SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1

SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1</th>
</tr>
<tr> [@clifford2012]
<td class="label">Symbol</td>
<td><strong>SAMHD1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SAM and HD Domain Containing Metal Dependent Hydrolase 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>20q11.23</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/9833" target="_blank">9833</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101347" target="_blank">ENSG00000101347</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606754" target="_blank">606754</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9Y3D9" target="_blank">Q9Y3D9</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Aicardi-Goutieres Syndrome](/diseases/aicardi-goutieres-syndrome), [Chronic Lymphocytic Leukemia](/diseases/chronic-lymphocytic-leukemia), [HIV Infection](/diseases/hiv)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitously expressed; high expression in brain, hematopoietic cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIME

SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1</th>
</tr>
<tr> [@clifford2012]
<td class="label">Symbol</td>
<td><strong>SAMHD1</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>SAM and HD Domain Containing Metal Dependent Hydrolase 1</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>20q11.23</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td><a href="https://www.ncbi.nlm.nih.gov/gene/9833" target="_blank">9833</a></td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td><a href="https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101347" target="_blank">ENSG00000101347</a></td>
</tr>
<tr>
<td class="label">OMIM</td>
<td><a href="https://omim.org/entry/606754" target="_blank">606754</a></td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/Q9Y3D9" target="_blank">Q9Y3D9</a></td>
</tr>
<tr>
<td class="label">Diseases</td>
<td>[Aicardi-Goutieres Syndrome](/diseases/aicardi-goutieres-syndrome), [Chronic Lymphocytic Leukemia](/diseases/chronic-lymphocytic-leukemia), [HIV Infection](/diseases/hiv)</td>
</tr>
<tr>
<td class="label">Expression</td>
<td>Ubiquitously expressed; high expression in brain, hematopoietic cells</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/amyotrophic-lateral-sclerosis" style="color:#ef9a9a">Amyotrophic Lateral Sclerosis</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">36 edges</a></td>
</tr>
</table>

SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1

Overview

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].

Gene Structure

The SAMHD1 gene spans approximately 40 kb and consists of 20 exons. The gene encodes a 626-amino acid protein with enzymatic activity.

Genomic Organization

• Chromosome: 20q11.23
• Location: chr20: 35020647-35061126
• Strand: Plus strand
• Exons: 20

Protein Structure and Function

Domain Architecture

SAMHD1 contains:

Enzymatic Activity

SAMHD1 functions as a dNTP triphosphohydrolase:

• Hydrolyzes dNTPs to deoxynucleosides and triphosphates
• Requires Mg2+ or Mn2+ for catalysis
• Tetramerization is required for activity
• Regulated by phosphorylation at Thr592

Biological Functions

Innate Immune Defense

DNA Metabolism

SAMHD1 in Disease

Aicardi-Goutieres Syndrome (AGS)

SAMHD1 mutations account for approximately 10% of AGS cases. Clinical features include:

• Progressive encephalopathy
• Intracranial calcifications
• Leukodystrophy
• Elevated interferon signature
• Chilblain lupus-like skin lesions

• Missense mutations (D208N, R145H, Q83X)
• Frameshift and nonsense mutations
• Splice-site mutations

Cancer Predisposition

SAMHD1 is a tumor suppressor:

• Loss-of-function increases cancer risk
• Associated with chronic lymphocytic leukemia (CLL)
• Mutations found in various malignancies

HIV Restriction

SAMHD1 restricts HIV-1 infection in:

• Myeloid cells (macrophages, dendritic cells)
• Resting CD4+ T cells
• Microglial cells

Expression Pattern

Tissue Distribution

SAMHD1 is ubiquitously expressed with highest levels in:

• Brain ([neurons](/entities/neurons), microglia)
• Hematopoietic cells (monocytes, macrophages)
• Spleen
• Lymph nodes
• Bone marrow

Cellular Localization

• Cytoplasmic and nuclear localization
• Associates with chromatin
• Nuclear import signals

Regulation

SAMHD1 expression is regulated by:

• Type I and II interferon signaling
• Cell cycle (cell cycle-dependent phosphorylation)
• DNA damage responses

Therapeutic Implications

HIV Treatment

Cancer Therapy

• SAMHD1 loss increases sensitivity to some chemotherapies
• dNTP pool modulation as cancer treatment strategy

AGS Treatment

• JAK inhibitors to suppress interferon signature
• Supportive neurological care

Key Publications

External Links

• NCBI Gene: [https://www.ncbi.nlm.nih.gov/gene/9833](https://www.ncbi.nlm.nih.gov/gene/9833)
• Ensembl: [https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101347](https://ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101347)
• OMIM: [https://omim.org/entry/606754](https://omim.org/entry/606754)
• UniProt: [https://www.uniprot.org/uniprot/Q9Y3D9](https://www.uniprot.org/uniprot/Q9Y3D9)

See Also

• [Aicardi-Goutieres Syndrome](/diseases/aicardi-goutieres-syndrome)
• [HIV and Neurodegeneration](/mechanisms/hiv-neurodegeneration)
• [DNA Damage and Repair in Neurodegeneration](/mechanisms/dna-damage-repair)
• [Innate Immune Signaling in AD](/mechanisms/innate-immune-signaling-ad)
• [Genes Index](/genes)
• [Proteins Index](/proteins)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving SAMHD1 — SAM and HD Domain Containing Metal Dependent Hydrolase 1 discovered through SciDEX knowledge graph analysis: