Identification of NAD⁺-dependent isocitrate dehydrogenase 3 γ-like (IDH3GL) gene and its genetic polymorphisms

We have identified a novel human gene designated as IDH3GL (isocitrate dehydrogenase 3 γ-like) that is expressed specifically in human testis. The gene corresponds in sequence to an EST (expressed sequence tag) A1476435 that was first detected by differential expression analysis using a microarray assay. The full-length cDNA sequence (1037 bp) was isolated from the human testis 5′-3′-RACE cDNA libraries and found to have 83% nucleotide sequence identity with part of the IDH3G (isocitrate dehydrogenase 3 γ). The IDH3GL gene consists of 3 exons spanning approximately 220 kb within the region of the NELL1 gene on chromosome 11p15.1. Sequence analysis of the IDH3GL cDNA revealed the presence of a premature stop codon at nucleotide positions 337-339 that results in a truncated peptide with 112 amino acids. This stop codon is conserved in various human ethnic populations and in the chimpanzee (Pan troglodytes). In order to assess the functional status of IDH3GL, especially in relation to the presence of the putative premature stop codon, single nucleotide polymorphisms (SNPs) were screened in the upstream, coding and non-coding regions of the IDH3GL gene in a Japanese population. As a result, a total of 10 SNPs were identified, seven were novel and one of them was a non-synonymous amino acid substitution from Leu to Val. We conclude that the IDH3GL gene sequence is a splice variant of the NELL1 gene and that it probably evolved from a transposed pseudogene of the IDH3 gene.