Alternative titles; symbols
HGNC Approved Gene Symbol: SNCG
Cytogenetic location: 10q23.2 Genomic coordinates (GRCh38): 10:86,955,759-86,963,258 (from NCBI)
Ji et al. (1997) used a high-throughput direct-differential cDNA sequencing approach to identify genes differentially expressed in normal breast as compared with breast cancer. Of many putative differentially expressed genes, a breast cancer-specific gene, BCSG1, which was expressed in high abundance in a breast cancer cDNA library but scarcely at all in a normal breast cDNA library, was identified as a putative breast cancer marker. In situ hybridization analysis demonstrated stage-specific BCSG1 expression as follows: BCSG1 was undetectable in normal or benign breast lesions, showing partial expression in ductal carcinoma in situ, but was expressed at an extremely high level in advanced infiltrating breast cancer. The predicted amino acid sequence of the BCSG1 gene product had a significant homology to the nonamyloid beta protein fragment of Alzheimer disease amyloid protein (163890). BCSG1 overexpression may indicate breast cancer malignant progression from benign or in situ carcinoma.
Lavedan et al. (1998) identified and characterized the same gene as a novel member of the human synuclein gene family, gamma-synuclein (SNCG). SNCG encodes a deduced 127-amino acid protein that is highly homologous to alpha-synuclein (SNCA; 163890) and beta-synuclein (SNCB; 602569). Northern blot analysis showed that the gene is principally expressed in the brain, particularly in the substantia nigra. Through a survey of an EST database, Lavedan et al. (1998) found that the SNCG gene may also be overexpressed in ovarian tumors.
Ninkina et al. (1998) cloned and characterized the same gene, which they called persyn. Persyn shares all the main structural features of alpha- and beta-synucleins, but has a distinctive pattern of expression during pre- and postnatal development of the mouse peripheral and central nervous systems. As with other synucleins, persyn is believed to be involved in the pathogenesis of human neurodegenerative diseases. However, in contrast to other synucleins, high levels of persyn mRNA expression are found in advanced breast carcinomas, suggesting an involvement of the encoded protein in breast tumor progression. Ninkina et al. (1998) used an antibody specific to human persyn to demonstrate that the level of this protein is increased in aging cerebral cortex and in breast tumors.
Lavedan et al. (1998) determined that the SNCG gene contains 5 exons.
By radiation hybrid analysis and fluorescence in situ hybridization (FISH), Lavedan et al. (1998) determined that the SNCG gene is located on 10q23. Ninkina et al. (1998) mapped the persyn gene to 10q23.2-q23.3 by FISH.
Ninkina et al. (1998) found no tumor-specific mutations of the PRSN gene in breast tumors and tumor cell lines, but 2 linked polymorphisms in the coding region were detected, both in mRNA and in exons 3 and 4 of the gene.
Lavedan et al. (1998) sequenced the entire coding region of the SNCG gene in probands of 71 families with apparent autosomal dominant Parkinson disease drawn from various ethnic backgrounds. They found no evidence of mutations, consistent with the finding of Spillantini et al. (1998) of alpha-synuclein but not beta- or gamma-synuclein in Lewy bodies or Lewy neurites.
The role of alpha-synuclein in pathogenesis of familial and idiopathic forms of Parkinson disease (PD; 168600) is well established. To assess the consequences of excess expression of SNCG on the nervous system, Ninkina et al. (2009) generated transgenic mice expressing high levels of mouse Sncg under control of Thy1 promoter. Homozygous Sncg transgenic mice developed severe age- and transgene dose-dependent neuropathology, motor deficits, and died prematurely. Histopathologic changes included aggregation of gamma-synuclein, accumulation of various inclusions in neuronal cell bodies and processes, and astrogliosis. These changes were seen throughout the nervous system but were most prominent in the spinal cord where they led to loss of spinal motor neurons. Western blot analysis showed that spinal motor neurons of transgenic mice had lower levels of Hspb1 (602195) compared to wildtype. Overexpression of Sncg in mouse neurons resulted in seriously compromised organization of neurofilaments in neuronal processes. Ninkina et al. (2009) suggested that downregulation of HSPB1 and disintegration of neurofilament network may play a role in motor neurons dysfunction and death.
Ji, H., Liu, Y. E., Jia, T., Wang, M., Liu, J., Xiao, G., Joseph, B. K., Rosen, C., Shi, Y. E. Identification of a breast cancer-specific gene, BCSG1, by direct differential cDNA sequencing. Cancer Res. 57: 759-764, 1997. [PubMed: 9044857]
Lavedan, C., Buchholtz, S., Auburger, G., Albin, R. L., Athanassiadou, A., Blancato, J., Burguera, J. A., Ferrell, R. E., Kostic, V., Leroy, E., Leube, B., Mota-Vieira, L., and 9 others. Absence of mutation in the beta- and gamma-synuclein genes in familial autosomal dominant Parkinson's disease. DNA Res. 5: 401-402, 1998. [PubMed: 10048491] [Full Text: https://doi.org/10.1093/dnares/5.6.401]
Lavedan, C., Leroy, E., Dehejia, A., Buchholtz, S., Dutra, A., Nussbaum, R. L., Polymeropoulos, M. H. Identification, localization and characterization of the human gamma-synuclein gene. Hum. Genet. 103: 106-112, 1998. [PubMed: 9737786] [Full Text: https://doi.org/10.1007/s004390050792]
Ninkina, N. N., Alimova-Kost, M. V., Paterson, J. W. E., Delaney, L., Cohen, B. B., Imreh, S., Gnuchev, N. V., Davies, A. M., Buchman, V. L. Organization, expression and polymorphism of the human persyn gene. Hum. Molec. Genet. 7: 1417-1424, 1998. [PubMed: 9700196] [Full Text: https://doi.org/10.1093/hmg/7.9.1417]
Ninkina, N., Peters, O., Millership, S., Salem, H., van der Putten, H., Buchman, V. L. Gamma-synucleinopathy: neurodegeneration associated with overexpression of the mouse protein. Hum. Molec. Genet. 18: 1779-1794, 2009. [PubMed: 19246516] [Full Text: https://doi.org/10.1093/hmg/ddp090]
Spillantini, M. G., Crowther, R. A., Jakes, R., Hasegawa, M., Goedert, M. alpha-synuclein in filamentous inclusions of Lewy bodies from Parkinson's disease and dementia with Lewy bodies. Proc. Nat. Acad. Sci. 95: 6469-6473, 1998. [PubMed: 9600990] [Full Text: https://doi.org/10.1073/pnas.95.11.6469]