hypoxanthine phosphoribosyltransferase


Summary: An enzyme that catalyzes the conversion of 5-phosphoribosyl-1-pyrophosphate and hypoxanthine, guanine, or MERCAPTOPURINE to the corresponding 5'-mononucleotides and pyrophosphate. The enzyme is important in purine biosynthesis as well as central nervous system functions. Complete lack of enzyme activity is associated with the LESCH-NYHAN SYNDROME, while partial deficiency results in overproduction of uric acid. EC

Top Publications

  1. Mastrangelo L, Kim J, Miyanohara A, Kang T, Friedmann T. Purinergic signaling in human pluripotent stem cells is regulated by the housekeeping gene encoding hypoxanthine guanine phosphoribosyltransferase. Proc Natl Acad Sci U S A. 2012;109:3377-82 pubmed publisher
    ..We propose that such mechanisms may play a role in the neuropathology of HPRT-deficiency LND and may point to potential molecular targets for modulation of this intractable neurological phenotype. ..
  2. Doak S, Jenkins G, Johnson G, Quick E, Parry E, Parry J. Mechanistic influences for mutation induction curves after exposure to DNA-reactive carcinogens. Cancer Res. 2007;67:3904-11 pubmed
    ..Chromosomal damage and point mutations were quantified with the micronucleus and hypoxanthine phosphoribosyltransferase forward mutation assays...
  3. Guibinga G, Hrustanovic G, Bouic K, Jinnah H, Friedmann T. MicroRNA-mediated dysregulation of neural developmental genes in HPRT deficiency: clues for Lesch-Nyhan disease?. Hum Mol Genet. 2012;21:609-22 pubmed publisher
    ..Nevertheless, we propose that these pleiotropic neurodevelopment effects of miR181a may play a role in the pathogenesis of LND. ..
  4. Torres R, Prior C, Puig J. Efficacy and safety of allopurinol in patients with hypoxanthine-guanine phosphoribosyltransferase deficiency. Metabolism. 2007;56:1179-86 pubmed
    ..Xanthine lithiasis, developing as a consequence of allopurinol therapy, should be preventable by adjustment of allopurinol dose...
  5. Langnaese K, John R, Schweizer H, Ebmeyer U, Keilhoff G. Selection of reference genes for quantitative real-time PCR in a rat asphyxial cardiac arrest model. BMC Mol Biol. 2008;9:53 pubmed publisher
    ..CypA is most favorable if restriction to a single reference gene for all time points is required. ..
  6. Porter C, DeGregori J. Interfering RNA-mediated purine analog resistance for in vitro and in vivo cell selection. Blood. 2008;112:4466-74 pubmed publisher
    ..These findings indicate that iPAR/6TG can be used for in vivo hematopoietic progenitor cell selection. ..
  7. Smith D, Jinnah H. Role of neuronal nitric oxide in the dopamine deficit of HPRT-deficient mice. Metab Brain Dis. 2007;22:39-43 pubmed
    ..Basal ganglia dopamine deficits manifest in both patients and hypoxanthine phosphoribosyltransferase (HPRT) mutant mice...
  8. Egami K, Yitta S, Kasim S, Lewers J, Roberts R, Lehar M, et al. Basal ganglia dopamine loss due to defect in purine recycling. Neurobiol Dis. 2007;26:396-407 pubmed
    ..These results suggest that dopamine loss in HPRT deficiency has a biochemical rather than anatomical basis and imply that purine recycling to be a biochemical process of particular importance to the function of dopaminergic neurons. ..
  9. Boitz J, Ullman B. A conditional mutant deficient in hypoxanthine-guanine phosphoribosyltransferase and xanthine phosphoribosyltransferase validates the purine salvage pathway of Leishmania donovani. J Biol Chem. 2006;281:16084-9 pubmed
    ..donovani, and that the purine sources within the macrophage to which the parasites have access are HGPRT or XPRT substrates. ..

