SAMD9 explained

Sterile alpha motif domain-containing protein 9 is a 1,589-amino-acid protein encoded by the SAMD9 gene.^[1] 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, 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.^[2] This can lead to loss of chromosome 7 as described for monosomy 7 and myelodysplastic syndrome and leukemia syndrome-2 (M7MLS2).^[3] Loss of chromosome 7/7q may be an adaptation to a growth restriction inherent in SAMD9/9L mutant cells.^[4]

Further reading

• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–4 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• The Sanger Centre . The Washington University Genome Sequencing Center . Toward a complete human genome sequence . Genome Research . 8 . 11 . 1097–1108 . November 1998 . 9847074 . 10.1101/gr.8.11.1097 . free .
• Topaz O, Indelman M, Chefetz I, Geiger D, Metzker A, Altschuler Y, Choder M, Bercovich D, Uitto J, Bergman R, Richard G, Sprecher E . 6 . A deleterious mutation in SAMD9 causes normophosphatemic familial tumoral calcinosis . American Journal of Human Genetics . 79 . 4 . 759–764 . October 2006 . 16960814 . 1592555 . 10.1086/508069 .
• Li CF, MacDonald JR, Wei RY, Ray J, Lau K, Kandel C, Koffman R, Bell S, Scherer SW, Alman BA . 6 . Human sterile alpha motif domain 9, a novel gene identified as down-regulated in aggressive fibromatosis, is absent in the mouse . BMC Genomics . 8 . 92 . April 2007 . 17407603 . 1855325 . 10.1186/1471-2164-8-92 . free .
• Dereure O . [SAMD9 mutation in normophosphatemic familial tumoral calcinosis] . Annales de Dermatologie et de Vénéréologie . 134 . 5 Pt 1 . 505 . May 2007 . 17507861 . 10.1016/S0151-9638(07)89230-1 .

Notes and References

1. Web site: Entrez Gene: SAMD9 sterile alpha motif domain containing 9.
2. 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 . 6 . SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7 . Nature Genetics . 48 . 7 . 792–7 . July 2016 . 27182967 . 10.1038/ng.3569 . 13270706 .
3. 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 . 6 . Germline SAMD9 mutation in siblings with monosomy 7 and myelodysplastic syndrome . Leukemia . 31 . 8 . 1827–30 . August 2017 . 28487541 . 5540771 . 10.1038/leu.2017.142 .
4. Hall T, Gurbuxani S, Crispino JD. Malignant progression of preleukemic disorders. Blood. 2024 May 30;143(22):2245-2255. doi: 10.1182/blood.2023020817. PMID: 38498034; PMCID: PMC11181356.