A host restriction triphosphorylhydrolase and dNTPase that contains an N-terminal STERILE ALPHA MOTIF and central, conserved ASPARTATE and HISTIDINE (HD) domain. It acts on single-stranded RNA, yielding deoxynucleosides and triphosphate, and functions in anti-viral defense through its dNTPase activity, reducing cellular dNTP levels below what is required for retroviral reverse transcription in DENDRITIC CELLS and MYELOID CELLS. It also has RIBONUCLEASE activity which blocks early replication of retroviruses such as HIV-1. Mutations in the SAMHD1 gene are associated with type 5 Aicardi-Goutieres syndrome (AGS5) and type 2 chilblain LUPUS (CHBL2).
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