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Table 1 Biological significance of selected validated orphans. The extent and significance of published research associated with a selection of validated orphans is detailed

From: A survey of orphan enzyme activities

EC No. Activity Year first published No. PubMed Publications Involving Orphan Significance Phosphogluconate 2-dehydrogenase 1961 2417 Positive reports of evaluation as a drug target against Trypanosome; trypanocidal activity has been reported; involved in 2-dehydro-D-gluconate degradation pathway 1-acylglycerophosphocholine O-acyltransferase 1967 256 Activity is present in lower eukaryotes, plants, and multiple mammalian tissues Heparosan-N- sulfate-glucuronate 5-epimerase 1979 16 Involved in the biosynthesis of heparan sulfate, which binds proteins to modulate signaling events in embryogenesis. Mouse gene knock-out results in late lethal phenotype.
Correction added in proof: Thanks to a comment by Dr. K. Robison and research by Dr. A. Shearer, we have found that is an artifactual orphan rather than a validated orphan. Genes for this enzyme have been identified in cow and mouse (J Biol Chem 272:28158 1997; J Biol Chem 276:20069 2001). Alkylglycerophosphate 2-O-acetyltransferase 1986 9 Involved in platelet activating factor biosynthesis; possible involvement in ischemia Alkylacetylglycerophosphatase 1986 9 Involved in platelet activation factor biosynthesis Glucose-1,6-bisphosphate synthase 1975 9 Present in several mammalian tissues. Involved in glucose metabolism 2-oxoaldehyde dehydrogenase (NAD+) 1967 9 Involved in the development of diabetic complications Thymine dioxygenase 1972 9 Present in both lower and higher eukaryotes Galactitol 2-dehydrogenase 1956 5 Insulin dysregulation Glutamine N-phenylacetyltransferase 1957 4 Investigated as a predictor of carotid endarterectomy in middle-aged individuals 2-oxoisovalerate dehydrogenase (acylating) 1969 4 Present in prokaryotes and eukaryotes. In the latter, participates in primary metabolism pathway for valine degradation
  1. E.C. is listed in italics because it was cloned and sequenced in 2006, after the completion of this study