MCID: PHS004
MIFTS: 39

Phosphoribosylpyrophosphate Synthetase Superactivity

Categories: Genetic diseases, Neuronal diseases, Nephrological diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Phosphoribosylpyrophosphate Synthetase Superactivity

MalaCards integrated aliases for Phosphoribosylpyrophosphate Synthetase Superactivity:

Name: Phosphoribosylpyrophosphate Synthetase Superactivity 53 23 24 55 71 28 69
Prps1 Superactivity 53 24 55 71
Gout, Prps-Related 53 24 13
Prpp Synthetase Superactivity 24 55
Severe Phosphoribosylpyrophosphate Synthetase Superactivity 55
Mild Phosphoribosylpyrophosphate Synthetase Superactivity 55
Severe Prpp Synthetase Superactivity 55
Mild Prpp Synthetase Superactivity 55
Prpp Synthetase Overactivity 24
Severe Prps1 Superactivity 55
Mild Prps1 Superactivity 55
Prs Superactivity 24
Prps-Related Gout 71
Prs Overactivity 24

Characteristics:

Orphanet epidemiological data:

55
phosphoribosylpyrophosphate synthetase superactivity
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Adolescent,Adult,Childhood,Infancy;
mild phosphoribosylpyrophosphate synthetase superactivity
Inheritance: X-linked recessive; Age of onset: Adolescent,Adult;
severe phosphoribosylpyrophosphate synthetase superactivity
Inheritance: X-linked recessive; Age of onset: Childhood,Infancy;

OMIM:

53
Inheritance:
x-linked recessive

Miscellaneous:
two main phenotypes, early-onset with neurologic defects and early-adult onset with gout
heterozygous females may have gout and/or sensorineural deafness


HPO:

31
phosphoribosylpyrophosphate synthetase superactivity:
Inheritance x-linked recessive inheritance


GeneReviews:

23
Penetrance Penetrance is complete in hemizygous males...

Classifications:



Summaries for Phosphoribosylpyrophosphate Synthetase Superactivity

OMIM : 53 Phosphoribosylpyrophosphate synthetase I superactivity is an X-linked inborn error of metabolism in which increased enzyme activity is associated with hyperuricemia and gout. Some affected individuals have neurodevelopmental abnormalities, particularly sensorineural deafness (Becker et al., 1988; Roessler et al., 1993). Although different kinetic defects affecting the PRPS1 enzyme have been identified in this disorder, the common pathway involves increased synthesis of phosphoribosylpyrophosphate (PRPP), which leads to increased uric acid and purine production (Becker, 2001). (300661)

MalaCards based summary : Phosphoribosylpyrophosphate Synthetase Superactivity, also known as prps1 superactivity, is related to purine-pyrimidine metabolic disorder and gout, and has symptoms including ataxia, hypertension and intellectual disability. An important gene associated with Phosphoribosylpyrophosphate Synthetase Superactivity is PRPS1 (Phosphoribosyl Pyrophosphate Synthetase 1), and among its related pathways/superpathways are Pyrimidine metabolism (KEGG) and Purine metabolism. Affiliated tissues include kidney, eye and skeletal muscle.

UniProtKB/Swiss-Prot : 71 Phosphoribosylpyrophosphate synthetase superactivity: Familial disorder characterized by excessive purine production, gout and uric acid urolithiasis.

Genetics Home Reference : 24 Phosphoribosylpyrophosphate synthetase superactivity (PRS superactivity) is characterized by the overproduction and accumulation of uric acid (a waste product of normal chemical processes) in the blood and urine. The overproduction of uric acid can lead to gout, which is arthritis caused by an accumulation of uric acid crystals in the joints. Individuals with PRS superactivity also develop kidney or bladder stones that may result in episodes of acute kidney failure.

GeneReviews: NBK1973

Related Diseases for Phosphoribosylpyrophosphate Synthetase Superactivity

Diseases related to Phosphoribosylpyrophosphate Synthetase Superactivity via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 purine-pyrimidine metabolic disorder 9.5 HPRT1 PPAT
2 gout 9.3 HPRT1 PRPS1

Symptoms & Phenotypes for Phosphoribosylpyrophosphate Synthetase Superactivity

Symptoms via clinical synopsis from OMIM:

53
Laboratory Abnormalities:
hyperuricemia
hyperuricosuria
increased activity of the prpp synthetase 1 enzyme

Genitourinary Kidneys:
uric acid urolithiasis
secondary renal insufficiency

Neurologic Central Nervous System:
neurodevelopmental impairment (early-onset form)
hypotonia (early-onset form)
locomotor delay (early-onset form)
mental retardation (early-onset form)
ataxia (early-onset form)

Skeletal:
gout
gouty arthritis

Head And Neck Ears:
sensorineural hearing loss (early-onset form)

Metabolic Features:
overproduction of uric acid and purines


Clinical features from OMIM:

300661

Human phenotypes related to Phosphoribosylpyrophosphate Synthetase Superactivity:

55 31 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 ataxia 55 31 hallmark (90%) Very frequent (99-80%) HP:0001251
2 hypertension 55 31 occasional (7.5%) Occasional (29-5%) HP:0000822
3 intellectual disability 55 31 frequent (33%) Frequent (79-30%) HP:0001249
4 muscular hypotonia 55 31 frequent (33%) Frequent (79-30%) HP:0001252
5 neurological speech impairment 55 31 frequent (33%) Frequent (79-30%) HP:0002167
6 sensorineural hearing impairment 55 31 hallmark (90%) Very frequent (99-80%) HP:0000407
7 renal insufficiency 55 31 frequent (33%) Frequent (79-30%) HP:0000083
8 arrhythmia 55 31 occasional (7.5%) Occasional (29-5%) HP:0011675
9 hyperuricemia 55 31 hallmark (90%) Very frequent (99-80%) HP:0002149
10 strabismus 55 31 occasional (7.5%) Occasional (29-5%) HP:0000486
11 cardiomyopathy 55 31 occasional (7.5%) Occasional (29-5%) HP:0001638
12 abnormal aortic morphology 55 31 frequent (33%) Frequent (79-30%) HP:0001679
13 abnormality of skeletal muscles 55 31 occasional (7.5%) Occasional (29-5%) HP:0040290
14 abnormality of eye movement 55 Occasional (29-5%)
15 gout 31 HP:0001997
16 motor delay 31 HP:0001270
17 generalized hypotonia 31 HP:0001290
18 hyperuricosuria 31 HP:0003149
19 uric acid nephrolithiasis 31 HP:0000791

Drugs & Therapeutics for Phosphoribosylpyrophosphate Synthetase Superactivity

Search Clinical Trials , NIH Clinical Center for Phosphoribosylpyrophosphate Synthetase Superactivity

Genetic Tests for Phosphoribosylpyrophosphate Synthetase Superactivity

Genetic tests related to Phosphoribosylpyrophosphate Synthetase Superactivity:

# Genetic test Affiliating Genes
1 Phosphoribosylpyrophosphate Synthetase Superactivity 28 PRPS1

Anatomical Context for Phosphoribosylpyrophosphate Synthetase Superactivity

MalaCards organs/tissues related to Phosphoribosylpyrophosphate Synthetase Superactivity:

38
Kidney, Eye, Skeletal Muscle, B Lymphoblasts

Publications for Phosphoribosylpyrophosphate Synthetase Superactivity

Articles related to Phosphoribosylpyrophosphate Synthetase Superactivity:

(show all 11)
# Title Authors Year
1
Phosphoribosylpyrophosphate synthetase superactivity and recurrent infections is caused by a p.Val142Leu mutation in PRS-I. ( 22246954 )
2012
2
The genetic and functional basis of purine nucleotide feedback- resistant phosphoribosylpyrophosphate synthetase superactivity. ( 7593598 )
1995
3
Human X-linked phosphoribosylpyrophosphate synthetase superactivity is associated with distinct point mutations in the PRPS1 gene. ( 8253776 )
1993
4
Phosphoribosylpyrophosphate Synthetase Superactivity ( 20301734 )
1993
5
Regulation of purine nucleotide synthesis in human B lymphoblasts with both hypoxanthine-guanine phosphoribosyltransferase deficiency and phosphoribosylpyrophosphate synthetase superactivity. ( 1311306 )
1992
6
Identification of distinct PRS1 mutations in two patients with X-linked phosphoribosylpyrophosphate synthetase superactivity. ( 1664177 )
1991
7
Regulation of nicotinamide-adenine dinucleotide synthesis in erythrocytes of patients with hypoxanthine-guanine phosphoribosyltransferase deficiency and a patient with phosphoribosylpyrophosphate synthetase superactivity. ( 2155755 )
1990
8
Inherited phosphoribosylpyrophosphate synthetase superactivity due to aberrant inhibitor and activator responsiveness. ( 3014841 )
1986
9
Phosphoribosylpyrophosphate synthetase superactivity. A study of five patients with catalytic defects in the enzyme. ( 3017368 )
1986
10
Selective expression of phosphoribosylpyrophosphate synthetase superactivity in human lymphoblast lines. ( 2414323 )
1985
11
Phosphoribosylpyrophosphate synthetase superactivity: detection, characterization of underlying defects, and treatment. ( 6326492 )
1984

Variations for Phosphoribosylpyrophosphate Synthetase Superactivity

UniProtKB/Swiss-Prot genetic disease variations for Phosphoribosylpyrophosphate Synthetase Superactivity:

71
# Symbol AA change Variation ID SNP ID
1 PRPS1 p.Asn114Ser VAR_004163 rs137852540
2 PRPS1 p.Asp183His VAR_004164 rs137852541
3 PRPS1 p.Asp52His VAR_016044 rs137852542
4 PRPS1 p.Leu129Ile VAR_016045 rs137852543
5 PRPS1 p.Ala190Val VAR_016046 rs137852544
6 PRPS1 p.His193Gln VAR_016047 rs137852545

ClinVar genetic disease variations for Phosphoribosylpyrophosphate Synthetase Superactivity:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 PRPS1 NM_002764.3(PRPS1): c.341A> G (p.Asn114Ser) single nucleotide variant Pathogenic rs137852540 GRCh37 Chromosome X, 106884166: 106884166
2 PRPS1 NM_002764.3(PRPS1): c.547G> C (p.Asp183His) single nucleotide variant Pathogenic rs137852541 GRCh37 Chromosome X, 106888423: 106888423
3 PRPS1 NM_002764.3(PRPS1): c.154G> C (p.Asp52His) single nucleotide variant Pathogenic rs137852542 GRCh37 Chromosome X, 106882556: 106882556
4 PRPS1 NM_002764.3(PRPS1): c.385C> A (p.Leu129Ile) single nucleotide variant Pathogenic rs137852543 GRCh37 Chromosome X, 106884210: 106884210
5 PRPS1 NM_002764.3(PRPS1): c.569C> T (p.Ala190Val) single nucleotide variant Pathogenic rs137852544 GRCh37 Chromosome X, 106888445: 106888445
6 PRPS1 NM_002764.3(PRPS1): c.579C> G (p.His193Gln) single nucleotide variant Pathogenic rs137852545 GRCh37 Chromosome X, 106888455: 106888455

Expression for Phosphoribosylpyrophosphate Synthetase Superactivity

Search GEO for disease gene expression data for Phosphoribosylpyrophosphate Synthetase Superactivity.

Pathways for Phosphoribosylpyrophosphate Synthetase Superactivity

Pathways related to Phosphoribosylpyrophosphate Synthetase Superactivity according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.9 HPRT1 PPAT PRPS1
2
Show member pathways
11.67 HPRT1 PPAT
3
Show member pathways
11.37 HPRT1 PPAT
4 10.23 HPRT1 PRPS1
5 10.23 HPRT1 PPAT PRPS1

GO Terms for Phosphoribosylpyrophosphate Synthetase Superactivity

Biological processes related to Phosphoribosylpyrophosphate Synthetase Superactivity according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 protein homotetramerization GO:0051289 9.16 HPRT1 PPAT
2 nucleoside metabolic process GO:0009116 9.13 HPRT1 PPAT PRPS1
3 purine nucleotide biosynthetic process GO:0006164 8.8 HPRT1 PPAT PRPS1

Molecular functions related to Phosphoribosylpyrophosphate Synthetase Superactivity according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 transferase activity GO:0016740 9.33 HPRT1 PPAT PRPS1
2 transferase activity, transferring glycosyl groups GO:0016757 8.96 HPRT1 PPAT
3 magnesium ion binding GO:0000287 8.62 HPRT1 PRPS1

Sources for Phosphoribosylpyrophosphate Synthetase Superactivity

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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