About Gene List

PF3D7_1224000 (GCH1)

Genome location: Pf3D7_12_v3:974,226..976,097(+)

Genome classification: Core

Function and Localization

Product Description: GTP cyclohydrolase 1

SignalP Peptide: N/A

# Transmembrane Domains: 0

EC Numbers: 3.5.4.16 (GTP cyclohydrolase I)

Curated GO (PlasmoDB):

Type GO Term Name
Component GO:0005737 cytoplasm
Component GO:0005739 mitochondrion
Component GO:0005634 nucleus
Function GO:0005525 GTP binding
Function GO:0003934 GTP cyclohydrolase I activity
Function GO:0008270 zinc ion binding
Process GO:0009396 folic acid-containing compound biosynthetic process
Process GO:0006730 one-carbon metabolic process
Process GO:0009410 response to xenobiotic stimulus
Process GO:0006729 tetrahydrobiopterin biosynthetic process

Expression by stage (LR - Le Roch et al., and MCA - Malaria Cell Atlas):

Stage LR class MCA mean MCA prop. zeros
Sporozoite not expressed N/A N/A
Ring expressed 0.36 0.83
Trophozoite expressed 1.51 0.31
Schizont expressed 0.45 0.73
Gametocyte not expressed 0.55 0.71

More info:

Resistome Mutations

Old (Pf3D7v3) Gene ID: PF3D7_1224000

Resistome Missense Mutations: None

Resistome Compounds with Missense Mutations: None

Resistome # Samples with Disruptive Mutations: 0 (0 missense, 0 "interesting" missense)

Essentiality (ABS)

Zhang Phenotype: Mutable in CDS

MIS: 1 | MFS: -2.119 | #Insertions: 6

PlasmoGEM Phenotype: Dispensable (Pb ortholog: PBANKA_1438900)

  • Relative Growth Rate: 0.93 ± 0.23
  • Confidence: 4.36

RMgmDB ABS Phenotype: Not different from wild type (Pb ortholog: PBANKA_1438900)

Modification: Disrupted | RMgm-4612

More info: PhenoPlasm Link

Binding Evidence

AlphaFill Uniprot ID: Q8I5H7

"Best" AlphaFill ligand hit: 3PO (triphosphate, Local RMSD=0.02) with 1WPL (Global RMSD=2.97)

BRENDA EC Inhibitors:

EC # Name EC Inhibitors
3.5.4.16 GTP cyclohydrolase I ATPADPGTPGDPCTPUTPKClGMPITPTTPEDTAdGTP...

No evidence of orthology to BindingDB entries

Orthology Information

Ortholog Group (OrthoMCL): OG6_101153

Most Similar Human Ortholog: P30793

TM-align score: 0.70 | RMSD: 2.56

Seq Identity: 0.31 | Length: 191 / 389

All Human Orthologs (OrthoMCL):

Gene ID Description
ENSG00000131979 GTP cyclohydrolase 1

Genetic Variation

MalariaGEN Pf7 (worldwide samples) # unique SNV/indels:

Homozygous genotype calls only

variant type common rare doubleton singleton
synonymous 3 13 5 21
disruptive 11 32 11 41
missense 11 32 10 37

Any inclusion in genotype call

variant type common rare doubleton singleton
synonymous 9 21 9 28
disruptive 24 56 29 86
missense 19 50 20 63

PlasmoDB Total SNPs: 75

Non-coding: 52 | Synonymous: 11 | Nonsynonymous: 12 | Stop Codon: 0

Protein Information

Protein Length: 389 | Molecular Weight (kDa): 45.877

UniProt ID(s): O97071, Q8I5H7

PDB ID(s): None

Isoelectric Point: 9.89

Protein Domain Annotations:

Source Family ID Description
InterPro IPR001474 GTP cyclohydrolase I
InterPro IPR020602 GTP cyclohydrolase I domain
PFam PF01227 GTP cyclohydrolase I domain
Superfamily SSF55620 N/A

Associated Publications

PMID Title Authors DOI/Link
12368864 Genome sequence of the human malaria parasite Plasmodium falciparum. Gardner MJ, Hall N, ..., Barrell B 10.1038/nature01097
23181666 Organellar proteomics reveals hundreds of novel nuclear proteins in the malariaparasite Plasmodium falciparum. Oehring SC, Woodcroft BJ, ..., Voss TS 10.1186/gb-2012-13-11-r108
24745605 Biochemical and functional characterization of Plasmodium falciparum GTPcyclohydrolase I. Kumpornsin K, Kotanan N, ..., Chookajorn T 10.1186/1475-2875-13-150
30265714 Amplification of GTP-cyclohydrolase 1 gene in Plasmodium falciparum isolates withthe quadruple mutant of dihydrofolate reductase and dihydropteroate synthasegenes in Ghana. Osei M, Ansah F, ..., Duah NO 10.1371/journal.pone.0204871
34494883 A Prioritized and Validated Resource of Mitochondrial Proteins in PlasmodiumIdentifies Unique Biology. van Esveld SL, Meerstein-Kessel L, ..., Huynen MA 10.1128/mSphere.00614-21