Samhd1 GEne

The SAMHD1 gene (SAMHD1 stands for SAM And HD Domain Containing Deoxynucleoside Triphosphate Triphosphohydrolase 1) is a protein coding gene located on chromosome 20q11.23. DAs gene encodes the SAMHD1 protein, a dGPT-dependent, highly conserved nuclease (triphosphohydrolase) designates.

SAMHD1 inhibits human immunodeficiency virus (HIV) replication in dendritic cells, in macrophages, and in monocytes. Inhibition occurs through the cleavage of deoxyribonucleotide triphosphates (dNTPs) into the deoxynucleoside and triphosphate. This hydrolytic cleavage renders them unavailable to reverse transcriptase during replication. Furthermore, SAMHD1 has 3',5'-exonuclease activity with specificity for single-stranded DNA and RNA. In dividing cells, SAMHD1 is inactivated by phosphorylation, whereas it is active in resting cells.

Mutation in the SAMHD1 gene leads to SAMHD1 dysfunction and disruption of nucleic acid metabolism with activation of the immune system by accumulated nucleic acids.

Mutations in the SAMHD1 gene (also in combination with a TREX1 mutation) lead to the development of Aicardi-Goutières syndrome and familial Chilblain lupus.

1. Crow YJ (2014) Aicardi-Goutières syndrome. In: Pagon RA et al. editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
2. Günther C (2015) Genetics of Lupus erythematosus. Dermatologist 66: 121-130
3. Raven B (2013) Aicardi-Goutières syndrome: clues from the RNase H2 knock-out mouse. J Mol Med (Berl) 91:1235-1240
4. Straussberg R et al (2015) A possible genotype-phenotype correlation in Ashkenazi-Jewish individuals with Aicardi-Goutières syndrome associated with SAMHD1 mutation. J Child Neurol 30:490-495
5. Sze A et al(2013) SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. J Mol Biol 425:4981-4994