Gene Report

Basic information

Related studies

Functional annotation

Related other genetic factors

Overlap with SZ and MDD

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Basic Info

Approved Symbol	GCH1
Previous Symbol	GCH, DYT5, DYT14
Symbol Alias	GTPCH1, DYT5a
Approved Name	GTP cyclohydrolase 1
Previous Name	dystonia 14
Name Alias	dopa-responsive dystonia
Location	14q22.1-q22.2
Position	chr14:54842008-54902852, -1
External Links	HGNC: 4193 Entrez Gene: 2643 Ensembl: ENSG00000131979 UCSC: uc001xbi.1
No. of Studies	2 (Positive: 1; Negative: 1; trend: 0)
Overlap with SZ?	NO
Overlap with MDD?	YES

Gene related studies (count: 2)

Reference	Tested Markers	Statistical Values/Author Comments	Result Category	Comment on Study
Kishi, T.,2012(b)	SNP: rs3783641, rs8007267, rs841 Haplotype: rs8007267 - rs378364 - rs841(C-T-C), rs8007267 - rs378364 - rs841(C-T-T), rs8007267 - rs378364 - rs841(T-A-C)	Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.	Negative	Comment on Study
Kealey, C.,2005	Other variant: GCH1_-959G/A	It provides preliminary support for an association between a novel GCHI variant and BPD within the Irish population.	Positive	Comment on Study

Gene functional annotation

Gene related GO terms (count: 37)

GO terms by PBA (count: 2)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0005634	nucleus	cellular component	IDA[16778797]	283
GO:0005509	calcium ion binding	molecular function	IEA	50

GO terms by database search (count: 35)

ID	Name	Type	Evidence[PMID]	No. of Genes in BDgene
GO:0006729	tetrahydrobiopterin biosynthetic process	biological process	IDA[7678411]; IMP[17101830]	3
GO:0034612	response to tumor necrosis factor	biological process	IDA[9445252]	3
GO:0050662	coenzyme binding	molecular function	IEA	3
GO:0032496	response to lipopolysaccharide	biological process	IDA[7678411]; IEP[15604419]	22
GO:0005829	cytosol	cellular component	IDA[2463916]; TAS	223
GO:0051260	protein homooligomerization	biological process	IDA[11087823]	13
GO:0006809	nitric oxide biosynthetic process	biological process	NAS[9445252]	8
GO:0003934	GTP cyclohydrolase I activity	molecular function	IDA[16778797]; IDA[11284739]	1
GO:0005515	protein binding	molecular function	IPI[16696853]	563
GO:0008270	zinc ion binding	molecular function	IDA[11087823]	77
GO:0034341	response to interferon-gamma	biological process	IDA[12607127]	2
GO:0046209	nitric oxide metabolic process	biological process	TAS	5
GO:0051000	positive regulation of nitric-oxide synthase activity	biological process	IDA[12176133]; IMP[17717598]	5
GO:0014916	regulation of lung blood pressure	biological process	IEA	1
GO:0005525	GTP binding	molecular function	IDA[14717702]	20
GO:0043234	protein complex	cellular component	IDA[11087823]	27
GO:0005654	nucleoplasm	cellular component	IDA	163
GO:0035998	7,8-dihydroneopterin 3'-triphosphate biosynthetic process	biological process	IEA	1
GO:0048265	response to pain	biological process	ISS	8
GO:0050884	neuromuscular process controlling posture	biological process	IMP[7874165]	2
GO:0042803	protein homodimerization activity	molecular function	IPI[1669853]	71
GO:0042559	pteridine-containing compound biosynthetic process	biological process	IDA[15721862]	1
GO:0042416	dopamine biosynthetic process	biological process	IDA[16338639]	6
GO:0030742	GTP-dependent protein binding	molecular function	IEA	2
GO:0050999	regulation of nitric-oxide synthase activity	biological process	TAS	6
GO:0051291	protein heterooligomerization	biological process	IEA	8
GO:0046654	tetrahydrofolate biosynthetic process	biological process	IEA	1
GO:0008152	metabolic process	biological process	IDA[3753653]	50
GO:0005737	cytoplasm	cellular component	IDA	322
GO:0031410	cytoplasmic vesicle	cellular component	IDA[3318829]	7
GO:0042311	vasodilation	biological process	IEA	6
GO:0031965	nuclear membrane	cellular component	IDA	15
GO:0045776	negative regulation of blood pressure	biological process	IEA	10
GO:0044281	small molecule metabolic process	biological process	TAS	117
GO:0008217	regulation of blood pressure	biological process	IMP[17717598]	12

Gene related KEGG pathways (count: 1)

KEGG pathways by PBA (count: 0)

