SAMHD1

Summary

SAMHD1 (SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1, HGNC:15925) is a protein-coding gene on chromosome 20q11.23, encoding Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 (Q9Y3Z3). 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.

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.

Source: NCBI Gene 25939 — RefSeq curated summary.

At a glance

• Gene–disease (curated): SAMHD1-related type 1 interferonopathy (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 2
• Clinical variants (ClinVar): 1,047 total — 90 pathogenic, 45 likely-pathogenic (top 3% of genes corpus-wide)
• GTEx eGene: eQTL in 13 tissues, sQTL in 3 (q < 0.05)
• Phenotypes (HPO): 91
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 1 cancer types (inferred from mutation patterns)
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.89 (unconstrained)
• MANE Select transcript: NM_015474
• Interaction hub: 1,930 STRING partners (top 8% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15925
Approved symbol	SAMHD1
Name	SAM and HD domain containing deoxynucleoside triphosphate triphosphohydrolase 1
Location	20q11.23
Locus type	gene with protein product
Status	Approved
Aliases	SBBI88, Mg11, HDDC1, MOP-5, AGS5
Ensembl gene	ENSG00000101347
Ensembl biotype	protein_coding
OMIM	606754
Entrez	25939

Gene structure

Transcript identifiers

Ensembl transcripts: 43 — 18 protein_coding, 17 nonsense_mediated_decay, 6 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000646673

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 3: 1

ENST00000646673, ENST00000262878, ENST00000465985, ENST00000642186, ENST00000642246, ENST00000642616, ENST00000643003, ENST00000643078, ENST00000643161, ENST00000643243, ENST00000643825, ENST00000643907, ENST00000643918, ENST00000644114, ENST00000644250, ENST00000644370, ENST00000644688, ENST00000645033, ENST00000645444, ENST00000646066, ENST00000646121, ENST00000646866, ENST00000646869, ENST00000646904, ENST00000647095, ENST00000647163, ENST00000647459, ENST00000682773, ENST00000683720, ENST00000683766, ENST00000866370, ENST00000866371, ENST00000866372, ENST00000866373, ENST00000926798, ENST00000970830, ENST00000970831, ENST00000981726, ENST00001094448, ENST00001108545, ENST00001108546, ENST00001112576, ENST00001132093

RefSeq mRNA: 3 — MANE Select: NM_015474 NM_001363729, NM_001363733, NM_015474

CCDS: CCDS13288, CCDS86953, CCDS86954

Canonical transcript exons

ENST00000646673 — 16 exons

Exon	Start	End
ENSE00000661812	36897822	36897959
ENSE00000661813	36898440	36898544
ENSE00000661815	36905364	36905503
ENSE00001622813	36911218	36911333
ENSE00001667406	36916949	36917049
ENSE00001711142	36912461	36912552
ENSE00001752622	36919364	36919519
ENSE00001793017	36916722	36916830
ENSE00003462531	36941039	36941111
ENSE00003535434	36930760	36930875
ENSE00003546823	36935029	36935189
ENSE00003598833	36927182	36927252
ENSE00003619308	36946738	36946804
ENSE00003692177	36904157	36904249
ENSE00003828814	36890229	36893066
ENSE00003903369	36951436	36951708

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 55.3990 / max 1593.0884, expressed in 1788 samples.

Highest expression (Bgee): monocyte, mononuclear cell, pericardium, leukocyte, epithelium of nasopharynx.

Genetic regulation across tissues (GTEx eQTL / sQTL)

SAMHD1 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 13 tissues and its splicing (sQTL) in 3 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

16 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Whole Blood	eqtl	4.5e-18	+0.18	20:36950277:A:G
Esophagus Mucosa	eqtl	9.0e-07	-0.17	20:36927789:T:G
Pituitary	sqtl	1.2e-03	-2.16	20:37579642:A:G
Ovary	eqtl	2.6e-03	+0.31	20:36916270:A:G
Brain Nucleus accumbens basal ganglia	eqtl	5.2e-03	-0.51	20:36328176:A:G
Stomach	eqtl	6.0e-03	+0.11	20:36889017:G:A
Muscle Skeletal	sqtl	1.1e-02	-0.56	20:36151566:T:G
Pancreas	eqtl	1.2e-02	-0.13	20:36925958:G:A
Nerve Tibial	sqtl	1.5e-02	+0.25	20:36898174:G:A
Cells Cultured fibroblasts	eqtl	2.2e-02	-0.08	20:36925110:C:A
Colon Transverse	eqtl	2.8e-02	-0.24	20:37557964:A:G
Nerve Tibial	eqtl	3.4e-02	+0.07	20:36811544:C:T
Brain Frontal Cortex BA9	eqtl	3.8e-02	+0.91	20:37413043:C:G
Brain Hippocampus	eqtl	3.9e-02	-3.10	20:36548499:C:G
Small Intestine Terminal Ileum	eqtl	4.4e-02	+0.72	20:37395294:G:A
Lung	eqtl	4.7e-02	+0.23	20:37381322:G:C

FANTOM5 promoters

7 alternative TSS:

Promoter ID	TPM avg	Samples expressed
187158	21.9408	1753
187159	14.8012	1594
187161	8.1769	674
187157	7.5907	1127
187160	1.1273	394
187163	0.9665	330
187162	0.7957	276

