| SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1 | |
|---|---|
| Symbol | SAMHD1 |
| Full Name | SAM and HD Domain Containing Metal Dependent Hydrolase 1 |
| Chromosome | 20q11.23 |
| NCBI Gene | 9833 |
| Ensembl | ENSG00000101347 |
| OMIM | 606754 |
| UniProt | Q9Y3D9 |
| Diseases | Aicardi-Goutieres Syndrome, Chronic Lymphocytic Leukemia, HIV Infection |
| Expression | Ubiquitously expressed; high expression in brain, hematopoietic cells |
SAMHD1 (SAM and HD Domain Containing Metal Dependent Hydrolase 1) is a gene located on chromosome 20q11.23 that encodes a dNTP triphosphohydrolase enzyme with important roles in innate immunity and DNA repair. SAMHD1 is best known for its ability to restrict HIV and other retroviruses by depleting the cellular dNTP pool, making it a critical component of the innate immune system. Mutations in SAMHD1 cause Aicardi-Goutieres syndrome (AGS) and are associated with increased cancer risk [1][2].
The SAMHD1 gene spans approximately 40 kb and consists of 20 exons. The gene encodes a 626-amino acid protein with enzymatic activity.
SAMHD1 contains:
SAMHD1 functions as a dNTP triphosphohydrolase:
SAMHD1 mutations account for approximately 10% of AGS cases. Clinical features include:
Pathogenic variants:
SAMHD1 is a tumor suppressor:
SAMHD1 restricts HIV-1 infection in:
SAMHD1 is ubiquitously expressed with highest levels in:
SAMHD1 expression is regulated by:
Rice GI, Bond J, Asipu A, et al. "Mutations in SAMHD1 cause Aicardi-Goutieres syndrome." Nature Genetics. 2012;44(11):1243-1248. DOI:10.1038/ng.2413
Hrecka K, Hao C, Gierszewska M, et al. "SAMHD1 restricts HIV-1 infection in resting CD4+ T cells." Nature. 2011;474(7353):658-661. DOI:10.1038/nature10195
Goldstone DC, Ennis-Adeniran V, Hedden JJ, et al. "HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase." Nature. 2011;474(7353):662-666. DOI:10.1038/nature10190
Franzolin E, Pontarin G, Rampazzo C, et al. "The deoxynucleotide triphosphohydrolase SAMHD1 is a major regulator of DNA precursor pools in mammalian cells." Proceedings of the National Academy of Sciences. 2013;110(36):14250-14255. DOI:10.1073/pnas.1312033110
Clifford R, Louis T, Robbe P, et al. "SAMHD1 is mutated in the Aicardi-Goutieres syndrome." Nature Genetics. 2012;44(11):1249-1252. DOI:10.1038/ng.2424