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.

The SAMHD1 gene may play a role in regulating the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediating proinflammatory tumor necrosis factor-alpha responses. Furthermore, it functions as a host restriction factor in the defense response to viruses. Mutations in this gene have been associated with Aicardi-Goutières syndrome and Chilblain lupus 2.

The encoded protein has deoxynucleoside triphosphate (dNTPase) activity, which is required to limit infection by viruses such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription, blocking early-stage viral replication in dendritic and other myeloid cells. Its ability to promote the degradation of nascent DNA at stalled replication forks is required to prevent the induction of type I interferons and thus prevent chronic inflammation. The ability to promote resection of DNA ends at stalled replication forks is independent of dNTPase activity. Enhances immunoglobulin hypermutation in B lymphocytes by promoting transversion mutation.

1. Crow YJ et al (2015) Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1. Am J Med Genet A 167A:296-312.