GCH1 - GTP cyclohydrolase 1 Gene

Also Known as GCH; DYT5; DYT14; DYT5a; GTPCH1; HPABH4B; GTP-CH-1

Species: Homo sapiens

Gene Type: protein coding

Gene ID: 2643

About GCH1

Cytogenetic location: 14q22.2 Genomic coordinates (GRCh38): 14:54,842,017-54,902,826 (from NCBI)

This gene has 6 transcripts (splice variants), 215 orthologues and is associated with 6 phenotypes. Broad expression in liver (RPKM 22.0), bone marrow (RPKM 9.4) and 19 other tissues.

Summary

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. [provided by RefSeq, Jul 2008]

GCH1 Products (8)

mRNA	Protein	Name
NM_000161.3	NP_000152.1	GTP cyclohydrolase 1 isoform 1
NM_001024024.2	NP_001019195.1	GTP cyclohydrolase 1 isoform 1
NM_001024070.2	NP_001019241.1	GTP cyclohydrolase 1 isoform 2
NM_001024071.2	NP_001019242.1	GTP cyclohydrolase 1 isoform 3
NM_000161.3	NP_000152.1	GTP cyclohydrolase 1 isoform 1
NM_001024024.2	NP_001019195.1	GTP cyclohydrolase 1 isoform 1
NM_001024070.2	NP_001019241.1	GTP cyclohydrolase 1 isoform 2
NM_001024071.2	NP_001019242.1	GTP cyclohydrolase 1 isoform 3

Gene Ontology

Molecular Function
Biological Process
Cellular Component

Molecular Function GO Annotation	Evidence	References	Source
enables GTP binding	IDA IDA: Inferred from direct assay	3753653	GOA
NOT enables GTP cyclohydrolase I activity	IDA IDA: Inferred from direct assay	8068008	GOA
enables GTP cyclohydrolase I activity	IDA IDA: Inferred from direct assay	3753653	GOA
enables GTPase activity	IDA IDA: Inferred from direct assay	2463916	GOA
enables identical protein binding	IPI IPI: Inferred from physical interaction	11087827	GOA
enables mitogen-activated protein kinase binding	IPI IPI: Inferred from physical interaction	19294699	GOA
enables protein binding	IPI IPI: Inferred from physical interaction	9092499	GOA
enables protein homodimerization activity	IPI IPI: Inferred from physical interaction	16696853	GOA
enables zinc ion binding	IDA IDA: Inferred from direct assay	11087827	GOA

Biological Process GO Annotation	Evidence	References	Source
involved in dopamine biosynthetic process	IDA IDA: Inferred from direct assay	16338639	GOA
acts upstream of or within neuromuscular process controlling posture	IMP IMP: Inferred from mutant phenotype	7874165	GOA
involved in positive regulation of nitric-oxide synthase activity	IDA IDA: Inferred from direct assay	12176133	GOA
involved in positive regulation of nitric-oxide synthase activity	IMP IMP: Inferred from mutant phenotype	17717598	GOA
involved in pteridine-containing compound biosynthetic process	IDA IDA: Inferred from direct assay	2463916	GOA
involved in regulation of blood pressure	IMP IMP: Inferred from mutant phenotype	17717598	GOA
involved in regulation of removal of superoxide radicals	IMP IMP: Inferred from mutant phenotype	19666465	GOA
involved in response to lipopolysaccharide	IDA IDA: Inferred from direct assay	7678411	GOA
NOT involved in response to lipopolysaccharide	IEP IEP: Inferred from expression pattern	15604419	GOA
involved in response to tumor necrosis factor	IDA IDA: Inferred from direct assay	9445252	GOA
involved in response to type II interferon	IDA IDA: Inferred from direct assay	7678411	GOA
involved in tetrahydrobiopterin biosynthetic process	IDA IDA: Inferred from direct assay	7678411	GOA
involved in tetrahydrobiopterin biosynthetic process	IMP IMP: Inferred from mutant phenotype	17101830	GOA

Cellular Component GO Annotation	Evidence	References	Source
located in cytoplasm	IDA IDA: Inferred from direct assay	10907721	GOA
located in cytoplasmic vesicle	IDA IDA: Inferred from direct assay	3318829	GOA
located in cytosol	IDA IDA: Inferred from direct assay	2463916	GOA
located in nucleus	IDA IDA: Inferred from direct assay	16778797	GOA
part of protein-containing complex	IDA IDA: Inferred from direct assay	11087823	GOA

EXP: Inferred from Experiment IDA: Inferred from direct assay IPI: Inferred from physical interaction IMP: Inferred from mutant phenotype IGI: Inferred from genetic interaction IEP: Inferred from expression pattern

GCH1 Protein Structure

GTP_cyclohydroI

0
100
200
250 a.a.

