SAMD9 Gene

The SAMD9 gene (SAMD9 stands for "Sterile Alpha Motif Domain Containing 9") is a protein-coding gene located on chromosome 7q21.2. Alternative splicing results in multiple transcript variants encoding the same protein.

The SAMD9 gene encodes a protein containing a sterile alpha motif domain. The SAMD9 protein is localized in the cytoplasm and may play a role in regulating cell proliferation and apoptosis.

Diseases associated with SAMD9 include:

• Mirage syndrome (Myelodysplasia, Infection, Restriction of Growth, Adrenal Hypoplasia, Genital Phenotypes; OMIM: 617053/ Onuma S et al. 2020).
• Familial Normophosphatemic Tumor Calcinosis (this is a rare, life-threatening disorder characterized by progressive deposition of calcified masses in skin and subcutaneous tissue. Serum phosphate levels are normal. Clinical features include painful calcified ulcers, and massive calcinosis in the mid and lower dermis, severe skin and bone infections, erythematous papular exanthema in infancy, conjunctivitis and gingivitis/ OMIM: 610455).
• Furthermore, GOF germline mutations of SAMD9 and SAMD9L cause a spectrum of multisystem disorders that confer a markedly increased risk of developing myeloid malignancies with somatic monosomy 7. Affected individuals had a highly variable clinical course ranging from mild and transient dyspoietic changes in the bone marrow to rapid progression to myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) with monosomy 7 (Wong JC et al. 2018).

1. Onuma S et al. (2020) MIRAGE syndrome caused by a novel missense variant (p.Ala1479Ser) in the SAMD9 gene. Hum Genome Var 7:4.
2. Wong JC et al. (2018) Germline SAMD9 and SAMD9L mutations are associated with extensive genetic evolution and diverse hematologic outcomes. JCI Insight 3(14):e121086.