HPRT1

HPRT1 is the gene that encodes the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT), a cytosolic enzyme that participates in the purine salvage pathway. The gene is located on the X chromosome (Xq26-q28) and is expressed in many tissues. HGPRT acts to recycle the purines hypoxanthine and guanine by converting them to inosine monophosphate (IMP) and guanosine monophosphate (GMP) using the donor molecule PRPP.

Biochemically, HGPRT reduces the loss of purines by salvaging them to nucleotides, thereby limiting the production of uric acid from nucleotide degradation. Deficiency of HGPRT disrupts purine salvage, leading to increased de novo purine synthesis and elevated uric acid production, which can contribute to hyperuricemia and urate crystal deposition.

Genetically, HPRT1 mutations cause X-linked disorders. In males, deleterious mutations typically result in Lesch-Nyhan syndrome, a severe condition characterized by hyperuricemia, gout, neurodevelopmental delay, dystonia, choreoathetoid movements, and self-injurious behavior. Partial deficiency can produce Kelley-Seegmiller syndrome with milder symptoms. Female carriers are usually asymptomatic or mildly affected due to X-inactivation.

Diagnosis and management include enzymatic activity assays in blood cells or direct genetic testing, along with monitoring and treating hyperuricemia (commonly with allopurinol) and addressing neurological and behavioral symptoms through multidisciplinary care. Prognosis varies with the level of residual HGPRT activity.

In research, HPRT1 serves as a widely used selectable marker in mammalian cell genetics. Cells lacking HGPRT activity resist certain toxic selections, while HGPRT-positive cells can be maintained in selective media such as hypoxanthine-aminopterin-thymidine (HAT) medium.