Hypoxanthine-guanine phosphoribosyltransferase

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Hypoxanthine phosphoribosyltransferase 1
Hypoxanthine-guanine phosphoribosyltransferase 1BZY.png
Ribbon diagram of a human HPRT tetramer. Magnesium ions visible in green. From PDB 1BZY.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM308000 MGI96217 HomoloGene56590 ChEMBL: 2360 GeneCards: HPRT1 Gene
EC number
RNA expression pattern
PBB GE HPRT1 202854 at tn.png
More reference expression data
Species Human Mouse
Entrez 3251 15452
Ensembl ENSG00000165704 ENSMUSG00000025630
UniProt P00492 P00493
RefSeq (mRNA) NM_000194 NM_013556
RefSeq (protein) NP_000185 NP_038584
Location (UCSC) Chr X:
133.59 – 133.65 Mb
Chr X:
52.99 – 53.02 Mb
PubMed search [1] [2]

Hypoxanthine-guanine phosphoribosyltransferase (HGPRT) is an enzyme encoded in humans by the HPRT1 gene.[1][2]

HGPRT is a transferase that catalyzes conversion of hypoxanthine to inosine monophosphate and guanine to guanosine monophosphate. This reaction transfers the 5-phosphoribosyl group from 5-phosphoribosyl 1-pyrophosphate (PRPP) to the purine. HGPRT plays a central role in the generation of purine nucleotides through the purine salvage pathway.


hypoxanthine phosphoribosyltransferase
EC number
CAS number 9016-12-0
IntEnz IntEnz view
ExPASy NiceZyme view
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

HGPRT catalyzes the following reactions:

Substrate Product Notes
hypoxanthine inosine monophosphate
guanine guanosine monophosphate Often called HGPRT. Performs this function only in some species.
xanthine xanthosine monophosphate Only certain HPRTs.

HGPRTase functions primarily to salvage purines from degraded DNA to reintroduce into purine synthetic pathways. In this role, it catalyzes the reaction between guanine and phosphoribosyl pyrophosphate (PRPP) to form GMP, or between hypoxanthine and phosphoribosyl pyrophosphate (PRPP) to form inosine monophosphate.

Substrates and inhibitors[edit]

Comparative homology modelling of this enzyme in L. donovani suggest that among all of the computationally screened compounds, pentamidine, 1,3-dinitroadamantane, acyclovir and analogs of acyclovir had higher binding affinities than the real substrate (guanosine monophosphate).[3]

Role in disease[edit]

Mutations in the gene lead to hyperuricemia:

  • Some men have partial (up to 20% less activity of the enzyme) HGPRT deficiency that causes high levels of uric acid in the blood, which leads to the development of gouty arthritis and the formation of uric acid stones in the urinary tract. This condition has been named the Kelley-Seegmiller syndrome.[4]
  • Lesch-Nyhan syndrome is due to deficiency of HGPRT caused by HPRT1 mutation [5]
  • Some mutations have been linked to gout, the risk of which is increased in hypoxanthine-guanine phosphoribosyltransferase deficiency.


Hybridomas are immortal (immune to cellular senescence), HGPRT+ cells that result from fusion of mortal, HGPRT+ plasma cells and immortal, HGPRT myeloma cells. They are created to produce monoclonal antibodies in biotechnology. HAT medium inhibits de novo synthesis of nucleic acids, killing myelomas that cannot switch over to salvage pathway, due to lack of HRPT1. Plasma cells eventually die from senesence, leaving pure hybridoma cells.

See also[edit]


  1. ^ "Entrez Gene: hypoxanthine phosphoribosyltransferase 1 (Lesch-Nyhan syndrome)". 
  2. ^ Finette BA; Kendall H; Vacek PM (August 2002). "Mutational spectral analysis at the HPRT locus in healthy children". Mutat. Res. 505 (1–2): 27–41. doi:10.1016/S0027-5107(02)00119-7. PMID 12175903. 
  3. ^ Ansari MY; Dikhit MR; Sahoo GC; Das P (April 2012). "Comparative modeling of HGPRT enzyme of L. donovani and binding affinities of different analogs of GMP". Int. J. Biol. Macromol. 50 (3): 637–49. doi:10.1016/j.ijbiomac.2012.01.010. PMID 22327112. 
  4. ^ Khattak FH; Morris IM; Harris K (May 1998). "Kelley-Seegmiller syndrome: a case report and review of the literature". Br. J. Rheumatol. 37 (5): 580–1. doi:10.1093/rheumatology/37.5.580c. PMID 9651092. 
  5. ^ Hladnik U; Nyhan WL; Bertelli M (September 2008). "Variable expression of HPRT deficiency in 5 members a family with the same mutation". Arch. Neurol. 65 (9): 1240–3. doi:10.1001/archneur.65.9.1240. PMID 18779430. 

Further reading[edit]

External links[edit]