PRPS1 phosphoribosyl pyrophosphate synthetase 1 [Homo sapiens] - Gene

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Summary

Official Symbol: PRPS1provided by HGNC
Official Full Name: phosphoribosyl pyrophosphate synthetase 1provided by HGNC
Primary source: HGNC:9462
Locus tag: RP11-540N4.1
See related: Ensembl:ENSG00000147224; HPRD:02413; MIM:304500; MIM:311850; Vega:OTTHUMG00000022167
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ARTS; DFN2; PRSI; CMTX5; DFNX1; PRS-I; PPRibP; KIAA0967
Summary: This gene encodes an enzyme that catalyzes the phosphoribosylation of ribose 5-phosphate to 5-phosphoribosyl-1-pyrophosphate, which is necessary for purine metabolism and nucleotide biosynthesis. Defects in this gene are a cause of phosphoribosylpyrophosphate synthetase superactivity, Charcot-Marie-Tooth disease X-linked recessive type 5 and Arts Syndrome. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

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Genomic context

Location :: Xq21.32-q24

Sequence :: Chromosome: X; NC_000023.10 (106871654..106894256)

See PRPS1 in Epigenomics, MapViewer

Chromosome X - NC_000023.10 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

Translocation of ARTS initiates a first wave of caspase activation leading to the subsequent release of additional mitochondrial factors, including cytochrome C and SMAC/Diablo.
Title: The IAP-antagonist ARTS initiates caspase activation upstream of cytochrome C and SMAC/Diablo.
Three HPRT1 mutations in Lesch-Nyhan families were identified but no mutation was identified in any patient in the analysis of PRPS1.
Title: Molecular analysis of X-linked inborn errors of purine metabolism: HPRT1 and PRPS1 mutations.
Refinements were made on the DFN2 locus on the X chromosome.
Title: Refinement of the locus for non-syndromic sensorineural deafness (DFN2).
In four hyperuricemic patients with mild neurological abnormality, molecular analysis of PRPS1 was performed , but no mutations in PRPP synthetase were found.
Title: Molecular analysis of two enzyme genes, HPRT1 and PRPS1, causing X-linked inborn errors of purine metabolism.
PRPS1 mutations; neurological phenotype in all four PRPS1-related disorders seems to result primarily from reduced levels of GTP & possibly other purine nucleotides including ATP, suggesting these disorders belong to the same disease spectrum [review]
Title: PRPS1 mutations: four distinct syndromes and potential treatment.
PRPS1 loss of function mutations cause a type of nonsyndromic X-linked sensorineural deafness, DFN2
Title: Loss-of-function mutations in the PRPS1 gene cause a type of nonsyndromic X-linked sensorineural deafness, DFN2.
The N114S mutation alters the secondary structure of PRS1;the structural alteration caused by the N114S mutation influences the conformation of the ATP-binding loop and leads to the loss of ATP-induced aggregation.
Title: N114S mutation causes loss of ATP-induced aggregation of human phosphoribosylpyrophosphate synthetase 1.
increased activity of this gene leads to gout
Title: [Increased activity of PRPP synthetase].
Missense mutations were identified at conserved amino acids in the PRPS1 gene on Xq22.3 in two families with a syndromic form of inherited peripheral neuropathy, one of Asian and one of European descent.
Title: Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (cmtx5).
Linkage analysis in a Dutch family and an Australian family suggested that the candidate gene for Arts syndrome is PRPS1, which maps to Xq22.1-q24.
Title: Arts syndrome is caused by loss-of-function mutations in PRPS1.

Submit: New GeneRIF Correction See all (13)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Arts syndrome, which is part of the spectrum of PRPS1-related disorders, is characterized by profound congenital sensorineural hearing impairment, early-onset hypotonia, delayed motor development, mild to moderate intellectual disability, ataxia, and increased risk of infection, all of which (with the exception of optic atrophy) present before age two years. Signs of peripheral neuropathy develop during early childhood. Twelve of 15 boys from the two Dutch families reported with Arts syndrome died before age six years of complications of infection. Carrier females can show late-onset (age >20 years) hearing impairment and other findings.

Diagnosis Testing

Sequence analysis of PRPS1, the only gene associated with Arts syndrome, has detected mutations in both kindreds reported to date.

Genetic Counseling

Arts syndrome is inherited in an X-linked manner. If the mother is a carrier, the chance of transmitting the PRPS1 mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may or may not be mildly affected. Males with Arts syndrome do not reproduce. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation in the family is known.

References

PMID: 20301738

Charcot-Marie-Tooth disease, X-linked recessive, 5

MIM: 311070

Summary from GeneReviews:

Disease Characteristics

X-linked Charcot-Marie-Tooth disease type 5 (CMTX5), part of the spectrum of PRPS1-related disorders, is characterized by peripheral neuropathy, early-onset (prelingual) bilateral profound sensorineural hearing loss, and optic neuropathy. The onset of peripheral neuropathy is between ages five and 12 years. The lower extremities are affected earlier and more severely than upper extremities. Initial manifestations often include foot drop or gait disturbance. Onset of visual impairment is between ages seven and 20 years. Intellect and life span are normal. Carrier females do not have findings of CMTX5.

Diagnosis Testing

Diagnosis is based on clinical findings, family history consistent with X-linked inheritance, and identification of a disease-causing mutation in PRPS1. Molecular genetic testing of PRPS1, the only gene known to be associated with CMTX5, is clinically available.

Genetic Counseling

CMTX5 is inherited in an X-linked manner. Carrier women have a 50% chance of transmitting the PRPS1 mutation in each pregnancy. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and typically will not be affected. Males pass the disease-causing mutation to all of their daughters and none of their sons. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the disease-causing mutation has been identified in the family.

Summary from GeneReviews:

Disease Characteristics

Phosphoribosylpyrophosphate synthetase (PRS) superactivity is characterized by hyperuricemia and hyperuricosuria and is divided into a severe phenotype with infantile or early-childhood onset and a milder phenotype with late-juvenile or early-adult onset. Variable combinations of sensorineural hearing loss, hypotonia, and ataxia observed in the severe type are not usually present in the mild type. In the mild type, uric acid crystalluria or a urinary stone is commonly the first clinical finding, followed later by gouty arthritis if serum urate concentration is not controlled.

Diagnosis Testing

Detection of overactivity of the PRS enzyme under a variety of laboratory conditions establishes the diagnosis; however, such testing is available on a research basis only. PRPS1, encoding ribose-phosphate pyrophosphokinase 1 (phosphoribosylpyrophosphate synthetase 1, or PRS1), is the only gene currently known to be associated with PRS superactivity. PRPS1 sequence analysis identifies point mutations in individuals with the severe early-onset form, which comprises approximately 25% of individuals with PRS superactivity.

Genetic Counseling

PRS superactivity is inherited in an X-linked manner. If the mother has a disease-causing mutation, the chance of transmitting the PRPS1 mutation in each pregnancy is 50%. Males who inherit the mutation will be affected; females who inherit the mutation will be carriers and may or may not be affected. Males pass the disease-causing mutation to all of their daughters and none of their sons. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if the mutation has been identified in the family.

References

PMID: 20301734

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Interactions

Products	Interactant	Other Gene	Source	Pubs	Description
P60891	Q9H8Y8	GORASP2	HPRD	PubMed
P60891	P60891	PRPS1	HPRD	PubMed
P60891	Q14558	PRPSAP1	HPRD	PubMed
P60891	Q9NZD8	SPG21	HPRD	PubMed
P60891	Q6EEV6	SUMO4	HPRD	PubMed
BioGRID:111615	BioGRID:117479	GORASP2	BioGRID	PubMed	Two-hybrid
BioGRID:111615	BioGRID:111615	PRPS1	BioGRID	PubMed	Two-hybrid
BioGRID:111615	BioGRID:111618	PRPSAP1	BioGRID	PubMed	Reconstituted Complex; Two-hybrid
BioGRID:111615	BioGRID:119474	SPG21	BioGRID	PubMed	Two-hybrid
BioGRID:111615	BioGRID:132223	SUMO4	BioGRID	PubMed	Affinity Capture-MS
BioGRID:111615	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS

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General gene information

Markers

RH36177 (e-PCR)
- UniSTS:64382

PRPS1_8569 (e-PCR)
- UniSTS:467848

AL035129 (e-PCR)
- UniSTS:94635

Genotypes

See PRPS1 SNP Geneview Report
See PRPS1 SNP Genotype Report
See PRPS1 SNP Variation Viewer Report

Related pseudogene(s)

2 found Review record(s) in Gene

Homology

Homologs of the PRPS1 gene: The PRPS1 gene is conserved in chimpanzee, , dog, cow, mouse, rat, zebrafish, S.cerevisiae, K.lactis, and .
Map Viewer (Mouse, Rat)

Pathways from BioSystems

5-Phosphoribose 1-diphosphate biosynthesis, organism-specific biosystem (from REACTOME)
5-Phosphoribose 1-diphosphate biosynthesis, organism-specific biosystem5-Phospho-alpha-D-ribose 1-diphosphate (PRPP) is a key intermediate in both the de novo and salvage pathways of purine and pyrimidine synthesis. PRPP and the enzymatic activity responsible for its s...
Metabolic pathways, organism-specific biosystem (from KEGG)
Metabolic pathways, organism-specific biosystem
Metabolic pathways
Metabolism, organism-specific biosystem (from REACTOME)
Metabolism, organism-specific biosystemMetabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as th...
Metabolism of carbohydrates, organism-specific biosystem (from REACTOME)
Metabolism of carbohydrates, organism-specific biosystemThese pathways together are responsible for: 1) the extraction of energy and carbon skeletons for biosyntheses from dietary sugars and related molecules; 2) the short-term storage of glucose in the b...
Nucleotide Metabolism, organism-specific biosystem (from WikiPathways)
Nucleotide Metabolism, organism-specific biosystemThe pathway outlined above focuses on purine metabolism and in particular that of guanine metabolism.
PRPP biosynthesis, ribose 5P => PRPP, organism-specific biosystem (from KEGG)
PRPP biosynthesis, ribose 5P => PRPP, organism-specific biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
PRPP biosynthesis, ribose 5P => PRPP, conserved biosystem (from KEGG)
PRPP biosynthesis, ribose 5P => PRPP, conserved biosystemPathway module; Carbohydrate and lipid metabolism; Central carbohydrate metabolism
Pentose phosphate pathway, organism-specific biosystem (from KEGG)
Pentose phosphate pathway, organism-specific biosystemThe pentose phosphate pathway is a process of glucose turnover that produces NADPH as reducing equivalents and pentoses as essential parts of nucleotides. There are two different phases in the pathwa...
Pentose phosphate pathway, conserved biosystem (from KEGG)
Pentose phosphate pathway, conserved biosystemThe pentose phosphate pathway is a process of glucose turnover that produces NADPH as reducing equivalents and pentoses as essential parts of nucleotides. There are two different phases in the pathwa...
Purine metabolism, organism-specific biosystem (from KEGG)
Purine metabolism, organism-specific biosystem
Purine metabolism
Purine metabolism, conserved biosystem (from KEGG)
Purine metabolism, conserved biosystem
Purine metabolism

