GCH1

is a	gene
is	mentioned by
Full name	GTP cyclohydrolase 1
Other names	GCH GTPCH
Related	GCHFR
EntrezGene	2643
PheGenI	2643
VariationViewer	2643
ClinVar	GCH1
GeneCards	GCH1
dbSNP	2643
Diseases	GCH1
SADR	2643
HugeNav	2643
wikipedia	GCH1
google	GCH1
gopubmed	GCH1
EVS	GCH1
HEFalMp	GCH1
MyGene2	GCH1
23andMe	GCH1
UniProt	P30793
Ensembl	ENSG00000131979
OMIM	600225
# SNPs	48

	Max Magnitude	Chromosome position
i5000643
i5000644
i5000649
i5000652
i5000654
i5000655
rs10483639	0	54,839,739
rs104894433	4.4	54,902,402
rs104894434	4	54,844,108
rs104894435	4	54,902,341
rs104894436	4.4	54,845,808
rs104894437	4.4	54,865,379
rs104894438	4.4	54,845,792
rs104894439	4.4	54,902,661
rs104894440	4.4	54,865,349
rs104894441	4.4	54,865,376
rs104894442	4	54,844,023
rs104894443	4	54,844,137
rs104894444	4.4	54,902,522
rs104894445	4	54,845,843
rs1064796560	0	54,902,363
rs11158026	0	54,882,151
rs12147422	0	54,877,297
rs1263510185	0	54,902,412
rs137852633	4	54,845,799
rs17128050	0	54,877,161
rs17738966	0	54,835,501
rs200891969	0	54,845,784
rs2878172	0	54,906,952
rs3759664	0	54,904,861
rs3783637	0	54,881,400
rs3783641	0	54,893,421
rs41298442	5	54,844,099
rs4411417	0	54,853,845
rs7142517	0	54,840,086
rs752688	0	54,844,851
rs753312849	0	54,902,489
rs770547722	0	54,902,425
rs8004018	0	54,883,978
rs8007201	0	54,858,130
rs8007267	0	54,912,273
rs841	2	54,843,774
rs886039378	0	54,845,784
rs886039379	6	54,844,138
rs886041708	0	54,902,505
rs961694546	0	54,902,439
rs988395114	0	54,845,787
rs998259	0	54,888,313

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
- The 3 SNPs defining this are: rs8007267(T) - rs3783641(A) - rs10483639(C) (listed in 5' to 3' order based on the GCH1 gene on the reverse strand, and, with alleles as defined in dbSNP on the forward strand)
  - The gs223 genoset defines carriers of a single "X" haplotype, and the gs224 genoset defines 'double cats', i.e. carriers of two X haplotypes (who carry C-A-T alleles for rs10483639-rs3783641-rs8007267)
rs841, which is in tight (~85 - 95%) linkage with the X haplotype

And for those wondering which GCH1 gene SNPs in SNPedia are tested by the platforms used by different companies along with ClinVar annotations, here's a table; feel free to suggest more GCH1 SNPs to add to SNPedia if you feel important ones are missing:

	In gene	On microarray	ClinVar CLNSIG	ClinVar CLNDBN
i5000643	GCH1	23andMe v4 23andMe v3
i5000644	GCH1	23andMe v4 23andMe v3
i5000649	GCH1	23andMe v4 23andMe v3
i5000652	GCH1	23andMe v4 23andMe v3
i5000654	GCH1	23andMe v4 23andMe v3
i5000655	GCH1	23andMe v4 23andMe v3
rs10483639	GCH1	23andMe v4 Ancestry v2 Ancestry v2c 23andMe v3 Affy GenomeWide 6 23andMe v1 23andMe v2 Ancestry v2d
rs104894433	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894434	GCH1	Ancestry v2 Ancestry v2d	5	Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
rs104894435	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
rs104894436	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894437	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894438	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894439	GCH1		5	Dystonia 5, Dopa-responsive type
rs104894440	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894441	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894442	GCH1	Ancestry v2 Ancestry v2d	5	Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
rs104894443	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	GTP cyclohydrolase I deficiency
rs104894444	GCH1	Ancestry v2 Ancestry v2d	5	Dystonia 5, Dopa-responsive type
rs104894445	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	GTP cyclohydrolase I deficiency
rs1064796560	GCH1		4	not provided
rs11158026	GCH1	Ancestry v2 23andMe v5 Ancestry v2c Ancestry v2d
rs12147422	GCH1	23andMe v4 23andMe v3 23andMe v1 23andMe v2
rs1263510185	GCH1
rs137852633	GCH1	Ancestry v2 Ancestry v2c Ancestry v2d	5	Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
rs17128050	GCH1	Affy GenomeWide 6 FTDNA2 HumanOmni1Quad Illumina Human 1M
rs17738966	GCH1	NatGeo2 23andMe v4 23andMe v3 23andMe v1 23andMe v2 Illumina Human 1M
rs200891969	GCH1	Ancestry v2 Ancestry v2d	4	Dystonia, dopa-responsive not specified not provided
rs2878172	GCH1	FamilyTreeDNA 23andMe v4 Ancestry v2 23andMe v3 FTDNA2 23andMe v1 23andMe v2 Illumina Human 1M Ancestry v2d
rs3759664	GCH1	Illumina Human 1M
rs3783637	GCH1	23andMe v4 Ancestry v2 23andMe v5 Ancestry v2c 23andMe v3 FTDNA2 HumanOmni1Quad 23andMe v1 23andMe v2 Illumina Human 1M Ancestry v2d
rs3783641	GCH1	23andMe v4 Ancestry v2 Ancestry v2c 23andMe v3 23andMe v1 23andMe v2 Ancestry v2d
rs41298442	GCH1	FamilyTreeDNA 23andMe v4 Ancestry v2 Ancestry v2c 23andMe v3 FTDNA2 23andMe v2 Ancestry v2d	5	Dystonia 5, Dopa-responsive type Dystonia, dopa-responsive, with or without hyperphenylalaninemia, autosomal recessive
rs4411417	GCH1	23andMe v4 Ancestry v2 23andMe v3 23andMe v1 23andMe v2 Ancestry v2d
rs7142517	GCH1	FamilyTreeDNA 23andMe v4 Ancestry v2 Ancestry v2c 23andMe v3 FTDNA2 HumanOmni1Quad 23andMe v1 23andMe v2 Illumina Human 1M Ancestry v2d
rs752688	GCH1	FamilyTreeDNA 23andMe v4 Ancestry v2 23andMe v3 FTDNA2 23andMe v1 23andMe v2 Ancestry v2d
rs753312849	GCH1
rs770547722	GCH1
rs8004018	GCH1	23andMe v4 Ancestry v2 23andMe v5 Ancestry v2c 23andMe v3 FTDNA2 HumanOmni1Quad Illumina Human 1M Ancestry v2d
rs8007201	GCH1	23andMe v4 23andMe v3 23andMe v1 Illumina Human 1M
rs8007267	GCH1	NatGeo2 23andMe v4 Ancestry v2 Ancestry v2c 23andMe v3 23andMe v1 23andMe v2 Illumina Human 1M Ancestry v2d
rs841	GCH1	23andMe v4 Ancestry v2c 23andMe v3 FTDNA2 HumanOmni1Quad Illumina Human 1M	2	Dystonia, dopa-responsive GTP cyclohydrolase I deficiency not specified
rs886039378	GCH1		4	not provided
rs886039379	GCH1		5	not provided
rs886041708	GCH1		5	not provided
rs961694546	GCH1
rs988395114	GCH1		4	not provided
rs998259	GCH1	FamilyTreeDNA 23andMe v4 23andMe v3 Affy GenomeWide 6 FTDNA2 23andMe v1 23andMe v2