Autosomal recessive DOPA responsive dystonia: genes and variants
Autosomal recessive DOPA responsive dystonia is linked to 2 analyzed proteins (TH and GCH1). 25 DNA variants are known to cause it; 58 more are uncertain, and 1 of those already look disease-causing on computable evidence.
Last updated 2026-09-30. Research information, not medical advice.
Also known as: Autosomal recessive dopa-responsive dystonia
Genes linked to Autosomal recessive DOPA responsive dystonia
TH: Tyrosine 3-monooxygenase
It catalyzes the rate-limiting conversion of tyrosine to L-DOPA before dopamine, norepinephrine, and epinephrine synthesis. Biallelic pathogenic variants cause tyrosine-hydroxylase deficiency, ranging from dopa-responsive dystonia to severe infantile parkinsonism.
25 disease-causing and 58 uncertain variants in TH are linked to Autosomal recessive DOPA responsive dystonia.
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.
0 disease-causing and 0 uncertain variants in GCH1 are linked to Autosomal recessive DOPA responsive dystonia.
Known disease-causing variants in Autosomal recessive DOPA responsive dystonia
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TH R233H | 233 | Disease-causing (★★) | |
| TH R233C | 233 | Disease-causing (★★) | |
| TH L236P | 236 | Disease-causing (★★) | |
| TH R328W | 328 | Disease-causing (★★) | |
| TH R337H | 337 | Disease-causing (★★) | |
| TH C359F | 359 | Disease-causing (★★) | |
| TH F375L | 375 | Disease-causing (★★) | |
| TH I382T | 382 | Disease-causing (★★) | |
| TH T399M | 399 | Disease-causing (★★) | |
| TH G428R | 428 | Disease-causing (★★) | |
| TH G247S | 247 | Disease-causing (★★) | |
| TH S307Y | 307 | Disease-causing (★★) | |
| TH G315S | 315 | Disease-causing (★★) | |
| TH I394T | 394 | Disease-causing (★★) | |
| TH G414R | 414 | Disease-causing (★★) | |
| TH R484C | 484 | Disease-causing (★★) | |
| TH P492L | 492 | Disease-causing (★★) | |
| TH A241T | 241 | Disease-causing (★★) | |
| TH Q412K | 412 | Disease-causing (★★) | |
| TH D498G | 498 | Disease-causing (★★) | |
| TH H246Y | 246 | Disease-causing (★) | |
| TH R441P | 441 | Disease-causing (★) | |
| TH F309S | 309 | Disease-causing (★) | |
| TH R319P | 319 | Disease-causing (★) | |
| TH A376V | 376 | Disease-causing (★) |
Uncertain variants in Autosomal recessive DOPA responsive dystonia that look disease-causing
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| TH Q412H | 412 | Uncertain (★) | +6: 2 other pathogenic changes within 3 positions; Q412K at the same position is pathogenic; not seen in the gnomAD population database; AlphaMissense 0.73 |
Diseases related to Autosomal recessive DOPA responsive dystonia
- GTP cyclohydrolase I deficiency, also linked to GCH1
- GTP cyclohydrolase I deficiency with hyperphenylalaninemia, also linked to GCH1
Frequently asked questions
Which genes are linked to Autosomal recessive DOPA responsive dystonia?
In CATVariant, Autosomal recessive DOPA responsive dystonia is linked to 2 analyzed proteins: TH (Tyrosine 3-monooxygenase) and GCH1 (GTP cyclohydrolase 1).
How many genetic variants are linked to Autosomal recessive DOPA responsive dystonia?
120 variants: 25 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 58 are of uncertain significance or have conflicting reports.
Which uncertain variants in Autosomal recessive DOPA responsive dystonia look disease-causing?
1 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example TH Q412H. 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.
Download every variant as CSV · Browse all diseases · Methods · About the Center