SAMHD1

Chr 20q11.23

SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1

Aliases:: SBBI88, Mg11, HDDC1, MOP-5, AGS5
MANE:: ENST00000646673.2

OMIM: 606754 ↗NCBI: 25939 ↗Ensembl ↗

Annotations refreshed 1 month ago.

Predicted protein structure

AlphaFold predicted structure

SAMHD1 · Q9Y3Z3

v62025-08-01

Predicted Aligned Error matrix for SAMHD1 — diagonal shows residue index, colour shows pairwise prediction confidence (lower is better) — Predicted Aligned Error

Mean pLDDT

88.2/ 100

Confident

626 residues

Confidence breakdown

Very high(≥ 90)75%
Confident(70–90)14%
Low(50–70)2%
Very low(< 50)10%

Open interactive 3D viewer

AlphaFold (Jumper et al., 2021) · CC BY 4.0

Clinical relevance (Genomics England PanelApp)

Diagnostic Grade (Green)

Adult onset leukodystrophy
BIALLELIC, autosomal or pseudoautosomal
Cerebral vascular malformations
BIALLELIC, autosomal or pseudoautosomal
Childhood onset dystonia, chorea or related movement disorder
BIALLELIC, autosomal or pseudoautosomal
COVID-19 research
BIALLELIC, autosomal or pseudoautosomal
DDG2P
BIALLELIC, autosomal or pseudoautosomal
Early onset or syndromic epilepsy
BIALLELIC, autosomal or pseudoautosomal
Fetal anomalies
BIALLELIC, autosomal or pseudoautosomal
Inherited white matter disorders
BIALLELIC, autosomal or pseudoautosomal

+14 more panels — install the extension to see the full list inline on any page.

Disease associations (Open Targets)

Aicardi-Goutières syndrome
0.81
Aicardi-Goutieres syndrome
0.77
Aicardi-Goutieres syndrome 5
0.76
neoplasm
0.54
chilblain lupus 2
0.54
hereditary disease
0.48
type 1 interferonopathy
0.46
chilblain lupus
0.46
thyroid gland carcinoma
0.40
familial chilblain lupus
0.37

Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.

Protein function (UniProt)

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Protein that acts both as a host restriction factor involved in defense response to virus and as a regulator of DNA end resection at stalled replication forks (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:26294762, PubMed:26431200, PubMed:28229507, PubMed:28834754, PubMed:29670289). Has deoxynucleoside triphosphate (dNTPase) activity, which is required to restrict infection by viruses, such as HIV-1: dNTPase activity reduces cellular dNTP levels to levels too low for retroviral reverse transcription to occur, blocking early-stage virus replication in dendritic and other myeloid cells (PubMed:19525956, PubMed:21613998, PubMed:21720370, PubMed:22056990, PubMed:23364794, PubMed:23601106, PubMed:23602554, PubMed:24336198, PubMed:25038827, PubMed:26101257, PubMed:26294762, PubMed:26431200, PubMed:28229507). Likewise, suppresses LINE-1 retrotransposon activity (PubMed:24035396, PubMed:24217394, PubMed:29610582). Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx (PubMed:21613998, PubMed:21720370). In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools (PubMed:23858451). Phosphorylation at Thr-592 acts as a switch to control dNTPase-dependent and -independent functions: it inhibits dNTPase activity and ability to restrict infection by viruses, while it promotes DNA end resection at stalled replication forks (PubMed:23601106, PubMed:23602554, PubMed:29610582, PubMed:29670289). Functions during S phase at stalled DNA replication forks to promote the resection of gapped or reversed forks: acts by stimulating the exonuclease activity of MRE11, activating the ATR-CHK1 pathway and allowing the forks to restart replication (PubMed:29670289). Its ability to promote degradation of nascent DNA at stalled replication forks is required to prevent induction of type I interferons, thereby preventing chronic inflammation (PubMed:27477283, PubMed:29670289). Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity (PubMed:29670289). Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation (By similarity)