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.
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.
Bartoloni
L
L
Division of Medical Genetics, University of Geneva Medical School and Cantonal Hospital of Geneva, Switzerland.
Wattenhofer
M
M
Kudoh
J
J
Berry
A
A
Shibuya
K
K
Kawasaki
K
K
Wang
J
J
Asakawa
S
S
Talior
I
I
Bonne-Tamir
B
B
Rossier
C
C
Michaud
J
J
McCabe
E R
ER
Minoshima
S
S
Shimizu
N
N
Scott
H S
HS
Antonarakis
S E
SE
D000595:Amino Acid Sequence; D020346:Aquaporins; D029681:Arabidopsis Proteins; D001483:Base Sequence; D002891:Chromosomes, Human, Pair 21; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D018076:DNA, Complementary; D020224:Expressed Sequence Tags; D005991:Glycerol Kinase / Q000235:genetics*; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics*; D008969:Molecular Sequence Data; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid
D020346:Aquaporins; D029681:Arabidopsis Proteins; D018076:DNA, Complementary; D026901:Membrane Transport Proteins; C488963:NLM1 protein, Arabidopsis; C036527:SLC37A1 protein, human; D005991:Glycerol Kinase