In humans, adenine phosphoribosyltransferase (APRT) and hypoxanthine-guanine phosphoribosyltransferase (HGPRT1) are two structurally related enzymes involved in purine recycling. Energy-intensive tissues, such as cardiac muscle and brain cells, extensively use this salvage pathway to maintain their purine levels. Several human diseases are associated with APRT (adenine phosphoribosyltransferase deficiency, MIM:614723) and HGPRT1 (hyperuricemia, HRPT-related, MIM:300323; and Lesch-Nyhan syndrome, LNS, MIM:300322).
Dmel\Aprt, ortholgous to human APRT, is the only recycling enzyme of the purine salvage pathway in Drosophila. No fly gene orthologous to human HGPRT1 has been identified. Some of the neural and other functions associated with HGPRT1 in human may be effected by Aprt in flies.
The human APRT gene has not been introduced into flies. Multiple UAS constructs of the human Hsap\HPRT1 gene have been introduced, including wild-type and a variant possibly implicated in disease; see the 'Disease-Implicated Variants' table below. Pan-neuronal expression of the variant, but not of the wild-type, results in mild locomotor and neurobehavioral impairment.
Animals homozygous for a loss-of-function mutation of Aprt survive to adulthood, but exhibit reduced longevity and various neurobehavioral phenotypes including bang-sensitive seizure, sleep defects and locomotor impairments; they also exhibit overproduction of uric acid that is rescued by allopurinol treatment. Many of these phenotypes are similar to those observed for Lesch-Nyhan syndrome, associated with deficiency of HGPRT1 in human.
[updated Jul. 2024 by FlyBase; FBrf0222196]
APRT deficiency is an autosomal recessive metabolic disorder that can lead to accumulation of the insoluble purine 2,8-dihydroxyadenine (DHA) in the kidney, which results in crystalluria and the formation of urinary stones. Clinical features include renal colic, hematuria, urinary tract infection, dysuria, and, in some cases, renal failure. [from MIM:614723; 2024.07.23]
Virtually complete deficiency of HPRT1 residual activity is associated with the Lesch-Nyhan syndrome, whereas partial deficiency (at least 8%) is associated with the hyperuricemia, HRPT-related. Lesch-Nyhan syndrome is characterized by abnormal metabolic and neurologic manifestations, including intellectual disability, spastic cerebral palsy, choreoathetosis, uric acid urinary stones, and self-destructive biting of fingers and lips. In contrast, hyperuricemia, HRPT-related is usually associated only with the clinical manifestations of excessive purine production, including renal stones, uric acid nephropathy, renal obstruction, and gout. [from MIM:300322 and MIM:300323; 2024.07.23]
All three diseases exhibit recessive inheritance. [from MIM:614723, MIM:300322 and MIM:300323; 2024.07.23]
Adenine Phosphoribosyltransferase (APRT) catalyzes a salvage reaction resulting in the formation of AMP, that is energetically less costly than de novo synthesis. [GeneCards, APRT; 2024.07.27]
Hypoxanthine Phosphoribosyltransferase 1 (HPRT1) converts guanine to guanosine monophosphate, and hypoxanthine to inosine monophosphate; plays a central role in the generation of purine nucleotides through the purine salvage pathway. [GeneCards, HPRT1; 2024.07.27]
One to one: 1 human gene to 1 Drosophila gene.
No ortholog of this gene has been identified in Drosophila.
High-scoring ortholog of human APRT (1 Drosophila to 1 human).
