Submission Details

The FAT2 gene is located on chromosome 5 at 5q33.1 and encodes the FAT atypical cadherin 2 protein, which helps regulate cell migration and is thought to be involved in cerebellar development by organizing the parallel fibers of granule cells. The FAT2 gene was first reported in relation to autosomal dominant spinocerebellar ataxia in 2017 (29053796: Nibbeling et al. 2017). Evidence supporting this gene-disease relationship includes limited case-level and experimental data. Heterozygous missense variants were identified in two unrelated individuals (29053796: Nibbeling et al. 2017). One of the variants segregated with the disease in six additional family members. The mechanism of disease is unknown, but in vitro analyses of the identified variants suggested they resulted in partial protein mislocalization to the golgi and in one case, increased cellular aggregation in the presence of calcium. FAT2 is also almost exclusively expressed in the cerebellum, where it localizes to the parallel fibers of granule cells (12213440: Nakayama et al. 2002). 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 that contradicts the gene-disease relationship.

PubMed IDs:

29053796 12213440

Assertion Criteria:

Click here to view assertion criteria

https://clinicalgenome.org/site/assets/files/2169/gene_curation_sop_2016_version_5_11_6_17.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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