Protein Preferred Names	Protein Names
GTP cyclohydrolase 1	GTP cyclohydrolase I

GCH1 Protein-protein interaction Information

Type	Protein Name	Protein ID	Interactor	Interactor Species	Interactor ID	Detection Method	References
Intra	GCH1	P30793	TNPO3	Homo sapiens	Q9Y5L0	Validated Y2H	32296183
Intra	GCH1	P30793	YWHAZ	Homo sapiens	P63104	Anti Tag CoIP	21988832
Intra	GCH1	P30793	YWHAZ	Homo sapiens	P63104	Y2H	21988832
Intra	GCH1	P30793	YWHAZ	Homo sapiens	P63104	Pull Down	21988832
Intra	GCH1	P30793	AHSA1	Homo sapiens	O95433	Y2H	16696853

Cross: Cross-species interaction Intra: Intraspecies interaction

Related Diseases

Diseases	Alias
Hyperphenylalaninemia, Bh4-Deficient, B	Gtp Cyclohydrolase I Deficiency HPABH4B Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To Gtp Cyclohydrolase I Deficiency Bh4-Deficient Hyperphenylalaninemia B Gtp Cyclohydrolase 1 Deficiency Tetrahydrobiopterin-Deficient Hyperphenylalaninemia B Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To Gtp Cyclohydrolase 1 Deficiency Gtpch Deficiency Hyperphenylalaninemia Due To Gtp Cyclohydrolase Deficiency Atypical Severe Phenylketonuria Due To Gtp Cyclohydrolase I Deficiency Gch1 Deficiency Guanosine Triphosphate Cyclohydrolase I Deficiency Hyperphenylalaninemia With Neopterin Deficiency
Dystonia, Dopa-Responsive	Dystonia 5 Dopa-Responsive Dystonia DRD Dyt5 Dystonia-Parkinsonism With Diurnal Fluctuation Dyt-Th Hpd With Diurnal Fluctuation Hereditary Progressive Dystonia With Diurnal Fluctuation Dystonia, Progressive, With Diurnal Variation Segawa Syndrome, Autosomal Dominant Dystonia, Dopa-Responsive, Autosomal Dominant Dopa-Responsive Dystonia, Autosomal Dominant Dystonia, Dopa-Responsive, With Or Without Hyperphenylalaninemia Dyt-Gch1 Dyt-Spr Dystonia 5, Dopa-Responsive Type Hereditary Progressive Dystonia With Marked Diurnal Fluctuation Autosomal Dominant Dopa-Responsive Dystonia Autosomal Dominant Segawa Syndrome Dystonia-5 Progressive Dystonia With Diurnal Fluctuation Dystonia, Type 5, Dopa-Responsive Type
Gtp Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia	Autosomal Dominant Dopa-Responsive Dystonia Autosomal Dominant Segawa Syndrome Dyt5a Hereditary Progressive Dystonia With Marked Diurnal Fluctuation Gtpch1-Deficient Drd Gtpch1-Deficient Dopa-Responsive Dystonia Dopa-Responsive Dystonia, With Or Without Hyperphenylalaninemia Dyt-Gch1 Dyt/Park-Gch1 Dopa-Responsive Dystonia Autosomal Dominant Segawa Syndrome Hpd With Marked Diurnal Fluctuation Dopa-Responsive Dystonia
Segawa Syndrome, Autosomal Recessive	Tyrosine Hydroxylase Deficiency Dystonia, Dopa-Responsive, Autosomal Recessive Parkinsonism, Infantile, Autosomal Recessive Segawa Syndrome, Recessive Dyt5b Th-Deficient Drd Tyrosine Hydroxylase-Deficient Dopa-Responsive Dystonia Autosomal Recessive Infantile Parkinsonism Autosomal Recessive Dopa-Responsive Dystonia Autosomal Recessive Dopa Responsive Dystonia Dopa-Responsive Dystonia, Autosomal Recessive Dopa Responsive Dystonia, Autosomal Recessive Dyt/Park-Th Dystonia, Dopa Responsive, Autosomal Recessive Th Deficiency Autosomal Recessive Segawa Syndrome Thy Segawa Syndrome Autosomal Recessive ARSEGS Thd Dystonia, Dopa-Responsive, With Or Without Hyperphenylalaninemia, Autosomal Recessive