More Information


  1. Meldgaard M, Fenger C, Lambertsen K, Pedersen M, Ladeby R, Finsen B. Validation of two reference genes for mRNA level studies of murine disease models in neurobiology. J Neurosci Methods. 2006;156:101-10 pubmed
    ..We furthermore demonstrate that above a certain threshold of test mRNA level changes and given high quality RNA processing, normalization to total RNA alone provides for equally reliable quantitative mRNA level results. ..
  2. Prior C, Torres R, Puig J. Hypoxanthine decreases equilibrative type of adenosine transport in lymphocytes from Lesch-Nyhan patients. Eur J Clin Invest. 2007;37:905-11 pubmed
    ..The aim of this study was to determine adenosine transporter subtypes affected by HPRT deficiency and by the associated hypoxanthine excess...
  3. Suzuki K, Mitsui K, Aizawa E, Hasegawa K, Kawase E, Yamagishi T, et al. Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors. Proc Natl Acad Sci U S A. 2008;105:13781-6 pubmed publisher
  4. Silver N, Cotroneo E, Proctor G, Osailan S, Paterson K, Carpenter G. Selection of housekeeping genes for gene expression studies in the adult rat submandibular gland under normal, inflamed, atrophic and regenerative states. BMC Mol Biol. 2008;9:64 pubmed publisher
    ..However, if normalising to multiple housekeeping genes, we recommend normalising to those identified by geNorm. For normalisation across the physiological states, we recommend the use of UBC. ..
  5. Silver N, Best S, Jiang J, Thein S. Selection of housekeeping genes for gene expression studies in human reticulocytes using real-time PCR. BMC Mol Biol. 2006;7:33 pubmed
    ..Using this simple approach, GAPDH was found to be the most suitable housekeeping gene for expression studies in reticulocytes while the commonly used B2M should be avoided. ..
  6. Shirley T, Lewers J, Egami K, Majumdar A, Kelly M, Ceballos Picot I, et al. A human neuronal tissue culture model for Lesch-Nyhan disease. J Neurochem. 2007;101:841-53 pubmed
    ..These cells combine the analytical power of multiple lines and a human, neuronal origin to provide an important tool to investigate the pathophysiology of HPRT deficiency...
  7. Pralong E, Pollo C, Coubes P, Bloch J, Roulet E, Tétreault M, et al. Electrophysiological characteristics of limbic and motor globus pallidus internus (GPI) neurons in two cases of Lesch-Nyhan syndrome. Neurophysiol Clin. 2005;35:168-73 pubmed
    ..In order to shed light on the pathophysiology of dystonia, we report the pallidal electrophysiological activity recorded in two patients during deep brain stimulation surgery (DBS)...
  8. Yang G, Banks K, Bonaguro R, Wilson G, Dreolini L, de Leeuw C, et al. Next generation tools for high-throughput promoter and expression analysis employing single-copy knock-ins at the Hprt1 locus. Genomics. 2009;93:196-204 pubmed publisher
    ..We have validated our tools as part of the Pleiades Promoter Project (http://www.pleiades.org), with the generation of brain-specific EGFP positive germline mouse strains. ..
  9. Ceballos Picot I, Mockel L, Potier M, Dauphinot L, Shirley T, Torero Ibad R, et al. Hypoxanthine-guanine phosphoribosyl transferase regulates early developmental programming of dopamine neurons: implications for Lesch-Nyhan disease pathogenesis. Hum Mol Genet. 2009;18:2317-27 pubmed publisher
    ..These results provide novel evidence that HPRT deficiency may affect dopaminergic neurons by influencing early developmental mechanisms...
  10. Samuel M, Munro J, Bryson S, Forrow S, Stevenson D, Olson M. Tissue selective expression of conditionally-regulated ROCK by gene targeting to a defined locus. Genesis. 2009;47:440-6 pubmed publisher
    ..K14-ROCKII:mER mice will be valuable for examining the role of ROCK in skin development and cancer. ..
  11. Di Domenico A, Christodoulou I, Pells S, McWhir J, Thomson A. Sequential genetic modification of the hprt locus in human ESCs combining gene targeting and recombinase-mediated cassette exchange. Cloning Stem Cells. 2008;10:217-30 pubmed publisher
    ..Finally, we report a double replacement strategy using two sequential gene targeting steps resulting in the targeted correction of an hprt-mutated hESC line. ..
