Affinage

INSIG2

Insulin-induced gene 2 protein · UniProt Q9Y5U4

Length
225 aa
Mass
24.8 kDa
Annotated
2026-06-10
79 papers in source corpus 21 papers cited in narrative 21 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

INSIG2 (Insig-2) is an endoplasmic reticulum membrane protein that serves as a central sterol-regulated brake on lipid biosynthesis, enforcing feedback control of both cholesterol and fatty acid synthesis (PMID:12242332, PMID:15866869). It acts through two principal effector arms: it binds SCAP (SREBP cleavage-activating protein) in a sterol-dependent manner to retain SCAP–SREBP complexes in the ER and block proteolytic SREBP maturation, and it binds HMG-CoA reductase to accelerate its ubiquitination and ER-associated degradation (PMID:12242332, PMID:15866869). Cryo-EM of the human Scap–Insig-2 complex resolved a 25-hydroxycholesterol molecule sandwiched between Scap's sterol-sensing domain and TMs 3–4 of Insig-2, defining the sterol-bridged interface that drives complex formation (PMID:33446483). A conserved juxtamembranous aspartate abutting the fourth transmembrane helix and an intramembrane glycine required for Insig-2 multimerization are each essential for both SCAP binding and reductase degradation (PMID:16606821, PMID:19617589). Beyond constitutive sterol sensing, Insig-2 integrates regulatory inputs: PKA phosphorylation of Ser-106 (a residue absent in Insig-1) in response to the polyunsaturated fatty acid EPA selectively blocks SREBP-1 processing and fatty acid synthesis without affecting cholesterol synthesis (PMID:39145929), and ROS-mediated oxidation of Cys215 prevents gp78-dependent ubiquitylation, stabilizing Insig-2 to suppress lipogenesis during myoblast differentiation (PMID:31953408). Insig-2 transcription is controlled by multiple nuclear and hormonal inputs—FXRα, HIF-1α, CREBH (glucagon/fasting), and a liver-specific insulin-repressed Insig-2a isoform—linking it to hepatic lipid metabolism and the cellular hypoxic response (PMID:12624180, PMID:17440045, PMID:28416613, PMID:27582413). Insig-2 also couples oxysterol sensing to the PERK–eIF2α–ATF4 stress axis (PMID:34298014).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2002 High

    Established that Insig-2 is the second ER-resident sensor that retains SCAP–SREBP complexes to block SREBP processing, distinct from Insig-1 in not requiring nuclear SREBPs for its expression.

    Evidence Sterol-regulated co-immunoprecipitation and functional overexpression in cultured mammalian cells

    PMID:12242332

    Open questions at the time
    • Did not resolve the molecular interface of SCAP binding
    • Relationship to HMG-CoA reductase degradation not yet tested
  2. 2003 High

    Showed that a liver-specific Insig-2a isoform from an alternative promoter is selectively repressed by insulin, providing a hormonal switch that licenses SREBP-1c-driven fatty acid synthesis during feeding.

    Evidence Promoter analysis, Northern/RT-PCR in mouse liver, streptozotocin diabetic rat and insulin injection models

    PMID:12624180

    Open questions at the time
    • Transcription factor mediating insulin repression not identified here
    • Did not separate fatty acid from cholesterol synthesis effects
  3. 2005 High

    Demonstrated an absolute requirement for Insig proteins in lipid feedback control, since loss of both Insig-1 and Insig-2 abolishes sterol-induced SREBP suppression and reductase degradation, both rescuable by either Insig.

    Evidence Mutagenesis-derived Insig-deficient SRD-15 CHO cells with genetic complementation

    PMID:15866869

    Open questions at the time
    • Functional redundancy between paralogs left isoform-specific roles unresolved
    • Did not address tissue-specific differences
  4. 2006 High

    Mapped a conserved juxtamembranous aspartate as essential for both Insig functions, linking SCAP binding and reductase degradation to a single structural determinant.

    Evidence Site-directed mutagenesis with dual SCAP-binding and reductase-ubiquitination readouts in mammalian cells

    PMID:16606821

    Open questions at the time
    • Did not define how the residue contributes mechanistically to sterol sensing
    • Structural basis unresolved at this stage
  5. 2010 Medium

    Identified Insig-2 multimerization, dependent on an intramembrane glycine, as a requirement for sterol regulation of both Scap and reductase.

    Evidence Mutagenesis (G39E) and functional complementation in CHO SRD-20 cells

    PMID:19617589

    Open questions at the time
    • Multimerization not directly demonstrated structurally
    • Stoichiometry of the functional oligomer unknown
  6. 2017 High

    Placed Insig-2 in the hypoxic response by showing HIF-1α directly induces INSIG2 transcription, accelerating HMGCR ubiquitination and degradation, coupling oxygen sensing to cholesterol synthesis control.

    Evidence ChIP, reporter assays, siRNA, pharmacologic HIF-1α stabilization in mice and ubiquitination assays

    PMID:28416613

    Open questions at the time
    • Physiological context for hypoxic cholesterol suppression not fully defined
    • Did not address SREBP arm under hypoxia
  7. 2016 Medium

    Showed glucagon/fasting acts via CREBH to upregulate the Insig-2a isoform, opposing insulin and protecting against hepatic steatosis through SREBP-1c suppression.

    Evidence Promoter binding, CREBH and Insig-2 knockdown, glucagon treatment and streptozotocin mouse model

    PMID:27582413

    Open questions at the time
    • No ChIP confirmation of CREBH binding to Insig-2a
    • Single-lab in vivo evidence
  8. 2020 High

    Revealed post-translational control of Insig-2 stability: gp78-mediated ubiquitylation on Cys215 drives degradation, while ROS oxidation of Cys215 blocks this and stabilizes Insig-2 to suppress lipogenesis during myogenesis.

    Evidence gp78 knockout mice, in vitro ubiquitylation, Cys215 mutagenesis, ROS manipulation and lipogenesis assays

    PMID:31953408

    Open questions at the time
    • Cys215 oxidation chemistry not fully defined
    • Relevance beyond muscle differentiation not established
  9. 2021 High

    Provided the near-atomic structural basis for sterol-mediated Scap–Insig-2 association, showing 25HC bridges Scap's sterol-sensing domain and Insig-2 TMs 3–4.

    Evidence Cryo-EM of the human Scap–Insig-2 complex with 25HC at 3.7 Å

    PMID:33446483

    Open questions at the time
    • Structure of the reductase-bound Insig-2 complex not resolved
    • Conformational dynamics during sterol release not captured
  10. 2021 Medium

    Linked insulin signaling to lipogenesis activation through CD36, which forms a complex with Insig-2 and disrupts the SCAP–Insig-2 interaction to permit SREBP1 processing.

    Evidence Co-IP, proximity ligation, CD36 liver-specific knockout mice, and pharmacological rescue with 25HC/betulin

    PMID:34974159

    Open questions at the time
    • Direct interface of CD36–Insig-2 binding undefined
    • Mechanism relies on inferred displacement of SCAP
  11. 2021 Medium

    Expanded Insig function beyond lipid feedback by showing Insig proteins couple oxysterol sensing to PERK–eIF2α–ATF4 activation and downstream cell death effectors.

    Evidence INSIG1/2-deficient CHO and Huh7 cells with genetic rescue and oxysterol treatment

    PMID:34298014

    Open questions at the time
    • Mechanism connecting Insig sterol binding to PERK activation undefined
    • Insig-2-specific contribution not isolated from Insig-1
  12. 2024 High

    Defined an Insig-2-specific phosphorylation switch: EPA-driven PKA phosphorylation of Ser-106 selectively blocks SREBP-1 processing and fatty acid synthesis, uncoupling it from cholesterol synthesis.

    Evidence In vitro PKA phosphorylation, S106A mutagenesis, PKA inhibition, and Insig-2-null fibroblast rescue with SREBP processing assays

    PMID:39145929

    Open questions at the time
    • How phospho-Ser-106 mechanistically discriminates SREBP-1 from SREBP-2 unresolved
    • In vivo relevance in liver physiology not established
  13. 2024 Medium

    Identified INSIG2 as a context-specific proliferation vulnerability in HBV-integrated hepatoma cells, acting upstream of CDK2 in G1-to-S progression.