Dystonia	Dystonic Disease Dystonic Disorder Dystonia Disorders Neuroleptic Dyskinesia
Oromandibular Dystonia
Hyperphenylalaninemia	Hyperphenylalaninaemia
Tetrahydrobiopterin Deficiency	Hyperphenylalaninemia Due To Tetrahydrobiopterin Deficiency Hyperphenylalaninemia, Non-Phenylketonuric Non-Phenylketonuric Hyperphenylalaninemia Bh4 Deficiency Hyperphenylalaninemia Caused By A Defect In Biopterin Metabolism Hyperphenylalaninemia Due To Bh4 Deficiency
Hyperphenylalaninemia, Bh4-Deficient, A	6-Pyruvoyl-Tetrahydropterin Synthase Deficiency Pts Deficiency HPABH4A Hyperphenylalaninemia, Tetrahydrobiopterin-Deficient, Due To Pts Deficiency Ptsd Bh4-Deficient Hyperphenylalaninemia A Hyperphenylalaninemia Due To 6-Pyruvoyltetrahydropterin Synthase Deficiency Tetrahydobioperin-Deficient Hyperphenylalaninemia Due To Pts Deficiency Hyperphenylalanemia, Bh4-Deficient, A Hyperphenylalaninemia Due To 6-Pyruvoyl-Tetrahydropterin Synthase Deficiency 6-Pyruvoyltetrahydropterin Synthase Deficiency Hyperphenylalaninemia Tetrahydrobiopterin-Deficient Due To Pts Deficiency Ptpsd Hyperphenylalaninemia, Bh4-Deficient, Type A
Hereditary Dystonia	Dystonia Hereditary Familial Dystonia
Parkinsonism	Parkinsonism-Plus Idiopathic Parkinsonism Primary Parkinsonism Paralysis Agitans Syndrome Parkinsonian Syndrome Trembling Paralysis Paralysis Agitans Shaking Palsy Shaking Paralysis
Movement Disease	Movement Disorders Movement Disorder
Phenylketonuria	Phenylalanine Hydroxylase Deficiency PKU Pah Deficiency Folling Disease Maternal Phenylketonuria Phenylketonurias Oligophrenia Phenylpyruvica Hyperphenylalaninemia, Non-Pku Mild Folling'S Disease Phenylalaninemia Mild Phenylketonuria Mild Pku Variant Pku Variant Phenylketonuria Mpku Deficiency Disease, Phenylalanine Hydroxylase Phenylketonuria, Maternal Phenylalanine Hydroxylase Deficiency Disease Hyperphenylalaninemic Embryopathy Maternal Pku Maternal Hyperphenylalaninemia Phenylketonuric Embryopathy Hyperphenylalaninemia HPA Non-Phenylketonuria Hyperphenylalaninemia NON-PKU HPA Phenylketonuria Maternal Classical Phenylketonuria Hyperphenylalaninaemia Pku - [Phenylketonuria]
Oculogyric Crisis
Segmental Dystonia
Thiamine Metabolism Dysfunction Syndrome 2	Biotin-Responsive Basal Ganglia Disease Basal Ganglia Disease, Biotin-Responsive THMD2 Bbgd Btbgd Encephalopathy, Thiamine-Responsive Thiamine Metabolism Dysfunction Syndrome 2, Biotin- Or Thiamine-Responsive Type Thiamine-Responsive Encephalopathy
Hemidystonia
Dystonia, Dopa-Responsive, Due To Sepiapterin Reductase Deficiency	Sepiapterin Reductase Deficiency Spr Deficiency Dopa-Responsive Dystonia Due To Sepiapterin Reductase Deficiency Srd Drd Due To Srd Dopa-Responsive Hypersomnia Dyt-Spr Dyt/Park-Spr Sr-Deficient Drd Autosomal Recessive Sepiapterin Reductase-Deficient Drd Spr DRDSPRD Motor And Cognitive Disorder Due To Sepiapterin Reductase Deficiency Psychomotor Disorders
