INSIG2
protein-codinginsulin induced gene 2
Gene 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]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~22.5 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to INSIG2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_016133.4. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 2 | 4 | |||
| missense | 19 | 19 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 25 | 0 | 2 | 27 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_057217.2 | 5 | MANE Select | |
| Ensembl | ENSP00000245787.4 | 5 | MANE Select | |
| RefSeq | NP_001308258.1 | 5 | Standard | |
| RefSeq | NP_001308259.1 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
Biological Process
- triglyceride metabolic process
- cholesterol biosynthetic process
- negative regulation of steroid biosynthetic process
- response to insulin
- SREBP signaling pathway
Molecular Function
- protein binding
- transcription factor binding
Cellular Component
- endoplasmic reticulum membrane
- SREBP-SCAP-Insig complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000245787
- Coding exons
- 5
- Length
- 22546
- Individuals with no LoFs
- 125731
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 10
- Defined
- 125741
- p
- 0.0000398
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.84 | 66 | 123 | 0.535 | 0.00000612 | 1446 |
| Missense (PolyPhen) | 19 | 53.758 | 0.35344 | 669 | ||
| Synonymous | -0.179 | 46 | 44.5 | 1.03 | 0.00000220 | 458 |
| Loss of Function | 2.12 | 4 | 11.9 | 0.337 | 6.34e-7 | 131 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000053 | 0.000053 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- 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. {ECO:0000269|PubMed:12242332, ECO:0000269|PubMed:16606821}.;
Recessive Scores
- pRec
- 0.205
Intolerance Scores
- LoFtool
- 0.235
- RVIS EVS
- -0.21
- RVIS percentile EVS
- 38.28
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.985
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |