Submission Details

The FOXP1 gene is located on chromosome 3 at 3p13 and encodes the forkhead box P1 protein, which is a transcriptional repressor that promotes columnar organization of spinal motor neurons and plays a role in specification and differentiation of lung epithelium, regulation of B-cell development and cardiac muscle cell proliferation. The FOXP1 gene was first reported in relation to autosomal dominant FOXP1-related intellectual disability syndrome in 2010 (20950788: Hamdan et al. 2010). At least six unique variants have been reported in humans, including missense and predicted null 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 (20950788: Hamdan et al. 2010; 26647308: Sollis et al. 2016; 28735298: Meerschaut et al. 2017). All variants occurred de novo. More evidence is available in the literature, but the maximum score for genetic evidence (12 pts.) has been reached. The mechanism of disease involves haploinsufficiency. This gene-disease relationship is also supported by expression data, in vitro functional assays, and data from a knockout mouse model (12687690: Ferland et al. 2013; 26647308: Sollis et al. 2016). In summary, FOXP1 is definitively associated with autosomal dominant FOXP1-related intellectual disability syndrome.

PubMed IDs:

20950788 26647308 28735298 12687690 25266127

Assertion Criteria:

Click here to view assertion criteria

https://clinicalgenome.org/site/assets/files/2165/gene_curation_sop_version_6_aug_2018_final.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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