Cervical Dystonia	Spasmodic Torticollis
Trigeminal Neuralgia	Tic Douloureux Trifacial Neuralgia Trifocal Neuralgia Neuralgia Of The Fifth Cranial Nerve Neuralgia Of 5th Cranial Nerve Infraorbital Neuralgia
Parkinson Disease, Late-Onset	Parkinson Disease Parkinson'S Disease PD PARK Parkinson Disease, Susceptibility To Late Onset Parkinson'S Disease Late Onset Parkinson Disease Paralysis Agitans Primary Parkinsonism Idiopathic Parkinson Disease Parkinson'S Parkinson Disease, Late-Onset, Susceptibility To Parkinson Disease, Age Of Onset, Modifier Lewy Body Parkinson Disease Idiopathic Parkinson'S Disease Pd - [Parkinson Disease] Parkinson Disease Nos Parkinson, Nos Primary Parkinson Disease
Spasmodic Dystonia	Laryngeal Dystonia
Multifocal Dystonia
Leber Optic Atrophy And Dystonia	LDYT Marsden Syndrome Leber Hereditary Optic Neuropathy With Dystonia Leber Hereditary Optic Neuropathy And Dystonia Familial Dystonia With Visual Failure And Striatal Lucencies Dystonia, Familial, With Visual Failure And Striatal Lucencies Leber Optic Atrophy With Dystonia Dystonia Familial, With Visual Failure And Striatal Lucencies Lhon And Dystonia Leber'S Hereditary Optic Neuropathy With Dystonia
Aromatic L-Amino Acid Decarboxylase Deficiency	Aadc Deficiency Dopa Decarboxylase Deficiency Ddc Deficiency Aromatic Amino Acid Decarboxylase Deficiency Deficiency Of Aromatic-L-Amino-Acid Decarboxylase AADCD Aromatic-L-Amino-Acid Decarboxylase Deficiency Aromatic L-Amino-Acid Decarboxylase Deficiency
Focal Dystonia	Dystonia, Focal, Task-Specific
Dystonia 3, Torsion, X-Linked	X-Linked Dystonia-Parkinsonism DYT3 Xdp Lubag Dystonia-Parkinsonism, X-Linked Torsion Dystonia-Parkinsonism, Filipino Type Dyt-Taf1 X-Linked Dystonia-Parkinsonism Syndrome X-Linked Torsion Dystonia-Parkinsonism Syndrome Dystonia Musculorum Deformans X-Linked Dystonia-Parkinsonism/Lubag Lubag Syndrome Dystonia-3 Torsion Dystonia-Parkinsonism Filipino Type X-Linked Torsion Dystonia 3 Dystonia, Torsion, X-Linked, Type 3
Dystonia 12	DYT12 Rdp Generalized Dystonia Dystonia-12 Rapid-Onset Dystonia-Parkinsonism Familial Dystonia Dystonia Musculorum Deformans Dystonic Disorders Idiopathic Familial Dystonia Dystonia-Parkinsonism, Rapid-Onset Fragments Of Torsion Dystonia Dyt-Atp1a3 Rapid-Onset Dystonia Parkinsonism Rodp Dystonia, Type 12 Dystonia 3, Torsion, X-Linked Idiopathic Non-Familial Dystonia Symptomatic Torsion Dystonia Dystonia Disorders
Dystonia 1, Torsion, Autosomal Dominant	Dystonia Musculorum Deformans 1 Dystonia Musculorum Deformans DYT1 Early-Onset Torsion Dystonia Eotd Dystonia-1, Torsion Torsion Dystonia 1 Autosomal Dominant Torsion Dystonia 1 Dystonia-1 Oppenheim'S Dystonia Oppenheim-Ziehen Disease Early Onset Torsion Dystonia Dystonia 3, Torsion, X-Linked
Blepharospasm
Focal Hand Dystonia	Organic Writer'S Cramp Dystonia, Focal, Task-Specific
