Submission Details

The ASH1L gene is located on chromosome 1 at 1q22 and encodes the ASH1 like histone lysine methyltransferase protein, which is responsible for methylating Lys-36 of histone H3. ASH1L was first reported in relation to autosomal dominant ASH1L-related intellectual disability in 2012 (23033978: de Ligt et al. 2012). At least six unique de novo variants have been reported, including missense, frameshift, stop-gained variants. Evidence supporting this gene-disease relationship includes case-level data and experimental data. Variants in this gene have been reported in at least six probands in three publications (23033978: de Ligt et al. 2012; 28191889: Stessman et al. 2017; 29276005: Faundes et al. 2018). More evidence is available in the literature, but the maximum score for genetic evidence has been reached. This gene-disease association is supported by somewhat limited experimental evidence, including expression of ASH1a in the zebrafish brain and during early epiphysial neurogenesis and a null zebrafish model that demonstrates importance of ASH1a in neurogenesis in zebrafish (12702659: Cau and Wilson 2003). In summary, there is strong evidence to support the relationship between ASH1L and autosomal dominant ASH1L-related intellectual disability.

PubMed IDs:

23033978 28191889 29276005 12702659

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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