Top tissues by expression

showing 100 of 298 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
monocyte	CL:0000576	99.27	gold quality
mononuclear cell	CL:0000842	99.23	gold quality
pericardium	UBERON:0002407	99.23	gold quality
leukocyte	CL:0000738	99.21	gold quality
epithelium of nasopharynx	UBERON:0001951	99.13	gold quality
bronchial epithelial cell	CL:0002328	99.11	gold quality
nasopharynx	UBERON:0001728	99.11	gold quality
lower lobe of lung	UBERON:0008949	99.09	gold quality
palpebral conjunctiva	UBERON:0001812	99.05	gold quality
peripheral nervous system	UBERON:0000010	99.02	gold quality
tibial nerve	UBERON:0001323	99.02	gold quality
trigeminal ganglion	UBERON:0001675	98.93	gold quality
visceral pleura	UBERON:0002401	98.76	gold quality
superficial temporal artery	UBERON:0001614	98.67	gold quality
mucosa of stomach	UBERON:0001199	98.50	gold quality
granulocyte	CL:0000094	98.48	gold quality
parietal pleura	UBERON:0002400	98.44	gold quality
trabecular bone tissue	UBERON:0002483	98.41	gold quality
sural nerve	UBERON:0015488	98.22	gold quality
mucosa of paranasal sinus	UBERON:0005030	98.15	gold quality
lower esophagus muscularis layer	UBERON:0035833	98.12	gold quality
lower esophagus	UBERON:0013473	98.06	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	97.97	gold quality
right lung	UBERON:0002167	97.96	gold quality
amniotic fluid	UBERON:0000173	97.91	gold quality
pleura	UBERON:0000977	97.81	gold quality
secondary oocyte	CL:0000655	97.76	gold quality
vena cava	UBERON:0004087	97.76	gold quality
saphenous vein	UBERON:0007318	97.74	gold quality
oral cavity	UBERON:0000167	97.62	gold quality
dorsal root ganglion	UBERON:0000044	97.60	gold quality
esophagus squamous epithelium	UBERON:0006920	97.53	gold quality
left uterine tube	UBERON:0001303	97.50	gold quality
synovial joint	UBERON:0002217	97.47	gold quality
lymph node	UBERON:0000029	97.39	gold quality
coronary artery	UBERON:0001621	97.32	gold quality
left coronary artery	UBERON:0001626	97.31	gold quality
endothelial cell	CL:0000115	97.27	gold quality
germinal epithelium of ovary	UBERON:0001304	96.91	gold quality
urethra	UBERON:0000057	96.85	gold quality
blood	UBERON:0000178	96.79	gold quality
skin of hip	UBERON:0001554	96.57	gold quality
right coronary artery	UBERON:0001625	96.57	gold quality
eye	UBERON:0000970	96.56	gold quality
pharyngeal mucosa	UBERON:0000355	96.55	gold quality
bronchus	UBERON:0002185	96.50	gold quality
epithelium of bronchus	UBERON:0002031	96.46	gold quality
medial globus pallidus	UBERON:0002477	96.45	gold quality
superior surface of tongue	UBERON:0007371	96.43	gold quality
upper lobe of lung	UBERON:0008948	96.42	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.35	gold quality
cauda epididymis	UBERON:0004360	96.31	gold quality
mammalian vulva	UBERON:0000997	96.30	gold quality
upper lobe of left lung	UBERON:0008952	96.28	gold quality
nasal cavity mucosa	UBERON:0001826	96.24	gold quality
pylorus	UBERON:0001166	96.17	gold quality
right uterine tube	UBERON:0001302	96.17	gold quality
peritoneum	UBERON:0002358	96.17	gold quality
adipose tissue of abdominal region	UBERON:0007808	96.16	gold quality
omental fat pad	UBERON:0010414	96.16	gold quality
subcutaneous adipose tissue	UBERON:0002190	96.08	gold quality
mammary duct	UBERON:0001765	96.07	gold quality
right atrium auricular region	UBERON:0006631	96.02	gold quality
spleen	UBERON:0002106	96.00	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.99	gold quality
tendon of biceps brachii	UBERON:0008188	95.92	gold quality
adipose tissue	UBERON:0001013	95.86	gold quality
caecum	UBERON:0001153	95.80	gold quality
oocyte	CL:0000023	95.76	gold quality
descending thoracic aorta	UBERON:0002345	95.76	gold quality
seminal vesicle	UBERON:0000998	95.72	gold quality
connective tissue	UBERON:0002384	95.70	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.66	gold quality
decidua	UBERON:0002450	95.65	gold quality
cardia of stomach	UBERON:0001162	95.64	gold quality
cardiac atrium	UBERON:0002081	95.61	gold quality
esophagus	UBERON:0001043	95.58	gold quality
nipple	UBERON:0002030	95.58	gold quality
globus pallidus	UBERON:0001875	95.56	gold quality
colonic epithelium	UBERON:0000397	95.45	gold quality
caput epididymis	UBERON:0004358	95.45	gold quality
urinary bladder	UBERON:0001255	95.27	gold quality
tendon	UBERON:0000043	95.25	gold quality
lung	UBERON:0002048	95.24	gold quality
epithelium of esophagus	UBERON:0001976	95.22	gold quality
small intestine	UBERON:0002108	95.22	gold quality
vermiform appendix	UBERON:0001154	95.14	gold quality
gall bladder	UBERON:0002110	95.13	gold quality
right ovary	UBERON:0002118	95.13	gold quality
tongue	UBERON:0001723	95.04	gold quality
bone marrow cell	CL:0002092	94.92	gold quality
nasal cavity epithelium	UBERON:0005384	94.91	gold quality
body of pancreas	UBERON:0001150	94.90	gold quality
thoracic aorta	UBERON:0001515	94.90	gold quality
penis	UBERON:0000989	94.88	gold quality
sigmoid colon	UBERON:0001159	94.88	gold quality
ectocervix	UBERON:0012249	94.85	gold quality
aorta	UBERON:0000947	94.78	gold quality
endometrium	UBERON:0001295	94.73	gold quality
ascending aorta	UBERON:0001496	94.73	gold quality

Single-cell (SCXA)

Detected in 27 experiment(s), a significant marker in 25.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	2155.52
E-CURD-6	yes	1428.25
E-MTAB-9801	yes	1121.56
E-MTAB-9067	yes	747.43
E-HCAD-6	yes	569.25
E-MTAB-7381	yes	526.18
E-HCAD-13	yes	346.78
E-MTAB-10018	yes	138.55
E-HCAD-4	yes	76.27
E-HCAD-1	yes	52.17
E-MTAB-10287	yes	44.78
E-HCAD-10	yes	39.95
E-CURD-46	yes	29.93
E-GEOD-135922	yes	27.74
E-MTAB-9221	yes	26.63

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Spleen	tissue	86.8	high
Appendix	tissue	83.8	medium
Lymph node	tissue	70.3	high
Choroid plexus	tissue	67.0
Lung	tissue	62.3	high
Adipose tissue	tissue	55.9	not detected
Fallopian tube	tissue	50.8	high
Tonsil	tissue	47.7	high
Urinary bladder	tissue	41.3	medium
Esophagus	tissue	40.4	high
Smooth muscle	tissue	40.1	medium
Adrenal gland	tissue	37.9	high
Gallbladder	tissue	36.9	medium
Vagina	tissue	33.8	high
Placenta	tissue	33.2	low
Small intestine	tissue	30.1	medium
Salivary gland	tissue	28.6	high
Thymus	tissue	27.4
Pancreas	tissue	27.3	high
Colon	tissue	26.9	medium
Rectum	tissue	26.8	low
Breast	tissue	25.5	medium
Duodenum	tissue	25.3	medium
Liver	tissue	24.3	not detected
Stomach 1	tissue	23.4	medium
Ovary	tissue	20.8	low
Spinal cord	tissue	20.7
Cervix	tissue	20.6	high
Locus coeruleus	tissue	20.6
Heart muscle	tissue	20.4	medium
Substantia nigra	tissue	20.4
Pituitary gland	tissue	20.3
Medulla oblongata	tissue	20.0
Pons	tissue	19.7
Hippocampus	tissue	19.5	medium
Tongue	tissue	19.3
Superior colliculi	tissue	19.2
Hypothalamus	tissue	18.8
Thalamus	tissue	18.7
Midbrain	tissue	18.3
Periaqueductal gray	tissue	17.4
Seminal vesicle	tissue	17.0	medium
Septum	tissue	17.0
Nucleus accumbens	tissue	16.9
Cerebral cortex	tissue	16.3	medium
Somatosensory cortex	tissue	16.3
Cerebellum	tissue	16.1	medium
Occipital cortex	tissue	15.3
Amygdala	tissue	15.0
Endometrium 1	tissue	14.8	medium
Motor cortex	tissue	14.8
Hippocampal formation	tissue	14.8
Entorhinal cortex	tissue	14.8
Retrosplenial and cingulate cortex	tissue	14.4
Prefrontal cortex	tissue	14.3
Temporal cortex	tissue	14.2
Ventral forebrain	tissue	13.9
Prostate	tissue	13.8	not detected
Skeletal muscle	tissue	13.7	not detected
Retrosplenial cortex	tissue	13.5

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (86.7), Lateral funiculus (white matter) (50.0), Anterior thalamic nucleus, ventral (37.3), Anterior funiculus (white matter) (35.2), Medial olivary nucleus (35.0).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CEBPG, FOXA2, HR, IRF1, IRF2, IRF6, IRF8, KLF6, NFKB1, NFKBIA, SPI1, STAT2, STAT3, STAT5A, STAT6, TBXT, TP53, TXK, ZHX2

miRNA regulators (miRDB)

Targeting SAMHD1 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 57 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-150-5P	99.99	66.69	1976
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-577	99.78	69.13	2479
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-4422	99.72	72.07	2908
HSA-MIR-10393-5P	99.65	68.01	1368
HSA-MIR-4649-3P	99.56	66.90	1783
HSA-MIR-7159-3P	99.51	70.17	1920
HSA-MIR-1275	99.47	67.90	2749
HSA-MIR-190B-3P	99.33	68.29	1382

