Alternative titles; symbols
HGNC Approved Gene Symbol: SNTG1
Cytogenetic location: 8q11.21 Genomic coordinates (GRCh38): 8:49,909,796-50,796,692 (from NCBI)
Syntrophins, such as SNTG1, are cytoplasmic peripheral membrane proteins that bind to the C-terminal domains of several dystrophin (300377) isoforms and to other dystrophin-related proteins (Piluso et al., 2000).
By searching an EST database using mouse and human syntrophins as probes, followed by screening human fetal brain and neuronal precursor cell cDNA libraries, Piluso et al. (2000) cloned SNTG1 and SNTG2 (608715). The deduced 517-amino acid SNTG1 protein has a calculated molecular mass of 57.9 kD. Syntrophins typically contain 2 pleckstrin (173570) homology (PH) domains, a PDZ domain that bisects the first PH domain, and a C-terminal 'syntrophin unique' (SU) domain that mediates dystrophin binding. SNTG1 and SNTG2 share significant similarity with other syntrophins in the PDZ domain, lower similarity in the PH domains, and weak similarity in the SU domain. In addition, SNTG1 and SNTG2 have an ATP/GTP-binding site motif A (P loop) and several potential phosphorylation sites. Northern blot analysis of several tissues, including skeletal muscle, detected a 7.0-kb SNTG1 transcript only in brain. By sequencing SNTG1 clones and PCR, Piluso et al. (2000) also identified alternatively spliced variants of SNTG1. In situ hybridization and immunohistochemical analysis of rat central nervous system showed widespread distribution of SNTG1 and SNTG2 throughout several cerebral and spinal areas. Transcripts for both SNTG1 and SNTG2 were localized in the perikaryon and proximal portion of neuronal processes.
By pull-down assays of recombinant proteins expressed in COS-7 cells and by yeast 2-hybrid analysis, Piluso et al. (2000) showed that SNTG1 bound to the C termini of dystrophin and beta-dystrobrevin (602415). SNTG1 interacted more weakly with the C terminus of alpha-dystrobrevin (601239).
Piluso et al. (2000) determined that the SNTG1 gene contains 19 exons. The first 2 exons are untranslated.
By genomic sequence analysis and radiation hybrid analysis, Piluso et al. (2000) mapped the SNTG1 gene to chromosome 8q11.
Bashiardes et al. (2004) described a family in which a pericentric inversion of chromosome 8, inv(8)(p23.2)(q11.21), cosegregated with idiopathic scoliosis (see 608765). They determined that the long arm break did not interrupt any known gene and occurred in a region of highly repetitive sequence elements. The short arm break occurred in a 32-kb region between exons 10 and 11 of the SNTG1 gene. Mutation analysis of SNTG1 exons in 152 sporadic idiopathic scoliosis patients revealed a 6-bp deletion in exon 10 in 1 patient and a 2-bp insertion/deletion mutation occurring in a polypyrimidine tract of intronic sequence approximately 20 bp upstream of the SNTG1 exon 5 splice site in 2 patients. These changes were not seen in a screen of 480 control chromosomes. Genomic DNAs from 7 affected individuals in the family of a patient carrying the 6-bp deletion were typed and the deletion was observed in only 5 of the 7. Because SNTG1 expression appeared to be restricted to neural lineages, the authors could not directly measure SNTG1 splice forms in any of the patients.
Bashiardes, S., Veile, R., Allen, M., Wise, C. A., Dobbs, M., Morcuende, J. A., Szappanos, L., Herring, J. A., Bowcock, A. M., Lovett, M. SNTG1, the gene encoding gamma-1-syntrophin: a candidate gene for idiopathic scoliosis. Hum. Genet. 115: 81-89, 2004. [PubMed: 15088139] [Full Text: https://doi.org/10.1007/s00439-004-1121-y]
Coolidge, C. J., Seely, R. J., Patton, J. G. Functional analysis of the polypyrimidine tract in pre-mRNA splicing. Nucleic Acids Res. 25: 888-896, 1997. [PubMed: 9016643] [Full Text: https://doi.org/10.1093/nar/25.4.888]
Piluso, G., Mirabella, M., Ricci, E., Belsito, A., Abbondanza, C., Servidei, S., Puca, A. A., Tonali, P., Puca, G. A., Nigro, V. Gamma-1- and gamma-2-syntrophins, two novel dystrophin-binding proteins localized in neuronal cells. J. Biol. Chem. 275: 15851-15860, 2000. [PubMed: 10747910] [Full Text: https://doi.org/10.1074/jbc.M000439200]