Exploratory Study of Dipraglurant (ADX48621) for the Treatment of Patients With Blepharospasm
NCT06412653	PHASE2	COMPLETED	Prospective Pilot Trial to Address Feasibility and Safety of Oral Zinc in GNAO1 Associated Disorders
NCT07304089	PHASE2	RECRUITING	A Study to Evaluate the Efficacy, Safety, and Tolerability of VIM0423 in Individuals With Isolated Dystonia
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)
NCT01433757	PHASE1	COMPLETED	Ampicillin for DYT-1 Dystonia Motor Symptoms
NCT01698450	PHASE1	COMPLETED	Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders
NCT02982304	PHASE1	UNKNOWN	Multi-Target Pallidal and Thalamic Deep Brain Stimulation for Hemi-Dystonia
NCT06117020	PHASE1	COMPLETED	Single and Multiple Ascending Dose Study of MTR-601 in Healthy Individuals
NCT06554288	PHASE1	RECRUITING	Pharmacogenomic Contributions to Trihexyphenidyl Biotransformation and Response in Children With Dystonic Cerebral Palsy
NCT03428009	Not specified	RECRUITING	Dystonia Genotype-Phenotype Correlation
NCT07018271	Not specified	NOT_YET_RECRUITING	A Study on the Use of Sulpegfilgrastim to Prevent the Incidence of Neutropenia With Infection in Newly Diagnosed Non-transplant Multiple Myeloma Patients
NCT03655223	Not specified	ENROLLING_BY_INVITATION	Early Check: Expanded Screening in Newborns
NCT03519711	PHASE1/PHASE2	COMPLETED	A Study of PTC923 (CNSA-001) in Primary Tetrahydrobiopterin (BH4) Deficient Participants With Hyperphenylalaninemia