Gene TH
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Also known as
Tyrosine Hydroxylase, TYH, DYT5, DYT14, DYT5bOverview
TH (Tyrosine Hydroxylase) encodes the rate-limiting enzyme in the synthesis of catecholamine neurotransmitters, including dopamine, norepinephrine, and epinephrine. Tyrosine hydroxylase catalyzes the conversion of L-tyrosine to L-DOPA, the precursor to dopamine, in neurons of the substantia nigra, locus coeruleus, and adrenal medulla. This enzyme requires tetrahydrobiopterin (BH4) as a cofactor and is subject to complex regulation by phosphorylation, feedback inhibition, and transcriptional control. TH activity is essential for normal motor function, cognitive processes, mood regulation, and the stress response through the sympathetic nervous system.Mutations in TH cause tyrosine hydroxylase deficiency, a rare autosomal recessive disorder that presents with a spectrum of severity from infantile parkinsonism-dystonia to complex encephalopathy with severe cognitive and motor impairment. The clinical presentation depends on the degree of residual enzyme activity, with complete deficiency causing the most severe phenotype. TH deficiency is one of the causes of dopa-responsive dystonia (DRD), which typically shows dramatic improvement with L-DOPA therapy. Beyond monogenic disorders, genetic variants in TH have been investigated for associations with Parkinson's disease susceptibility, ADHD, mood disorders, and responses to dopaminergic medications. Understanding TH genetics can inform diagnosis of rare movement disorders and may contribute to personalized approaches in neuropsychiatric conditions.