GCH1
Chr 14ADARGTP cyclohydrolase 1
Also known as: DYT14, DYT5, DYT5a, GCH, GTP-CH-1, GTPCH1, HPABH4B
The protein is GTP cyclohydrolase I, the rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis that converts GTP to 7,8-dihydroneopterin triphosphate, with BH4 serving as an essential cofactor for aromatic amino acid hydroxylases and nitric oxide synthases. Loss-of-function mutations cause dopa-responsive dystonia (autosomal dominant) and BH4-deficient hyperphenylalaninemia (autosomal recessive). The pathogenic mechanism involves loss of enzyme function leading to BH4 deficiency and subsequent impairment of dopamine and other neurotransmitter synthesis.
Definitive — sufficient evidence for diagnostic panels
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
More LoF-intolerant than ~75% of genes
Mild missense constraint
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.
ClinVar Variant Classifications
0 submitted variants in ClinVar
Protein Context — Lollipop Plot
GCH1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Long-read Genome Sequencing for the Molecular Diagnosis of Dystonia
NOT YET RECRUITINGPersonalized Perioperative Analgesia Platform (PPAP) for Pediatric Spine Fusion Surgery (sIRB)
RECRUITINGPrecision Analgesia for Cardiac Surgery
NOT YET RECRUITINGExternal Resources
Links to major genomics databases and tools