HGNC Approved Gene Symbol: SYN2
Cytogenetic location: 3p25.2 Genomic coordinates (GRCh38): 3:12,004,388-12,192,032 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 3p25.2 | {Schizophrenia, susceptibility to} | 181500 | Autosomal dominant | 3 |
The synapsins are a family of 4 synaptic vesicle-associated proteins, synapsins Ia, Ib, IIa, and IIb, that have been implicated in modulation of neurotransmitter release and in synaptogenesis (Greengard et al., 1993). They are products from alternative splicing of 2 distinct genes, SYN1 (313440) and SYN2.
Using rat Syn2 as probe, Xie (1996) cloned SYN2 from a human brain cDNA library. The deduced protein contains 478 amino acids.
By use of microarray expression profiling of prefrontal cortex from matched pairs of patients with schizophrenia (181500) and control subjects and hierarchical data analysis, Mirnics et al. (2000) found that transcripts encoding proteins involved in the regulation of presynaptic function were decreased in all subjects with schizophrenia. Genes of presynaptic function showed a different combination of decreased expression across subjects. Over 250 other gene groups did not show altered expression. Selected presynaptic function gene microarray observations were verified by in situ hybridization. Two of the most consistently changed transcripts in the presynaptic functional gene group, N-ethylmaleimide-sensitive factor (601633) and synapsin-2, were decreased in 10 of 10 and 9 of 10 subjects with schizophrenia, respectively. The combined data suggested that subjects with schizophrenia share a common abnormality in presynaptic function.
Synapsin II has been proposed as a candidate gene for vulnerability to schizophrenia on the basis of its function and its location in a region of the genome implicated by linkage studies in families with schizophrenia. Chen et al. (2004) reported positive association of synapsin II with schizophrenia in a case-control study. However, since case-control analyses can generate false-positive results in the presence of minor degrees of population stratification, Chen et al. (2004) performed a replication study in 366 additional Han Chinese probands and their parents by use of analyses of transmission/disequilibrium for 3 in/del markers and 3 single-nucleotide polymorphisms. Positive association was observed for rs2307981, rs2308169, rs308963, rs795009, and rs2307973. For transmission of 6-marker haplotypes, a global P value of high significance was found. They concluded that this confirmed the previous study and provided further support for the role of synapsin II variants in susceptibility to schizophrenia.
Using Southern blot analysis of DNA from a panel of human/hamster somatic cell hybrids, Li et al. (1995) mapped the SYN2 gene to human chromosome 3. The mouse homolog was mapped to chromosome 6 in a region containing at least 2 neurologic mutants of the mouse. Furthermore, that region of mouse chromosome 6 shows homology to the short arm of human chromosome 3, suggesting that SYN2 resides on 3p.
Overlapping gene groups (OGGs) arise when exons of 1 gene are contained within the introns of another. Typically, the 2 overlapping genes are encoded on opposite DNA strands. Karlin et al. (2002) analyzed examples of OGGs, including TIMP4 (601915) and SYN2; as the former maps to chromosome 3p25, so too must the latter.
Chen, Q., He, G., Qin, W., Chen, Q., Zhao, X., Duan, S., Liu, X., Feng, G., Xu, Y., St Clair, D., Li, M., Wang, J., Xing, Y., Shi, J., He, L. Family-based association study of synapsin II and schizophrenia. Am. J. Hum. Genet. 75: 873-877, 2004. [PubMed: 15449241] [Full Text: https://doi.org/10.1086/425588]
Chen, Q., He, G., Wang, X. Y., Chen, Q. Y., Liu, X. M., Gu, Z. Z., Liu, J., Li, K. Q., Wang, S. J., Zhu, S. M., Feng, G. Y., He, L. Positive association between synapsin II and schizophrenia. Biol. Psychiat. 56: 177-181, 2004. [PubMed: 15271586] [Full Text: https://doi.org/10.1016/j.biopsych.2004.05.010]
Greengard, P., Valtorta, F., Czernik, A. J., Benfenati, F. Synaptic vesicle phosphoproteins and regulation of synaptic function. Science 259: 780-785, 1993. [PubMed: 8430330] [Full Text: https://doi.org/10.1126/science.8430330]
Karlin, S., Chen, C., Gentles, A. J., Cleary, M. Associations between human disease genes and overlapping gene groups and multiple amino acid runs. Proc. Nat. Acad. Sci. 99: 17008-17013, 2002. [PubMed: 12473749] [Full Text: https://doi.org/10.1073/pnas.262658799]
Li, L., Chin, L.-S., Greengard, P., Copeland, N. G., Gilbert, D. J., Jenkins, N. A. Localization of the synapsin II (SYN2) gene to human chromosome 3 and mouse chromosome 6. Genomics 28: 365-366, 1995. [PubMed: 8530057] [Full Text: https://doi.org/10.1006/geno.1995.1162]
Mirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., Levitt, P. Molecular characterization of schizophrenia viewed by microarray analysis of gene expression in prefrontal cortex. Neuron 28: 53-67, 2000. [PubMed: 11086983] [Full Text: https://doi.org/10.1016/s0896-6273(00)00085-4]
Xie, Y. Cloning and sequencing analysis of a human synapsin IIb-encoding brain cDNA. Gene 173: 289-290, 1996. [PubMed: 8964517] [Full Text: https://doi.org/10.1016/0378-1119(96)00234-x]