  12. Palais G, Nguyen Dinh Cat A, Friedman H, Panek Huet N, Millet A, Tronche F, et al. Targeted transgenesis at the HPRT locus: an efficient strategy to achieve tightly controlled in vivo conditional expression with the tet system. Physiol Genomics. 2009;37:140-6 pubmed publisher
    ..strategy and an embryonic stem (ES) cell line supporting efficient germ-line transmission, we used hypoxanthine phosphoribosyltransferase (HPRT) targeting to insert a single copy tet-inducible construct designed to allow both ..
  13. Song S, Friedmann T. Tissue-specific aberrations of gene expression in HPRT-deficient mice: functional complexity in a monogenic disease?. Mol Ther. 2007;15:1432-43 pubmed
    ..Knowledge of these secondary genetic defects may help in the identification of targets for drug- and gene-based therapy. ..
  14. Welin M, Egeblad L, Johansson A, Stenmark P, Wang L, Flodin S, et al. Structural and functional studies of the human phosphoribosyltransferase domain containing protein 1. FEBS J. 2010;277:4920-30 pubmed publisher
    ..The data obtained in the present study indicate that PRTFDC1 does not have a direct catalytic role in the nucleotide salvage pathway. ..
  15. Schmouth J, Bonaguro R, Corso Díaz X, Simpson E. Modelling human regulatory variation in mouse: finding the function in genome-wide association studies and whole-genome sequencing. PLoS Genet. 2012;8:e1002544 pubmed publisher
  16. Lewers J, Ceballos Picot I, Shirley T, Mockel L, Egami K, Jinnah H. Consequences of impaired purine recycling in dopaminergic neurons. Neuroscience. 2008;152:761-72 pubmed publisher
  17. Tanic N, Perovic M, Mladenovic A, Ruzdijic S, Kanazir S. Effects of aging, dietary restriction and glucocorticoid treatment on housekeeping gene expression in rat cortex and hippocampus-evaluation by real time RT-PCR. J Mol Neurosci. 2007;32:38-46 pubmed
    ..Our results demonstrate the importance of the right choice of HKG and suggest the appropriate endogenous control to be used for TaqMan RT-PCR analysis of mRNA expression in rat cortex and hippocampus for selected experimental paradigms. ..
  18. Bertelli M, Alushi B, Veicsteinas A, Jinnah H, Micheli V. Gene expression and mRNA editing of serotonin receptor 2C in brains of HPRT gene knock-out mice, an animal model of Lesch-Nyhan disease. J Clin Neurosci. 2009;16:1061-3 pubmed publisher
    ..The above alteration found in HPRT-deficient mice is similar to those found in other animal models used to study aggressive and self-injurious behaviour. ..
  19. Guibinga G, Hsu S, Friedmann T. Deficiency of the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase (HPRT) dysregulates neurogenesis. Mol Ther. 2010;18:54-62 pubmed publisher
    ..These results represent direct experimental evidence for aberrant neurogenesis in HPRT deficiency and suggest developmental roles for other housekeeping genes in neurodevelopmental disease. ..
  20. Jarrett S, Novak M, Dabernat S, Daniel J, Mellon I, Zhang Q, et al. Metastasis suppressor NM23-H1 promotes repair of UV-induced DNA damage and suppresses UV-induced melanomagenesis. Cancer Res. 2012;72:133-43 pubmed publisher
    ..Taken together, our data show a critical role for NM23 isoforms in limiting mutagenesis and suppressing UVR-induced melanomagenesis. ..
  21. Kinast L, von der Ohe J, Burhenne H, Seifert R. Impairment of adenylyl cyclase 2 function and expression in hypoxanthine phosphoribosyltransferase-deficient rat B103 neuroblastoma cells as model for Lesch-Nyhan disease: BODIPY-forskolin as pharmacological tool. Naunyn Schmiedebergs Arch Pharmacol. 2012;385:671-83 pubmed publisher
    ..We discuss the pathophysiological implications of our data for LND. ..
