INSIG1
insulin induced gene 1
Basic information
Region (hg38): 7:155297776-155310235
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the INSIG1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | |||||
| missense | 13 | 14 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 13 | 1 | 1 |
Variants in INSIG1
This is a list of pathogenic ClinVar variants found in the INSIG1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 7-155298299-A-G | not specified | Uncertain significance (Jan 03, 2022) | ||
| 7-155298302-A-C | not specified | Uncertain significance (May 09, 2024) | ||
| 7-155298322-T-A | not specified | Uncertain significance (Dec 04, 2024) | ||
| 7-155298328-C-T | not specified | Uncertain significance (Aug 11, 2024) | ||
| 7-155298376-G-A | not specified | Uncertain significance (Oct 26, 2021) | ||
| 7-155298380-C-G | not specified | Uncertain significance (Jun 16, 2023) | ||
| 7-155298385-G-A | not specified | Uncertain significance (Nov 17, 2023) | ||
| 7-155298386-T-C | not specified | Uncertain significance (Jan 03, 2024) | ||
| 7-155298521-C-G | not specified | Likely benign (Sep 23, 2023) | ||
| 7-155298571-G-T | not specified | Uncertain significance (Sep 14, 2023) | ||
| 7-155298617-T-C | not specified | Uncertain significance (Sep 10, 2024) | ||
| 7-155298642-C-G | not specified | Uncertain significance (Jul 30, 2024) | ||
| 7-155298649-A-G | not specified | Uncertain significance (Apr 22, 2022) | ||
| 7-155301611-A-G | not specified | Uncertain significance (Jun 30, 2023) | ||
| 7-155301638-C-G | not specified | Uncertain significance (Nov 17, 2023) | ||
| 7-155301657-A-G | not specified | Uncertain significance (Feb 27, 2023) | ||
| 7-155302391-G-C | not specified | Uncertain significance (Nov 13, 2024) | ||
| 7-155302775-C-T | not specified | Uncertain significance (Sep 16, 2021) | ||
| 7-155302843-T-C | Benign (Aug 16, 2018) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| INSIG1 | protein_coding | protein_coding | ENST00000340368 | 5 | 12460 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.00128 | 0.867 | 125740 | 0 | 8 | 125748 | 0.0000318 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.90 | 91 | 158 | 0.575 | 0.00000817 | 1775 |
| Missense in Polyphen | 36 | 83.879 | 0.42919 | 931 | ||
| Synonymous | 1.45 | 51 | 66.0 | 0.773 | 0.00000360 | 585 |
| Loss of Function | 1.31 | 6 | 10.6 | 0.567 | 4.54e-7 | 116 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000609 | 0.0000609 |
| Ashkenazi Jewish | 0.0000999 | 0.0000992 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000269 | 0.0000264 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000342 | 0.0000327 |
| Other | 0.000169 | 0.000163 |
dbNSFP
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. Initiates the sterol-mediated ubiquitin-mediated endoplasmic reticulum-associated degradation (ERAD) of HMGCR via recruitment of the reductase to the ubiquitin ligase, AMFR/gp78. May play a role in growth and differentiation of tissues involved in metabolic control. May play a regulatory role during G0/G1 transition of cell growth. {ECO:0000269|PubMed:12202038, ECO:0000269|PubMed:12535518, ECO:0000269|PubMed:16168377, ECO:0000269|PubMed:16399501, ECO:0000269|PubMed:16606821}.;
- Pathway
- Sterol Regulatory Element-Binding Proteins (SREBP) signalling
(Consensus)
Recessive Scores
- pRec
- 0.171
Intolerance Scores
- loftool
- 0.652
- rvis_EVS
- -0.14
- rvis_percentile_EVS
- 42.88
Haploinsufficiency Scores
- pHI
- 0.131
- hipred
- Y
- hipred_score
- 0.671
- ghis
- 0.560
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- E
- gene_indispensability_pred
- N
- gene_indispensability_score
- 0.492
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Insig1
- Phenotype
- cellular phenotype; homeostasis/metabolism phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan); liver/biliary system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span);
Gene ontology
- Biological process
- triglyceride metabolic process;cholesterol biosynthetic process;cell population proliferation;negative regulation of steroid biosynthetic process;SREBP signaling pathway;cellular response to sterol;SREBP-SCAP complex retention in endoplasmic reticulum;inner ear morphogenesis;middle ear morphogenesis;cholesterol homeostasis;negative regulation of fat cell differentiation;negative regulation of fatty acid biosynthetic process;roof of mouth development;cranial suture morphogenesis;negative regulation of protein exit from endoplasmic reticulum;negative regulation of cargo loading into COPII-coated vesicle
- Cellular component
- endoplasmic reticulum;endoplasmic reticulum membrane;SREBP-SCAP-Insig complex
- Molecular function
- protein binding