SAMD9

{{Short description|Protein-coding gene in the species Homo sapiens}}

{{Infobox_gene}}

Sterile alpha motif domain-containing protein 9 is a 1,589-amino-acid protein encoded by the SAMD9 gene.{{cite web | title = Entrez Gene: SAMD9 sterile alpha motif domain containing 9| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=54809| access-date = }} This cytoplasmic protein is a tumor suppressor that has a role in cell proliferation and the innate immune response to viral infection. Like its paralog, SAMD9-like (SAMD9L) protein,{{harvnb|Topaz|Indelman|Chefetz|Geiger|Metzker|Altschuler|Choder|Bercovich|Uitto|Bergman|Richard|Sprecher|2006}} its N-terminus contains a sterile alpha motif (SAM).

Deleterious mutations of this gene cause normophosphatemic familial tumoral calcinosis (NFTC). On the other hand, mutations that increase the activity of SAMD9 cause myelodysplasia, infection, restriction of growth, adrenal hypoplasia (small adrenal glands with diminished function), genital phenotypes, and enteropathy (MIRAGE) syndrome.{{cite journal | vauthors = Narumi S, Amano N, Ishii T, Katsumata N, Muroya K, Adachi M, Toyoshima K, Tanaka Y, Fukuzawa R, Miyako K, Kinjo S, Ohga S, Ihara K, Inoue H, Kinjo T, Hara T, Kohno M, Yamada S, Urano H, Kitagawa Y, Tsugawa K, Higa A, Miyawaki M, Okutani T, Kizaki Z, Hamada H, Kihara M, Shiga K, Yamaguchi T, Kenmochi M, Kitajima H, Fukami M, Shimizu A, Kudoh J, Shibata S, Okano H, Miyake N, Matsumoto N, Hasegawa T | display-authors = 6 | title = SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7 | journal = Nature Genetics | volume = 48 | issue = 7 | pages = 792–7 | date = July 2016 | pmid = 27182967 | doi = 10.1038/ng.3569 | s2cid = 13270706 }} This can lead to loss of chromosome 7 as described for monosomy 7 and myelodysplastic syndrome and leukemia syndrome-2 (M7MLS2).{{cite journal | vauthors = Schwartz JR, Wang S, Ma J, Lamprecht T, Walsh M, Song G, Raimondi SC, Wu G, Walsh MF, McGee RB, Kesserwan C, Nichols KE, Cauff BE, Ribeiro RC, Wlodarski M, Klco JM | display-authors = 6 | title = Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome | journal = Leukemia | volume = 31 | issue = 8 | pages = 1827–30 | date = August 2017 | pmid = 28487541 | pmc = 5540771 | doi = 10.1038/leu.2017.142 }} Loss of chromosome 7/7q may be an adaptation to a growth restriction inherent in SAMD9/9L mutant cells.{{cite journal |vauthors=Hall T, Gurbuxani S, Crispino JD |title=Malignant progression of preleukemic disorders |journal=Blood |volume=143 |issue=22 |pages=2245–55 |date=May 2024 |pmid=38498034 |doi=10.1182/blood.2023020817 |pmc=11181356 |pmc-embargo-date=May 30, 2025 }}