GCH1 (GTP Cyclohydrolase 1)
Key enzyme in tetrahydrobiopterin biosynthesis and neurotransmitter regulation
Gene Information Card
| Symbol | GCH1 |
|---|---|
| Full Name | GTP Cyclohydrolase 1 |
| Gene Type | protein-coding |
| Chromosomal Location | 14q22.2 |
| NCBI Gene ID | 2643 ncbi.nlm.nih.gov/gene/2643 |
| Ensembl ID | ENSG00000131979 |
| UniProt ID | P30793 |
| OMIM ID | 600225 |
| HGNC ID | 4193 |
| Aliases | GCH, DYT5, GTPCH1, HPABH4B, BH4-deficient hyperphenylalaninemia B |
Description
The GCH1 gene encodes GTP cyclohydrolase 1, the first and rate-limiting enzyme in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for aromatic amino acid hydroxylases (phenylalanine, tyrosine, and tryptophan hydroxylases) and nitric oxide synthases. Mutations in GCH1 cause autosomal dominant dopa-responsive dystonia (DYT5) and autosomal recessive BH4-deficient hyperphenylalaninemia.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Dopa-responsive dystonia (DYT5) | Loss-of-function mutations reduce BH4 levels, impairing dopamine synthesis in nigrostriatal neurons | OMIM #128230 |
| BH4-deficient hyperphenylalaninemia type B | Biallelic mutations cause severe BH4 deficiency, leading to hyperphenylalaninemia and neurotransmitter depletion | OMIM #233910 |
| Segawa syndrome | Same as dopa-responsive dystonia; early-onset dystonia with diurnal fluctuation | ClinVar |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Liver | 12.3 | Medium |
| Brain (cerebellum) | 8.7 | Medium |
| Adrenal gland | 6.5 | Low |
| Kidney | 4.2 | Low |
| Heart | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HepG2 | 15.4 | Hepatocellular carcinoma cell line |
| SH-SY5Y | 9.8 | Neuroblastoma cell line |
| HEK293 | 7.3 | Embryonic kidney cells |
| A549 | 3.1 | Lung carcinoma cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.626C>T (p.Pro209Leu) | Missense | Common in DYT5 | Reduced enzyme activity |
| c.823G>A (p.Gly275Arg) | Missense | Rare | Loss of function |
| c.1A>G (p.Met1?) | Start loss | Very rare | Complete loss of protein |
| c.671_672del (p.Val224fs) | Frameshift | Reported | Loss of function |
Mutation functional classification
Loss of Function (LOF)
Most GCH1 mutations reduce or abolish GTP cyclohydrolase activity, leading to BH4 deficiency and impaired dopamine synthesis.
Gain of Function (GOF)
Not described for GCH1.
Dominant Negative (DN)
Some missense mutations in dopa-responsive dystonia exert a dominant-negative effect on the tetrameric enzyme complex.
View complete mutation data：
Gene Ontology (GO)
| • GTP cyclohydrolase I activity | • tetrahydrobiopterin biosynthetic process |
| • dopamine biosynthetic process | • nitric oxide biosynthetic process |
| • response to oxidative stress |
Pathways
• Tetrahydrobiopterin (BH4) biosynthesis
• Catecholamine biosynthesis
• Nitric oxide signaling
Protein Summary
GTP cyclohydrolase 1 is a homodecameric enzyme that catalyzes the conversion of GTP to 7,8-dihydroneopterin triphosphate, the first step in BH4 synthesis. BH4 is a critical cofactor for phenylalanine hydroxylase, tyrosine hydroxylase, tryptophan hydroxylase, and all nitric oxide synthases. Deficiency leads to neurotransmitter imbalances and metabolic disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| GCH1 Knockout HEK293 Cell Line | EDC07929 | Human | 2643 | Details Get a Quote |
| GCH1 Knockout A-549 Cell Line | EDJ-KQ27406 | Human | 2643 | Details Get a Quote |
| GCH1 Knockout HCT 116 Cell Line | EDJ-KQ27407 | Human | 2643 | Details Get a Quote |
| GCH1 Knockout HeLa Cell Line | EDJ-KQ27408 | Human | 2643 | Details Get a Quote |
| GCH1 Knockout HaCaT Cell Line | EDC08217 | Human | 2643 | Details Get a Quote |
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