Affinage

NANOS3

Nanos homolog 3 · UniProt P60323

Round 2 corrected
Length
173 aa
Mass
18.8 kDa
Annotated
2026-04-29
115 papers in source corpus 15 papers cited in narrative 15 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

NANOS3 is a conserved RNA-binding zinc-finger protein essential for the maintenance and survival of primordial germ cells (PGCs) in both sexes. It suppresses germ cell apoptosis through both Bax-dependent and Bax-independent pathways, and its protein dosage directly determines PGC population size (PMID:12947200, PMID:18436203, PMID:24091668). NANOS3 represses target mRNAs post-transcriptionally by recruiting the CCR4-NOT deadenylase complex via a conserved NIM motif that binds CNOT1 and through interaction with CNOT8, and it cooperates with Pumilio proteins (PUM1, PUM2) to regulate mRNA stability, poly(A) tail length, and cell cycle progression—including G1 delay in spermatogonia and G2/M control via PUM1-dependent repression of FOXM1 (PMID:24736845, PMID:25416063, PMID:18089289, PMID:35743036). Loss-of-function mutations in NANOS3, including p.Glu120Lys in the zinc-finger domain and the hypomorphic p.Arg153Trp allele, are associated with premature ovarian insufficiency and male infertility (PMID:24091668, PMID:25054146).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 2003 High

    The fundamental requirement for Nanos3 in germ cell biology was established when targeted disruption in mice demonstrated that Nanos3 is essential for PGC maintenance in both sexes, extending the conserved Nanos function from invertebrates to mammals.

    Evidence Gene knockout in mice with complete loss of germ cells in both sexes

    PMID:12947200

    Open questions at the time
    • Molecular targets of NANOS3 in PGCs unknown
    • Mechanism of germ cell loss (apoptosis vs. dedifferentiation) not resolved
    • Redundancy with other NANOS paralogs not tested
  2. 2007 Medium

    NANOS3 was linked to cell cycle regulation and to a conserved translational repression mechanism when overexpression caused G1 accumulation in spermatogonia and co-immunoprecipitation revealed interaction with Pumilio2.

    Evidence Overexpression in spermatogonial cells; flow cytometry; co-immunoprecipitation with PUM2

    PMID:18089289

    Open questions at the time
    • Reciprocal validation of PUM2 interaction not shown
    • Direct RNA targets mediating G1 delay unidentified
    • Endogenous loss-of-function in spermatogonia not performed
  3. 2008 High

    The anti-apoptotic mechanism was dissected: Nanos3 suppresses PGC death through both Bax-dependent and Bax-independent pathways, as Nanos3/Bax double knockout only partially rescues germ cells.

    Evidence Nanos3-null × Bax-null double knockout mice with lineage tracing

    PMID:18436203

    Open questions at the time
    • Identity of the Bax-independent apoptotic pathway unknown
    • Direct mRNA targets mediating anti-apoptotic function not identified
  4. 2010 High

    The basis for germ-cell-specific NANOS3 expression was resolved: the 3′UTR is necessary and sufficient to restrict protein expression to germ cells by destabilizing Nanos3 mRNA in somatic cells.

    Evidence Transgenic reporter mice with CAG promoter ± Nanos3 3′UTR; mRNA stability analysis

    PMID:20174582

    Open questions at the time
    • Trans-acting factors mediating somatic destabilization via the 3′UTR not identified
    • Whether the same mechanism operates in human germ cells unknown
  5. 2013 Medium

    A direct link between NANOS3 dosage and human fertility was established when a patient-derived p.Arg153Trp mutation was shown to reduce NANOS3 protein stability, and mouse models confirmed that PGC number is controlled by NANOS3 protein levels.

    Evidence Patient mutation screening; in vitro protein stability assay; PGC quantification at varying Nanos3 dosage in mice

    PMID:24091668

    Open questions at the time
    • Mechanism of reduced protein stability not structurally resolved
    • Cohort size for the human mutation is small
    • Additional causative mutations not yet mapped
  6. 2014 High

    The core post-transcriptional repression mechanism was elucidated: NANOS proteins recruit the CCR4-NOT deadenylase complex via a conserved NIM motif binding CNOT1, with crystal structure revealing aromatic residue insertion into a hydrophobic pocket; simultaneously, NANOS3 was shown to also interact with the CCR4-NOT subunit CNOT8, distinguishing it from NANOS2 which primarily binds CNOT1.

    Evidence Crystal structure of NIM–CNOT1 complex; mutagenesis; translational repression reporters; Co-IP of NANOS3 with CNOT8 in transgenic mice

    PMID:24736845 PMID:25416063

    Open questions at the time
    • Crystal structure solved for NANOS1 NIM, not NANOS3 NIM specifically
    • Physiological RNA targets of the NANOS3–CNOT8 axis in germ cells not mapped
    • Whether CNOT8 and CNOT1 interactions are mutually exclusive for NANOS3 unclear
  7. 2015 Medium

    An unexpected non-germline role was uncovered: NANOS3 directly binds vimentin mRNA, regulates its poly(A) tail length, and promotes EMT and invasiveness in lung cancer cells, demonstrating that its RNA-regulatory activities extend beyond germ cell biology.

    Evidence RNA immunoprecipitation; poly(A) tail assays; invasion assays; NANOS3 overexpression/silencing in NSCLC cell lines

    PMID:25904364

    Open questions at the time
    • Physiological relevance to tumor progression in vivo not demonstrated
    • Whether CCR4-NOT is involved in poly(A) tail regulation of vimentin by NANOS3 not tested
  8. 2018 Medium

    Direct RNA-binding by NANOS3 was demonstrated for the first time: NANOS3 in complex with PUM1 binds the SIAH1 3′UTR and represses its expression, and patient-derived NANOS3 mutations abolish this repression.

    Evidence EMSA demonstrating direct RNA binding; luciferase 3′UTR reporter assays; patient mutation functional analysis

    PMID:30269240

    Open questions at the time
    • Genome-wide identification of direct NANOS3 RNA targets not performed
    • Structural basis of NANOS3–RNA interaction not resolved at atomic level
  9. 2020 Medium

    A functional partnership between NANOS3 and DND1 in germ cell tumor suppression was revealed: Dnd1/Nanos3 double mutant mice show synergistically increased testicular teratoma incidence.

    Evidence Dnd1/Nanos3 double knockout mice in 129 background; teratoma incidence quantification

    PMID:32339196

    Open questions at the time
    • Whether DND1–NANOS3 interaction is direct and RNA-dependent not resolved
    • Molecular targets co-regulated by DND1 and NANOS3 in teratoma suppression unknown
  10. 2021 High

    Molecular discrimination between NANOS2 and NANOS3 was clarified: NANOS3 fails to bind CNOT1 directly in male germ cells and shows poor DND1 recruitment compared with NANOS2, explaining their non-redundant functions despite overlapping expression.

    Evidence Conditional knockout mice; chimeric NANOS protein constructs; in vivo and in vitro binding assays

    PMID:33199444

    Open questions at the time
    • How NANOS3 achieves target specificity without strong CNOT1 or DND1 binding is not resolved
    • Whether compensatory RNA-binding partners exist for NANOS3 is unknown
  11. 2022 Medium

    NANOS3's cell-cycle control was extended to G2/M: NANOS3 cooperates with PUM1 to repress FOXM1 mRNA via its 3′UTR, establishing a specific target and mechanism for NANOS3-mediated G2/M regulation in a human PGC model.

    Evidence RNA-seq after NANOS3 overexpression in TCam-2 cells; 3′UTR luciferase reporter assays for FOXM1

    PMID:35743036

    Open questions at the time
    • Endogenous NANOS3 loss-of-function effect on FOXM1 not shown
    • FOXM1 as transcriptional activator of NANOS3 is based on bioinformatic prediction only

Open questions

Synthesis pass · forward-looking unresolved questions
  • A genome-wide map of direct NANOS3 RNA targets in germ cells, the structural basis of NANOS3 zinc-finger–RNA recognition, and the identity of the Bax-independent apoptotic pathway suppressed by NANOS3 remain unresolved.
  • No CLIP-seq or equivalent transcriptome-wide target identification for NANOS3
  • No atomic-resolution structure of NANOS3 zinc-finger bound to RNA
  • Bax-independent anti-apoptotic mechanism molecularly undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0140098 catalytic activity, acting on RNA 3 GO:0003723 RNA binding 2
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-8953854 Metabolism of RNA 4 R-HSA-1474165 Reproduction 3 R-HSA-1640170 Cell Cycle 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CNOT1CNOT8DND1PUM1PUM2
Complex memberships
CCR4-NOT deadenylase complex

Evidence

Reading pass · 15 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 Mouse Nanos3 is expressed in migrating primordial germ cells (PGCs) and its genetic elimination results in the complete loss of germ cells in both sexes, establishing a conserved role for Nanos proteins in PGC maintenance across invertebrates and vertebrates. Gene knockout (targeted disruption) in mice; genetic epistasis comparison with Drosophila nanos Science High 12947200
2008 Nanos3 maintains the germ cell lineage by suppressing both Bax-dependent and Bax-independent apoptotic pathways; double knockout of Nanos3 and Bax only partially rescues PGC survival, indicating that Nanos3 protects PGCs through multiple anti-apoptotic mechanisms. Double knockout mouse model (Nanos3-null × Bax-null); lineage tracing using Nanos3-Cre-pA knock-in Developmental biology High 18436203
2007 In prepubertal testis, Nanos3 is expressed in undifferentiated spermatogonia; its over-expression causes G1-phase cell cycle accumulation, indicating a role in delaying spermatogonial cell cycle progression. Nanos3 interacts with the RNA-binding protein Pumilio2, consistent with a conserved translational repressor activity. Overexpression in spermatogonial cells; flow cytometry cell-cycle analysis; co-immunoprecipitation with Pumilio2; retinoic acid treatment demonstrating down-regulation Developmental biology Medium 18089289
2010 The Nanos3 3′UTR is necessary and sufficient to restrict NANOS3 protein expression specifically to germ cells in mouse embryos; Nanos3 mRNA is transcribed in both germ and somatic cells but is destabilized in somatic cells through a 3′UTR-mediated mechanism, enabling germ-cell-specific translation. Transgenic reporter mice using CAG promoter driving exogenous gene with/without Nanos3 3′UTR; analysis of mRNA stability and protein expression in germ vs. somatic cells PloS one High 20174582
2011 NANOS3 functions in human germ cell development: knockdown of NANOS3 (via morpholinos or shRNA) in human embryonic stem cell-derived germ cells reduces germ cell numbers and decreases expression of germ cell genes required for pluripotency and meiotic initiation. NANOS3 protein localizes to germ cell nuclei and co-localizes with chromosomal DNA during mitosis/meiosis. Morpholino and shRNA knockdown in hESC-derived germ cells; immunofluorescence localization; gene expression analysis Human molecular genetics Medium 21421998
2013 A NANOS3 missense mutation (p.Arg153Trp) identified in a premature ovarian insufficiency patient decreases NANOS3 protein stability (hypomorphic allele); the size of the PGC population is directly controlled by NANOS3 protein dosage in mouse models. Patient mutation screening; in vitro protein stability assay; mouse model PGC counting at varying NANOS3 dosage Cell death & disease Medium 24091668
2014 All three human NANOS paralogs (NANOS1-3) interact with the CNOT1 C-terminal domain of the CCR4-NOT deadenylase complex via a conserved NIM (CNOT1-interacting motif); crystal structure of the NANOS1 NIM–CNOT1 complex shows that conserved aromatic residues insert into a hydrophobic pocket on CNOT1. Substitution of these aromatic residues abolishes CNOT1 binding and abrogates translational repression by NANOS1-3. Crystal structure determination; binding assays; mutagenesis of NIM aromatic residues; translational repression reporter assays Genes & development High 24736845