    Evidence Genome-wide CRISPR screen, siRNA/CRISPR knockout, CDK2 inhibitor epistasis and cell cycle analysis

    PMID:38287498

    Open questions at the time
    • Mechanism linking Insig-2 to CDK2 unknown
    • Specificity to HBV-integrated context not mechanistically explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple regulatory inputs (transcriptional, phosphorylation, redox, and protein-displacement) are integrated in vivo to set tissue-specific lipid synthesis thresholds remains unresolved.
  • No unified in vivo model integrating CREBH/insulin/HIF-1α/FXRα transcriptional control with Ser-106 phosphorylation and Cys215 redox switching
  • Structural basis of the Insig-2–HMGCR complex unresolved
  • Non-canonical roles (mitochondrial Bax, cancer cell cycle) lack mechanistic dissection

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 3 GO:0008289 lipid binding 2 GO:0140313 molecular sequestering activity 2
Localization
GO:0005783 endoplasmic reticulum 3
Pathway
R-HSA-1430728 Metabolism 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-8953897 Cellular responses to stimuli 2
Partners
CD36GP78HMGCRSCAP
Complex memberships
SCAP–Insig-2 complex

Evidence

Reading pass · 21 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 Insig-2 is an ER membrane protein that binds SCAP (SREBP cleavage-activating protein) in a sterol-regulated fashion, thereby retaining SCAP-SREBP complexes in the ER and preventing proteolytic processing of SREBPs in the Golgi, thus blocking cholesterol synthesis. Unlike Insig-1, Insig-2 expression does not require nuclear SREBPs, and at high expression levels Insig-2 cannot block SCAP movement in the absence of exogenous sterols. Protein binding assays, sterol-regulated co-immunoprecipitation, functional overexpression in cultured mammalian cells Proceedings of the National Academy of Sciences of the United States of America High 12242332
2003 A liver-specific transcript of Insig-2 (Insig-2a), driven by an alternative promoter, is selectively down-regulated by insulin. Insig-2a mRNA increases during fasting and in streptozotocin-treated diabetic rats; insulin injection reduces it. Both Insig-2a and Insig-2b encode identical proteins but differ in regulation. The insulin-mediated fall in Insig-2a is proposed to permit SREBP-1c processing and stimulate fatty acid synthesis. Promoter analysis, Northern/RT-PCR in mouse liver, streptozotocin rat model, insulin injection experiments Proceedings of the National Academy of Sciences of the United States of America High 12624180
2005 Cells deficient in both Insig-1 and Insig-2 (SRD-15 CHO cells) show no sterol-induced inhibition of SREBP processing and no sterol-induced ubiquitination/degradation of HMG-CoA reductase. Sterol regulation of both processes is fully restored by transfection of either Insig-1 or Insig-2, demonstrating an absolute requirement for Insig proteins in lipid homeostasis feedback control. Gamma-irradiation mutagenesis, selection in 25-hydroxycholesterol, genetic complementation with expression plasmids in CHO cells The Journal of biological chemistry High 15866869
2006 A conserved juxtamembranous aspartic acid residue (Asp-205 in Insig-1; corresponding residue in Insig-2) abutting the fourth transmembrane helix at the cytosolic side of the ER membrane is essential for both Insig functions: (1) sterol-dependent binding to SCAP and suppression of SREBP cleavage, and (2) acceleration of sterol-stimulated HMG-CoA reductase ubiquitination and degradation. Alanine substitution at this position abolishes both activities. Site-directed mutagenesis, co-immunoprecipitation of SCAP binding, SREBP processing assay, reductase ubiquitination assay in mammalian cells Proceedings of the National Academy of Sciences of the United States of America High 16606821
2007 Activation of the farnesoid X receptor (FXRα) directly induces Insig-2 transcription via two functional FXRα response elements identified within intron 2 of the mouse Insig-2 gene. FXRα activation increases hepatic Insig-2 protein levels and reduces HMG-CoA reductase protein levels, contributing to decreased cholesterol synthesis. No induction was observed in FXRα-/- mice. EMSA, reporter gene assays, chromatin immunoprecipitation, agonist treatment and FXRα knockout mouse model, Western blotting Molecular endocrinology (Baltimore, Md.) High 17440045
