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 57 24 25 59 75 29 6 73
Prps1 Superactivity 57 25 59 75
Gout, Prps-Related 57 25 13
Prpp Synthetase Superactivity 25 59
Severe Phosphoribosylpyrophosphate Synthetase Superactivity 59
Mild Phosphoribosylpyrophosphate Synthetase Superactivity 59
Superactivity, Phosphoribosylpyrophosphate Synthetase 40
Severe Prpp Synthetase Superactivity 59
Mild Prpp Synthetase Superactivity 59
Prpp Synthetase Overactivity 25
Severe Prps1 Superactivity 59
Mild Prps1 Superactivity 59
Prs Superactivity 25
Prps-Related Gout 75
Prs Overactivity 25

Characteristics:

Orphanet epidemiological data:

59
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:

57
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:

32
phosphoribosylpyrophosphate synthetase superactivity:
Inheritance x-linked recessive inheritance


GeneReviews:

24
Penetrance Penetrance is complete in hemizygous males...

Classifications:



Summaries for Phosphoribosylpyrophosphate Synthetase Superactivity

OMIM : 57 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. An important gene associated with Phosphoribosylpyrophosphate Synthetase Superactivity is PRPS1 (Phosphoribosyl Pyrophosphate Synthetase 1), and among its related pathways/superpathways are Purine metabolism (KEGG) and Purine metabolism (REACTOME). Affiliated tissues include kidney, eye and skeletal muscle, and related phenotypes are hypertension and intellectual disability

Genetics Home Reference : 25 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.

UniProtKB/Swiss-Prot : 75 Phosphoribosylpyrophosphate synthetase superactivity: Familial disorder characterized by excessive purine production, gout and uric acid urolithiasis.

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 9.2 HPRT1 PPAT
2 gout 8.9 HPRT1 PRPS1

Symptoms & Phenotypes for Phosphoribosylpyrophosphate Synthetase Superactivity

Symptoms via clinical synopsis from OMIM:

57
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:

59 32 (show all 19)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertension 59 32 occasional (7.5%) Occasional (29-5%) HP:0000822
2 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
3 ataxia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001251
4 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
5 neurological speech impairment 59 32 frequent (33%) Frequent (79-30%) HP:0002167
6 sensorineural hearing impairment 59 32 hallmark (90%) Very frequent (99-80%) HP:0000407
7 renal insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0000083
8 arrhythmia 59 32 occasional (7.5%) Occasional (29-5%) HP:0011675
9 hyperuricemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0002149
10 strabismus 59 32 occasional (7.5%) Occasional (29-5%) HP:0000486
11 cardiomyopathy 59 32 occasional (7.5%) Occasional (29-5%) HP:0001638
12 abnormal aortic morphology 59 32 frequent (33%) Frequent (79-30%) HP:0001679
13 abnormality of skeletal muscles 59 32 occasional (7.5%) Occasional (29-5%) HP:0040290
14 abnormality of eye movement 59 Occasional (29-5%)
15 gout 32 HP:0001997
16 motor delay 32 HP:0001270
17 generalized hypotonia 32 HP:0001290
18 hyperuricosuria 32 HP:0003149
19 uric acid nephrolithiasis 32 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 29 PRPS1

Anatomical Context for Phosphoribosylpyrophosphate Synthetase Superactivity

MalaCards organs/tissues related to Phosphoribosylpyrophosphate Synthetase Superactivity:

41
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:

75
# 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
(show all 38)
# Gene Variation Type Significance SNP ID Assembly Location
1 PRPS1 NM_002764.3(PRPS1): c.341A> G (p.Asn114Ser) single nucleotide variant Likely pathogenic rs137852540 GRCh37 Chromosome X, 106884166: 106884166
2 PRPS1 NM_002764.3(PRPS1): c.341A> G (p.Asn114Ser) single nucleotide variant Likely pathogenic rs137852540 GRCh38 Chromosome X, 107640936: 107640936
3 PRPS1 NM_002764.3(PRPS1): c.547G> C (p.Asp183His) single nucleotide variant Pathogenic rs137852541 GRCh37 Chromosome X, 106888423: 106888423
4 PRPS1 NM_002764.3(PRPS1): c.547G> C (p.Asp183His) single nucleotide variant Pathogenic rs137852541 GRCh38 Chromosome X, 107645193: 107645193
5 PRPS1 NM_002764.3(PRPS1): c.154G> C (p.Asp52His) single nucleotide variant Pathogenic rs137852542 GRCh37 Chromosome X, 106882556: 106882556
6 PRPS1 NM_002764.3(PRPS1): c.154G> C (p.Asp52His) single nucleotide variant Pathogenic rs137852542 GRCh38 Chromosome X, 107639326: 107639326
7 PRPS1 NM_002764.3(PRPS1): c.385C> A (p.Leu129Ile) single nucleotide variant Pathogenic rs137852543 GRCh37 Chromosome X, 106884210: 106884210
8 PRPS1 NM_002764.3(PRPS1): c.385C> A (p.Leu129Ile) single nucleotide variant Pathogenic rs137852543 GRCh38 Chromosome X, 107640980: 107640980
9 PRPS1 NM_002764.3(PRPS1): c.569C> T (p.Ala190Val) single nucleotide variant Pathogenic rs137852544 GRCh37 Chromosome X, 106888445: 106888445
10 PRPS1 NM_002764.3(PRPS1): c.569C> T (p.Ala190Val) single nucleotide variant Pathogenic rs137852544 GRCh38 Chromosome X, 107645215: 107645215
11 PRPS1 NM_002764.3(PRPS1): c.579C> G (p.His193Gln) single nucleotide variant Pathogenic rs137852545 GRCh37 Chromosome X, 106888455: 106888455
12 PRPS1 NM_002764.3(PRPS1): c.579C> G (p.His193Gln) single nucleotide variant Pathogenic rs137852545 GRCh38 Chromosome X, 107645225: 107645225
13 PRPS1 NM_002764.3(PRPS1): c.456A> G (p.Leu152=) single nucleotide variant Benign/Likely benign rs61735617 GRCh37 Chromosome X, 106885646: 106885646
14 PRPS1 NM_002764.3(PRPS1): c.456A> G (p.Leu152=) single nucleotide variant Benign/Likely benign rs61735617 GRCh38 Chromosome X, 107642416: 107642416
15 PRPS1 NM_002764.3(PRPS1): c.*725T> C single nucleotide variant Likely benign rs183744100 GRCh38 Chromosome X, 107650757: 107650757
16 PRPS1 NM_002764.3(PRPS1): c.*725T> C single nucleotide variant Likely benign rs183744100 GRCh37 Chromosome X, 106893987: 106893987
17 PRPS1 NM_002764.3(PRPS1): c.*178G> A single nucleotide variant Likely benign rs576933222 GRCh38 Chromosome X, 107650210: 107650210
18 PRPS1 NM_002764.3(PRPS1): c.*178G> A single nucleotide variant Likely benign rs576933222 GRCh37 Chromosome X, 106893440: 106893440
19 PRPS1 NM_002764.3(PRPS1): c.*538G> C single nucleotide variant Uncertain significance rs1057515727 GRCh38 Chromosome X, 107650570: 107650570
20 PRPS1 NM_002764.3(PRPS1): c.*538G> C single nucleotide variant Uncertain significance rs1057515727 GRCh37 Chromosome X, 106893800: 106893800
21 PRPS1 NM_002764.3(PRPS1): c.-153delG deletion Likely benign rs768856537 GRCh38 Chromosome X, 107628476: 107628476
22 PRPS1 NM_002764.3(PRPS1): c.-153delG deletion Likely benign rs768856537 GRCh37 Chromosome X, 106871706: 106871706
23 PRPS1 NM_002764.3(PRPS1): c.444G> A (p.Glu148=) single nucleotide variant Likely benign rs201285459 GRCh38 Chromosome X, 107642404: 107642404
24 PRPS1 NM_002764.3(PRPS1): c.444G> A (p.Glu148=) single nucleotide variant Likely benign rs201285459 GRCh37 Chromosome X, 106885634: 106885634
25 PRPS1 NM_002764.3(PRPS1): c.*166G> A single nucleotide variant Uncertain significance rs371265973 GRCh38 Chromosome X, 107650198: 107650198
26 PRPS1 NM_002764.3(PRPS1): c.*166G> A single nucleotide variant Uncertain significance rs371265973 GRCh37 Chromosome X, 106893428: 106893428
27 PRPS1 NM_002764.3(PRPS1): c.*389G> C single nucleotide variant Uncertain significance rs5962870 GRCh38 Chromosome X, 107650421: 107650421
28 PRPS1 NM_002764.3(PRPS1): c.*389G> C single nucleotide variant Uncertain significance rs5962870 GRCh37 Chromosome X, 106893651: 106893651
29 PRPS1 NM_002764.3(PRPS1): c.*762G> T single nucleotide variant Uncertain significance rs768310830 GRCh38 Chromosome X, 107650794: 107650794
30 PRPS1 NM_002764.3(PRPS1): c.*762G> T single nucleotide variant Uncertain significance rs768310830 GRCh37 Chromosome X, 106894024: 106894024
31 PRPS1 NM_002764.3(PRPS1): c.*938dupA duplication Uncertain significance rs1057515728 GRCh38 Chromosome X, 107650970: 107650970
32 PRPS1 NM_002764.3(PRPS1): c.*938dupA duplication Uncertain significance rs1057515728 GRCh37 Chromosome X, 106894200: 106894200
33 PRPS1 NM_002764.3(PRPS1): c.*88C> T single nucleotide variant Uncertain significance rs1057515726 GRCh38 Chromosome X, 107650120: 107650120
34 PRPS1 NM_002764.3(PRPS1): c.*88C> T single nucleotide variant Uncertain significance rs1057515726 GRCh37 Chromosome X, 106893350: 106893350
35 PRPS1 NM_002764.3(PRPS1): c.*159G> A single nucleotide variant Uncertain significance rs747334780 GRCh38 Chromosome X, 107650191: 107650191
36 PRPS1 NM_002764.3(PRPS1): c.*159G> A single nucleotide variant Uncertain significance rs747334780 GRCh37 Chromosome X, 106893421: 106893421
37 PRPS1 NM_002764.3(PRPS1): c.*538G> T single nucleotide variant Uncertain significance rs1057515727 GRCh38 Chromosome X, 107650570: 107650570
38 PRPS1 NM_002764.3(PRPS1): c.*538G> T single nucleotide variant Uncertain significance rs1057515727 GRCh37 Chromosome X, 106893800: 106893800

Expression for Phosphoribosylpyrophosphate Synthetase Superactivity

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

Pathways for Phosphoribosylpyrophosphate Synthetase Superactivity

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 9.32 HPRT1 PPAT
2 animal organ regeneration GO:0031100 9.26 PPAT PRPS1
3 ribose phosphate metabolic process GO:0019693 9.16 PPAT PRPS1
4 nucleoside metabolic process GO:0009116 9.13 HPRT1 PPAT PRPS1
5 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
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
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40 LOVD
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44 MeSH
45 MESH via Orphanet
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54 NINDS
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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