Dystonia 11, Myoclonic	Myoclonic Dystonia Myoclonus-Dystonia Syndrome DYT11 Myoclonic Dystonia 11 Alcohol-Responsive Dystonia Myoclonus, Hereditary Essential Dystonia-11, Myoclonic Myoclonus-Dystonia Dystonia 11 Hereditary Essential Myoclonus Dystonia, Alcohol-Responsive Dyt-Sgce Dystonia, Alcohol Responsive Dystonia-11 Dystonia, Myoclonic Dystonia, Myoclonic, Type 11
Pheochromocytoma	Pheochromocytoma, Susceptibility To Phaeochromocytoma Adrenal Gland Chromaffin Paraganglioma Adrenal Gland Chromaffinoma Adrenal Gland Paraganglioma Adrenal Gland Pheochromocytoma Chromaffin Paraganglioma Of The Adrenal Gland Intraadrenal Paraganglioma PCC Chromaffin Cell Tumor Medullary Chromaffinoma Medullary Paraganglioma Pheochromoblastoma Pheochromocytomas Chromaffin Cell Neoplasm Pheochromocytoma, Malignant
Gliosarcoma	Glioblastoma With Sarcomatous Component Sarcomatous Glioblastoma
Bipolar Disorder	Bipolar Depression Manic Disorder Depression, Bipolar Bipolar Disorder Manic Phase Depressive-Manic Psych. Manic Bipolar Affective Disorder Manic Bipolar I Disorder Manic Depression Manic Depressive Disorder Mixed Bipolar Disorder Bipolar Affective Disorder Bipolar Affective Psychosis Bipolar Spectrum Disorder Manic Depressive Illness Depression Bipolar Bipolar Disorder, Mixed Major Affective Disorder Major Affective Disorder 1 Major Affective Disorder 2
Alternating Hemiplegia Of Childhood	Alternating Hemiplegia Ahc Alternating Hemiplegia Syndrome Hemiplegia, Alternating, Of Childhood Hemiplegia, Crossed
Leber Plus Disease	Leber Congenital Amaurosis Lca Leber'S Amaurosis Leber'S Disease Amaurosis Congenita Of Leber Amaurosis Congenita Of Leber, Type 1 Lhon Plus Disease Congenital Absence Of The Rods And Cones Congenital Retinal Blindness Crb Congenital Amaurosis Of Retinal Origin Leber'S Congenital Amaurosis Leber Congenital Amaurosis 1 Leber'S Congenital Tapetoretinal Degeneration Leber'S Congenital Tapetoretinal Dysplasia Lca1 Leber Congenital Amaurosis Type 1 Retinal Blindness, Congenital Amaurosis, Leber Congenital Dysgenesis Neuroepithelialis Retinae Hereditary Epithelial Dysplasia Of Retina Hereditary Retinal Aplasia Heredoretinopathia Congenitalis Leber Abiotrophy Leber Congenital Tapetoretinal Degeneration Lebers Congenital Amaurosis Optic Atrophy, Hereditary, Leber

Diseases	Alias
Waldenstroem'S Macroglobulinemia	Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma Waldenstroem'S Macroglobulinemia Waldenstroem'S Macroglobulinemia Macroglobulinemia Of Waldenstrom Lymphoplasmacytic Lymphoma With Igm Gammopathy Lymphoplasmacytic Lymphoma

Related Agents

Pre-clinical Phase

Pre-clinical Phase

Bioactive Molecules (4)

Cat. No.	Product Name	Effect	Purity	Rare Diseases
HY-171894	AXSP0056BS		/	Unkown
HY-RS05327	GCH1 Human Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS18133	Gch1 Mouse Pre-designed siRNA Set A	Pre-designed Set	/	Unkown
HY-RS24608	Gch1 Rat Pre-designed siRNA Set A	Pre-designed Set	/	Unkown

Orthologs Information

Species	Symbol	Source	ID
Canis familiaris	GCH1	VGNC	VGNC:41145
Rattus norvegicus	GCH1	RGD	RGD:61992
Macaca mulatta	GCH1	VGNC	VGNC:72900
Bos taurus	GCH1	VGNC	VGNC:29286
Mus musculus	GCH1	MGD	MGI:95675
Felis catus	GCH1	VGNC	VGNC:104393
Others	GCH1	NCBI