Functional genomics

gnomAD constraint: pLI 2.4e-07, LOEUF 0.889, missense Z 1.52 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000646673 — one region, missense o/e 0.85. ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• SAMHD1 mediates TNF-alpha stimulation of lung fibroblasts. (PMID:18546154)
• Study describes mutations in SAMHD1 as the cause of Aicardi-Goutieres syndrome (AGS) at the AGS5 locus and present data to show that SAMHD1 may act as a negative regulator of the cell-intrinsic antiviral response. (PMID:19525956)
• I510T mutation of p63 was detected in both RHS and AEC syndrome patients and mutation of S541 residue can lead to either RHS (S541Y) or AEC syndrome (S541F). (PMID:20156774)
• Arthropathy with progressive contractures should now be considered part of the spectrum of Aicardi-Goutieres syndrome because of SAMHD1 mutations. (PMID:20358604)
• report on four adult siblings with c.490C>T (p.Arg164X) mutation in SAMHD1, a gene most recently described in Aicardi-Goutieres syndrome, on both alleles in all affected siblings (PMID:20842748)
• A homozygous deletion of the SAMHD1 gene caused atypical Aicardi-Goutieres syndrome, presenting in utero with white matter destruction and associated with multiple mtDNA deletions. (PMID:21102625)
• Autosomal dominant inheritance of a heterozygous mutation in SAMHD1 causing familial chilblain lupus. (PMID:21204240)
• The inflammatory vasculopathies of the brain found in the patients with SAMHD1 mutation indicate its important roles in immunoregulation and cerebral vascular hemeostasis. (PMID:21402907)
• Vpx induces proteasomal degradation of SAMHD1 (PMID:21613998)
• conclude that intracerebral large artery disease is a common phenomenon in patients with SAMHD1 mutations (PMID:21633013)
• Vpx relieves the inhibition of lentivirus infection in macrophages by loading SAMHD1 onto the CRL4(DCAF1) E3 ubiquitin ligase, leading to highly efficient proteasome-dependent degradation of the protein (PMID:21720370)
• SAMHD1 functions as a myeloid-cell-specific HIV-1 restriction factor by inhibiting viral DNA synthesis.[Review] (PMID:21740548)
• human SAMHD1 is a potent dGTP-stimulated triphosphohydrolase that converts deoxynucleoside triphosphates to the constituent deoxynucleoside and inorganic triphosphate (PMID:22056990)
• Vpx targets SAMHD1 for degradation in a viral strategy to control cellular deoxynucleotide levels for efficient replication (PMID:22069334)
• we propose that SAMHD1 protects primary CD14+ monocytes from HIV-1 infection (PMID:22174685)
• Vpx prevented the SAMHD1-mediated decrease in dNTP concentration and induced the degradation of human and rhesus macaque SAMHD1 but had no effect on mouse SAMHD1 (PMID:22327569)
• Data suggest that SAMHD1 has a role in the nucleus that, if disrupted by mutation, leads to cytosolic accumulation of SAMHD1 and autoimmune disease. (PMID:22461318)
• Polymorphisms of SAMHD1 are unlikely to contribute to the infection and natural control of HIV-1 in European and African-American individuals. (PMID:22530776)
• Vpx degradation of SAMHD1 is sufficiently rapid to enable appropriate progression of reverse transcription in monocyte-derived macrophages (PMID:22589553)
• Cytoplasmic variants of SAMHD1 potently block lentiviral infection and are resistant to Vpx-mediated degradation. (PMID:22691373)
• In this Progress article, we describe how SAMHD1 regulates the pool of intracellular nucleotides to control HIV replication and the innate immune response. (PMID:22926205)
• SAMHD1 imposes an effective restriction to HIV-1 infection in the large pool of noncycling CD4(+) T cells in vivo. (PMID:22972397)
• SAMHD1 is targeted by HIV-2 Vpx for ubiquitination and degradation in the nucleus. (PMID:22973040)
• anti-HIV activity of SAMHD1 (PMID:22978176)
• Studies indicate that restriction factors APOBEC3G, TRIM5, Tetherin and SAMHD1 exhibit direct antiviral activity. (PMID:22999946)
• there are several Vpx residues required for SAMHD1 degradation (PMID:23076149)
• Here, authors identified SAMHD1 as the restriction factor preventing efficient HIV-1 viral DNA synthesis in non-cycling resting CD4+ T-cells. (PMID:23092122)
• Here, authors identified two naturally occurring splice variants lacking exons 8-9 and 14, respectively. (PMID:23092512)
• results showed that SAMHD1 blocks infection of HIV-2, feline immunodeficiency virus (FIV), bovine immunodeficiency virus (BIV), Equine infectious anemia virus (EIAV), N-tropic murine leukemia virus (N-MLV), and B-tropic murine leukemia virus (B-MLV) (PMID:23158101)
• SAMHD1-mediated reduction of the intracellular dNTP pool in DCs is a common mechanism of HIV-1 restriction in myeloid cells. Endogenous expression of SAMHD1 in primary DCs or CD4+ T-lymphocytes is not upregulated by type I IFNs. (PMID:23231760)
• SAMHD1, by controlling the sensitivity of monocyte-derived dendritic cells to HIV-1 infection during intercellular contacts, impacts their ability to sense the virus and to trigger an innate immune response. (PMID:23269793)
• The nuclease activity of SAMHD1 could represent an additional mechanism contributing to HIV-1 restriction and suppression of the autoimmune response through direct cleavage of viral and endogenous nucleic acids. (PMID:23364794)
• Mutations associated with Aicardi-Goutieres syndrome exhibit both impaired nucleic acid-binding and complex formation implicating interaction with nucleic acids as an integral aspect of SAMHD1 function. (PMID:23371319)
• Promoter methylation regulates SAMHD1 gene expression in human CD4+ T cells (PMID:23426363)
• SAMHD1 tetramers are the biologically active form of this dNTPase and provide new insights into the functional organization of SAMHD1. (PMID:23426366)
• The results suggest that SAMHD1 has broad anti-retroviral activity against which most viruses have not found an escape. (PMID:23497255)
• Effective immune control of viral replication in HIV-2-infected individuals is not associated with increased Vpx-mediated degradation of SAMHD1. (PMID:23497283)
• SAMHD1 overexpression induced by IL-12/IL-18 was not dependent on IFN-gamma. (PMID:23526823)
• SAMHD1 phosphorylated on residue T592 is unable to block retroviral infection. (PMID:23601106)
• The phosphorylation of SAMHD1 at Thr592 by cyclin A2/CDK1 is a key regulatory mechanism of its antiviral activity. (PMID:23602554)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	samhd1	ENSDARG00000071288
mus_musculus	Samhd1	ENSMUSG00000027639
rattus_norvegicus	Samhd1	ENSRNOG00000006418
drosophila_melanogaster	fal	FBGN0028380
caenorhabditis_elegans		WBGENE00022673

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1927468) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 3 distinct phenotype terms.

