SAMHD1

Chr 20ADAR

SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1

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

The SAMHD1 protein functions as a deoxynucleoside triphosphatase that restricts viral replication by depleting cellular dNTP pools and regulates DNA replication fork stability. Mutations cause Aicardi-Goutières syndrome 5, an early-onset interferonopathy presenting with neurologic features, and chilblain lupus 2, with both autosomal recessive and autosomal dominant inheritance patterns reported. This gene is extremely intolerant to loss-of-function variants, indicating its critical cellular role.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.942 OMIM phenotypes
Clinical SummarySAMHD1
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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.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.94LOEUF
pLI 0.000
Z-score 1.86
OE 0.67 (0.490.94)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
1.55Z-score
OE missense 0.77 (0.690.85)
267 obs / 348.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.67 (0.490.94)
00.351.4
Missense OE0.77 (0.690.85)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 25 / 37.2Missense obs/exp: 267 / 348.3Syn Z: 0.89
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSAMHD1-related Aicardi-Goutieres syndromeLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6356th %ile
GOF
0.6248th %ile
LOF
0.3067th %ile

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Top 5 full-text resultsSearch PubTator3 ↗