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
kinase activity	IEA Inferred from Electronic Annotation more info
magnesium ion binding	IEA Inferred from Electronic Annotation more info
nucleotide binding	IEA Inferred from Electronic Annotation more info
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
ribose phosphate diphosphokinase activity	EXP Inferred from Experiment more info
ribose phosphate diphosphokinase activity	IDA Inferred from Direct Assay more info	PubMed
ribose phosphate diphosphokinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
transferase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
5-phosphoribose 1-diphosphate biosynthetic process	TAS Traceable Author Statement more info
carbohydrate metabolic process	TAS Traceable Author Statement more info
cellular biosynthetic process	IEA Inferred from Electronic Annotation more info
hypoxanthine biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
nervous system development	IMP Inferred from Mutant Phenotype more info	PubMed
nucleoside metabolic process	IEA Inferred from Electronic Annotation more info
purine base metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
purine nucleotide biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed
pyrimidine nucleotide biosynthetic process	NAS Non-traceable Author Statement more info	PubMed
ribonucleoside monophosphate biosynthetic process	IEA Inferred from Electronic Annotation more info
small molecule metabolic process	TAS Traceable Author Statement more info
urate biosynthetic process	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
cytosol	TAS Traceable Author Statement more info

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General protein information

Preferred Names: ribose-phosphate pyrophosphokinase 1

Names: ribose-phosphate pyrophosphokinase 1; deafness 2, perceptive, congenital; ribose-phosphate diphosphokinase 1; phosphoribosyl pyrophosphate synthase I; deafness, X-linked 2, perceptive, congenital; dJ1070B1.2 (phosphoribosyl pyrophosphate synthetase 1)

NP_001191331.1

EC 2.7.6.1

NP_002755.1

EC 2.7.6.1

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008407.1 RefSeqGene

Range

5001..27603

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204402.1 → NP_001191331.1 ribose-phosphate pyrophosphokinase 1 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 1. The resulting isoform (2) is shorter at the N-terminus compared to isoform 1.

Source sequence(s)

AK316467, AL137787, D00860, DC411129

UniProtKB/TrEMBL

B7ZB02

UniProtKB/Swiss-Prot

P60891

Conserved Domains (1) summary

cd06223
Location:1 – 70
Blast Score: 139

PRTases_typeI; Phosphoribosyl transferase (PRT)-type I domain
NM_002764.3 → NP_002755.1 ribose-phosphate pyrophosphokinase 1 isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AL137787, BC001605

Consensus CDS

CCDS14529.1

UniProtKB/Swiss-Prot

P60891

Related

ENSP00000361512, OTTHUMP00000023807, ENST00000372435, OTTHUMT00000057840

Conserved Domains (3) summary

PRK01259
Location:4 – 313
Blast Score: 1185

PRK01259; ribose-phosphate pyrophosphokinase; Provisional

pfam13793
Location:4 – 120
Blast Score: 552

Pribosyltran_N; N-terminal domain of ribose phosphate pyrophosphokinase

cd06223
Location:147 – 274
Blast Score: 228

PRTases_typeI; Phosphoribosyl transferase (PRT)-type I domain

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000023.10 Reference GRCh37.p5 Primary Assembly

Range

106871654..106894256

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000155.1 Alternate HuRef

Range

96496454..96518960

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AL137787.11	CAI42172.1
		CAI42173.1
		CAI42174.1
genomic	AL137787.11	CAI42172.1
		CAI42173.1
		CAI42174.1
genomic	AL772400.3	CAI41097.1
		CAI41098.1
		CAI41099.1
genomic	AL772400.3	CAI41097.1
		CAI41098.1
		CAI41099.1
genomic	CH471120.2	EAX02709.1
		EAX02710.1
		EAX02711.1
genomic	D28133.1	BAA05675.1
mRNA	AK223169.1	BAD96889.1
mRNA	AK297968.1	BAG60278.1
mRNA	AK307748.1	None
mRNA	AK312706.1	BAG35584.1
mRNA	AK316467.1	BAH14838.1
mRNA	BC001605.1	AAH01605.1
mRNA	D00860.1	BAA00733.1
mRNA	DC411129.1	None
mRNA	X15331.1	CAA33386.1
other-genetic	DQ895833.2	ABM86759.1
other-genetic	EU176362.1	ABW03813.1

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
P60891.2	GenPept	UniProtKB/Swiss-Prot:P60891
Q15244	GenPept	UniProtKB/TrEMBL:Q15244
Q53FW2	GenPept	UniProtKB/TrEMBL:Q53FW2