The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by Re... See more...

Aliases for INSIG2 Gene

Aliases for INSIG2 Gene

  • Insulin Induced Gene 2 2 3 5
  • Insulin-Induced Gene 2 Protein 3 4
  • INSIG-2 3 4
  • Insulin Induced Protein 2 3
  • INSIG2 Membrane Protein 3

External Ids for INSIG2 Gene

Previous GeneCards Identifiers for INSIG2 Gene

  • GC02P116766
  • GC02P118752
  • GC02P118949
  • GC02P118941
  • GC02P118562
  • GC02P111173
  • GC02P118846

Summaries for INSIG2 Gene

Entrez Gene Summary for INSIG2 Gene

  • The protein encoded by this gene is highly similar to the protein product encoded by gene INSIG1. Both INSIG1 protein and this protein are endoplasmic reticulum proteins that block the processing of sterol regulatory element binding proteins (SREBPs) by binding to SREBP cleavage-activating protein (SCAP), and thus prevent SCAP from escorting SREBPs to the Golgi. [provided by RefSeq, Jul 2008]

GeneCards Summary for INSIG2 Gene

INSIG2 (Insulin Induced Gene 2) is a Protein Coding gene. Diseases associated with INSIG2 include Dystonia, Dopa-Responsive, Due To Sepiapterin Reductase Deficiency and Leptin Deficiency Or Dysfunction. Among its related pathways are Regulation of cholesterol biosynthesis by SREBP (SREBF) and Metabolism. Gene Ontology (GO) annotations related to this gene include transcription factor binding. An important paralog of this gene is INSIG1.

UniProtKB/Swiss-Prot Summary for INSIG2 Gene

  • Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR.

Gene Wiki entry for INSIG2 Gene

Additional gene information for INSIG2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for INSIG2 Gene

Genomics for INSIG2 Gene

GeneHancer (GH) Regulatory Elements for INSIG2 Gene

Promoters and enhancers for INSIG2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH02J118084 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 514.7 -0.5 -478 6.5 EP300 FOXK2 ZBTB40 ZNF217 ZSCAN5C SIN3A NRF1 POLR2G NCOR1 JUND INSIG2 lnc-CCDC93-10 DDX18 ENSG00000236255 CCDC93 HTR5BP LOC102723413
GH02J118053 Enhancer 1.4 UCNEbase Ensembl ENCODE 20.4 -30.5 -30488 9.3 CTCF SIN3A SP1 EP300 RCOR1 RAD21 TRIM22 BCL11A RELA CBFB CCDC93 INSIG2 HTR5BP ENSG00000235066 DDX18 LOC102723413 lnc-CCDC93-10
GH02J118112 Enhancer 1.2 Ensembl ENCODE dbSUPER 6.5 +24.8 24849 3 ZNF217 TCF12 POLR2G CUX1 EP300 GATAD2B CTBP1 FOXA2 OSR2 NR2F2 HTR5BP CCDC93 INSIG2 HSALNG0018255 lnc-CCDC93-5
GH02J118047 Enhancer 0.9 Ensembl 9 -39.6 -39642 4.4 CTCF JUND FOS EP300 REST RAD21 TRIM22 ATF2 NFYB SMC3 CCDC93 RN7SL111P HTR5BP INSIG2 LOC102723413 lnc-CCDC93-10 ENSG00000235066
GH02J118121 Enhancer 0.9 ENCODE dbSUPER 6.9 +35.2 35218 3.4 CTCF POLR2G EP300 RFX1 ATF2 FOS FOSL2 CEBPB NBN JUN lnc-CCDC93-5 INSIG2 DDX18 HTR5BP HSALNG0018255
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around INSIG2 on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for INSIG2

Top Transcription factor binding sites by QIAGEN in the INSIG2 gene promoter:
  • AML1a
  • AREB6
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • PPAR-alpha
  • RFX1

Genomic Locations for INSIG2 Gene

Genomic Locations for INSIG2 Gene
chr2:118,088,452-118,110,997
(GRCh38/hg38)
Size:
22,546 bases
Orientation:
Plus strand
chr2:118,846,028-118,868,573
(GRCh37/hg19)
Size:
22,546 bases
Orientation:
Plus strand

Genomic View for INSIG2 Gene

Genes around INSIG2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
INSIG2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for INSIG2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for INSIG2 Gene

Proteins for INSIG2 Gene

  • Protein details for INSIG2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y5U4-INSI2_HUMAN
    Recommended name:
    Insulin-induced gene 2 protein
    Protein Accession:
    Q9Y5U4
    Secondary Accessions:
    • A8K5W8
    • Q8TBI8

    Protein attributes for INSIG2 Gene

    Size:
    225 amino acids
    Molecular mass:
    24778 Da
    Quaternary structure:
    • Binds to the SCAP-SREBF2 complex only in the presence of sterols. Interacts with RNF139. Interacts with RNF145 (PubMed:29374057).
    Miscellaneous:
    • Does not require nuclear SREBPs for its expression. When nuclear SREBP activity is low, is the only form of INSIG present in the cell.
    SequenceCaution:
    • Sequence=AAD43048.1; Type=Frameshift; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for INSIG2 Gene

neXtProt entry for INSIG2 Gene

Post-translational modifications for INSIG2 Gene

  • Ubiquitination at Lys216
  • Modification sites at PhosphoSitePlus

Other Protein References for INSIG2 Gene

No data available for DME Specific Peptides for INSIG2 Gene

Domains & Families for INSIG2 Gene

Gene Families for INSIG2 Gene

Human Protein Atlas (HPA):
  • Predicted membrane proteins

Protein Domains for INSIG2 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for INSIG2 Gene

GenScript: Design optimal peptide antigens:
  • Insulin-induced gene 2 protein (INSI2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9Y5U4

UniProtKB/Swiss-Prot:

INSI2_HUMAN :
  • Belongs to the INSIG family.
Family:
  • Belongs to the INSIG family.
genes like me logo Genes that share domains with INSIG2: view

Function for INSIG2 Gene

Molecular function for INSIG2 Gene

UniProtKB/Swiss-Prot Function:
Mediates feedback control of cholesterol synthesis by controlling SCAP and HMGCR. Functions by blocking the processing of sterol regulatory element-binding proteins (SREBPs). Capable of retaining the SCAP-SREBF2 complex in the ER thus preventing it from escorting SREBPs to the Golgi. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR.

Phenotypes From GWAS Catalog for INSIG2 Gene

Gene Ontology (GO) - Molecular Function for INSIG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005515 protein binding IPI 12242332
GO:0008134 transcription factor binding IEA --
genes like me logo Genes that share ontologies with INSIG2: view
genes like me logo Genes that share phenotypes with INSIG2: view

Animal Models for INSIG2 Gene

MGI Knock Outs for INSIG2:

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for INSIG2 Gene

Localization for INSIG2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for INSIG2 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for INSIG2 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 4
extracellular 2
nucleus 2
cytosol 2
golgi apparatus 2
cytoskeleton 1
mitochondrion 1
peroxisome 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for INSIG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005783 endoplasmic reticulum IEA --
GO:0005789 endoplasmic reticulum membrane IEA,TAS --
GO:0016020 membrane IEA --
GO:0016021 integral component of membrane IEA --
GO:0032937 SREBP-SCAP-Insig complex IDA 12242332
genes like me logo Genes that share ontologies with INSIG2: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for INSIG2 Gene

Pathways & Interactions for INSIG2 Gene

genes like me logo Genes that share pathways with INSIG2: view

SIGNOR curated interactions for INSIG2 Gene

Inactivates:
Is inactivated by:

Gene Ontology (GO) - Biological Process for INSIG2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006629 lipid metabolic process IEA --
GO:0006641 triglyceride metabolic process IEA --
GO:0006695 cholesterol biosynthetic process IEA --
GO:0006991 response to sterol depletion IEA --
GO:0008202 steroid metabolic process IEA --
genes like me logo Genes that share ontologies with INSIG2: view

Drugs & Compounds for INSIG2 Gene

(1) Drugs for INSIG2 Gene - From: PharmGKB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
antipsychotics Pharma 0
genes like me logo Genes that share compounds with INSIG2: view

Transcripts for INSIG2 Gene

mRNA/cDNA for INSIG2 Gene

6 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
8 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for INSIG2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7a · 7b · 7c ^ 8
SP1: - -
SP2: -
SP3: - - - -
SP4: -
SP5:
SP6:

Relevant External Links for INSIG2 Gene

GeneLoc Exon Structure for
INSIG2

Expression for INSIG2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for INSIG2 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for INSIG2 Gene

This gene is overexpressed in Heart (64.0).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB and MOPED for INSIG2 Gene



Protein tissue co-expression partners for INSIG2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for INSIG2

SOURCE GeneReport for Unigene cluster for INSIG2 Gene:

Hs.7089

Evidence on tissue expression from TISSUES for INSIG2 Gene

  • Nervous system(4.6)
  • Liver(2.7)
genes like me logo Genes that share expression patterns with INSIG2: view

No data available for mRNA differential expression in normal tissues , mRNA Expression by UniProt/SwissProt and Phenotype-based relationships between genes and organs from Gene ORGANizer for INSIG2 Gene

Orthologs for INSIG2 Gene

This gene was present in the common ancestor of chordates.

Orthologs for INSIG2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia INSIG2 31 30
  • 99.7 (n)
OneToOne
cow
(Bos Taurus)
Mammalia INSIG2 31 30
  • 96 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia INSIG2 31
  • 95 (a)
OneToOne
dog
(Canis familiaris)
Mammalia INSIG2 31 30
  • 94.52 (n)
OneToOne
mouse
(Mus musculus)
Mammalia Insig2 17 31 30
  • 87.41 (n)
rat
(Rattus norvegicus)
Mammalia Insig2 30
  • 86.07 (n)
chicken
(Gallus gallus)
Aves INSIG2 31
  • 91 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia INSIG2 31
  • 84 (a)
OneToOne
zebrafish
(Danio rerio)
Actinopterygii insig2 31 30
  • 67.58 (n)
OneToOne
Species where no ortholog for INSIG2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • platypus (Ornithorhynchus anatinus)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • tropical clawed frog (Silurana tropicalis)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for INSIG2 Gene

ENSEMBL:
Gene Tree for INSIG2 (if available)
TreeFam:
Gene Tree for INSIG2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for INSIG2: view image

Paralogs for INSIG2 Gene

Paralogs for INSIG2 Gene

(1) SIMAP similar genes for INSIG2 Gene using alignment to 2 proteins:

  • INSI2_HUMAN
  • F8WCG8_HUMAN
genes like me logo Genes that share paralogs with INSIG2: view

Variants for INSIG2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for INSIG2 Gene

SNP ID Clinical significance and condition Chr 02 pos Variation AA Info Type
770694 Benign: not provided 118,103,297(+) T/C SYNONYMOUS_VARIANT
780834 Benign: not provided 118,107,180(+) A/G SYNONYMOUS_VARIANT,INTRON_VARIANT

Additional dbSNP identifiers (rs#s) for INSIG2 Gene

Structural Variations from Database of Genomic Variants (DGV) for INSIG2 Gene

Variant ID Type Subtype PubMed ID
esv1042101 CNV deletion 17803354
esv1244468 CNV deletion 17803354
esv1527073 CNV deletion 17803354
esv1675960 CNV deletion 17803354
esv21565 CNV loss 19812545
esv2269282 CNV deletion 18987734
esv2596819 CNV deletion 19546169
esv2720611 CNV deletion 23290073
esv3560010 CNV deletion 23714750
esv3560011 CNV deletion 23714750
nsv1114130 CNV deletion 24896259
nsv1153185 CNV deletion 26484159
nsv820793 CNV deletion 20802225
nsv955105 CNV deletion 24416366

Variation tolerance for INSIG2 Gene

Residual Variation Intolerance Score: 51.2% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 0.39; 8.66% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for INSIG2 Gene

Human Gene Mutation Database (HGMD)
INSIG2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
INSIG2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for INSIG2 Gene

Disorders for INSIG2 Gene

MalaCards: The human disease database

(3) MalaCards diseases for INSIG2 Gene - From: DISEASES

- elite association - COSMIC cancer census association via MalaCards

Additional Disease Information for INSIG2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with INSIG2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for INSIG2 Gene

Publications for INSIG2 Gene

  1. Association study of polymorphisms in insulin induced gene 2 (INSIG2) with antipsychotic-induced weight gain in European and African-American schizophrenia patients. (PMID: 20373477) Tiwari AK … Kennedy JL (Human psychopharmacology 2010) 3 23 41 54
  2. Interactions among genetic variants from SREBP2 activating-related pathway on risk of coronary heart disease in Chinese Han population. (PMID: 19740467) Liu X … Gu D (Atherosclerosis 2010) 3 23 41 54
  3. 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? (PMID: 18195716) Le Hellard S … Steen VM (Molecular psychiatry 2009) 3 23 41 54
  4. Association of morbid obesity with FTO and INSIG2 allelic variants. (PMID: 18347269) Chu X … Gerhard GS (Archives of surgery (Chicago, Ill. : 1960) 2008) 3 23 41 54
  5. The INSIG1 gene, not the INSIG2 gene, associated with coronary heart disease: tagSNPs and haplotype-based association study. The Beijing Atherosclerosis Study. (PMID: 18989534) Liu X … Gu D (Thrombosis and haemostasis 2008) 3 23 41 54

Products for INSIG2 Gene

Sources for INSIG2 Gene