2014 NANOS3 associates with the CCR4-NOT deadenylation complex through a direct interaction with CNOT8, whereas NANOS2 binds CNOT1; this difference in CCR4-NOT subunit targeting contributes to the molecular basis of functional redundancy and differences between NANOS2 and NANOS3 in male germ cell development. P-bodies are absent when both NANOS2 and NANOS3 are depleted. Co-immunoprecipitation of NANOS3 with CNOT8; transgenic mouse lines; comparison with NANOS2–CNOT1 interaction Biology open Medium 25416063
2014 A homozygous NANOS3 p.Glu120Lys mutation located in the second C2HC zinc-finger motif impairs NANOS3's ability to prevent apoptosis, as shown by flow cytometry and confocal microscopy; in silico modelling suggests destabilization of protein–RNA interaction. Flow cytometry and confocal microscopy apoptosis assays of mutant vs. wild-type NANOS3; in silico molecular modelling BioMed research international Medium 25054146
2015 NANOS3 promotes epithelial–mesenchymal transition (EMT) and invasiveness in human lung cancer cells: NANOS3 overexpression enhances invasiveness, represses E-cadherin transcriptionally, and up-regulates vimentin post-transcriptionally. NANOS3 directly binds vimentin mRNAs, regulates poly(A) tail length, and protects vimentin mRNA from microRNA-mediated repression. NANOS3 overexpression and silencing in NSCLC lines; invasion assays; RT-PCR/Western blot; poly(A) tail assays; RNA immunoprecipitation for vimentin mRNA binding The Journal of pathology Medium 25904364
2016 NANOS3 overexpression in human embryonic stem cells prolongs pluripotency and delays differentiation; a connection between NANOS3 and inhibition of apoptosis was observed. NANOS3 overexpression in hESCs; global transcriptional analysis; in vitro germ cell differentiation assays; xenotransplantation PloS one Low 27768780
2018 NANOS3, in complex with PUM1, directly binds the 3′UTR of SIAH1 mRNA and represses its expression independently of PUM-binding elements; this is the first report demonstrating direct RNA binding by a NANOS protein. NANOS3 mutations found in infertile patients disrupt repression of the SIAH1 reporter. Luciferase reporter assays; EMSA; direct RNA-binding assay; patient mutation analysis Cellular and molecular life sciences Medium 30269240
2020 DND1 interacts with NANOS3 in germ cells; double mutants for Dnd1 and Nanos3 show a synergistic increase in testicular teratoma incidence in 129 mice, indicating that DND1 and NANOS3 act together to suppress teratoma formation from PGCs. Conventional Dnd1-knockout mouse line; Dnd1/Nanos3 double mutants; teratoma incidence quantification; Western blot for DND1 protein levels PloS one Medium 32339196
2021 NANOS3 in mouse male germ cells fails to bind CNOT1 (an NANOS2 interactor at the N-terminal), and NANOS3 shows poor DND1 recruitment compared with NANOS2; conditional double knockout of Nanos2 and Nanos3 leads to rapid germ cell loss, and in vivo/in vitro experiments show that DND1–NANOS2 binding depends specifically on the NANOS2 zinc-finger structure. Conditional knockout mice; chimeric NANOS protein constructs; in vivo and in vitro binding assays for CNOT1 and DND1 interaction Development High 33199444
2022 NANOS3 and NANOS1 control distinct stages of the cell cycle in a human primordial germ cell model (TCam-2 cells): NANOS3 overexpression primarily affects G2/M phase transition. NANOS3 in complex with PUM1 mediates 3′UTR-dependent repression of FOXM1 mRNA, a transcription factor critical for G2/M progression; FOXM1 in turn potentially acts as a transcriptional activator of NANOS3. RNA-sequencing after NANOS3/NANOS1 overexpression; cell cycle analysis; 3′UTR reporter assays for FOXM1; bioinformatic analysis of publicly available RNA-seq datasets International journal of molecular sciences Medium 35743036

Source papers

Stage 0 corpus · 115 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2003 Conserved role of nanos proteins in germ cell development. Science (New York, N.Y.) 463 12947200
1996 Normalization and subtraction: two approaches to facilitate gene discovery. Genome research 401 8889548
2004 The DNA sequence and biology of human chromosome 19. Nature 271 15057824
2004 cGMP catabolism by phosphodiesterase 5A regulates cardiac adrenergic stimulation by NOS3-dependent mechanism. Circulation research 182 15576651
2015 Endothelial nitric oxide synthase: From biochemistry and gene structure to clinical implications of NOS3 polymorphisms. Gene 115 26428312
1994 Isolation and chromosomal localization of the human endothelial nitric oxide synthase (NOS3) gene. Genomics 109 7514568
2008 Nanos3 maintains the germ cell lineage in the mouse by suppressing both Bax-dependent and -independent apoptotic pathways. Developmental biology 106 18436203
2014 Structural basis for the Nanos-mediated recruitment of the CCR4-NOT complex and translational repression. Genes & development 98 24736845
2007 The role of shear stress on ET-1, KLF2, and NOS-3 expression in the developing cardiovascular system of chicken embryos in a venous ligation model. Physiology (Bethesda, Md.) 90 18073411
2012 Analysis of meiosis regulators in human gonads: a sexually dimorphic spatio-temporal expression pattern suggests involvement of DMRT1 in meiotic entry. Molecular human reproduction 86 22899867
2011 NANOS3 function in human germ cell development. Human molecular genetics 80 21421998
2015 ASK1 Inhibitor Halts Progression of Diabetic Nephropathy in Nos3-Deficient Mice. Diabetes 78 26180085
2019 Cannabidiol Overcomes Oxaliplatin Resistance by Enhancing NOS3- and SOD2-Induced Autophagy in Human Colorectal Cancer Cells. Cancers 75 31195721
2019 The midbody interactome reveals unexpected roles for PP1 phosphatases in cytokinesis. Nature communications 74 31586073
1999 Association between Alzheimer's disease and the NOS3 gene. Annals of neurology 71 10514107
2007 Three endothelial nitric oxide (NOS3) gene polymorphisms in hypertensive and normotensive individuals: meta-analysis of 53 studies reveals evidence of publication bias. Journal of hypertension 69 17762636
2010 An endocardial pathway involving Tbx5, Gata4, and Nos3 required for atrial septum formation. Proceedings of the National Academy of Sciences of the United States of America 60 20974940
2007 Potential role of Nanos3 in maintaining the undifferentiated spermatogonia population. Developmental biology 60 18089289
2020 A DNA-based fluorescent probe maps NOS3 activity with subcellular spatial resolution. Nature chemical biology 56 32152543
2001 Endothelial nitric oxide synthase gene (NOS3) variant and hypertension in pregnancy. American journal of medical genetics 52 11745998
2010 Nos3 protects against systemic inflammation and myocardial dysfunction in murine polymicrobial sepsis. Shock (Augusta, Ga.) 51 19997049
2015 Aqueous Humor Outflow Physiology in NOS3 Knockout Mice. Investigative ophthalmology & visual science 47 26225628
2013 A NANOS3 mutation linked to protein degradation causes premature ovarian insufficiency. Cell death & disease 47 24091668
2010 NOS3 gene polymorphisms are associated with risk markers of cardiovascular disease, and interact with omega-3 polyunsaturated fatty acids. Atherosclerosis 43 20409549
2013 Interaction between DMRT1 function and genetic background modulates signaling and pluripotency to control tumor susceptibility in the fetal germ line. Developmental biology 41 23473982
2009 Phosphodiesterase 5 restricts NOS3/Soluble guanylate cyclase signaling to L-type Ca2+ current in cardiac myocytes. Journal of molecular and cellular cardiology 40 19345227
1997 Migraine association and linkage studies of an endothelial nitric oxide synthase (NOS3) gene polymorphism. Neurology 37 9270610
2014 Homozygous inactivating mutation in NANOS3 in two sisters with primary ovarian insufficiency. BioMed research international 35 25054146
2011 Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activity. Cardiovascular research 35 21421555
2010 Polymorphisms in NOS3, ACE and PAI-1 genes and risk of spontaneous recurrent miscarriage in the Gaza Strip. Medical principles and practice : international journal of the Kuwait University, Health Science Centre 35 20134171
2017 Association of NOS3 gene polymorphisms with essential hypertension in Sudanese patients: a case control study. BMC medical genetics 31 29132319
2019 Activation of the STAT1 Pathway Accelerates Periodontitis in Nos3 Mice. Journal of dental research 30 31329047
2015 Evidence of Aortopathy in Mice with Haploinsufficiency of Notch1 in Nos3-Null Background. Journal of cardiovascular development and disease 28 25914885
2012 Nitric oxide synthase 3 (NOS3) 4b/a, T-786C and G894T polymorphisms in association with diabetic retinopathy susceptibility: a meta-analysis. Ophthalmic genetics 28 22506535
2008 Gastroschisis: a gene-environment model involving the VEGF-NOS3 pathway. American journal of medical genetics. Part C, Seminars in medical genetics 28 18655103
2014 Interaction of NANOS2 and NANOS3 with different components of the CNOT complex may contribute to the functional differences in mouse male germ cells. Biology open 25 25416063
2010 A meta-analysis of three polymorphisms in the endothelial nitric oxide synthase gene (NOS3) and their effect on the risk of diabetic nephropathy. Human genetics 25 20049477
2021 Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer. Frontiers in oncology 24 33747912
2018 Replication of a Gene-Diet Interaction at CD36, NOS3 and PPARG in Response to Omega-3 Fatty Acid Supplements on Blood Lipids: A Double-Blind Randomized Controlled Trial. EBioMedicine 24 29703528
2018 Role of long non-coding RNAs expression (ANRIL, NOS3-AS, and APOA1-AS) in development of atherosclerosis in Egyptian systemic lupus erythematosus patients. Clinical rheumatology 24 30128915
2011 Reproductive factors and NOS3 variant interactions in primary open-angle glaucoma. Molecular vision 24 22025889
2018 microRNAs regulate nitric oxide release from endothelial cells by targeting NOS3. Journal of thrombosis and thrombolysis 23 29948755
2015 Redox regulation of metabolic and signaling pathways by thioredoxin and glutaredoxin in NOS-3 overexpressing hepatoblastoma cells. Redox biology 23 26210445
2021 Loss of ITGB3 in ovine conceptuses decreases conceptus expression of NOS3 and SPP1: implications for the developing placental vasculature†. Biology of reproduction 22 33232974
2015 Functional G894T (rs1799983) polymorphism and intron-4 VNTR variant of nitric oxide synthase (NOS3) gene are susceptibility biomarkers of obesity among Tunisians. Obesity research & clinical practice 22 25956856
2013 Haplotypes of NOS3 gene polymorphisms in dilated cardiomyopathy. PloS one 21 23923002
2009 Polymorphisms of the NOS3 gene in Southern Chilean subjects with coronary artery disease and controls. Clinica chimica acta; international journal of clinical chemistry 21 19931521
2008 Placenta-restricted expression of LTR-derived NOS3. Placenta 21 18474398
2019 CNDP1, NOS3, and MnSOD Polymorphisms as Risk Factors for Diabetic Nephropathy among Type 2 Diabetic Patients in Malaysia. Journal of nutrition and metabolism 20 30719346
2016 Generation of exogenous germ cells in the ovaries of sterile NANOS3-null beef cattle. Scientific reports 20 27117862
2009 T-786C polymorphism of the NOS-3 gene and the endothelial cell response to fluid shear stress-a proteome analysis. Journal of proteome research 20 19320461
2007 Mutation analysis of NANOS3 in 80 Chinese and 88 Caucasian women with premature ovarian failure. Fertility and sterility 20 17418157
2023 Deletion of adipocyte NOS3 potentiates high-fat diet-induced hypertension and vascular remodelling via chemerin. Cardiovascular research 19 37897505
2015 CpG signalling, H2A.Z/H3 acetylation and microRNA-mediated deferred self-attenuation orchestrate foetal NOS3 expression. Clinical epigenetics 19 25699114
2015 A new pattern of primordial germ cell migration in olive flounder (Paralichthys olivaceus) identified using nanos3. Development genes and evolution 19 26025098
2013 Conserved mechanisms for germ cell-specific localization of nanos3 transcripts in teleost species with aquaculture significance. Marine biotechnology (New York, N.Y.) 19 24091820
2010 The Nanos3-3'UTR is required for germ cell specific NANOS3 expression in mouse embryos. PloS one 19 20174582
2018 NOS3 Inhibition Confers Post-Ischemic Protection to Young and Aging White Matter Integrity by Conserving Mitochondrial Dynamics and Miro-2 Levels. The Journal of neuroscience : the official journal of the Society for Neuroscience 18 29891729
2016 Over Expression of NANOS3 and DAZL in Human Embryonic Stem Cells. PloS one 18 27768780
2013 Interaction between the NOS3 gene and obesity as a determinant of risk of type 2 diabetes: the Atherosclerosis Risk in Communities study. PloS one 18 24278136
2011 The effects of NOS3 Glu298Asp variant on colorectal cancer risk and progression in Turkish population. Molecular biology reports 18 21706163
2002 A polymorphism of the Nos3 gene and age at natural menopause. Fertility and sterility 18 12477509
2022 Rheum officinale Baill. Treats zebrafish embryo thrombosis by regulating NOS3 expression in the arginine biosynthesis pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 35182903
2021 Generation of chimeric mice with spermatozoa fully derived from embryonic stem cells using a triple-target CRISPR method for Nanos3†. Biology of reproduction 17 32965494
2018 The NOS3 G894T (rs1799983) and -786T/C (rs2070744) polymorphisms are associated with elite swimmer status. Biology of sport 17 30765915
2009 NANOS3 gene mutations in men with isolated sterility phenotype. Molecular reproduction and development 17 19565640
2023 Biotransformed bear bile powder ameliorates diet-induced nonalcoholic steatohepatitis in mice through modulating arginine biosynthesis via FXR/PXR-PI3K-AKT-NOS3 axis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 16 37806086
2019 Associations of the NOS3 rs1799983 polymorphism with circulating nitric oxide and lipid levels: a systematic review and meta-analysis. Postgraduate medical journal 16 31138610
2013 Possible relation between the NOS3 gene GLU298ASP polymorphism and bladder cancer in Turkey. Asian Pacific journal of cancer prevention : APJCP 16 23621215
2008 Habitual energy expenditure modifies the association between NOS3 gene polymorphisms and blood pressure. American journal of hypertension 16 18246059
2018 PUM1 and PUM2 exhibit different modes of regulation for SIAH1 that involve cooperativity with NANOS paralogues. Cellular and molecular life sciences : CMLS 15 30269240
2015 The human NANOS3 gene contributes to lung tumour invasion by inducing epithelial-mesenchymal transition. The Journal of pathology 15 25904364
2009 Genetic and pharmacogenetic associations between NOS3 polymorphisms, blood pressure, and cardiovascular events in hypertension. American journal of hypertension 15 19407804
2020 Association of NOS3 and ANGPT2 Gene Polymorphisms with Survival in Patients with Hepatocellular Carcinoma Receiving Sorafenib: Results of the Multicenter Prospective INNOVATE Study. Clinical cancer research : an official journal of the American Association for Cancer Research 14 32371540
2011 Association of NOS3 tag polymorphisms with hypoxic-ischemic encephalopathy. Croatian medical journal 14 21674837
2011 Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study. BMC pregnancy and childbirth 14 22051068
2010 NOS3 gene rs1799983 polymorphism and incident dementia in elderly stroke survivors. Neurobiology of aging 14 20691505
2003 Localization of NOS-1 in the sarcolemma region of a subpopulation of atrial cardiomyocytes including myoendocrine cells and NOS-3 in vascular and endocardial endothelial cells of the rat heart. Acta histochemica 14 12666987
2023 USP7 controls NGN3 stability and pancreatic endocrine lineage development. Nature communications 13 37117185
2021 The Role of Single-Nucleotide Variants of NOS1, NOS2, and NOS3 Genes in the Comorbidity of Arterial Hypertension and Tension-Type Headache. Molecules (Basel, Switzerland) 13 33809023
2020 Relation of nitric oxide synthase gene (NOS3) polymorphisms to varicocele risk and post-varicocelectomy seminal oxidative stress reduction. Andrologia 13 32022285
2020 Mouse dead end1 acts with Nanos2 and Nanos3 to regulate testicular teratoma incidence. PloS one 13 32339196
2018 NOS3 Polymorphisms and Chronic Kidney Disease. Jornal brasileiro de nefrologia 13 29927456
2017 Genetic Deletion of the NOS3 Gene in CAV1-/- Mice Restores Aqueous Humor Outflow Function. Investigative ophthalmology & visual science 13 28973370
2015 Association study of NOS3 gene polymorphisms and hypertension in the Han Chinese population. Nitric oxide : biology and chemistry 13 26391643
2021 Folic acid oversupplementation during pregnancy disorders lipid metabolism in male offspring via regulating arginase 1-associated NOS3-AMPKα pathway. Clinical nutrition (Edinburgh, Scotland) 12 34864452
2020 NOS3 Gene rs1799983 and rs2070744 Polymorphisms in Patients with Unstable Angina. Journal of vascular research 12 32224624
2019 Association between NOS3 polymorphisms and osteonecrosis of the femoral head. Artificial cells, nanomedicine, and biotechnology 12 31007072
2015 G894T and 4a/b polymorphisms of NOS3 gene are not associated with cancer risk: a meta-analysis. Asian Pacific journal of cancer prevention : APJCP 12 25854385
2015 Tumor Necrosis Factor (TNF) -308G>A, Nitric Oxide Synthase 3 (NOS3) +894G>T Polymorphisms and Migraine Risk: A Meta-Analysis. PloS one 12 26098763
2014 Endothelial function and insulin resistance in early postmenopausal women with cardiovascular risk factors: importance of ESR1 and NOS3 polymorphisms. PloS one 12 25077953
2008 Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism in Chinese. Journal of molecular neuroscience : MN 12 18183499
2021 Genetic Variants in PTGS1 and NOS3 Genes Increase the Risk of Upper Gastrointestinal Bleeding: A Case-Control Study. Frontiers in pharmacology 11 34290607
2019 Combined inhibition of CCR2 and ACE provides added protection against progression of diabetic nephropathy in Nos3-deficient mice. American journal of physiology. Renal physiology 11 31566438
2019 Association between endothelial nitric oxide synthase (NOS3) rs2070744 and the risk for migraine. The pharmacogenomics journal 11 31792366
2018 Influence of MBL2 and NOS3 polymorphisms on spontaneous preterm birth in North East Brazil: genetics and preterm birth. The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians 11 29886784
2017 NOS3 gene variants and male infertility: Association of 4a/4b with oligoasthenozoospermia. Andrologia 11 28466478
2016 Association between NOS3 genetic variants and coronary artery disease in the Han population. Genetics and molecular research : GMR 11 27323132
2022 Distinct Roles of NANOS1 and NANOS3 in the Cell Cycle and NANOS3-PUM1-FOXM1 Axis to Control G2/M Phase in a Human Primordial Germ Cell Model. International journal of molecular sciences 10 35743036
2022 ApoE/NOS3 Knockout Mice as a Novel Cardiovascular Disease Model of Hypertension and Atherosclerosis. Genes 10 36360235
2019 Effect of miR-134 against myocardial hypoxia/reoxygenation injury by directly targeting NOS3 and regulating PI3K/Akt pathway. Acta cirurgica brasileira 10 31618402
2017 Functional Variations in the NOS3 Gene Are Associated With Erectile Dysfunction Susceptibility, Age of Onset and Severity in a Han Chinese Population. The journal of sexual medicine 10 28268155
2015 Polymorphisms in NOS3, MTHFR, APOB and TNF-α Genes and Risk of Coronary Atherosclerotic Lesions in Iranian Patients. Research in cardiovascular medicine 10 26878010
2014 Association of NOS3 gene variants and clinical contributors of hypoxic-ischemic encephalopathy. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 10 25140814
2012 The interaction of AGT and NOS3 gene polymorphisms with conventional risk factors increases predisposition to hypertension. Journal of the renin-angiotensin-aldosterone system : JRAAS 10 22791701
2006 NOS3 gene polymorphisms and exercise hemodynamics in postmenopausal women. International journal of sports medicine 10 16761221
2021 Genetic and structural analysis of the in vivo functional redundancy between murine NANOS2 and NANOS3. Development (Cambridge, England) 9 33199444
2020 Nanos3, a cancer-germline gene, promotes cell proliferation, migration, chemoresistance, and invasion of human glioblastoma. Cancer cell international 9 32508533
2013 Polymorphisms of the NOS3 gene and risk of myocardial infarction in the Tunisian population. Cytokine 9 24095258
2010 NAT1, NOS3, and TYMS genotypes and the risk of conotruncal cardiac defects. Birth defects research. Part A, Clinical and molecular teratology 9 21254360
2016 Mutation analysis of NANOS3 in Brazilian women with primary ovarian failure. Clinics (Sao Paulo, Brazil) 6 28076512
2021 Gene Alterations and Expression Spectrum of NANOS3 in Nonobstructive Azoospermia. Reproductive sciences (Thousand Oaks, Calif.) 0 34417763