  22. Keough D, Skinner Adams T, Jones M, Ng A, Brereton I, Guddat L, et al. Lead compounds for antimalarial chemotherapy: purine base analogs discriminate between human and P. falciparum 6-oxopurine phosphoribosyltransferases. J Med Chem. 2006;49:7479-86 pubmed
    ..These and other bases were effective in inhibiting the growth of the parasite in vitro, giving IC(50) values as low as 1 microM. ..
  23. Keebaugh A, Sullivan R, Thomas J. Gene duplication and inactivation in the HPRT gene family. Genomics. 2007;89:134-42 pubmed publisher
    b>Hypoxanthine phosphoribosyltransferase (HPRT1) is a key enzyme in the purine salvage pathway, and mutations in HPRT1 cause Lesch-Nyhan disease...
  24. Calcagno A, Chewning K, Wu C, Ambudkar S. Plasma membrane calcium ATPase (PMCA4): a housekeeper for RT-PCR relative quantification of polytopic membrane proteins. BMC Mol Biol. 2006;7:29 pubmed
  25. Albertini R, Sram R, Vacek P, Lynch J, Rossner P, Nicklas J, et al. Molecular epidemiological studies in 1,3-butadiene exposed Czech workers: female-male comparisons. Chem Biol Interact. 2007;166:63-77 pubmed
    ..However, as in the first, differences in the metabolic detoxification of BD as reflected in relative amounts of the M1 and M2 urinary metabolites were associated with genotypes, this time both GST and EH. ..
  26. Bertelli M, Cecchin S, Lapucci C, Jacomelli G, Jinnah H, Pandolfo M, et al. Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch-Nyhan disease). Clin Chim Acta. 2006;373:104-7 pubmed
    ..Altered adenosine transport across the membrane of HPRT-deficient lymphocytes has been reported, suggesting adenosine involvement in LND...
  27. Barber R, Hickenbotham P, Hatch T, Kelly D, Topchiy N, Almeida G, et al. Radiation-induced transgenerational alterations in genome stability and DNA damage. Oncogene. 2006;25:7336-42 pubmed
    ..Our data also provide important clues on the still unknown mechanisms of radiation-induced genomic instability. ..
  28. Boitz J, Ullman B. Leishmania donovani singly deficient in HGPRT, APRT or XPRT are viable in vitro and within mammalian macrophages. Mol Biochem Parasitol. 2006;148:24-30 pubmed
    ..In addition these studies revealed the presence of an adenine aminohydrolase enzyme in L. donovani axenic amastigotes, an activity previously thought to be restricted to promastigotes. ..
  29. Everaert B, Boulet G, Timmermans J, Vrints C. Importance of suitable reference gene selection for quantitative real-time PCR: special reference to mouse myocardial infarction studies. PLoS ONE. 2011;6:e23793 pubmed publisher
  30. Pombo Suarez M, Calaza M, Gomez Reino J, Gonzalez A. Reference genes for normalization of gene expression studies in human osteoarthritic articular cartilage. BMC Mol Biol. 2008;9:17 pubmed publisher
  31. Kang T, Guibinga G, Jinnah H, Friedmann T. HPRT deficiency coordinately dysregulates canonical Wnt and presenilin-1 signaling: a neuro-developmental regulatory role for a housekeeping gene?. PLoS ONE. 2011;6:e16572 pubmed publisher
  32. van Wijngaarden P, Brereton H, Coster D, Williams K. Stability of housekeeping gene expression in the rat retina during exposure to cyclic hyperoxia. Mol Vis. 2007;13:1508-15 pubmed
    ..05). We conclude that ARBP and HPRT exhibit expression that is sufficiently stable under conditions of varying oxygen tension, to permit their use as housekeeping genes in at least one model of OIR in the neonatal rat. ..
  33. Farhadi H, Lepage P, Forghani R, Friedman H, Orfali W, Jasmin L, et al. A combinatorial network of evolutionarily conserved myelin basic protein regulatory sequences confers distinct glial-specific phenotypes. J Neurosci. 2003;23:10214-23 pubmed
  34. Huo L, Nagasawa H, Little J. HPRT mutants induced in bystander cells by very low fluences of alpha particles result primarily from point mutations. Radiat Res. 2001;156:521-5 pubmed
    ..5 cGy involved point mutations, confirming our hypothesis that they are induced by a different mechanism. ..
