Sterile alpha motif domain-containing protein 9 (SAMD9)

SAMD9 (Sterile alpha motif domain-containing protein 9) is a large cytoplasmic multidomain protein involved in antiviral defense, tumor suppression, and regulation of cellular proliferation and apoptosis[1][2][4][5]. It contains predicted domains including a Sterile alpha motif (SAM), an Alba domain, a SIR2-like domain, a P-loop NTPase domain, TPR motifs, and an OB-fold; its architecture is reminiscent of NOD-like receptors[2]. SAMD9 functions as a pattern-recognition receptor for cytosolic double-stranded DNA and RNA, triggering immune defenses against viruses including poxviruses[1][3][4]. Its molecular activities are mediated by an N-terminal tRNase endoribonuclease domain that depletes specific transfer RNAs (notably tRNA^Phe) upon activation, inhibiting protein synthesis and inducing a proteotoxic stress response[2]. Gain-of-function mutations in SAMD9 can enhance its growth-inhibitory effects, causing disorders such as MIRAGE syndrome and pediatric myelodysplastic syndromes, while loss-of-function or impairment can predispose to infection or malignancy[1][2][4]. There are currently no known drugs that directly target SAMD9, but its effector domain is a candidate therapeutic target in related diseases[1]. SAMD9 mutations serve as important biomarkers for patient diagnosis and risk stratification[4]. Safety concerns for targeting or modulating SAMD9 include risk of excessive translation inhibition, multisystem developmental defects, and bone marrow failure syndromes in case of gain-of-function, as well as immunodeficiency or tumor development if inhibited or lost[1][2][4].

Other names

Sterile alpha motif domain containing 9C7orf5DRIF1KIAA2004OEF1OEF2M7MLS2MIRAGENFTCFLJ20073expressed in aggressive fibromatosis