KEGG pathways by database search (count: 1)

ID	Name	No. of Genes in BDgene	Brief Description
hsa00790	Folate biosynthesis	7

Gene related BioCarta pathways (count: 0)

Gene related interactors from protein-protein interactions data in HPRD (count: 7)

Gene	Interactor	Interactor in BDgene?	Experiment Type	PMID
GCH1	RLF	YES	yeast 2-hybrid	16696853
GCH1	ATP1B1	YES	yeast 2-hybrid	16696853
GCH1	RPH3A	NO	in vivo	7802677
GCH1	RAB26	NO	yeast 2-hybrid	16696853
GCH1	AHSA1	NO	yeast 2-hybrid	16696853
GCH1	GCHFR	NO	in vitro	8702680
GCH1	HSPA8	NO	yeast 2-hybrid	16696853

Related other genetic factors

Gene related SNPs (count: 25)

Literature-origin SNPs (count: 3)

rs_ID	Location	Functional Annotation	No. of Studies (Positive/Negative/Trend)
rs3783641	chr14:54893421 - 54893421(1)	intron_variant; non_coding_transcript_variant	1(0/1/0)
rs8007267	chr14:54912273 - 54912273(1)		1(0/1/0)
rs841	chr14:54843774 - 54843774(1)	3_prime_UTR_variant; intron_variant; non_coding_transcript_exon_variant; non_coding_transcript_variant; splice_region_variant	1(0/1/0)

LD-proxies (count: 22)

rs_ID	Location	Functional Annotation
rs4411417	chr14:54853845 - 54853845(1)	intron_variant; non_coding_transcript_variant
rs10133662	chr14:54849552 - 54849552(1)	intron_variant; non_coding_transcript_variant
rs7155309	chr14:54856133 - 54856133(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs2878168	chr14:54854067 - 54854067(1)	intron_variant; non_coding_transcript_variant
rs10483639	chr14:54839739 - 54839739(1)	downstream_gene_variant
rs17128004	chr14:54839522 - 54839522(1)	downstream_gene_variant
rs10131232	chr14:54849190 - 54849190(1)	intron_variant; non_coding_transcript_variant
rs752688	chr14:54844851 - 54844851(1)	intron_variant; non_coding_transcript_variant
rs2057368	chr14:54837291 - 54837291(1)	downstream_gene_variant
rs2145945	chr14:54837362 - 54837362(1)	downstream_gene_variant
rs2057369	chr14:54837343 - 54837343(1)	downstream_gene_variant
rs9671455	chr14:54862362 - 54862362(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant
rs8007201	chr14:54858130 - 54858130(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs8020798	chr14:54886650 - 54886650(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs12587434	chr14:54858865 - 54858865(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs12589758	chr14:54859144 - 54859144(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant
rs9671371	chr14:54861917 - 54861917(1)	downstream_gene_variant; intron_variant; non_coding_transcript_variant
rs3759664	chr14:54904861 - 54904861(1)	upstream_gene_variant
rs8017210	chr14:54895118 - 54895118(1)	intron_variant; non_coding_transcript_variant
rs2878172	chr14:54906952 - 54906952(1)	upstream_gene_variant
rs7147201	chr14:54892159 - 54892159(1)	intron_variant; non_coding_transcript_variant
rs17128052	chr14:54889807 - 54889807(1)	intron_variant; non_coding_transcript_variant; upstream_gene_variant

Gene related CNVs (count: 0)

Gene related other variants (count: 1)

Variant Name	Variant Type	Location in Gene	No. of Studies (Positive/Negative/Trend)
GCH1_-959G/A	point mutation		1 (1/0/0)

Gene related regions (count: 5)

Region Name	Position	No. of Studies (Positive/Negative/Trend)
14q22-24	chr14:50400000-78800000	1 (0/0/1)
Chr 14	chr14:0-107043718	2 (0/2/0)
14q22	chr14:50400000-57600000	1 (0/1/0)
14q12-q22.3	chr14:24100000-57600000	1 (1/0/0)
14q13.1-q24.1	chr14:32900000-69800000	1 (0/1/0)

Overlap with schizophrenia (SZ) and major depressive disorder (MDD)

Gene relationship with SZ

Gene relationship with MDD

Overlap with MDD from cross-disorder studies (count: 1)

Reference	Description	Category in MDD
22770721	Results suggest that GCH1 may predict response to SSRI in MDD in the Japanese population. Nevertheless, a replication study using larger samples may be required for conclusive results, since our sample size was small.	Negative

Overlap with MDD from candidate gene intersection analysis (count: 0)

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Region: chr14:54842008..54902852 View in gBrowse