GCH1 is the gene responsible for the first, and rate-limiting, step in producing tetrahydrobiopterin (BH4) which is used as a cofactor in the production or conversion of several neurotransmitters.
Please note that reference GCH1 sequences use the reverse strand. Many journal articles will use minus orientation when reporting results, even for cases where the dbSNP orientation is plus. Some of the significant SNPs in this gene have ambiguous flips which can make interpreting things difficult.
GCH1 activity is regulated by GCHFR.
SNPs are common in the GCH1 gene, and most are benign. However, there are both rare and not-so-rare variants that have clinical consequences.
Rare variants associated with dystonia include:
- Autosomal dominant, loss-of-function mutations; these usually do not lead to hyperphenylalaninemia and so are not detected by newborn screening
- Autosomal recessive, reduction-in-function mutations; these do usually lead to hyperphenylalaninemia, so they are usually detected by newborn screening
Certain more common variants include:
- The variants comprising the "X" haplotype
- rs841, which is in tight (~85 - 95%) linkage with the X haplotype