  35. Simhadri S, Kramata P, Zajc B, Sayer J, Jerina D, Hinkle D, et al. Benzo[a]pyrene diol epoxide-deoxyguanosine adducts are accurately bypassed by yeast DNA polymerase zeta in vitro. Mutat Res. 2002;508:137-45 pubmed
    ..This corresponds to a probability of mutation lower than 0.3%, the limit of detection, and demonstrates the remarkable fidelity of yeast pol zeta in translesion synthesis past these BP DB-dG lesions in vitro. ..
  36. Nicklas J. Pseudogenes of the human HPRT1 gene. Environ Mol Mutagen. 2006;47:212-8 pubmed
    ..This gene with unknown function is almost completely homologous to HPRT1 in exon structure (except for a 21 bp (seven amino acid) insertion in exon 1) and 68% homologous in amino acid sequence. ..
  37. Kraakman van der Zwet M, Wiegant W, Zdzienicka M. Brca2 (XRCC11) deficiency results in enhanced mutagenesis. Mutagenesis. 2003;18:521-5 pubmed
    ..In addition, following exposure to IR, a 2.3-fold increase in mutant frequency per Gy was found for V-C8 in comparison with wild-type V79. These data suggest a potential risk from ionizing radiation for BRCA2 patients. ..
  38. Arnaudeau C, Lundin C, Helleday T. DNA double-strand breaks associated with replication forks are predominantly repaired by homologous recombination involving an exchange mechanism in mammalian cells. J Mol Biol. 2001;307:1235-45 pubmed
    ..We propose that the presence of DSB associated with replication forks rapidly induces HR via an exchange mechanism and that HR plays a more prominent role in the repair of such DSB than does NHEJ. ..
  39. Kenner O, Kneisel A, Klingler J, Bartelt B, Speit G, Vogel W, et al. Targeted gene correction of hprt mutations by 45 base single-stranded oligonucleotides. Biochem Biophys Res Commun. 2002;299:787-92 pubmed
    ..The correction efficiency was very low but reproducible. We suggest that this system allows one to investigate targeted gene correction in dependence on the target sequence and the oligonucleotides used. ..
  40. Li Z, Zhang H, McManus T, McCormick J, Lawrence C, Maher V. hREV3 is essential for error-prone translesion synthesis past UV or benzo[a]pyrene diol epoxide-induced DNA lesions in human fibroblasts. Mutat Res. 2002;510:71-80 pubmed
    ..However, the conclusion is supported by the fact that in a similar study with a strain expressing a high level of antisense hREV1, a very similar result was obtained, i.e. UV or BPDE mutagenesis was virtually eliminated. ..
  41. van Larebeke N, Koppen G, Nelen V, Schoeters G, Van Loon H, Albering H, et al. Differences in HPRT mutant frequency among middle-aged Flemish women in association with area of residence and blood lead levels. Biomarkers. 2004;9:71-84 pubmed
    ..Here, we report the hypoxanthine phosphoribosyltransferase gene (HPRT) variant frequencies for 99 non-smoking women aged 50-65 years...
  42. Zhou H, Ivanov V, Gillespie J, Geard C, Amundson S, Brenner D, et al. Mechanism of radiation-induced bystander effect: role of the cyclooxygenase-2 signaling pathway. Proc Natl Acad Sci U S A. 2005;102:14641-6 pubmed
    ..These results provide evidence that the COX-2-related pathway, which is essential in mediating cellular inflammatory response, is the critical signaling link for the bystander phenomenon. ..
  43. Deutsch S, Long K, Rosse R, Mastropaolo J, Eller J. Hypothesized deficiency of guanine-based purines may contribute to abnormalities of neurodevelopment, neuromodulation, and neurotransmission in Lesch-Nyhan syndrome. Clin Neuropharmacol. 2005;28:28-37 pubmed
    ..sex-linked recessive disorder resulting from almost complete deficiency of the activity of hypoxanthine phosphoribosyltransferase (HPRT)...