2004 A functional vitamin D response element was identified in the murine Insig-2 promoter. This element specifically binds the RXR–VDR heterodimer and directs 1,25-(OH)2D3-dependent transcriptional activation of Insig-2, transiently inducing Insig-2 expression in 3T3-L1 cells, potentially contributing to the anti-adipogenic action of vitamin D. EMSA, reporter gene assay, 1,25-(OH)2D3 treatment of 3T3-L1 cells, RT-PCR Molecular endocrinology (Baltimore, Md.) Medium 15528275
2010 Insig-2 multimerization is required for sterol regulation in CHO cells. A glycine residue (Gly-39) in the first membrane-spanning segment of Insig-2 is critical for this function; mutation to glutamic acid (G39E) produces a nonfunctional protein unable to confer sterol regulation upon Scap or HMG-CoA reductase. The corresponding intramembrane glycine in Insig-1 is similarly important. Mutagenesis of CHO cell line (SRD-20), DNA sequencing, functional overexpression assays for SCAP and reductase regulation Journal of lipid research Medium 19617589
2010 The human INSIG2 promoter contains a functional Ets-consensus motif in its proximal region. The Ets family member SAP1a binds this region and is required for basal INSIG2 transcription. Insulin activates the human INSIG2 promoter through a mechanism mediated by phosphorylated SAP1a. Promoter deletion analysis, chromatin immunoprecipitation, RNA interference, mutational analysis of promoter elements in human liver cells The Journal of biological chemistry Medium 20145255
2017 HIF-1α directly activates INSIG-2 gene transcription under hypoxia in human fibroblasts. Accumulated Insig-2 protein binds HMG-CoA reductase and triggers accelerated ubiquitination and ER-associated degradation of the enzyme. Pharmacologic stabilization of HIF-1α in mouse liver stimulated HMGCR degradation in a manner requiring prior HMGCR ubiquitination and the presence of Insig-2 protein. Transcription reporter assays, ChIP, siRNA knockdown, pharmacologic HIF-1α stabilization in mice, ubiquitination assays, Western blotting The Journal of biological chemistry High 28416613
2016 The liver-specific isoform Insig-2a is positively regulated by the cyclic AMP-responsive element-binding protein H (CREBH), which binds conserved CRE-BP binding elements in the Insig-2a enhancer region. Glucagon and fasting activate CREBH, upregulating Insig-2a to inhibit SREBP-1c activation and hepatic de novo lipogenesis. Genetic depletion of CREBH decreases Insig-2a expression leading to SREBP-1c activation and hepatic steatosis. siRNA knockdown of Insig-2 disrupts this inhibitory effect. CREBH binding to Insig-2a promoter/enhancer, siRNA knockdown of CREBH and Insig-2, glucagon treatment, streptozotocin mouse model, lipid accumulation assays Scientific reports Medium 27582413
2020 Insig-2 is ubiquitylated on Cys215 by the E3 ubiquitin ligase gp78, leading to its degradation in hepatocytes and undifferentiated C2C12 myoblasts. During myoblast differentiation into myotubes, elevated reactive oxygen species (ROS) oxidize Cys215, preventing ubiquitylation and stabilizing Insig-2. Stabilized Insig-2 downregulates lipogenesis via inhibition of the SREBP pathway in myotubes. The YECK tetrapeptide containing Cys215 is highly conserved in amniotes. gp78-deficient mice (tissue fractionation), ubiquitylation assays, ROS manipulation, site-directed mutagenesis of Cys215, lipogenesis assays, evolutionary sequence analysis Nature communications High 31953408
2021 Cryo-electron microscopy of the human Scap–Insig-2 complex in the presence of 25-hydroxycholesterol (25HC) at 3.7 Å average resolution revealed that a 25HC molecule is sandwiched between the S4–S6 segments of Scap's sterol-sensing domain and TMs 3 and 4 of Insig-2 in the luminal leaflet of the membrane. Unwinding of the middle of the Scap-S4 segment is critical for 25HC binding and Insig-2 association. Cryo-electron microscopy structural determination Science (New York, N.Y.) High 33446483
2021 CD36, activated by insulin, forms a complex with Insig-2 that disrupts the SCAP–Insig-2 interaction, thereby allowing SREBP1 to translocate from ER to Golgi for processing and activating hepatic de novo lipogenesis. Treatment with 25-hydroxycholesterol or betulin (which enhance SCAP–Insig interaction) reversed the effect of CD36 on SREBP1 cleavage. Co-immunoprecipitation, proximity ligation assay, CD36 liver-specific knockout mice, CD36 overexpression in HepG2 cells, pharmacological rescue with 25HC/betulin Molecular metabolism Medium 34974159
2021 INSIG-1 and INSIG-2 mediate oxysterol-dependent activation of the PERK–eIF2α–ATF4 axis. Oxysterols with high affinity for Insig (27-HC and 25-HC) markedly induce ATF4 protein upregulation, and this is attenuated in INSIG1/2-deficient CHO cells and rescued by either INSIG1 or INSIG2. Binding of 25HC to INSIG is critical for ATF4 induction via PERK–eIF2α activation, promoting cell death through Chop, Chac1, and Trb3. INSIG1/2 double-deficient CHO cells, INSIG1/INSIG2 single knockout in Huh7 cells, genetic rescue, oxysterol treatment, Western blotting for PERK-eIF2α-ATF4 pathway The Journal of biological chemistry Medium 34298014
2024 Eicosapentaenoic acid (EPA), a polyunsaturated fatty acid, inhibits fatty acid synthesis specifically through Insig-2 by activating adenylate cyclase, which induces PKA to phosphorylate serine-106 in Insig-2. Phospho-Insig-2 selectively blocks proteolytic processing of SREBP-1 (not SREBP-2), thereby specifically blocking fatty acid synthesis without affecting cholesterol synthesis. Insig-1 lacks serine-106 and is not phosphorylated at this site. EPA inhibition was reduced by S106A mutation of Insig-2, by PKA inhibitor KT5720, and was absent in fibroblasts lacking Insig-2. In vitro PKA phosphorylation assay, site-directed mutagenesis (S106A), PKA inhibitor treatment, Insig-2-deficient human fibroblasts, SREBP-1 and SREBP-2 processing assays in human fibroblasts and rat hepatocytes Proceedings of the National Academy of Sciences of the United States of America High 39145929
2017 miR-96 directly targets the 3' UTR of INSIG2 (but not INSIG1) and reduces Insig-2 protein levels, resulting in increased nuclear SREBP-1 and SREBP-2 forms and upregulation of their target gene mRNAs. This was demonstrated in INSIG1 knockout human fibroblasts to isolate the Insig-2-specific effect. 3' UTR reporter assays, miR-96 overexpression in INSIG1 KO human fibroblasts, Western blotting for SREBP nuclear forms, RT-PCR for target genes Animal cells and systems Medium 30460077
2008 Overexpression of Insig-2 in colon cancer cells localizes to the mitochondria/heavy membrane fraction and associates with conformationally changed Bax protein, suppressing Bax expression and activation upon chemotherapeutic drug treatment, thereby inhibiting apoptosis. Insig-2 overexpression also increased cell proliferation, invasion, and anchorage-independent growth. Insig-2 overexpression in colon cancer cells, subcellular fractionation, co-immunoprecipitation with Bax, apoptosis assays, proliferation and invasion assays International journal of cancer Low 18464289
2008 Overexpression of Insig-2 in 3T3-L1 cells (via pEGFP-C3-insig2) results in expression of the fusion protein in the endoplasm and down-regulation of adiponectin mRNA and AP2 mRNA transcription, suggesting Insig-2 influences fat metabolism gene expression in preadipocytes. Eukaryotic expression plasmid construction, lipofectamine transfection, RT-PCR for downstream gene expression, fluorescence microscopy Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology Low 17428382
2018 Hepatic mTOR–AKT2–Insig-2a signaling contributes to the improvement of hepatic steatosis after Roux-en-Y Gastric Bypass (RYGB). Adenovirus-mediated S6K1 overexpression suppressed AKT2 while stimulating Insig-2a expression, and inhibited SREBP-1c and downstream lipogenic genes, reducing lipid deposition in hepatocytes. RYGB enhanced mTOR activity and Insig-2a while decreasing AKT2 and lipogenic pathways. Diet-induced obese mouse model, RYGB surgery, rapamycin treatment, Ad-S6K1 adenovirus infusion, Western blotting, primary hepatocyte oleic acid loading Biochimica et biophysica acta. Molecular basis of disease Low 30562559
2017 Overexpression of Insig-2 in adipose-derived stem cells (ASCs) suppresses atypical antipsychotic (clozapine/olanzapine/risperidone)-induced SREBP-1 activation and downstream lipid biosynthesis gene expression during adipogenic differentiation. AAP treatment reduces endogenous Insig-2 protein, which can be reversed by Insig-2 transfection. Insig-2 plasmid transfection in ASCs, Western blotting for SREBP-1 and lipid biosynthesis genes, adipogenic differentiation induction Scientific reports Low 28883496
2024 INSIG2 is identified as a vulnerability factor for HBV-integrated hepatoma cells. siRNA-mediated INSIG2 knockdown or CRISPR deletion impairs cell proliferation specifically in HBV-integrated HepG2.2.15 cells but not in parental HepG2 cells. This effect involves suppression of cell cycle and DNA replication pathways, downregulation of CDK2, and delayed G1-to-S transition. CDK2 inhibitor blocked the rescue, placing INSIG2 upstream of CDK2 in HBV-integrated hepatoma cell cycle progression. Genome-wide CRISPR loss-of-function screen, siRNA knockdown, CRISPR deletion, CDK2 inhibitor treatment, cell cycle analysis, co-siRNA rescue with HBV siRNA Cancer science Medium 38287498

Source papers

Stage 0 corpus · 79 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Insig-2, a second endoplasmic reticulum protein that binds SCAP and blocks export of sterol regulatory element-binding proteins. Proceedings of the National Academy of Sciences of the United States of America 444 12242332
2003 Liver-specific mRNA for Insig-2 down-regulated by insulin: implications for fatty acid synthesis. Proceedings of the National Academy of Sciences of the United States of America 247 12624180
2021 CD36 promotes de novo lipogenesis in hepatocytes through INSIG2-dependent SREBP1 processing. Molecular metabolism 164 34974159
2007 The association of a SNP upstream of INSIG2 with body mass index is reproduced in several but not all cohorts. PLoS genetics 115 17465681
2005 Integrating QTL and high-density SNP analyses in mice to identify Insig2 as a susceptibility gene for plasma cholesterol levels. Genomics 109 16126366
2017 Hypoxia-inducible factor 1α activates insulin-induced gene 2 (Insig-2) transcription for degradation of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase in the liver. The Journal of biological chemistry 95 28416613
2008 Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? Molecular psychiatry 91 18195716
2008 Assessing gene-treatment interactions at the FTO and INSIG2 loci on obesity-related traits in the Diabetes Prevention Program. Diabetologia 84 18839134
2021 A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols. Science (New York, N.Y.) 78 33446483
2010 Association of HTR2C, but not LEP or INSIG2, genes with antipsychotic-induced weight gain in a German sample. Pharmacogenomics 68 20504252
2005 Isolation of sterol-resistant Chinese hamster ovary cells with genetic deficiencies in both Insig-1 and Insig-2. The Journal of biological chemistry 65 15866869
2009 Meta-analysis of the INSIG2 association with obesity including 74,345 individuals: does heterogeneity of estimates relate to study design? PLoS genetics 56 19851442
2006 INSIG-2 promoter polymorphism and obesity related phenotypes: association study in 1428 members of 248 families. BMC medical genetics 52 17137505
2010 Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics. The pharmacogenomics journal 47 20877301
2009 Influence of common variants near INSIG2, in FTO, and near MC4R genes on overweight and the metabolic profile in adolescence: the TRAILS (TRacking Adolescents' Individual Lives Survey) Study. The American journal of clinical nutrition 44 20007308
2007 Regulation of hepatic Insig-2 by the farnesoid X receptor. Molecular endocrinology (Baltimore, Md.) 44 17440045
2007 The common genetic variant upstream of INSIG2 gene is not associated with obesity in Indian population. Clinical genetics 44 17489846
2006 Juxtamembranous aspartic acid in Insig-1 and Insig-2 is required for cholesterol homeostasis. Proceedings of the National Academy of Sciences of the United States of America 43 16606821
2016 Glucagon regulates hepatic lipid metabolism via cAMP and Insig-2 signaling: implication for the pathogenesis of hypertriglyceridemia and hepatic steatosis. Scientific reports 41 27582413
2008 Non-replication of genome-wide based associations between common variants in INSIG2 and PFKP and obesity in studies of 18,014 Danes. PloS one 40 18682847
2007 INSIG2 gene polymorphism is not associated with obesity in Caucasian, Afro-Caribbean and Indian subjects. International journal of obesity (2005) 39 17471297
2004 Identification of a functional vitamin D response element in the murine Insig-2 promoter and its potential role in the differentiation of 3T3-L1 preadipocytes. Molecular endocrinology (Baltimore, Md.) 37 15528275
2008 Association of morbid obesity with FTO and INSIG2 allelic variants. Archives of surgery (Chicago, Ill. : 1960) 34 18347269
2008 INSIG2 polymorphism is neither associated with BMI nor with phenotypes of lipoprotein metabolism. Obesity (Silver Spring, Md.) 33 18239574
2008 INSIG2 gene rs7566605 polymorphism is associated with severe obesity in Japanese. Journal of human genetics 33 18615239
2010 Association study of polymorphisms in insulin induced gene 2 (INSIG2) with antipsychotic-induced weight gain in European and African-American schizophrenia patients. Human psychopharmacology 31 20373477
2011 Influence of common variants in FTO and near INSIG2 and MC4R on growth curves for adiposity in African- and European-American youth. European journal of epidemiology 30 21544599
2007 Evidence of an influence of a polymorphism near the INSIG2 on weight loss during a lifestyle intervention in obese children and adolescents. Diabetes 30 18003761
2008 Association of the common genetic variant upstream of INSIG2 gene with obesity related phenotypes in Chinese children and adolescents. Biomedical and environmental sciences : BES 28 19263810
2016 Pig fatness in relation to FASN and INSIG2 genes polymorphism and their transcript level. Molecular biology reports 25 26965892
2011 Polymorphisms of INSIG2, MC4R, and LEP are associated with obesity- and metabolic-related traits in schizophrenic patients. Journal of clinical psychopharmacology 23 22020349
2008 The single nucleotide polymorphism upstream of insulin-induced gene 2 ( INSIG2) is associated with the prevalence of hypercholesterolaemia, but not with obesity, in Japanese American women. The British journal of nutrition 23 18570692
2017 Overexpression of Insig-2 inhibits atypical antipsychotic-induced adipogenic differentiation and lipid biosynthesis in adipose-derived stem cells. Scientific reports 21 28883496
2010 Characterization of the human insulin-induced gene 2 (INSIG2) promoter: the role of Ets-binding motifs. The Journal of biological chemistry 21 20145255
2008 No association between INSIG2 Gene rs7566605 polymorphism and being overweight in Japanese population. Obesity (Silver Spring, Md.) 21 18223638
2008 INSIG2 gene polymorphism is associated with increased subcutaneous fat in women and poor response to resistance training in men. BMC medical genetics 21 19105843
2020 Competitive oxidation and ubiquitylation on the evolutionarily conserved cysteine confer tissue-specific stabilization of Insig-2. Nature communications 19 31953408
2012 INSIG2 variants, dietary patterns and metabolic risk in Samoa. European journal of clinical nutrition 19 22968099
2009 Absence of association between the INSIG2 gene polymorphism (rs7566605) and obesity in the European Youth Heart Study (EYHS). Obesity (Silver Spring, Md.) 15 19197262
2008 Insig2 is associated with colon tumorigenesis and inhibits Bax-mediated apoptosis. International journal of cancer 15 18464289
2015 Association of INSIG2 polymorphism with overweight and LDL in children. PloS one 13 25607990
2009 Common INSIG2 polymorphisms are associated with age-related changes in body size and high-density lipoprotein cholesterol from young adulthood to middle age. Metabolism: clinical and experimental 13 20045156
2011 Insig2 is overexpressed in pancreatic cancer and its expression is induced by hypoxia. Cancer science 12 21443541
2009 The INSIG2 rs7566605 genetic variant does not play a major role in obesity in a sample of 24,722 individuals from four cohorts. BMC medical genetics 12 19523229
2009 A tagging SNP in INSIG2 is associated with obesity-related phenotypes among Samoans. BMC medical genetics 12 20028541
2009 Lack of association between a common polymorphism near the INSIG2 gene and BMI, myocardial infarction, and cardiovascular risk factors. Obesity (Silver Spring, Md.) 11 19197259
2008 Potential association of INSIG2 rs7566605 polymorphism with body weight in a Chinese subpopulation. European journal of human genetics : EJHG 11 18270535
2008 The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study. Thrombosis and haemostasis 11 18989534
2014 Association of INSIG2 rs9308762 with ALT level independent of BMI. Journal of pediatric gastroenterology and nutrition 10 24458218
2017 Common Genetic Variant of insig2 Gene rs7566605 Polymorphism Is Associated with Severe Obesity in North India. Iranian biomedical journal 9 28160769
2016 Four novel polymorphisms of buffalo INSIG2 gene are associated with milk production traits in Chinese buffaloes. Molecular and cellular probes 9 27687066
2011 Influence of obesity-susceptibility loci (MC4R and INSIG2) on the outcome of weight loss and amelioration of co-morbidity in obese patients treated by a gastric-bypass. Bulletin de la Societe des sciences medicales du Grand-Duche de Luxembourg 9 22272442
2024 Phosphorylation of Insig-2 mediates inhibition of fatty acid synthesis by polyunsaturated fatty acids. Proceedings of the National Academy of Sciences of the United States of America 8 39145929
2021 Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2α-ATF4 axis. The Journal of biological chemistry 8 34298014
2011 Two candidate genes (FTO and INSIG2) for fat accumulation in four canids: chromosome mapping, gene polymorphisms and association studies of body and skin weight of red foxes. Cytogenetic and genome research 8 21846970
2010 An INSIG2 polymorphism affects glucose homeostasis in Sardinian obese children and adolescents. Annals of human genetics 8 20645959
2017 Regulation of INSIG2 by microRNA-96. Animal cells and systems 7 30460077
2014 Controversial association results for INSIG2 on body mass index may be explained by interactions with age and with MC4R. European journal of human genetics : EJHG 7 24518831
2013 Isolation, sequence characterization, and tissue transcription profiles of two novel buffalo genes: INSIG1 and INSIG2. Tropical animal health and production 7 23860946
2010 INSIG2 promoter variant, obesity markers and lipid parameters - No association in a large Slavonic Caucasian population sample. Folia biologica 7 20653998
2010 The INSIG2 rs7566605 polymorphism is not associated with body mass index and breast cancer risk. BMC cancer 7 20955599
2024 Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells. Cancer science 6 38287498
2021 Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women. Cancer medicine 6 33586351
2018 Hepatic mTOR-AKT2-Insig2 signaling pathway contributes to the improvement of hepatic steatosis after Roux-en-Y Gastric Bypass in mice. Biochimica et biophysica acta. Molecular basis of disease 6 30562559
2017 INSIG2 rs7566605 single nucleotide variant and global DNA methylation index levels are associated with weight loss in a personalized weight reduction program. Molecular medicine reports 6 29138870
2014 Genetic associations of the INSIG2 rs7566605 polymorphism with obesity-related metabolic traits in Malaysian Malays. Genetics and molecular research : GMR 6 25062423
2010 Intramembrane glycine mediates multimerization of Insig-2, a requirement for sterol regulation in Chinese hamster ovary cells. Journal of lipid research 6 19617589
2011 INSIG2 G-102A promoter variant exhibits context-dependent effect on HDL-cholesterol levels but not on BMI in Caucasians. Folia biologica 5 21978759
2009 Association analyses of the INSIG2 polymorphism in the obesity and cholesterol levels of Korean populations. BMC medical genetics 5 19772594
2013 Association between intramuscular fat in the arm following arm training and INSIG2. Scandinavian journal of medicine & science in sports 4 23941145
2013 FTO and INSIG2 Genotyping Combined with Metabolic and Anthropometric Phenotyping of Morbidly Obese Patients. Molecular syndromology 4 24167462
2021 Associations of the SREBF2 Gene and INSIG2 Polymorphisms with Obesity and Dyslipidemia in Thai Psychotic Disorder Patients Treated with Risperidone. Journal of personalized medicine 3 34683084
2019 INSIG2 gene polymorphism is associated with higher blood pressure and triglyceride levels in Brazilian obese subjects. Nutricion hospitalaria 2 31144980
2010 [Association of abnormal lipid metabolism with INSIG2 gene variant in overweight and obese children]. Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi 2 21163096
2009 INSIG2 is Associated with Lower Gain in Weight-for-Length Between Birth and Age 6 Months. Clinical medicine. Pediatrics 2 20354568
2009 Upstream genetic variant near INSIG2, influences response to carnitine supplementation in bipolar patients with valproate-induced weight gain. Acta neuropsychiatrica 2 26953751
2008 [Effect of different glucose concentrations on the expressions of insig-1 and insig-2 mRNA during the differentiation of 3T3-L1 cells]. Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 2 18382059
2010 Association of an INSIG2 obesity allele with cardiovascular phenotypes is gender and age dependent. BMC cardiovascular disorders 1 20920244
2007 [Construction and expression of fusion gene eukaryotic expression plasmid of pEGFP-C(3)-insig2 and its influence to downstream genes]. Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology 0 17428382

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