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INSIG2 insulin induced gene 2 [ Homo sapiens (human) ]

Gene ID: 51141, updated on 25-Nov-2025
Official Symbol
INSIG2provided by HGNC
Official Full Name
insulin induced gene 2provided by HGNC
Primary source
HGNC:HGNC:20452
See related
Ensembl:ENSG00000125629 MIM:608660; AllianceGenome:HGNC:20452
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
INSIG-2
Summary
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]
Expression
Ubiquitous expression in liver (RPKM 12.3), lung (RPKM 10.5) and 25 other tissues See more
Orthologs
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See INSIG2 in Genome Data Viewer
Location:
2q14.1-q14.2
Exon count:
7
Annotation release Status Assembly Chr Location
RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (118088471..118110997)
RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (118521717..118544171)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (118846047..118868573)

Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC102723413 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16438 Neighboring gene uncharacterized LOC107985940 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16439 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16440 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:118873325-118874524 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr2:118880595-118881794 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16441 Neighboring gene uncharacterized LOC124907879 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:118899713-118900386 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16442 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16443 Neighboring gene testis associated oncogenic lncRNA

Go to nucleotide: Graphics FASTA GenBank

  • Project title: Tissue-specific circular RNA induction during human fetal development
  • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
  • BioProject: PRJNA270632
  • Publication: PMID 26076956
  • Analysis date: Mon Apr 2 22:54:59 2018

Related articles in PubMed

  1. [Association of abnormal lipid metabolism with INSIG2 gene variant in overweight and obese children]. Wang HJ, et al. Zhonghua Liu Xing Bing Xue Za Zhi, 2010 Jun. PMID 21163096
  2. Insulin-induced gene 2 involvement in human adipocyte metabolism and body weight regulation. Krapivner S, et al. J Clin Endocrinol Metab, 2008 May. PMID 18319320
  3. Association of INSIG2 rs9308762 with ALT level independent of BMI. Guan L, et al. J Pediatr Gastroenterol Nutr, 2014 Feb. PMID 24458218
  4. Insig2 is associated with colon tumorigenesis and inhibits Bax-mediated apoptosis. Li CG, et al. Int J Cancer, 2008 Jul 15. PMID 18464289, Free PMC Article
  5. Association between intramuscular fat in the arm following arm training and INSIG2. Popadic Gacesa JZ, et al. Scand J Med Sci Sports, 2014 Dec. PMID 23941145

See all (118) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.
    Title: Genome-wide loss-of-function genetic screen identifies INSIG2 as the vulnerability of hepatitis B virus-integrated hepatoma cells.
  2. Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior.
    Title: Insulin-induced gene 2 expression is associated with cervical adenocarcinoma malignant behavior.
  3. Structural basis for sterol sensing by Scap and Insig.
    Title: Structural basis for sterol sensing by Scap and Insig.
  4. Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2alpha-ATF4 axis.
    Title: Insulin-induced genes INSIG1 and INSIG2 mediate oxysterol-dependent activation of the PERK-eIF2α-ATF4 axis.
  5. Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study.
    Title: Association of CNR1 and INSIG2 polymorphisms with antipsychotics-induced weight gain: a prospective nested case-control study.
  6. Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.
    Title: Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.
  7. A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
    Title: A structure of human Scap bound to Insig-2 suggests how their interaction is regulated by sterols.
  8. The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus.
    Title: The CC Genotype of Insulin-Induced Gene 2 rs7566605 Is a Protective Factor of Hypercholesteremia Susceptible to Mild Cognitive Impairment, Especially to the Executive Function of Patients with Type 2 Diabetes Mellitus.
  9. the gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis; findings highlight the importance of the protein kinase activity of PCK1 in the activation of SREBPs, lipogenesis and the development of hepatocellular carcinoma
    Title: The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.
  10. polymorphism rs7566605 of the INSIG2 gene is associated with higher triglycerides levels and blood pressure values, which are also considered as risk factors for the development of metabolic syndrome
    Title: INSIG2 gene polymorphism is associated with higher blood pressure and triglyceride levels in Brazilian obese subjects.
Submit: New GeneRIF Correction See all GeneRIFs (85)

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

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels.
EBI GWAS Catalog
Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture.
EBI GWAS Catalog

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Clone Names

  • MGC26273

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables lipid binding IEA
Inferred from Electronic Annotation
more info
  
enables oxysterol binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein sequestering activity IDA
Inferred from Direct Assay
more info
 PubMed 
Process Evidence Code Pubs
involved_in SREBP signaling pathway IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in SREBP signaling pathway IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in SREBP-SCAP complex retention in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in SREBP-SCAP complex retention in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in cellular response to insulin stimulus IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cholesterol biosynthetic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in cholesterol biosynthetic process IDA
Inferred from Direct Assay
more info
 PubMed 
acts_upstream_of_or_within cholesterol biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cholesterol metabolic process IEA
Inferred from Electronic Annotation
more info
  
involved_in cholesterol metabolic process NAS
Non-traceable Author Statement
more info
 PubMed 
acts_upstream_of_or_within cranial suture morphogenesis IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within inner ear morphogenesis IEA
Inferred from Electronic Annotation
more info
  
involved_in lipid metabolic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within middle ear morphogenesis IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within negative regulation of fatty acid biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within negative regulation of steroid biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
involved_in regulation of transcription by RNA polymerase II NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in response to fatty acid IEA
Inferred from Electronic Annotation
more info
  
involved_in response to insulin IEA
Inferred from Electronic Annotation
more info
  
involved_in response to lipid IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within response to sterol depletion IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within roof of mouth development IEA
Inferred from Electronic Annotation
more info
  
involved_in steroid metabolic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within sterol biosynthetic process IEA
Inferred from Electronic Annotation
more info
  
acts_upstream_of_or_within triglyceride metabolic process IEA
Inferred from Electronic Annotation
more info
  
Component Evidence Code Pubs
part_of SREBP-SCAP-Insig complex IBA
Inferred from Biological aspect of Ancestor
more info
  
part_of SREBP-SCAP-Insig complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of SREBP-SCAP-Insig complex NAS
Non-traceable Author Statement
more info
 PubMed 
is_active_in endoplasmic reticulum IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endoplasmic reticulum IDA
Inferred from Direct Assay
more info
 PubMed 
is_active_in endoplasmic reticulum membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in endoplasmic reticulum membrane IEA
Inferred from Electronic Annotation
more info
  
located_in endoplasmic reticulum membrane NAS
Non-traceable Author Statement
more info
 PubMed 
located_in endoplasmic reticulum membrane TAS
Traceable Author Statement
more info
  
Preferred Names
insulin-induced gene 2 protein
Names
INSIG2 membrane protein
insulin induced protein 2

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

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

mRNA and Protein(s)

  1. NM_001321329.2 → NP_001308258.1  insulin-induced gene 2 protein isoform a

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) and variant 1 both encode the same isoform (a).
    Source sequence(s)
    AC009303, AF527632, AW264638, BE888848
    Consensus CDS
    CCDS2122.1
    UniProtKB/Swiss-Prot
    A8K5W8, Q8TBI8, Q9Y5U4
    Related
    ENSP00000534831.1, ENST00000864772.1
    Conserved Domains (1) summary
    pfam07281
    Location:31 → 211
    INSIG; Insulin-induced protein (INSIG)

  2. NM_001321330.2 → NP_001308259.1  insulin-induced gene 2 protein isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) and variants 4 and 5 all encode the same isoform (b).
    Source sequence(s)
    AC009303, AF527632, AW264638, DC364733, HY053967
    UniProtKB/TrEMBL
    B4DQ23
    Conserved Domains (1) summary
    pfam07281
    Location:1 → 103
    INSIG; Insulin-induced protein (INSIG)

  3. NM_001321331.2 → NP_001308260.1  insulin-induced gene 2 protein isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) and variants 3 and 5 all encode the same isoform (b).
    Source sequence(s)
    AC009303, AF527632, AW264638, BX647805, HY053967
    UniProtKB/TrEMBL
    B4DQ23
    Related
    ENST00000485520.5
    Conserved Domains (1) summary
    pfam07281
    Location:1 → 103
    INSIG; Insulin-induced protein (INSIG)

  4. NM_001321332.2 → NP_001308261.1  insulin-induced gene 2 protein isoform b

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) and variants 3 and 4 all encode the same isoform (b).
    Source sequence(s)
    AC009303, AF527632, AW264638, BE888848, BX647805
    UniProtKB/TrEMBL
    B4DQ23
    Conserved Domains (1) summary
    pfam07281
    Location:1 → 103
    INSIG; Insulin-induced protein (INSIG)

  5. NM_001321333.2 → NP_001308262.1  insulin-induced gene 2 protein isoform c

    Status: REVIEWED

    Source sequence(s)
    AC009303, AF527632, AK021692, AW264638, HY053967
    UniProtKB/Swiss-Prot
    Q9Y5U4
    Conserved Domains (1) summary
    pfam07281
    Location:1 → 67
    INSIG; Insulin-induced protein (INSIG)

  6. NM_016133.4 → NP_057217.2  insulin-induced gene 2 protein isoform a

    See identical proteins and their annotated locations for NP_057217.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) and variant 2 both encode the same isoform (a).
    Source sequence(s)
    AC009303, AF527632, AW264638, HY053967
    Consensus CDS
    CCDS2122.1
    UniProtKB/Swiss-Prot
    A8K5W8, Q8TBI8, Q9Y5U4
    Related
    ENSP00000245787.4, ENST00000245787.9
    Conserved Domains (1) summary
    pfam07281
    Location:31 → 211
    INSIG; Insulin-induced protein (INSIG)

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    118088471..118110997
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047444640.1 → XP_047300596.1  insulin-induced gene 2 protein isoform X1

    UniProtKB/Swiss-Prot
    A8K5W8, Q8TBI8, Q9Y5U4
    Related
    ENSP00000534834.1, ENST00000864775.1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    118521717..118544171
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054342404.1 → XP_054198379.1  insulin-induced gene 2 protein isoform X1

    UniProtKB/Swiss-Prot
    A8K5W8, Q8TBI8, Q9Y5U4

  2. XM_054342405.1 → XP_054198380.1  insulin-induced gene 2 protein isoform X1

    UniProtKB/Swiss-Prot
    A8K5W8, Q8TBI8, Q9Y5U4
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q9Y5U4.2 GenPept UniProtKB/Swiss-Prot:Q9Y5U4

Gene LinkOut

The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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