Sterile alpha motif domain-containing protein 9-like (SAMD9L)

Sterile alpha motif domain-containing protein 9-like (SAMD9L) is a large cytoplasmic multidomain protein, paralogous to SAMD9, broadly expressed in human tissues, and is involved in the regulation of cellular proliferation, antiviral immunity, and protein synthesis. Structurally, SAMD9L contains a sterile alpha motif (SAM) domain for nucleic acid (RNA, DNA) binding, an Alba domain, SIR2 deacetylase-like domain, P-loop NTPase domain, TPR (tetratricopeptide repeat) motifs, and an OB-fold, resembling the overall architecture of NOD-like receptors. Functionally, SAMD9L restricts pathogen replication (notably poxviruses), suppresses inappropriate cell growth largely via translational repression (tRNA cleavage and codon-specific ribosomal stalling), and acts as a tumor suppressor. Mutations in SAMD9L—especially gain-of-function variants—are associated with bone marrow failure, pediatric myelodysplastic syndromes, immune deficiency, and familial predisposition to cancer or ataxia syndromes. No clinically approved drugs target SAMD9L to date, but its central role in hematological and immunological disease suggests future therapeutic potential.

Other names

C7orf6DRIF2KIAA2005UEFFLJ39885ATXPCC7DELqDEL7qM7MLS1MLSM7SCA49UEF1

Not applicable (no approved drugs). Experimentally, GoF or LoF mutations in SAMD9L can alter nucleic acid cleavage, translational repression, and proteotoxic stress induction—all potential mechanistic points for future therapeutic interventions.