CleftGeneDB-Search

Gene: GCH1

Basic information

Tag	Content
Uniprot ID	P30793; Q6FHY7; Q9Y4I8;
Entrez ID	2643
Genbank protein ID	AAB16861.1; AAB42186.1; CAA83213.1; AAB23166.1; AAH25415.1; CAB77391.1; CAG38788.1; EAW80647.1; AAB60633.1; AAD38866.1; AAB23165.1; CAB77392.1; AAB23164.1; AAD38868.1; CAA78908.1;
Genbank nucleotide ID	NM_000161.2; NM_001024070.1; NM_001024071.1; NM_001024024.1;
Ensembl protein ID	ENSP00000445246; ENSP00000477796; ENSP00000419045; ENSP00000378890; ENSP00000444011;
Ensembl nucleotide ID	ENSG00000131979
Gene name	GTP cyclohydrolase 1
Gene symbol	GCH1
Organism	Homo sapiens
NCBI taxa ID	9606
Cleft type
Developmental stage
Data sources	Manually collected
Reference	26215833
Functional description	Positively regulates nitric oxide synthesis in umbilical vein endothelial cells (HUVECs). May be involved in dopamine synthesis. May modify pain sensitivity and persistence. Isoform GCH-1 is the functional enzyme, the potential function of the enzymatically inactive isoforms remains unknown.
Sequence	MEKGPVRAPA EKPRGARCSN GFPERDPPRP GPSRPAEKPP RPEAKSAQPA DGWKGERPRS 60 EEDNELNLPN LAAAYSSILS SLGENPQRQG LLKTPWRAAS AMQFFTKGYQ ETISDVLNDA 120 IFDEDHDEMV IVKDIDMFSM CEHHLVPFVG KVHIGYLPNK QVLGLSKLAR IVEIYSRRLQ 180 VQERLTKQIA VAITEALRPA GVGVVVEATH MCMVMRGVQK MNSKTVTSTM LGVFREDPKT 240 REEFLTLIRS

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

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PDB ID
1FB1

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Protein disorder information

Orthologous information

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Relation	Gene symbol	Entrez ID	UniProt ID	Developmental stage	Species	Evidence	Details
1:1 ortholog	GCH1	2643	P30793		Homo sapiens	Publication	More>>
1:1 ortholog	GCH1	286815	F1MZ14		Bos taurus	Prediction	More>>
1:1 ortholog	GCH1	609393	E2RI70		Canis lupus familiaris	Prediction	More>>
1:1 ortholog	GCH1		A0A452F7E4		Capra hircus	Prediction	More>>
1:1 ortholog	Gch1	14528	Q05915	E14.5	Mus musculus	Prediction	More>>
1:1 ortholog	GCH1		A0A2I3RQP8		Pan troglodytes	Prediction	More>>
1:1 ortholog	GCH1		A0A287BGL7		Sus scrofa	Prediction	More>>
1:1 ortholog	GCH1	100286831	G1SIY3		Oryctolagus cuniculus	Prediction	More>>
1:1 ortholog	Gch1	29244	P22288		Rattus norvegicus	Prediction	More>>
1:1 ortholog	gch1	100192219	E7FGQ8		Danio rerio	Prediction	More>>

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Identified variants/mutations related to cleft phenotype

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Gene symbol	Significant Variants/SNPS	Methods	PubMed ID
GCH1	rs17128077	Single Nucleotide Polymorphism Selection and Genotyping	26215833

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Other genetic variants/mutations

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ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
rs41298432	p.Pro23Leu	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54902596G>A	UniProt,dbSNP
rs104894433	p.Arg88Trp	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54902402G>A	UniProt,dbSNP
rs104894435	p.Gly108Asp	missense variant	Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)	NC_000014.9:g.54902341C>T	UniProt,dbSNP
rs1393095176	p.Asp115Asn	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54902321C>T	UniProt,dbSNP
rs104894437	p.Asp134Val	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54865379T>A	UniProt,dbSNP
rs104894441	p.Ile135Lys	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54865376A>T	UniProt,dbSNP
rs104894440	p.His144Pro	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54865349T>G	UniProt,dbSNP
rs104894445	p.Arg184His	missense variant	Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)	NC_000014.9:g.54845843C>T	UniProt,dbSNP
rs762208304	p.Val191Ile	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54845823C>T	UniProt,dbSNP
rs104894438	p.Gly201Glu	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54845792C>T	UniProt,dbSNP
rs104894443	p.Met211Ile	missense variant	Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)	NC_000014.9:g.54844137C>T	UniProt,dbSNP
rs1348562494	p.Met213Val	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54844133T>C	UniProt,dbSNP
rs104894434	p.Met221Thr	missense variant	Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)	NC_000014.9:g.54844108A>G	UniProt,dbSNP
rs41298442	p.Lys224Arg	missense variant	Hyperphenylalaninemia, BH4-deficient, B (HPABH4B)	NC_000014.9:g.54844099T>C	UniProt,dbSNP
rs104894442	p.Arg249Ser	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54844023C>G	UniProt,dbSNP
VAR_002632	p.Gly15Asp	Missense	-	-	UniProt
VAR_002633	p.Pro23Leu	missense variant	Dystonia, dopa-responsive (DRD)	NC_000014.9:g.54902596G>A	UniProt
VAR_016888	p.Leu71Gln	Missense	Dystonia, dopa-responsive (DRD) [MIM:128230]	-	UniProt
VAR_016889	p.Ala74Val	Missense	Dystonia, dopa-responsive (DRD) [MIM:128230]	-	UniProt
VAR_072733	p.Tyr75Cys	Missense	-	-	UniProt

