SAMHD1

Chr 20ADAR

SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1

Also known as: CHBL2, DCIP, HDDC1, MOP-5, SBBI88, hSAMHD1

NCBI Gene: 25939ENSG00000101347UniProt: Q9Y3Z3

This gene may play a role in regulation of the innate immune response. The encoded protein is upregulated in response to viral infection and may be involved in mediation of tumor necrosis factor-alpha proinflammatory responses. Mutations in this gene have been associated with Aicardi-Goutieres syndrome. [provided by RefSeq, Mar 2010]

Primary Disease Associations & Inheritance

?Chilblain lupus 2MIM #614415
AD
Aicardi-Goutieres syndrome 5MIM #612952
AR
683
ClinVar variants
121
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— SAMHD1
🧬
Gene-Disease Validity (ClinGen)
SAMHD1-related type 1 interferonopathy · ARDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
121 Pathogenic / Likely Pathogenic· 320 VUS of 683 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.94LOEUF
pLI 0.000
Z-score 1.86
OE 0.67 (0.49–0.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.55Z-score
OE missense 0.77 (0.69–0.85)
267 obs / 348.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.67 (0.49–0.94)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.77 (0.69–0.85)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.0.90
0≤1.21.6
LoF obs/exp: 25 / 37.2Missense obs/exp: 267 / 348.3Syn Z: 0.89

ClinVar Variant Classifications

683 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic76
Likely Pathogenic45
VUS320
Likely Benign215
Benign5
Conflicting22
76
Pathogenic
45
Likely Pathogenic
320
VUS
215
Likely Benign
5
Benign
22
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
32
0
44
0
76
Likely Pathogenic
23
6
15
1
45
VUS
5
251
47
17
320
Likely Benign
1
4
97
113
215
Benign
1
0
3
1
5
Conflicting
—22
Total62261206132683

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SAMHD1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

SAMHD1-related Aicardi-Goutieres syndrome

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

?Chilblain lupus 2

MIM #614415

Molecular basis of disorder known

Autosomal dominant

Aicardi-Goutieres syndrome 5

MIM #612952

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — SAMHD1
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Aicardi-Goutières syndrome: A monogenic type I interferonopathy.
Liu A et al.·Scand J Immunol
2023Review
Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.
de Jesus AA et al.·J Clin Invest
2020Clinical trial
Characterization of human disease phenotypes associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR, and IFIH1.
Crow YJ et al.·Am J Med Genet A
2015
Genomic and epigenomic insights into the origin, pathogenesis, and clinical behavior of mantle cell lymphoma subtypes.
Nadeu F et al.·Blood
2020
Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study.
Rice GI et al.·Lancet Neurol
2013
SAMHD1 in cancer: curse or cure?
Schott K et al.·J Mol Med (Berl)
2022Review
HIV-2/SIV Vpx targets a novel functional domain of STING to selectively inhibit cGAS-STING-mediated NF-κB signalling.
Su J et al.·Nat Microbiol
2019Functional
Systemic complications of Aicardi Goutières syndrome using real-world data.
Peixoto de Barcelos I et al.·Mol Genet Metab
2024
Hexosamine biosynthetic pathway promotes the antiviral activity of SAMHD1 by enhancing O-GlcNAc transferase-mediated protein O-GlcNAcylation.
Hu J et al.·Theranostics
2021
Trio Whole Exome Sequencing in Chinese Childhood-Onset Lupus Reveals Novel Candidate Genes.
Ma J et al.·Arthritis Rheumatol
2025
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools