SAMHD1 SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: SAMHD1provided by HGNC
Official Full Name: SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1provided by HGNC
Primary source: HGNC:HGNC:15925
See related: Ensembl:ENSG00000101347 MIM:606754; AllianceGenome:HGNC:15925
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: DCIP; CHBL2; HDDC1; MOP-5; SBBI88; hSAMHD1
Summary: 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]
Expression: Ubiquitous expression in appendix (RPKM 54.7), spleen (RPKM 47.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 20q11.23

Exon count:: 16

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	20	NC_000020.11 (36889773..36951708, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	20	NC_060944.1 (38614121..38676051, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (35518176..35580111, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Deciphering the role of SAMHD1 in endometrial cancer progression.
Title: Deciphering the role of SAMHD1 in endometrial cancer progression.
Acetylation of SAMHD1 at lysine 580 is crucial for blocking HIV-1 infection.
Title: Acetylation of SAMHD1 at lysine 580 is crucial for blocking HIV-1 infection.
SAMHD1 dysfunction induces IL-34 expression via NF-kappaB p65 in neuronal SH-SY5Y cells.
Title: SAMHD1 dysfunction induces IL-34 expression via NF-κB p65 in neuronal SH-SY5Y cells.
SAMHD1 compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of Aicardi-Goutieres syndrome.
Title: SAMHD1 compound heterozygous rare variants associated with moyamoya and mitral valve disease in the absence of other features of Aicardi-Goutières syndrome.
Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels.
Title: Gene editing of SAMHD1 in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction, and cellular dNTP levels.
Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.
Title: Guanine-containing ssDNA and RNA induce dimeric and tetrameric structural forms of SAMHD1.
Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma.
Title: Activation of STING by SAMHD1 Deficiency Promotes PANoptosis and Enhances Efficacy of PD-L1 Blockade in Diffuse Large B-cell Lymphoma.
SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.
Title: SAMHD1-induced endosomal FAK signaling promotes human renal clear cell carcinoma metastasis by activating Rac1-mediated lamellipodia protrusion.
SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia.
Title: SAMHD1 single nucleotide polymorphisms impact outcome in children with newly diagnosed acute myeloid leukemia.
SAMHD1 impairs type I interferon induction through the MAVS, IKKepsilon, and IRF7 signaling axis during viral infection.
Title: SAMHD1 impairs type I interferon induction through the MAVS, IKKε, and IRF7 signaling axis during viral infection.

Submit: New GeneRIF Correction See all GeneRIFs (224)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Aicardi-Goutieres syndrome 5 MedGen: C2749659 OMIM: 612952 GeneReviews: Aicardi-Goutieres Syndrome	not available
Chilblain lupus 2 MedGen: C3280721 OMIM: 614415 GeneReviews: Not available	not available

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 replication is restricted by SAMHD1 in dividing THP-1 monocytic cells as shown through genome editing with CRISPR/Cas9 or overexpression of SAMHD1	PubMed
HIV-1 replication is restricted by SAMHD1 in monocyte-derived Langerhans cells and dendritic cells	PubMed
HIV-1 replication is restricted by SAMHD1, but addition of exogenous deoxynucleotides bypasses this restriction	PubMed
HIV-1 replication is restricted by SAMHD1 in monocyte-derived macrophage-like cells (PMA-treated U937 cells)	PubMed
Knockdown of SAMHD1 by siRNA enhances HIV-1 infectivity in mature monocyte-derived dendritic cells or macrophages	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	HIV-1-exposed monocyte-derived dendritic cells induce weak secretion of IFN-gamma and low amounts of intracellular Gag expression in the presence of SAMHD1	PubMed
	gag	HIV-1 Gag processing and formation of a mature virion are required to allow the release of Vpx, leading to cellular SAMHD1 degradation in the nucleus	PubMed
capsid	gag	SAMHD1 expression is decreased during T-cell proliferation and is associated with higher susceptibility to HIV-1 infection in terms of percentages of HIV-1 p24 positive cells	PubMed
reverse transcriptase	gag-pol	SAMHD1 restricts HIV-1 replication by depleting the dNTP pool, which is required for the synthesis of the viral DNA by HIV-1 reverse transcriptase (RT)	PubMed
	gag-pol	SAMHD1 degrades deoxynucleoside triphosphates (dNTPs) to deprive viruses of dNTPs, and is counteracted by HIV-2/SIV Vpx protein	PubMed
	gag-pol	SAMHD1 restricts replication of the HIV-1 RT mutant V148I, which has lower affinity for dNTPs compared to WT, in cultured cells and in mice	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH48138 (e-PCR)
- UniSTS:26377

