Cloning and Characterization of a Putative Human Glycerol 3-Phosphate Permease Gene (SLC37A1 or G3PP) on 21q22.3: Mutation Analysis in Two Candidate Phenotypes, DFNB10 and a Glycerol Kinase Deficiency

• Published in: Genomics (San Diego, Calif.) Vol. 70; no. 2; pp. 190 - 200
• Main Authors: Bartoloni, Lucia, Wattenhofer, Marie, Kudoh, Jun, Berry, Asher, Shibuya, Kazunori, Kawasaki, Kazuhiko, Wang, Jun, Asakawa, Shuichi, Talior, Ilana, Bonne-Tamir, Batsheva, Rossier, Colette, Michaud, Joelle, McCabe, Edward R.B., Minoshima, Shinsei, Shimizu, Nobuyoshi, Scott, Hamish S., Antonarakis, Stylianos E.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.12.2000; Elsevier
• Subjects: Amino Acid Sequence; Aquaporins; Arabidopsis Proteins; Base Sequence; Biological and medical sciences; chromosome 21; Chromosomes, Human, Pair 21; Cloning, Molecular; DFNB10 gene; DNA Mutational Analysis; DNA, Complementary; Expressed Sequence Tags; Fundamental and applied biological sciences. Psychology; Genes. Genome; GK gene; glpT protein; glycerol 3-phosphate; glycerol 3-phosphate permease; Glycerol Kinase - genetics; HC21 gene; Humans; Membrane Transport Proteins - chemistry; Membrane Transport Proteins - genetics; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Phenotype; Reverse Transcriptase Polymerase Chain Reaction; Sequence Homology, Amino Acid; Genetic mapping; Human; Complementary DNA; Splicing; Gene; Nucleotide sequence; Chromosome G21; Homology; Mutation
• ISSN: 0888-7543; 1089-8646
• DOI: 10.1006/geno.2000.6395

Using multiple exons trapped from human chromosome 21 (HC21)-specific cosmids with homology to a putative Arabidopsis thaliana glycerol 3-phosphate permease, we have determined the full-length cDNA sequence of a novel HC21 gene encoding a putative sugar-phosphate transporter (HGMW-approved symbol SLC37A1, aka G3PP). The predicted protein has 12 putative transmembrane domains and is also highly homologous to bacterial glpT proteins. The transcript was precisely mapped to 21q22.3 between D21S49 and D21S113. Comparison of the SLC37A1 cDNA to genomic sequence revealed that the gene encompasses 82 kb, and it is split into 19 coding exons and 7 untranslated exons, which are alternatively spliced in a complex and tissue-specific manner. Glycerol 3-phosphate (G3P) is produced by glycerol kinase (GK) and is found in several biochemical pathways in different cellular compartments, such as the glycerol phosphate shuttle and glycerophospholipid synthesis. Thus SLC37A1 mutations may cause a phenotype similar to GK deficiency. Mutational analyses of SLC37A1 in seven patients with no mutations in the GK gene and low GK activity revealed only nonpathogenetic sequence variants, excluding SLC37A1 as the gene for the phenotype in these patients. SLC37A1 maps in the refined critical region of the autosomal recessive deafness locus, DFNB10, on 21q22.3. Mutation analyses also excluded SLC37A1 as the gene for DFNB10.