MEIS1

Inheritance Pattern: AD

Disease ID:MONDO:0002049

Submitter: ClinGen

*MEIS1* was first reported in relation to congenital thrombocytopenia in 2022 (Steinberg-Shemer et al., 2022 PMID: 35130804). *MEIS1* is a homeobox gene that acts as a transcriptional regulator of genes involved in embryonic development, cell differentiation, hematopoiesis, and neural development. To date, there has been one report of a de novo heterozygous variant in *MEIS1* causing severe congenital thrombocytopenia. Additionally, MEIS1 overexpression is common in leukemias (specifically MLL-fusion-induced leukemia) and is caused by upstream activation of oncogenes interacting with MEIS1, not specific variants in the MEIS1 gene, and is not included in this curation. Evidence supporting this gene-disease curation includes case level data and experimental data. Summary of Case Level Data (1 point): One de novo heterozygous splicing variant (c. 432+5G>C) that has been shown to lead exon skipping and a premature stop codon. This variant as been reported in a single proband. Summary of Experimental Evidence (2.5 points): This gene disease relationship is supported by mouse model systems (Azcoitia et al., 2005 PMID: 15882575; Hisa et al., 2004 PMID: 14713950; Miller et al., 2016 PMID: 26986211), a zebrafish model (Cvejic et al., 2011 PMID: 21048033) and functional alteration in non-patient cells (Wang et al., 2018 PMID: 29358086). 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. This gene-disease relationship was curated by the ClinGen Hemostasis and Thrombosis (H/T) Gene Curation Expert Panel using Gene Clinical Validity Standard Operating Procedures (SOP), Version 11.