RH45857 (e-PCR)
- UniSTS:22359

1452 (e-PCR)
- UniSTS:8814

RH66067 (e-PCR)
- UniSTS:31117

WI-11878 (e-PCR)
- UniSTS:5537

SAMHD1_9434 (e-PCR)
- UniSTS:468669

A005D07 (e-PCR)
- UniSTS:78026

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables GTP binding	IEA Inferred from Electronic Annotation more info
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
NOT enables RNA nuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables RNA nuclease activity	IDA Inferred from Direct Assay more info	PubMed
enables dGTP binding	IDA Inferred from Direct Assay more info	PubMed
enables dGTPase activity	IBA Inferred from Biological aspect of Ancestor more info
enables dGTPase activity	IDA Inferred from Direct Assay more info	PubMed
enables deoxynucleoside triphosphate hydrolase activity	IDA Inferred from Direct Assay more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables nucleic acid binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IDA Inferred from Direct Assay more info	PubMed
involved_in DNA strand resection involved in replication fork processing	IDA Inferred from Direct Assay more info	PubMed
involved_in dATP catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in dGTP catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in dGTP catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to virus	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to virus	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to virus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in deoxyribonucleotide catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in double-strand break repair via homologous recombination	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	NAS Non-traceable Author Statement more info	PubMed
involved_in innate immune response	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of type I interferon-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein homotetramerization	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of innate immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of innate immune response	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of innate immune response	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in somatic hypermutation of immunoglobulin genes	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info
located_in site of double-strand break	IDA Inferred from Direct Assay more info	PubMed
located_in tetraspanin-enriched microdomain	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: deoxynucleoside triphosphate triphosphohydrolase SAMHD1

Names: SAM domain and HD domain 1; SAM domain and HD domain-containing protein 1; dNTPase; dendritic cell-derived IFNG-induced protein; monocyte protein 5

NP_001350658.1

EC 3.1.5.-

NP_001350662.1

EC 3.1.5.-

NP_056289.2

EC 3.1.5.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_017059.1 RefSeqGene

Range

5001..65020

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_281

mRNA and Protein(s)

NM_001363729.2 → NP_001350658.1 deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform 2

Status: REVIEWED

Source sequence(s)

AB208944, AK027811, AK311150, AL079335, CA306490

Consensus CDS

CCDS86953.1

Related

ENSP00000262878.5, ENST00000262878.5

Conserved Domains (2) summary

cd09508
Location:41 → 110

SAM_HD; SAM domain of HD-phosphohydrolase

cl26231
Location:115 → 503

YdhJ; HD superfamily phosphohydrolase [General function prediction only]
NM_001363733.2 → NP_001350662.1 deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform 3

Status: REVIEWED

Source sequence(s)

AK027811, AL079335, BE937520, BP252994, R26128

Consensus CDS

CCDS86954.1

UniProtKB/TrEMBL

A0A2R8YCS7

Related

ENSP00000493928.1, ENST00000643918.1

Conserved Domains (2) summary

cd09508
Location:41 → 110

SAM_HD; SAM domain of HD-phosphohydrolase

cl26231
Location:115 → 504

YdhJ; HD superfamily phosphohydrolase [General function prediction only]
NM_015474.4 → NP_056289.2 deoxynucleoside triphosphate triphosphohydrolase SAMHD1 isoform 1

See identical proteins and their annotated locations for NP_056289.2

Status: REVIEWED

Source sequence(s)

AB208944, AK027811, AK311150, AL079335

Consensus CDS

CCDS13288.1

UniProtKB/Swiss-Prot

B4E2A5, E1P5V2, Q5JXG8, Q8N491, Q9H004, Q9H005, Q9H3U9, Q9Y3Z3

Related

ENSP00000493536.2, ENST00000646673.2

Conserved Domains (4) summary

cd09508
Location:41 → 110

SAM_HD; SAM domain of HD-phosphohydrolase

smart00454
Location:42 → 109

SAM; Sterile alpha motif

COG1078
Location:115 → 504

YdhJ; HD superfamily phosphohydrolase [General function prediction only]

cd00077
Location:162 → 335

HDc; Metal dependent phosphohydrolases with conserved 'HD' motif