GTP cyclohydrolase I deficiency: genes and variants
GTP cyclohydrolase I deficiency is linked to 1 analyzed protein (GCH1). 19 DNA variants are known to cause it; 135 more are uncertain, and 3 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Genes linked to GTP cyclohydrolase I deficiency
GCH1: GTP cyclohydrolase 1
It catalyzes the rate-limiting step in tetrahydrobiopterin synthesis, supplying an essential cofactor for dopamine, serotonin, norepinephrine, and nitric-oxide production. Dominant loss-of-function variants classically cause dopa-responsive dystonia, while biallelic deficiency can produce severe neurotransmitter disease.
19 disease-causing and 135 uncertain variants in GCH1 are linked to GTP cyclohydrolase I deficiency.
Known disease-causing variants in GTP cyclohydrolase I deficiency
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| GCH1 T94M | 94 | Disease-causing (★★) | |
| GCH1 Q180R | 180 | Disease-causing (★★) | |
| GCH1 R184H | 184 | Disease-causing (★★) | |
| GCH1 G203R | 203 | Disease-causing (★★) | |
| GCH1 V205E | 205 | Disease-causing (★★) | |
| GCH1 R241Q | 241 | Disease-causing (★★) | |
| GCH1 M1V | 1 | Disease-causing (★★) | |
| GCH1 M211T | 211 | Disease-causing (★) | |
| GCH1 T94K | 94 | Disease-causing (★) | |
| GCH1 R178S | 178 | Disease-causing (★) | |
| GCH1 M1L | 1 | Disease-causing (★) | |
| GCH1 L91Q | 91 | Disease-causing (★) | |
| GCH1 M211V | 211 | Disease-causing (★) | |
| GCH1 L71P | 71 | Disease-causing (★) | |
| GCH1 E84G | 84 | Disease-causing (★) | |
| GCH1 A98V | 98 | Disease-causing (★) | |
| GCH1 P147L | 147 | Disease-causing (★) | |
| GCH1 I193N | 193 | Disease-causing (★) | |
| GCH1 G201R | 201 | Disease-causing (★) |
Uncertain variants in GTP cyclohydrolase I deficiency that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| GCH1 R184C | 184 | Conflicting reports (★) | +6: in a 3D region that tolerates change poorly (1R); R184H at the same position is pathogenic; REVEL 0.891 | |
| GCH1 R178G | 178 | Conflicting reports (★) | +6: 2 other pathogenic changes within 3 positions; R178S at the same position is pathogenic; REVEL 0.938 | |
| GCH1 P147T | 147 | Uncertain (★) | +6: P147L at the same position is pathogenic; REVEL 0.954 |
Diseases related to GTP cyclohydrolase I deficiency
- Autosomal recessive DOPA responsive dystonia, also linked to GCH1
- GTP cyclohydrolase I deficiency with hyperphenylalaninemia, also linked to GCH1
Frequently asked questions
Which genes are linked to GTP cyclohydrolase I deficiency?
In CATVariant, GTP cyclohydrolase I deficiency is linked to 1 analyzed protein: GCH1 (GTP cyclohydrolase 1).
How many genetic variants are linked to GTP cyclohydrolase I deficiency?
165 variants: 19 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 135 are of uncertain significance or have conflicting reports.
Which uncertain variants in GTP cyclohydrolase I deficiency look disease-causing?
3 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example GCH1 R184C, GCH1 R178G and GCH1 P147T. These are leads for expert review, not diagnoses.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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