Showing 1 to 20 of 307 entries

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Disease or phenotype associated information

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Disease ID	Disease Name	Disease Type	Source
C0000768	Congenital Abnormality	group	BEFREE
C0002895	Anemia, Sickle Cell	disease	BEFREE
C0003467	Anxiety	disease	HPO
C0003850	Arteriosclerosis	disease	BEFREE
C0003864	Arthritis	disease	BEFREE
C0004153	Atherosclerosis	disease	BEFREE
C0005586	Bipolar Disorder	disease	BEFREE;LHGDN;PSYGENET
C0006012	Borderline Personality Disorder	disease	BEFREE
C0006111	Brain Diseases	group	BEFREE
C0006287	Bronchopulmonary Dysplasia	disease	BEFREE
C0007114	Malignant neoplasm of skin	disease	BEFREE
C0007193	Cardiomyopathy, Dilated	group	BEFREE
C0007222	Cardiovascular Diseases	group	BEFREE
C0007398	Catatonia	disease	BEFREE
C0007789	Cerebral Palsy	disease	BEFREE
C0009081	Congenital clubfoot	disease	HPO
C0009375	Colonic Neoplasms	group	BEFREE
C0010054	Coronary Arteriosclerosis	disease	BEFREE
C0010068	Coronary heart disease	disease	BEFREE
C0011053	Deafness	phenotype	HPO

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Gene Ontology (GO)/biological pathways

GO:Molecular Function

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GO ID	GO Term	Evidence
GO:0003924	GTPase activity	IDA
GO:0003934	GTP cyclohydrolase I activity	IDA
GO:0003934	GTP cyclohydrolase I activity	IBA
GO:0005509	calcium ion binding	IEA
GO:0005515	protein binding	IPI
GO:0005525	GTP binding	IDA
GO:0005525	GTP binding	IBA
GO:0008270	zinc ion binding	IDA
GO:0008270	zinc ion binding	IBA
GO:0030742	GTP-dependent protein binding	IEA
GO:0031369	translation initiation factor binding	IEA
GO:0042802	identical protein binding	IPI
GO:0042803	protein homodimerization activity	IPI
GO:0044877	protein-containing complex binding	IEA
GO:0050662	coenzyme binding	IEA
GO:0051019	mitogen-activated protein kinase binding	IPI

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GO:Biological Process

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GO ID	GO Term	Evidence
GO:0006729	tetrahydrobiopterin biosynthetic process	IMP
GO:0006729	tetrahydrobiopterin biosynthetic process	IBA
GO:0006729	tetrahydrobiopterin biosynthetic process	IDA
GO:0006809	nitric oxide biosynthetic process	NAS
GO:0008217	regulation of blood pressure	IMP
GO:0010460	positive regulation of heart rate	IEA
GO:0014916	regulation of lung blood pressure	IEA
GO:0032496	response to lipopolysaccharide	IDA
GO:0032496	response to lipopolysaccharide	IEP
GO:0034341	response to interferon-gamma	IDA
GO:0034612	response to tumor necrosis factor	IDA
GO:0035998	7,8-dihydroneopterin 3'-triphosphate biosynthetic process	IEA
GO:0042311	vasodilation	IEA
GO:0042416	dopamine biosynthetic process	IDA
GO:0042559	pteridine-containing compound biosynthetic process	IDA
GO:0045776	negative regulation of blood pressure	IEA
GO:0046654	tetrahydrofolate biosynthetic process	IEA
GO:0048265	response to pain	ISS
GO:0050884	neuromuscular process controlling posture	IMP
GO:0051000	positive regulation of nitric-oxide synthase activity	IDA

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GO:Cellular Component

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GO ID	GO Term	Evidence
GO:0005634	nucleus	IDA
GO:0005654	nucleoplasm	IDA
GO:0005737	cytoplasm	IDA
GO:0005737	cytoplasm	IBA
GO:0005829	cytosol	IDA
GO:0005829	cytosol	TAS
GO:0031410	cytoplasmic vesicle	IDA
GO:0031965	nuclear membrane	IDA
GO:0032991	protein-containing complex	IDA
GO:0044306	neuron projection terminus	TAS

