HGNC Approved Gene Symbol: SYT14
SNOMEDCT: 783060009;
Cytogenetic location: 1q32.2 Genomic coordinates (GRCh38) : 1:209,938,217-210,171,389 (from NCBI)
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 1q32.2 | ?Spinocerebellar ataxia, autosomal recessive 11 | 614229 | Autosomal recessive | 3 |
The SYT14 gene encodes synaptotagmin 14, a member of the synaptotagmin family of genes that encode membrane-trafficking proteins (summary by Doi et al., 2011).
By searching databases for sequences encoding synaptotagmin-like C2 domains, Fukuda (2003) identified mouse and human SYT14 and SYT16 (610950). The deduced 555-amino acid mouse and human SYT14 proteins contain conserved N-terminal extracellular cysteines, followed by a transmembrane domain and C-terminal C-type tandem C2 domains. Database analysis identified a SYT14 homolog in Drosophila, but not in nematode, plant, or yeast. RT-PCR detected highest Syt14 expression in mouse heart and testis, with moderate expression in kidney. In mouse embryos, expression was weak on day 7 and strong on days 11, 15, and 17.
By Northern blot analysis, Quintero-Rivera et al. (2007) detected a 2.9-kb SYT14 transcript in various human brain regions, including corpus callosum, amygdala, caudate nucleus, hippocampus, and thalamus. A smaller 2.5-kb related transcript was also identified, consistent with a synaptotagmin pseudogene.
Doi et al. (2011) found high expression of the SYT14 gene in human fetal and adult brain tissue and in mouse brain, where it showed particularly high expression in the cerebellum. Immunohistochemical analysis showed localization of SYT14 to Purkinje cells in the human and mouse cerebellum. Immunocytochemistry of COS-1 cells transfected with wildtype SYT14 showed perinuclear and submembranous staining.
Fukuda (2003) found that mouse Syt14 formed oligomers independent of Ca(2+). Oligomerization was mainly mediated by fatty-acylated cysteines between the transmembrane domain and spacer domain. The C2 domains of Syt14 bound liposomes made up of phosphatidylcholine and phosphatidylserine.
By genomic sequence analysis, Fukuda (2003) mapped the SYT14 gene to chromosome 4q13.1. However, by genomic sequence analysis, Herrero-Turrion et al. (2006) determined that the SYT14 gene maps to chromosome 1q32.2 and that the gene on chromosome 4q32 is SYT14L (610892).
Fukuda (2003) mapped the mouse Syt14 gene to chromosome 1H6.
Quintero-Rivera et al. (2007) reported a 12-year-old girl with a de novo balanced translocation t(1;3)(q32.2;q25.2) that disrupted the SYT14 gene at the 1q32 breakpoint. The girl had developmental delay, cerebral atrophy, macrocephaly, and seizures. FISH and Southern blot analysis confirmed that the SYT14 gene was disrupted in intron 3; the 3q25 breakpoint contained no known genes or conserved non-genic sequences. Of note, the mother also had macrocephaly, although she did not have the translocation.
By homozygosity mapping followed by whole-exome sequencing in 2 Japanese brothers with autosomal recessive spinocerebellar ataxia-11 (SCAR11; 614229) and mild to moderate psychomotor retardation, Doi et al. (2011) identified a homozygous mutation in the SYT14 gene (G484D; 610949.0001).
In 2 Japanese brothers, born of consanguineous parents, with autosomal recessive spinocerebellar ataxia-11 (SCAR11; 614229), Doi et al. (2011) identified a homozygous 1451G-A transition in exon 8 of the SYT14 gene, resulting in a gly484-to-asp (G484D) substitution in a highly conserved residue in the second C2 domain. The mutation was not found in 576 Japanese control chromosomes. The patients had mild to moderate psychomotor retardation and developed limb and truncal ataxia with dysarthria in their fifties. In vitro functional expression studies in COS-1 cells showed abnormal intracellular localization of the mutant protein compared to wildtype. Whereas wildtype showed perinuclear and submembranous intracellular localization, the mutant protein formed a reticular pattern in the cytoplasm, did not show submembranous distribution, and was abnormally retained in the endoplasmic reticulum, consistent with improper folding.
Doi, H., Yoshida, K., Yasuda, T., Fukuda, M., Fukuda, Y., Morita, H., Ikeda, S., Kato, R., Tsurusaki, Y., Miyake, N., Saitsu, H., Sakai, H., Miyatake, S., Shiina, M., Nukina, N., Koyano, S., Tsuji, S., Kuroiwa, Y., Matsumoto, N. Exome sequencing reveals a homozygous SYT14 mutation in adult-onset, autosomal-recessive spinocerebellar ataxia with psychomotor retardation. Am. J. Hum. Genet. 89: 320-327, 2011. [PubMed: 21835308] [Full Text: https://doi.org/10.1016/j.ajhg.2011.07.012]
Fukuda, M. Molecular cloning, expression, and characterization of a novel class of synaptotagmin (Syt XIV) conserved from Drosophila to humans. J. Biochem. 133: 641-649, 2003. [PubMed: 12801916] [Full Text: https://doi.org/10.1093/jb/mvg082]
Herrero-Turrion, M. J., Fukuda, M., Mollinedo, F. Cloning and genomic characterization of sytdep, a new synaptotagmin XIV-related gene. Biochem. Biophys. Res. Commun. 340: 386-394, 2006. [PubMed: 16376304] [Full Text: https://doi.org/10.1016/j.bbrc.2005.11.184]
Quintero-Rivera, F., Chan, A., Donovan, D. J., Gusella, J. F., Ligon, A. H. Disruption of a synaptotagmin (SYT14) associated with neurodevelopmental abnormalities. Am. J. Med. Genet. 143A: 558-563, 2007. [PubMed: 17304550] [Full Text: https://doi.org/10.1002/ajmg.a.31618]