GCH1 GTP cyclohydrolase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: GCH1provided by HGNC
Official Full Name: GTP cyclohydrolase 1provided by HGNC
Primary source: HGNC:HGNC:4193
See related: Ensembl:ENSG00000131979 MIM:600225; AllianceGenome:HGNC:4193
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: GCH; DYT5; DYT14; DYT5a; GTPCH1; HPABH4B; GTP-CH-1
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]
Expression: Broad expression in liver (RPKM 22.0), bone marrow (RPKM 9.4) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q22.2

Exon count:: 10

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (54842017..54902826, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (49047244..49108020, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (55308735..55369544, complement)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Long non-coding RNA lung cancer-associated transcript 1 regulates ferroptosis via microRNA-34a-5p-mediated GTP cyclohydrolase 1 downregulation in lung cancer cells.
Title: Long non‑coding RNA lung cancer‑associated transcript 1 regulates ferroptosis via microRNA‑34a‑5p‑mediated GTP cyclohydrolase 1 downregulation in lung cancer cells.
GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner.
Title: GTP Cyclohydrolase Drives Breast Cancer Development and Promotes EMT in an Enzyme-Independent Manner.
Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.
Title: Tyrosine hydroxylase variants influence protein expression, cellular localization, stability, enzymatic activity and the physical interaction between tyrosine hydroxylase and GTP cyclohydrolase 1.
Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.
Title: Nitrosative stress induced by homocysteine thiolactone drives vascular cognitive impairments via GTP cyclohydrolase 1 S-nitrosylation in vivo.
CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis.
Title: CircLRFN5 inhibits the progression of glioblastoma via PRRX2/GCH1 mediated ferroptosis.
Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson's disease.
Title: Association analysis of SYT11, FGF20, GCH1 rare variants in Parkinson's disease.
GCH1 mutations in hereditary spastic paraplegia.
Title: GCH1 mutations in hereditary spastic paraplegia.
Polymorphisms of Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 genes in trigeminal neuralgia.
Title: Polymorphisms of Nav1.6 sodium channel, Brain-derived Neurotrophic Factor, Catechol-O-methyltransferase and Guanosine Triphosphate Cyclohydrolase 1 genes in trigeminal neuralgia.
Biophysical and structural investigation of the regulation of human GTP cyclohydrolase I by its regulatory protein GFRP.
Title: Biophysical and structural investigation of the regulation of human GTP cyclohydrolase I by its regulatory protein GFRP.
Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.
Title: Oxidative Stress, GTPCH1, and Endothelial Nitric Oxide Synthase Uncoupling in Hypertension.

Submit: New GeneRIF Correction See all GeneRIFs (152)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Dystonia 5 MedGen: C1851920 OMIM: 128230 GeneReviews: GTP Cyclohydrolase 1-Deficient Dopa-Responsive Dystonia	Compare labs
GTP cyclohydrolase I deficiency with hyperphenylalaninemia MedGen: CN305333 OMIM: 233910 GeneReviews: Not available	Compare labs

Copy number response

Description
Copy number response Triplosensitivity No evidence available (Last evaluated 2023-02-14) ClinGen Genome Curation Page Haploinsufficency Sufficient evidence for dosage pathogenicity (Last evaluated 2023-02-14) ClinGen Genome Curation PagePubMed

EBI GWAS Catalog

Description
Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of GTP cyclohydrolase 1 (GCH1) in primary human brain microvascular endothelial cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G35399 (e-PCR)
- UniSTS:27158

D4S283 (e-PCR)
- UniSTS:63660

D14S1260 (e-PCR)
- UniSTS:34488

D14S1057 (e-PCR), detects polymorphism
- UniSTS:34500

D14S1190 (e-PCR)
- UniSTS:33272

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IBA Inferred from Biological aspect of Ancestor more info
enables GTP binding	IDA Inferred from Direct Assay more info	PubMed
enables GTP cyclohydrolase I activity	IBA Inferred from Biological aspect of Ancestor more info
NOT enables GTP cyclohydrolase I activity	IDA Inferred from Direct Assay more info	PubMed
enables GTP cyclohydrolase I activity	IDA Inferred from Direct Assay more info	PubMed
enables GTP-dependent protein binding	IEA Inferred from Electronic Annotation more info
enables GTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables mitogen-activated protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables protein-containing complex binding	IEA Inferred from Electronic Annotation more info
enables zinc ion binding	IBA Inferred from Biological aspect of Ancestor more info
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in dihydrobiopterin metabolic process	IEA Inferred from Electronic Annotation more info
involved_in dopamine biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of blood pressure	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cellular senescence	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within neuromuscular process controlling posture	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nitric oxide biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of heart rate	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of nitric-oxide synthase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of nitric-oxide synthase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of telomere maintenance via telomerase	IEA Inferred from Electronic Annotation more info
involved_in protein-containing complex assembly	IEA Inferred from Electronic Annotation more info
involved_in pteridine-containing compound biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of blood pressure	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of lung blood pressure	IEA Inferred from Electronic Annotation more info
involved_in regulation of removal of superoxide radicals	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to lipopolysaccharide	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in response to lipopolysaccharide	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to pain	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to tumor necrosis factor	IDA Inferred from Direct Assay more info	PubMed
involved_in response to type II interferon	IDA Inferred from Direct Assay more info	PubMed
involved_in tetrahydrobiopterin biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in tetrahydrobiopterin biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in tetrahydrobiopterin biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in tetrahydrofolate biosynthetic process	IEA Inferred from Electronic Annotation more info
involved_in vasodilation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
located_in neuron projection terminus	TAS Traceable Author Statement more info	PubMed
located_in nuclear membrane	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: GTP cyclohydrolase 1

Names: GTP cyclohydrolase I; GTP-CH-I; dystonia 14; guanosine 5'-triphosphate cyclohydrolase I

NP_000152.1

EC 3.5.4.16

NP_001019195.1

EC 3.5.4.16

NP_001019241.1

EC 3.5.4.16

NP_001019242.1

EC 3.5.4.16

NP_001411033.1

EC 3.5.4.16

NP_001411034.1

EC 3.5.4.16

XP_047287217.1

EC 3.5.4.16

XP_054231824.1

EC 3.5.4.16

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008647.2 RefSeqGene

Range

5000..65809

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_000161.3 → NP_000152.1 GTP cyclohydrolase 1 isoform 1

See identical proteins and their annotated locations for NP_000152.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as Type I, represents the longest transcript. Variants 1 and 2 encode the longest isoform (1), which is the active enzyme.

Source sequence(s)

AL133444, AL160471

Consensus CDS

CCDS9720.1

UniProtKB/Swiss-Prot

P30793, Q6FHY7, Q9Y4I8

Related

ENSP00000419045.2, ENST00000491895.7

Conserved Domains (2) summary

cd00642
Location:66 → 250

GTP_cyclohydro1; GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In ...

NF033930
Location:8 → 56

pneumo_PspA; pneumococcal surface protein A
NM_001024024.2 → NP_001019195.1 GTP cyclohydrolase 1 isoform 1

See identical proteins and their annotated locations for NP_001019195.1

Status: REVIEWED

Description

Transcript Variant: This variant (2), also known as Type V, differs in the 3' UTR, compared to variant 1. Variants 1 and 2 both encode the functional enzyme, isoform 1.

Source sequence(s)

AL133444, AL160471

Consensus CDS

CCDS9720.1

UniProtKB/Swiss-Prot

P30793, Q6FHY7, Q9Y4I8

Related

ENSP00000378890.1, ENST00000395514.5

Conserved Domains (2) summary

cd00642
Location:66 → 250

GTP_cyclohydro1; GTP cyclohydrolase I (GTP-CH-I) catalyzes the conversion of GTP into dihydroneopterin triphosphate. The enzyme product is the precursor of tetrahydrofolate in eubacteria, fungi, and plants and of the folate analogs in methanogenic bacteria. In ...

NF033930
Location:8 → 56

pneumo_PspA; pneumococcal surface protein A
NM_001024070.2 → NP_001019241.1 GTP cyclohydrolase 1 isoform 2

See identical proteins and their annotated locations for NP_001019241.1

Status: REVIEWED

Description

Transcript Variant: This variant (3), also known as Type IV, uses alternate, in-frame splice sites in the 3' coding region and 3' UTR, compared to variant 1. The resulting non-functional protein (isoform 2) is shorter and has a distinct C-terminus, compared to isoform 1.

Source sequence(s)

AL133444, AL160471

Consensus CDS

CCDS41954.1

UniProtKB/Swiss-Prot

P30793

Related

ENSP00000444011.2, ENST00000543643.6

Conserved Domains (2) summary

NF033930
Location:8 → 56

pneumo_PspA; pneumococcal surface protein A

cl00263
Location:66 → 209

TFold; Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl ...
NM_001024071.2 → NP_001019242.1 GTP cyclohydrolase 1 isoform 3

See identical proteins and their annotated locations for NP_001019242.1

Status: REVIEWED

Description

Transcript Variant: This variant (4), also known as Type II, lacks an alternate in-frame exon in the 3' coding region and uses a downstream stop codon, compared to variant 1. The resulting non-functional protein (isoform 3) is shorter and has a distinct C-terminus, compared to variant 1.

Source sequence(s)

AL133444, AL160471

Consensus CDS

CCDS45110.1

UniProtKB/Swiss-Prot

P30793

Related

ENSP00000445246.2, ENST00000536224.2

Conserved Domains (2) summary

NF033930
Location:8 → 56

pneumo_PspA; pneumococcal surface protein A

cl00263
Location:66 → 209

TFold; Tunnelling fold (T-fold). The five known T-folds are found in five different enzymes with different functions: dihydroneopterin-triphosphate epimerase (DHNTPE), dihydroneopterin aldolase (DHNA) , GTP cyclohydrolase I (GTPCH-1), 6-pyrovoyl ...
NM_001424104.1 → NP_001411033.1 GTP cyclohydrolase 1 isoform 4

Status: REVIEWED

Source sequence(s)

AL133444, AL160471
NM_001424105.1 → NP_001411034.1 GTP cyclohydrolase 1 isoform 5

Status: REVIEWED

Source sequence(s)

AL133444, AL160471