Mouse phenotype (MP)	Records
abnormal response to infection	1
abnormal cell physiology	1
increased susceptibility to Retroviridae infection	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q0VCA5	76.5%	Diamond
Xenopus laevis	Q6INN8	66.7%	Diamond
Gallus gallus	Q5ZJL9	66.0%	Diamond
Dictyostelium discoideum	B0G107	39.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MTCL2	protein-coding	140710
TLDC2	protein-coding	140711
RBL1	protein-coding	5933
DSN1	protein-coding	79980
MROH8	protein-coding	140699
RPN2	protein-coding	6185

Protein

Protein identifiers

Deoxynucleoside triphosphate triphosphohydrolase SAMHD1 — Q9Y3Z3 (reviewed: Q9Y3Z3)

Alternative names: Dendritic cell-derived IFNG-induced protein, Monocyte protein 5, SAM domain and HD domain-containing protein 1

All UniProt accessions (13): Q9Y3Z3, A0A2R8Y586, A0A2R8Y5D2, A0A2R8Y755, A0A2R8Y7R5, A0A2R8YCS7, A0A2R8YD90, A0A2R8YDI8, A0A2R8YF18, A0A2R8YF51, A0A2R8YFV6, A0A2R8YG48, A0A804HL67

UniProt curated annotations — full annotation on UniProt →

Function. 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. 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. Likewise, suppresses LINE-1 retrotransposon activity. Not able to restrict infection by HIV-2 virus; because restriction activity is counteracted by HIV-2 viral protein Vpx. In addition to virus restriction, dNTPase activity acts as a regulator of DNA precursor pools by regulating dNTP pools. 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. 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. 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. Ability to promote DNA end resection at stalled replication forks is independent of dNTPase activity. Enhances immunoglobulin hypermutation in B-lymphocytes by promoting transversion mutation.

Subunit / interactions. Homodimer; in absence of GTP and dNTP. Homotetramer; in GTP- and dNTP-bound form. Interacts with MRE11; leading to stimulate the exonuclease activity of MRE11. Interacts with RBBP8/CtIP. Interacts (via its C-terminus) with CD81. (Microbial infection) Interacts with HIV-2 viral protein Vpx; promoting interaction with a E3 ubiquitin-protein ligase complex containing DCAF1, leading to subsequent ubiquitination and degradation of SAMHD1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in heart, skeletal muscle, spleen, liver, small intestine, placenta, lung and peripheral blood leukocytes. No expression is seen in brain and thymus.

Post-translational modifications. Phosphorylation at Thr-592 by CDK1 acts as a switch to control deoxynucleoside triphosphate (dNTPase)-dependent and -independent functions. Phosphorylation at Thr-592 takes place in cycling cells: it reduces the stability of the homotetramer, impairing the dNTPase activity and subsequent ability to restrict infection by viruses. It also inhibits ability to suppress LINE-1 retrotransposon activity. In contrast, phosphorylation at Thr-592 promotes DNA end resection at stalled replication forks in response to DNA damage. (Microbial infection) Phosphorylation at Thr-592 by Epstein-Barr virus kinase BGLF4 and human cytomegalovirus/HCMV UL97 leads to a reduced level of dCTPase and dTTPase activity and the loss of viral restriction. (Microbial infection) Ubiquitinated following interaction with HIV-2 viral protein Vpx; Vpx promotes interaction and with a DCX (DDB1-CUL4-X-box) E3 ubiquitin ligase, leading to proteasomal degradation.

Disease relevance. Aicardi-Goutieres syndrome 5 (AGS5) [MIM:612952] A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. The disease is caused by variants affecting the gene represented in this entry. Chilblain lupus 2 (CHBL2) [MIM:614415] A rare cutaneous form of lupus erythematosus. Affected individuals present with painful bluish-red papular or nodular lesions of the skin in acral locations precipitated by cold and wet exposure. The disease is caused by variants affecting the gene represented in this entry.

Activity regulation. Allosterically activated and regulated via the combined actions of GTP and dNTPs (dATP, dGTP, dTTP and dCTP): Allosteric site 1 binds GTP, while allosteric site 2 binds dNTP. Allosteric activation promotes the formation of highly active homotetramers. Phosphorylation at Thr-592 impairs homotetramerization, thereby inhibiting dNTPase activity, leading to reduced ability to restrict infection by viruses.

Cofactor. Binds 1 Mn(2+) ion per subunit.

Domain organisation. In human, and in contrast to mouse protein, the SAM domain is not required for deoxynucleoside triphosphate (dNTPase) activity and ability to restrict infection by viruses.

Induction. By IFNG/IFN-gamma. Up-regulated in TNF treated lung fibroblasts.

Miscellaneous. Catalytically inactive. Catalytically inactive.

Similarity. Belongs to the SAMHD1 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q9Y3Z3-1	1	yes
Q9Y3Z3-3	3, delta8-9
Q9Y3Z3-4	4, delta14

RefSeq proteins (3): NP_001350658, NP_001350662, NP_056289* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001660	SAM	Domain
IPR003607	HD/PDEase_dom	Domain
IPR006674	HD_domain	Domain
IPR013761	SAM/pointed_sf	Homologous_superfamily
IPR050135	dGTPase-like	Family

Pfam: PF01966, PF07647

Enzyme classification (BRENDA)

• EC 3.1.5.B1 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Catalyzed reactions (Rhea)

• dGTP + H2O = 2’-deoxyguanosine + triphosphate + H(+) (RHEA:15193)
• a 2’-deoxyribonucleoside 5’-triphosphate + H2O = a 2’-deoxyribonucleoside + triphosphate + H(+) (RHEA:46148)
• dATP + H2O = 2’-deoxyadenosine + triphosphate + H(+) (RHEA:67648)
• dTTP + H2O = thymidine + triphosphate + H(+) (RHEA:80079)
• dCTP + H2O = 2’-deoxycytidine + triphosphate + H(+) (RHEA:80083)

UniProt features (241 total): binding site 82, mutagenesis site 49, helix 44, strand 19, sequence variant 14, turn 9, modified residue 8, sequence conflict 4, cross-link 4, domain 2, splice variant 2, chain 1, region of interest 1, compositionally biased region 1, active site 1

Structure

Experimental structures (PDB)

showing 30 of 76 structures by resolution:

PDB	Title	Method	Resolution (Å)
6DWD	SAMHD1 Bound to Clofarabine-TP in the Catalytic Pocket and Allosteric Pocket	X-RAY DIFFRACTION	1.7
4MZ7	Structural insight into dGTP-dependent activation of tetrameric SAMHD1 deoxynucleoside …	X-RAY DIFFRACTION	1.8
4BZB	Crystal structure of the tetrameric dGTP-bound SAMHD1 mutant catalytic core	X-RAY DIFFRACTION	1.83
7LTT	SAMHD1(113-626) H206R D207N R366C	X-RAY DIFFRACTION	1.9
6DW5	SAMHD1 Bound to Gemcitabine-TP in the Catalytic Pocket	X-RAY DIFFRACTION	1.93
6DW4	SAMHD1 Bound to Cladribine-TP in the Catalytic Pocket and Allosteric Pocket	X-RAY DIFFRACTION	1.99
4TNP	Structural basis of cellular dNTP regulation, SAMHD1-GTP-dCTP-cCTP complex	X-RAY DIFFRACTION	2
6TX0	Crystal structure of tetrameric human D137N-SAMHD1 (residues 109-626) with XTP, dAMPNPP …	X-RAY DIFFRACTION	2.01
4QFY	Crystal structure of the tetrameric dGTP/dCTP-bound SAMHD1 (RN206) mutant catalytic core	X-RAY DIFFRACTION	2.1
4QG4	Crystal structure of the tetrameric GTP/dATP/ATP-bound SAMHD1 (H210A) mutant catalytic …	X-RAY DIFFRACTION	2.1
4RXP	The structure of GTP-dATP-bound SAMHD1	X-RAY DIFFRACTION	2.1
4RXQ	The structure of GTP-dUTP-bound SAMHD1	X-RAY DIFFRACTION	2.1
4TO4	Structure basis of cellular dNTP regulation, SAMHD1-GTP-dGTP-dCTP complex	X-RAY DIFFRACTION	2.1
6U6Z	Human SAMHD1 bound to deoxyribo(TG*TTCA)-oligonucleotide	X-RAY DIFFRACTION	2.1
4RXR	The structure of GTP-dCTP-bound SAMHD1	X-RAY DIFFRACTION	2.12
6CM2	SAMHD1 HD domain bound to decitabine triphosphate	X-RAY DIFFRACTION	2.14
4QFX	Crystal structure of the tetrameric dGTP/dATP-bound SAMHD1 (RN206) mutant catalytic core	X-RAY DIFFRACTION	2.2
4QG1	Crystal structure of the tetrameric GTP/dATP-bound SAMHD1 (RN206) mutant catalytic core	X-RAY DIFFRACTION	2.2
4RXS	The structure of GTP-dTTP-bound SAMHD1	X-RAY DIFFRACTION	2.2
4TO3	Structural basis of cellular dNTP regulation, SAMHD1-dGTP-dGTP-dCTP complex	X-RAY DIFFRACTION	2.2
6DW3	SAMHD1 Bound to Cytarabine-TP in the Catalytic Pocket	X-RAY DIFFRACTION	2.2
6XU1	Crystal structure of tetrameric human H215A-SAMHD1 (residues 109-626) with GTP, dAMPNPP …	X-RAY DIFFRACTION	2.2
4QG2	Crystal structure of the tetrameric GTP/dATP/ATP-bound SAMHD1 (RN206) mutant catalytic …	X-RAY DIFFRACTION	2.25
6TXF	Crystal structure of tetrameric human D137N-SAMHD1 (residues 109-626) with XTP, dAMPNPP …	X-RAY DIFFRACTION	2.25
4TO2	Structure basis of cellular dNTP regulation, SAMHD1-dGTP-dGTP-dGTP/dTTP complex	X-RAY DIFFRACTION	2.27
7A5Y	Crystal structure of tetrameric human H215A-SAMHD1 (residues 109-626) with Rp-dGTP-alphaS …	X-RAY DIFFRACTION	2.29
4QFZ	Crystal structure of the tetrameric dGTP/dTTP-bound SAMHD1 (RN206) mutant catalytic core	X-RAY DIFFRACTION	2.3
4QG0	Crystal structure of the tetrameric dGTP/dUTP-bound SAMHD1 (RN206) mutant catalytic core	X-RAY DIFFRACTION	2.3
4TO0	Structure basis of cellular dNTP regulation, SAMHD1-GTP-dATP-dCTP complex	X-RAY DIFFRACTION	2.3
4ZWG	Crystal structure of the GTP-dATP-bound catalytic core of SAMHD1 phosphomimetic T592E …	X-RAY DIFFRACTION	2.3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y3Z3-F1	88.45	0.75

Human Protein Atlas

Protein class: Predicted intracellular proteins, Plasma proteins, Disease related genes, Human disease related genes

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; plasma membrane

Antibody reliability (HPA): IH enhanced · IF supported

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1)

Position	Role
233

Ligand- & substrate-binding residues (82)

Position	Role
119	dGTP
119	dTTP
137	GTP
142	GTP
145	GTP
149	dATP
149	dCTP
149	dGTP
149	dTTP
150	dGTP
156	dATP
156	dCTP
156	dGTP
156	dTTP
164	dATP
164	dCTP
164	dGTP
164	dTTP
167	Mn(2+)
206	Mn(2+)
207	Mn(2+)
210	dATP
210	dCTP
210	dTTP
215	dATP
215	dCTP
215	dTTP
311	Mn(2+)
312	dATP
312	dCTP
312	dGTP
312	dTTP
315	dATP
315	dCTP
315	dGTP
315	dTTP
319	dATP
319	dCTP
319	dGTP
319	dTTP
333	dATP
333	dCTP
333	dGTP
333	dTTP
352	dATP
352	dCTP
352	dGTP
352	dTTP
354	dATP
354	dCTP
116	GTP
354	dGTP
354	dTTP
358	dATP
358	dGTP
366	dATP
366	dCTP
366	dGTP
372	dCTP
374	dGTP

…and 22 more — see UniProt.

Post-translational modifications (12)

Type	Positions
N-acetylmethionine	1
Phosphoserine	18, 33, 93
Phosphothreonine	21, 25, 592
(microbial infection) phosphothreonine	592
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	467, 469, 492, 622

Mutagenesis-validated functional residues (49)

Position	Phenotype
77	increased stability of the tetramer and increased deoxynucleoside triphosphate (dntpase) activity; when associated with f-77 and f-80 and …
80	increased stability of the tetramer and increased deoxynucleoside triphosphate (dntpase) activity; when associated with f-77 and r-111.
111	increased stability of the tetramer and increased deoxynucleoside triphosphate (dntpase) activity; when associated with f-77 and f-80.
137	impairs homotetramerization and nearly abolishes dntpase activity.
142	impairs homotetramerization and nearly abolishes dntpase activity; when associated with k-145.
143	abolished ability to restrict infection by viruses.
145	impairs homotetramerization and nearly abolishes dntpase activity. abolished ability to restrict infection by viruses.
145	impairs homotetramerization and nearly abolishes dntpase activity; when associated with e-145.
149	abolished dntpase activity without affecting homotetramerization. abolished dntpase activity; when associated with a-319.
164	abolished ability to restrict infection by viruses.
167	abolished ability to restrict infection by viruses.
206–207	abolishes zinc binding and dntpase activity. does not affect ability to promote dna end resection at stalled replication forks.
206	abolished ability to restrict infection by viruses.
207	abolished ability to restrict infection by viruses.
207	loss of dntpase activity.
210	abolished dntpase activity without affecting homotetramerization.
215	abolished dntpase activity without affecting homotetramerization.
226	loss of function in defense response to virus.
233	abolished dntpase activity without affecting homotetramerization. abolished ability to restrict infection by viruses.
311	loss of function in defense response to virus. loss of dntpase activity. does not affect oligomerization.
312	abolishes dntpase activity; when associated with a-315 and a-366. does not affect ability to promote dna end resection at stalled …
315	abolished ability to restrict infection by viruses. abolishes dntpase activity; when associated with a-312 and a-366. does not affect …
319	abolishes dntpase activity; when associated with a-149.
321	abolished ability to restrict infection by viruses.
330	impaired homotetramerization and slightly reduced dntpase activity. impaired homotetramerization and reduced dntpase activity; when …

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 7; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

7 pathways:

ID	Pathway	Evidence
R-HSA-909733	Interferon alpha/beta signaling	curated
R-HSA-8956319	Nucleotide catabolism	curated
R-HSA-1280215	Cytokine Signaling in Immune system	—
R-HSA-168256	Immune System	—
R-HSA-913531	Interferon Signaling	—
R-HSA-1430728	Metabolism	—
R-HSA-15869	Metabolism of nucleotides	—

MSigDB gene sets: 574 (showing top): GOBP_DNA_TEMPLATED_DNA_REPLICATION_MAINTENANCE_OF_FIDELITY, GOMF_RNA_NUCLEASE_ACTIVITY, CHIARADONNA_NEOPLASTIC_TRANSFORMATION_KRAS_DN, GOBP_PROTEIN_HOMOTETRAMERIZATION, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, BROWNE_HCMV_INFECTION_8HR_UP, GOMF_NUCLEASE_ACTIVITY, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_UP, GRAESSMANN_RESPONSE_TO_MC_AND_SERUM_DEPRIVATION_UP, GOBP_RESPONSE_TO_TYPE_I_INTERFERON, GOBP_NEGATIVE_REGULATION_OF_INNATE_IMMUNE_RESPONSE, GOBP_CARBOHYDRATE_DERIVATIVE_CATABOLIC_PROCESS, MORI_IMMATURE_B_LYMPHOCYTE_UP, DARWICHE_SKIN_TUMOR_PROMOTER_DN

GO Biological Process (16): double-strand break repair via homologous recombination (GO:0000724), dGTP catabolic process (GO:0006203), immune response (GO:0006955), DNA damage response (GO:0006974), deoxyribonucleotide catabolic process (GO:0009264), somatic hypermutation of immunoglobulin genes (GO:0016446), innate immune response (GO:0045087), regulation of innate immune response (GO:0045088), dATP catabolic process (GO:0046061), protein homotetramerization (GO:0051289), defense response to virus (GO:0051607), negative regulation of type I interferon-mediated signaling pathway (GO:0060339), DNA strand resection involved in replication fork processing (GO:0110025), immune system process (GO:0002376), DNA replication (GO:0006260), DNA repair (GO:0006281)

GO Molecular Function (16): nucleic acid binding (GO:0003676), single-stranded DNA binding (GO:0003697), RNA binding (GO:0003723), RNA nuclease activity (GO:0004540), GTP binding (GO:0005525), zinc ion binding (GO:0008270), dGTPase activity (GO:0008832), dGTP binding (GO:0032567), deoxynucleoside triphosphate hydrolase activity (GO:0106375), nucleotide binding (GO:0000166), catalytic activity (GO:0003824), protein binding (GO:0005515), hydrolase activity (GO:0016787), triphosphoric monoester hydrolase activity (GO:0016793), identical protein binding (GO:0042802), metal ion binding (GO:0046872)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), site of double-strand break (GO:0035861), tetraspanin-enriched microdomain (GO:0097197), chromosome (GO:0005694)

Reactome top-level categories

5 top-level categories:

Category	Pathways
Metabolism of nucleotides	1
Interferon Signaling	1
Immune System	1
Metabolism	1
Cytokine Signaling in Immune system	1

GO top-level categories

59 GO namespaces:

Category	Terms
DNA metabolic process	3
purine deoxyribonucleotide catabolic process	2
deoxyribonucleoside triphosphate catabolic process	2
purine deoxyribonucleoside triphosphate catabolic process	2
binding	2
anion binding	2
triphosphoric monoester hydrolase activity	2
cellular anatomical structure	2
recombinational repair	1
double-strand break repair	1
dGTP metabolic process	1
immune system process	1
response to stimulus	1
cellular response to stress	1
catabolic process	1
deoxyribonucleotide metabolic process	1
somatic diversification of immune receptors via somatic mutation	1
somatic diversification of immunoglobulins	1
immune response	1
defense response to symbiont	1
regulation of response to biotic stimulus	1
regulation of defense response	1
regulation of response to external stimulus	1
innate immune response	1
regulation of immune response	1
dATP metabolic process	1
protein homooligomerization	1
protein tetramerization	1
defense response	1
response to virus	1
negative regulation of cytokine-mediated signaling pathway	1
negative regulation of innate immune response	1
type I interferon-mediated signaling pathway	1
regulation of type I interferon-mediated signaling pathway	1
replication fork processing	1
5’-3’ DNA exonuclease activity	1
biological_process	1
DNA biosynthetic process	1
DNA damage response	1
DNA binding	1
nucleic acid binding	1
nuclease activity	1
catalytic activity, acting on RNA	1
guanyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
guanyl deoxyribonucleotide binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
molecular_function	1
catalytic activity	1
phosphoric ester hydrolase activity	1
protein binding	1
cation binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
site of DNA damage	1
plasma membrane	1
intracellular membraneless organelle	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 22 of 37 annotations. The rest are phylogenetic / computational / electronic (IEA).

22 experimentally-supported GO terms:

GO term	NS	Evidence
DNA damage response	BP	direct assay
DNA strand resection involved in replication fork processing	BP	direct assay
dATP catabolic process	BP	direct assay
dGTP catabolic process	BP	direct assay
defense response to virus	BP	direct assay
deoxyribonucleotide catabolic process	BP	direct assay
double-strand break repair via homologous recombination	BP	direct assay
negative regulation of type I interferon-mediated signaling pathway	BP	direct assay
protein homotetramerization	BP	direct assay
regulation of innate immune response	BP	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
site of double-strand break	CC	direct assay
tetraspanin-enriched microdomain	CC	direct assay
RNA binding	MF	direct assay
RNA nuclease activity	MF	direct assay
dGTP binding	MF	direct assay
dGTPase activity	MF	direct assay
deoxynucleoside triphosphate hydrolase activity	MF	direct assay
nucleic acid binding	MF	direct assay
single-stranded DNA binding	MF	direct assay
zinc ion binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,930 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SAMHD1	RNASEH2B	Q5TBB1	945
SAMHD1	RNASEH2A	O75792	942
SAMHD1	RNASEH2C	Q8TDP1	940
SAMHD1	TREX1	Q9NSU2	914
SAMHD1	TRIM5	Q9C035	818
SAMHD1	APOBEC3G	Q9HC16	814
SAMHD1	DCAF1	Q9Y4B6	794
SAMHD1	BST2	Q10589	759
SAMHD1	ADAR	P55265	733
SAMHD1	IFNA13	P01562	722
SAMHD1	IFNAR1	P17181	686
SAMHD1	MX2	P20592	681
SAMHD1	CUL4A	Q13619	672
SAMHD1	IFIH1	Q9BYX4	666
SAMHD1	SERINC5	Q86VE9	660

IntAct

Human interaction partners of SAMHD1 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

8 partners by confidence:

Partner	Interaction type	MIscore	Records
CDK2	association	0.530	1
LGALS3BP	physical association	0.500	1
TIRAP	physical association	0.500	1
DYSF	proximity	0.450	2
AIP	association	0.350	3
B2M	association	0.350	1
SF1	association	0.350	1
PHLDA3	physical association	0.000	1

BioGRID (285 interactions; top human partners by supporting records): CCNA2 (Affinity Capture-MS; 7 records), CDK1 (Affinity Capture-Western; 6 records), CDK2 (Affinity Capture-MS; 6 records), VPRBP (Biochemical Activity; 6 records), NONO (Affinity Capture-MS; 5 records), TRIM21 (Affinity Capture-MS; 5 records), USP7 (Affinity Capture-MS; 5 records), CHUK (Affinity Capture-Western; 4 records), EEF1A1 (Two-hybrid; 4 records), IKBKB (Affinity Capture-Western; 4 records), CUL3 (Affinity Capture-MS; 3 records), CCNA1 (Affinity Capture-Western; 2 records), CCNF (Affinity Capture-MS; 2 records), CCNL2 (Affinity Capture-Western; 2 records), DDB1 (Affinity Capture-MS; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CDK1	down-regulates	SAMHD1	phosphorylation

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 1 cancer types — PCM.

intOGen’s role is a computational inference from cohort mutation patterns and may diverge from the gene’s curated/literature role; read it alongside the evidence above.

Genetic variants

Variant evidence for SAMHD1: 1,047 ClinVar records (135 pathogenic / likely pathogenic); 1 PharmGKB clinical annotation; 2 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

1,047 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	90
Likely pathogenic	45
Uncertain significance	363
Likely benign	436
Benign	25

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 135 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
4067	NM_015474.4(SAMHD1):c.433C>T (p.Arg145Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	7
126407	NM_015474.4(SAMHD1):c.1411-2A>G	Pathogenic	criteria provided, multiple submitters, no conflicts	7
4071	NM_015474.4(SAMHD1):c.1642C>T (p.Gln548Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	5
126413	NM_015474.4(SAMHD1):c.649_650insG (p.Phe217fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	4
1453548	NM_015474.4(SAMHD1):c.703C>T (p.Gln235Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
2501214	NM_015474.4(SAMHD1):c.869G>A (p.Arg290His)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	3
872202	NM_015474.4(SAMHD1):c.434G>C (p.Arg145Pro)	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
1066893	NM_015474.4(SAMHD1):c.509+1G>A	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
2308668	NM_015474.4(SAMHD1):c.349-6_354del	Likely pathogenic	criteria provided, multiple submitters, no conflicts	2
4070	NM_015474.4(SAMHD1):c.445C>T (p.Gln149Ter)	Pathogenic	criteria provided, single submitter	3
997718	NM_015474.4(SAMHD1):c.109G>T (p.Glu37Ter)	Pathogenic	criteria provided, single submitter	2
581566	NM_015474.4(SAMHD1):c.1408del (p.Arg470fs)	Pathogenic	criteria provided, single submitter	1
639026	NM_015474.4(SAMHD1):c.494_495dup (p.Glu166fs)	Pathogenic	criteria provided, single submitter	1
639210	NM_015474.4(SAMHD1):c.700G>T (p.Glu234Ter)	Pathogenic	criteria provided, single submitter	1
840434	NM_015474.4(SAMHD1):c.939G>A (p.Trp313Ter)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore SAMHD1’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 42 predictions of 1,475):

Position(s)	Effect	Δscore	Sites
20:36904155–36904156	donor_loss	1.0000	5
20:36904250–36904251	acceptor_loss	1.0000	4
20:36911216–36911217	donor_loss	1.0000	6
20:36912459–36912460	donor_loss	1.0000	5
20:36912553–36912554	acceptor_loss	1.0000	6
20:36916832	acceptor_loss	1.0000
20:36916843	acceptor_gain	1.0000
20:36919362–36919363	donor_loss	1.0000	5
20:36919520–36919521	acceptor_loss	1.0000	3
20:36946805–36946806	acceptor_loss	1.0000	6

AlphaMissense

1,314 missense substitutions predicted likely pathogenic (of 4,152 scored), across 329 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D319	8	0.990	0.995
D120	8	0.979	0.991
D311	8	0.978	0.994
D309	8	0.977	0.993
H167	8	0.973	0.990
D314	8	0.973	0.995
H210	8	0.969	0.987
D207	8	0.965	0.991
H215	8	0.964	0.991
H206	8	0.961	0.994
D424	8	0.951	0.994
D264	8	0.948	0.983
H376	8	0.946	0.983
H233	8	0.934	0.977
F520	8	0.927	0.994
H162	8	0.926	0.975
H123	8	0.911	0.992
D195	8	0.902	0.965
F267	8	0.902	0.979
F141	8	0.884	0.989

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000304

Disease associations

OMIM: gene MIM:606754 | disease phenotypes: MIM:612952, MIM:225750, MIM:614415, MIM:254500

GenCC curated gene-disease

5 curated gene-disease records:

Disease	Classification	Inheritance	Records
Aicardi-Goutieres syndrome 5	Definitive	Autosomal recessive	6
Moyamoya disease	Strong	Autosomal recessive
familial chilblain lupus	Supportive	Autosomal dominant
Aicardi-Goutieres syndrome	Supportive	Autosomal dominant
chilblain lupus 2	Limited	Autosomal dominant

ClinGen Gene-Disease Validity

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

1 validity classifications:

Disease	Classification	Inheritance
SAMHD1-related type 1 interferonopathy	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (19 panels, 19 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

19 panels:

Panel	Rating
COVID-19 research	green
Cerebral vascular malformations	green
DDG2P	green
Dystonia, chorea or related movement disorder, childhood onset	green
Early onset or syndromic epilepsy	green
Fetal anomalies	green
Hypotonic infant	green
Inherited white matter disorders	green
Intellectual disability	green
Intracerebral calcification disorders	green
Leukodystrophy, adult onset	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Paediatric disorders	green
Primary immunodeficiency or monogenic inflammatory bowel disease	green
Rare genetic inflammatory skin disorders	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
White matter disorders and cerebral calcification - childhood onset	green

Mondo (8): Aicardi-Goutieres syndrome 5 (MONDO:0013059), Aicardi-Goutieres syndrome (MONDO:0018866), chilblain lupus 2 (MONDO:0013739), SAMHD1-related type 1 interferonopathy (MONDO:0700260), plasma cell myeloma (MONDO:0009693), cerebral palsy (MONDO:0006497), Moyamoya disease (MONDO:0016820), familial chilblain lupus (MONDO:0018827)

Orphanet (3): Aicardi-Goutières syndrome (Orphanet:51), Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

showing 60 of 91 phenotypes (HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000054	Micropenis
HP:0000252	Microcephaly
HP:0000369	Low-set ears
HP:0000444	Convex nasal ridge
HP:0000496	Abnormality of eye movement
HP:0000501	Glaucoma
HP:0000508	Ptosis
HP:0000625	Eyelid coloboma
HP:0000639	Nystagmus
HP:0000737	Irritability
HP:0000819	Diabetes mellitus
HP:0000821	Hypothyroidism
HP:0000958	Dry skin
HP:0000965	Cutis marmorata
HP:0000992	Cutaneous photosensitivity
HP:0001063	Acrocyanosis
HP:0001087	Developmental glaucoma
HP:0001250	Seizure
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001276	Hypertonia
HP:0001288	Gait disturbance
HP:0001332	Dystonia
HP:0001337	Tremor
HP:0001357	Plagiocephaly
HP:0001369	Arthritis
HP:0001371	Flexion contracture
HP:0001433	Hepatosplenomegaly
HP:0001609	Hoarse voice
HP:0001639	Hypertrophic cardiomyopathy
HP:0001640	Cardiomegaly
HP:0001873	Thrombocytopenia
HP:0001955	Unexplained fevers
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002079	Hypoplasia of the corpus callosum
HP:0002119	Ventriculomegaly
HP:0002132	Porencephalic cyst
HP:0002135	Basal ganglia calcification
HP:0002139	Arrhinencephaly
HP:0002187	Profound intellectual disability
HP:0002313	Spastic paraparesis
HP:0002315	Headache
HP:0002352	Leukoencephalopathy
HP:0002371	Loss of speech
HP:0002376	Developmental regression
HP:0002415	Leukodystrophy
HP:0002510	Spastic tetraplegia
HP:0002514	Cerebral calcification
HP:0002650	Scoliosis
HP:0002828	Multiple joint contractures
HP:0002910	Elevated circulating hepatic transaminase concentration
HP:0002960	Autoimmunity
HP:0003040	Arthropathy
HP:0003552	Muscle stiffness
HP:0003577	Congenital onset
HP:0003593	Infantile onset
HP:0003623	Neonatal onset
HP:0004322	Short stature

GWAS associations

2 associations:

Study	Trait	p-value
GCST011126_32	Caffeine consumption from coffee or tea	5e-9
GCST008163_35	Height	4e-7

EFO canonical traits (from GWAS)

2 canonical traits:

EFO ID	Trait name
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement

MeSH disease descriptors

5 disease descriptors:

Descriptor	Name	Tree numbers
D002547	Cerebral Palsy	C10.228.140.140.254
D009072	Moyamoya Disease	C10.228.140.300.200.600; C10.228.140.300.510.200.737; C14.907.137.615; C14.907.253.123.620; C14.907.253.560.200.737
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650
C535607	Aicardi-Goutieres syndrome *(supp.)*
C535608	Aicardi-Goutieres syndrome 5 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523507 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

PharmGKB clinical annotations

1 annotations by evidence level (1 strongest → 4):

Variant	Association	Level	Drugs	Phenotypes
rs8124728	Toxicity	3	stavudine	HIV infectious disease;Peripheral Nervous System Diseases

PharmGKB variants

1 variants:

Variant	Genes	Level	Score	#Clin annots	Drugs
rs8124728	SAMHD1, TLDC2	3	2.75	1	stavudine

PharmGKB variant annotations

Per-publication pharmacogenomic findings for this gene (significant associations).

1 published findings:

Variant	Drug(s)	Category	Finding	PMID
rs8124728	stavudine	Toxicity	Allele A is associated with decreased risk of Peripheral Nervous System Diseases due to stavudine in people with HIV Infections as compared to allele G.	PMID:30273369

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Nucleoside synthesis and metabolism

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
NVP-BHG712	Inhibition	8.44	pKd
TH6342	Inhibition	5.24	pIC50

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

2 potent at pChembl≥5 of 4 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.44	Kd	3.627	nM	CHEMBL3752910
8.44	ED50	3.627	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 6100 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149338: Binding affinity to human SAMHD1 incubated for 45 mins by Kinobead based pull down assay	kd	0.0036	uM

CTD chemical–gene interactions

79 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression	6
methylmercuric chloride	decreases expression, increases expression	3
Nickel	decreases expression, increases expression	3
bisphenol F	increases expression, affects cotreatment	2
mercuric bromide	decreases expression, affects cotreatment	2
entinostat	increases expression, affects cotreatment	2
(+)-JQ1 compound	increases expression	2
Air Pollutants	affects cotreatment, affects expression, increases abundance, decreases expression	2
Dexamethasone	increases expression, affects cotreatment	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Smoke	decreases expression	2
Cyclosporine	decreases expression	2
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
bufotalin	decreases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, affects expression, increases abundance	1
bisphenol A	increases methylation	1
2,2’-methylenebis(4-methyl-6-tert-butylphenol)	affects expression, affects response to substance	1
titanium dioxide	increases expression	1
trichostatin A	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression, increases abundance	1
cobaltous chloride	decreases expression	1
ochratoxin A	increases expression	1
4-hydroxy-2-nonenal	affects binding	1
deoxyguanosine triphosphate	decreases abundance	1

ChEMBL screening assays

4 unique, capped per target: 3 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4420589	Binding	Substrate activity at SAMHD1 in human THP1 cells assessed as reduction in cytarabine triphosphate formation at 10 ug/ml incubated for 6 hrs by liquid chromatography tandem mass spectrometry relative to control human THP1 cells with CRISP/CA	Samhd1 modulation for treating resistance to cancer therapy
CHEMBL5483194	Functional	Compound was evaluated for the inhibition of human recombinant SAMHD1 at 5uM in a enzyme-coupled malachite green assay	Identification and evaluation of small-molecule inhibitors against the dNTPase SAMHD1 via a comprehensive screening funnel — *iScience*

Cellosaurus cell lines

15 cell lines: 9 induced pluripotent stem cell, 5 cancer cell line, 1 transformed cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C1P4	CRTDi008-A	Induced pluripotent stem cell	Male
CVCL_C1P5	CRTDi009-A	Induced pluripotent stem cell	Female
CVCL_C1P6	CRTDi009-B	Induced pluripotent stem cell	Female
CVCL_C1P7	CRTDi010-A	Induced pluripotent stem cell	Male
CVCL_C4SB	CRTDi010-B	Induced pluripotent stem cell	Male
CVCL_C4SC	CRTDi008-B	Induced pluripotent stem cell	Male
CVCL_D7ZY	Ubigene A-549 SAMHD1 KO	Cancer cell line	Male
CVCL_D9RA	Ubigene HEK293 SAMHD1 KO	Transformed cell line	Female
CVCL_E8F8	THP1-Dual KO-SAMHD1	Cancer cell line	Male
CVCL_TK00	HAP1 SAMHD1 (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 348 trials:

NCT	Phase	Status	Title
NCT00029224	Phase 4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	Phase 4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	Phase 4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	Phase 4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	Phase 4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	Phase 4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	Phase 4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	Phase 4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	Phase 4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	Phase 4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	Phase 4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	Phase 4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	Phase 4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	Phase 4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	Phase 4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	Phase 4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	Phase 4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	Phase 4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	Phase 4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	Phase 4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	Phase 4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	Phase 4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	Phase 4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	Phase 4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	Phase 4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	Phase 4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	Phase 4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	Phase 4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	Phase 4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	Phase 4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	Phase 4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	Phase 4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	Phase 4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	Phase 4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	Phase 4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	Phase 4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	Phase 4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	Phase 4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	Phase 4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	Phase 4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting
NCT06409702	Phase 4	RECRUITING	Treatment of High-risk Newly Diagnosed Multiple Myeloma With Minimal Residual Disease Detection
NCT06425276	Phase 4	COMPLETED	Evaluate Safety and Efficacy of High-dose Melphalan HCL for Injection in MM Patients With Auto-HSC Transplantation
NCT07030517	Phase 4	ACTIVE_NOT_RECRUITING	A Study to Assess Safety of Teclistamab in Indian Participants With Relapsed and Refractory Multiple Myeloma
NCT07094048	Phase 4	RECRUITING	Immunoglobulins in Multiple Myeloma Patients Receiving a BCMA-Directed T Cell Engager
NCT07101445	Phase 4	RECRUITING	Evaluating Premedication Regimens (Methylprednisolone vs Dexamethasone-based) for the Prevention of Systemic and Injection Site Reactions to Motixafortide in Patients With Multiple Myeloma Undergoing Stem Cell Mobilization, PARADE Trial
NCT07154537	Phase 4	ACTIVE_NOT_RECRUITING	Pneumococcal Conjugated Vaccine 13 (PCV13) for Patients With Multiple Myeloma (MM)
NCT07334535	Phase 4	NOT_YET_RECRUITING	Isa-VRD in TIE HRMM
NCT07474961	Phase 4	NOT_YET_RECRUITING	BLOOD-dose: A Platform Trial Evaluating Dose Optimization in Hematological Diseases.
NCT04205578	Phase 3	UNKNOWN	NBP in Patients With Moyamoya Disease of High Risk for Ischemic Cerebrovascular Events
NCT00001561	Phase 3	COMPLETED	Active Immunization of Sibling Bone Marrow Transplant Donors Against Purified Myeloma Protein of the Recipient Undergoing Allogeneic Bone Marrow Transplantation
NCT00002548	Phase 3	COMPLETED	SWOG-9321 Melphalan, TBI, and Transplant vs Combo Chemo in Untreated Myeloma
NCT00002556	Phase 3	COMPLETED	Combination Chemotherapy With or Without High Dose Cyclophosphamide and Recombinant Interferon Alfa-2b in Treating Patients With Previously Untreated Stage I-III Multiple Myeloma
NCT00002850	Phase 3	COMPLETED	Antibiotic Therapy in Preventing Early Infection in Patients With Multiple Myeloma Who Are Receiving Chemotherapy
NCT00005834	Phase 3	TERMINATED	S9922 Combination Chemo Plus Filgrastim With or Without Thalidomide in Refractory Multiple Myeloma
NCT00037791	Phase 3	COMPLETED	Safety and Efficacy of (PN-152,243)/PN-196,444 in the Prevention of Thrombocytopenia
NCT00038233	Phase 3	COMPLETED	Thalidomide for Multiple Myeloma
NCT00048230	Phase 3	COMPLETED	PS-341 (VELCADE™) Versus High-Dose Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
NCT00056160	Phase 3	COMPLETED	CC-5013 Plus Dexamethasone Versus Dexamethasone Alone in Previously Treated Subjects With Multiple Myeloma
NCT00057564	Phase 3	COMPLETED	A Study of Combination Thalidomide Plus Dexamethasone Therapy vs. Dexamethasone Therapy Alone in Previously Untreated Subjects With Multiple Myeloma
NCT00063726	Phase 3	COMPLETED	A Study of PS-341 Given to Patients With Multiple Myeloma Who Experienced Progressive Disease After Receiving Dexamethasone in M34101-039

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for SAMHD1 across ~30M SureChEMBL compounds — explore on Sugi Predict.