  44. Boer P, Brosh S, Wasserman L, Hammel I, Zoref Shani E, Sperling O. Decelerated rate of dendrite outgrowth from dopaminergic neurons in primary cultures from brains of hypoxanthine phosphoribosyltransferase-deficient knockout mice. Neurosci Lett. 2001;303:45-8 pubmed
    Lesch-Nyhan syndrome (LNS), caused by the complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT), is characterized by a neurological deficit, the etiology of which is still unclear...
  45. Yoshioka M, O Neill J, Vacek P, Finette B. Gestational age and gender-specific in utero V(D)J recombinase-mediated deletions. Cancer Res. 2001;61:3432-8 pubmed
    ..031). Developmental and gender-specific differences in HPRT deletions mediated by V(D)J recombinase provide insight into the gender-specific differences seen in infant leukemia. ..
  46. Ammenheuser M, Bechtold W, Abdel Rahman S, Rosenblatt J, Hastings Smith D, Ward J. Assessment of 1,3-butadiene exposure in polymer production workers using HPRT mutations in lymphocytes as a biomarker. Environ Health Perspect. 2001;109:1249-55 pubmed
    ..4 and 0.6. The correlations among BD exposure and the biomarkers of internal exposure and genotoxicity suggest that occupational exposure to BD, in the range of 1-3 ppm, may be associated with adverse biological effects. ..
  47. Schretlen D, Harris J, Park K, Jinnah H, del Pozo N. Neurocognitive functioning in Lesch-Nyhan disease and partial hypoxanthine-guanine phosphoribosyltransferase deficiency. J Int Neuropsychol Soc. 2001;7:805-12 pubmed
    ..The variants produced scores that were intermediate between those of patients with LND and normal participants on nearly every cognitive measure. We discuss these findings in terms of what is known about the neuropathology of LND...
  48. Minami T, Donovan D, Tsai J, Rosenberg R, Aird W. Differential regulation of the von Willebrand factor and Flt-1 promoters in the endothelium of hypoxanthine phosphoribosyltransferase-targeted mice. Blood. 2002;100:4019-25 pubmed
    ..to target the promoters of 2 different genes, namely von Willebrand factor (VWF) and Flt-1, to the hypoxanthine phosphoribosyltransferase (Hprt) gene locus...
  49. Majumdar A, Puri N, Cuenoud B, Natt F, Martin P, Khorlin A, et al. Cell cycle modulation of gene targeting by a triple helix-forming oligonucleotide. J Biol Chem. 2003;278:11072-7 pubmed
    ..Successful protocols for TFO-mediated manipulation of chromosomal sequences are likely to reflect a combination of appropriate oligonucleotide chemistry and manipulation of the cell biology. ..
  50. Kang S, Kiefer C, Yang T. Role of the promoter in maintaining transcriptionally active chromatin structure and DNA methylation patterns in vivo. Mol Cell Biol. 2003;23:4150-61 pubmed
    ..These findings suggest that the promoter and active transcription play a relatively limited role in maintaining transcriptionally potentiated epigenetic states. ..
  51. Noskov V, Kouprina N, Leem S, Koriabine M, Barrett J, Larionov V. A genetic system for direct selection of gene-positive clones during recombinational cloning in yeast. Nucleic Acids Res. 2002;30:E8 pubmed
    ..This method produces positive YAC recombinants at a frequency of approximately 40%. This novel TAR cloning method provides a powerful tool for structural and functional analysis of complex genomes...
  52. Albertini R. HPRT mutations in humans: biomarkers for mechanistic studies. Mutat Res. 2001;489:1-16 pubmed
    ..Most recently, HPRT is finding use in studies of in vivo selection for in vivo mutations arising in either somatic or germinal cells. ..
  53. O Neill J. Mutation carrier testing in Lesch-Nyhan syndrome families: HPRT mutant frequency and mutation analysis with peripheral blood T lymphocytes. Genet Test. 2004;8:51-64 pubmed
    ..This approach provides a rapid assay that yields information on carrier status within 10 days of sample receipt...