Submission Details

The SYP gene is located on chromosome X at Xp11.23 and encodes the synaptophysin protein, which is associated with regulation of synaptic vesicle endocytosis and is the most abundant synaptic vesicle protein by mass, accounting for about 10% of total vesicle protein. Variants in the SYP gene were first reported in relation to X-linked intellectual disability in 2007 (19377476: Tarpey et al. 2009). This study reported two frameshift variants predicted to result in premature truncation and one each of a frameshift variant leading to elongation and a missense variant. The two frameshift variants resulting in premature truncation, showed mislocalization and impaired synaptobrevin II retreival in syp-/- cultured neurons (23966691: Gordon and Cousin, 2013). The missense variant and the frameshift variant leading to elongation only showed impaired synaptobrevin II retreival. In summary, there is limited evidence to support this gene-disease relationship. Although more evidence is needed to support a causal role, no convincing evidence has emerged thatcontradicts the gene-disease relationship.

PubMed IDs:

19377476 23966691

Assertion Criteria:

Click here to view assertion criteria

https://www.clinicalgenome.org/site/assets/files/3975/gene-disease_validity_standard_operating_procedures_version_7-1.pdf

Submitter Submitted Date:

10/15/2020

The GenCC data are available free of restriction under a CC0 1.0 Universal (CC0 1.0) Public Domain Dedication. The GenCC requests that you give attribution to GenCC and the contributing sources whenever possible and appropriate. The accepted Flagship manuscript is now available from Genetics in Medicine (https://www.gimjournal.org/article/S1098-3600(22)00746-8/fulltext).

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