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Reactome Pathway

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Reactome ID	Reactome Term	Evidence
R-HSA-1430728	Metabolism	TAS
R-HSA-1474151	Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation	TAS
R-HSA-196854	Metabolism of vitamins and cofactors	TAS
R-HSA-8978934	Metabolism of cofactors	TAS

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Drugs and compounds information

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ID	Drug Name	Action	PubMed
C000611646	bisphenol F	bisphenol F results in increased expression of GCH1 mRNA	30951980
C000944	dicrotophos	dicrotophos results in decreased expression of GCH1 mRNA	28302478
C002791	bismuth tripotassium dicitrate	bismuth tripotassium dicitrate results in increased expression of GCH1 mRNA	15912405
C003402	sapropterin	[4-hydroxy-2-nonenal results in decreased activity of GCH1 protein] which results in decreased chemical synthesis of sapropterin	17872449
C003402	sapropterin	Ascorbic Acid inhibits the reaction [[4-hydroxy-2-nonenal results in decreased activity of GCH1 protein] which results in decreased chemical synthesis of sapropterin]	17872449
C003402	sapropterin	lactacystin inhibits the reaction [[4-hydroxy-2-nonenal results in decreased activity of GCH1 protein] which results in decreased chemical synthesis of sapropterin]	17872449
C003402	sapropterin	EPO protein inhibits the reaction [GCH1 mutant form results in decreased abundance of sapropterin]	25041251
C003402	sapropterin	GCH1 mutant form results in decreased abundance of sapropterin	25041251
C003402	sapropterin	GCH1 protein results in increased chemical synthesis of sapropterin	14551046
C003402	sapropterin	EPO protein inhibits the reaction [[GCH1 gene mutant form results in increased oxidation of sapropterin] which results in increased chemical synthesis of 7,8-dihydrobiopterin]	25490417
C003402	sapropterin	GCH1 gene mutant form results in increased oxidation of and results in decreased abundance of sapropterin	25490417
C003402	sapropterin	[GCH1 gene mutant form results in increased oxidation of sapropterin] which results in increased chemical synthesis of 7,8-dihydrobiopterin	25490417
C003402	sapropterin	GCH1 protein affects the abundance of sapropterin	21963838
C003402	sapropterin	[Resveratrol results in increased expression of GCH1 mRNA] which results in increased abundance of sapropterin	20610621
C003402	sapropterin	2,4-diaminohypoxanthine inhibits the reaction [[GCH1 protein co-treated with Guanosine Triphosphate] results in increased chemical synthesis of sapropterin]	7756597
C003402	sapropterin	GCH1 protein affects the chemical synthesis of sapropterin	20610621
C003402	sapropterin	[GCH1 protein co-treated with Guanosine Triphosphate] results in increased chemical synthesis of sapropterin	7756597
C003402	sapropterin	GCH1 protein results in increased chemical synthesis of sapropterin	11368234
C004925	methylmercuric chloride	methylmercuric chloride results in decreased expression of GCH1 mRNA	23179753
C004925	methylmercuric chloride	methylmercuric chloride results in increased expression of GCH1 mRNA	28001369

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Functional annotations

Keywords

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Keyword ID	Keyword Term
KW-0002	3D-structure
KW-0021	Allosteric enzyme
KW-0025	Alternative splicing
KW-0225	Disease mutation
KW-0342	GTP-binding
KW-0378	Hydrolase
KW-0479	Metal-binding
KW-0539	Nucleus
KW-0547	Nucleotide-binding
KW-0586	Phenylketonuria
KW-0597	Phosphoprotein
KW-0621	Polymorphism
KW-0783	Tetrahydrobiopterin biosynthesis
KW-0862	Zinc
KW-0908	Parkinsonism
KW-0963	Cytoplasm
KW-1023	Dystonia
KW-1185	Reference proteome

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Interpro

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InterPro ID	InterPro Term
IPR001474	GTP_CycHdrlase_I
IPR018234	GTP_CycHdrlase_I_CS
IPR020602	GTP_CycHdrlase_I_dom
IPR043133	GTP-CH-I_C/QueF
IPR043134	GTP-CH-I_N

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PROSITE

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PROSITE ID	PROSITE Term
PS00859	GTP_CYCLOHYDROL_1_1
PS00860	GTP_CYCLOHYDROL_1_2

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Pfam

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Pfam ID	Pfam Term
PF01227	GTP_cyclohydroI

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Gene: GCH1

Basic information

Gene expression information

Gene expression in different tissues (GTEx V7)

Gene expression in different tissues (ENCODE)

Protein structural annotations

3D structure in PDB database

Protein disorder information

Orthologous information

Identified variants/mutations related to cleft phenotype

Other genetic variants/mutations

Disease or phenotype associated information

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Drugs and compounds information

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction