Reactome | Defective HPRT1 does not convert guanine or hypoxanthine to GMP or IMP

Defective HPRT1 does not convert guanine or hypoxanthine to GMP or IMP

Stable Identifier

R-HSA-9734274

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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Defective HPRT1 does not convert guanine or hypoxanthine to GMP or IMP

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Normally in humans, guanine and hypoxanthine can be salvaged by conversion to GMP and IMP, catalyzed by HPRT1 (hypoxanthine guanine phosphoribosyltransferase). In the absence of HPRT1 activity, however, accumulated guanine and hypoxanthine are catabolized by XDH (xanthine dehydrogenase / oxidase) to urate. Hundreds of variants in HPRT1 have been identified, associated with phenotypes ranging from Lesch-Nyhan Syndrome in individuals with little or no HPRT1 activity, to hyperuricemia and gout in individuals with higher levels of HPRT1 activity. Here, we have annotated the failure of normal guanine and hypoxanthine salvage reactions due to three missense mutant alleles of HPRT1, originally identified in patients with Lesch-Nyhan Syndrome (Davidson et al. 1989, Fujimori et al. 1992, Laróvere et al. 2007) and shown when expressed in vitro to encode proteins with no detectable catalytic activity (Fu & Jinnah 2012).

Literature References

PubMed ID	Title	Journal	Year
22157001	Genotype-phenotype correlations in Lesch-Nyhan disease: moving beyond the gene Fu, R, Jinnah, HA	J Biol Chem	2012
17454734	Hypoxanthine-guanine phosphoribosyltransferase deficiency: biochemical and molecular findings in six Argentine patients Guelbert, N, Randall, M, O'Neill, JP, Laróvere, LE, de Kremer, RD, Czornyj, L, Fairbanks, LD	Nucleosides Nucleotides Nucleic Acids	2007
2738157	Molecular basis of hypoxanthine-guanine phosphoribosyltransferase deficiency in ten subjects determined by direct sequencing of amplified transcripts Davidson, BL, Palella, TD, Tarlé, SA, Kelley, WN	J Clin Invest	1989
1282899	A germ line mutation within the coding sequence for the putative 5-phosphoribosyl-1-pyrophosphate binding site of hypoxanthine-guanine phosphoribosyltransferase (HPRT) in a Lesch-Nyhan patient: missense mutations within a functionally important region probably cause disease Fujimori, S, Akaoka, I, Kamatani, N, Tagaya, T	Hum Genet	1992

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Defective HPRT1 disrupts guanine and hypoxanthine salvage (Homo sapiens)

Catalyst Activity

purine phosphoribosyltransferase activity of HPRT1 tetramer mutants [cytosol]

Physical Entity

HPRT1 tetramer mutants [cytosol] (Homo sapiens)

Activity

purine phosphoribosyltransferase activity (GO:0106130)

Normal reaction

HPRT1 catalyzes the conversion of guanine or hypoxanthine to GMP or IMP (Homo sapiens)

Functional status

Loss of function of HPRT1 tetramer mutants [cytosol]

Normal Entity

HPRT1 tetramer [cytosol] (Homo sapiens)

Disease Entity

HPRT1 tetramer [cytosol] (Homo sapiens)

Status

loss of function via point mutation

Disease

Name	Identifier	Synonyms
Lesch-Nyhan syndrome	DOID:1919	Lesch - Nyhan syndrome, X-linked hyperuricemia, hypoxanthine guanine phosphoribosyltransferase deficiency, HG-PRT deficiency, deficiency of IMP pyrophosphorylase, Complete hypoxanthine-guanine phosphoribosyltransferase deficiency, Hypoxanthine-guanine phosphoribosyltransferase deficiency, Hypoxanthine-guanine-phosphoribosyltransferase deficiency

Authored

D'Eustachio, P (2021-07-02)

Reviewed

Jassal, B (2021-07-09)

Created

D'Eustachio, P (2021-06-16)