INSIG1

insulin induced gene 1

Basic information

Region (hg38): 7:155297775-155310235

Links

ENSG00000186480 ∙ NCBI:3638 ∙ OMIM:602055 ∙ HGNC:6083 ∙ Uniprot:O15503 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the INSIG1 gene.

• Inborn genetic diseases (9 variants)
• not provided (1 variants)

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	1
missense			9			9
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	9	0	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)
7-155298376-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 (Aug 17, 2022)
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 (May 27, 2022)
7-155302775-C-T		not specified	Uncertain significance (Sep 16, 2021)
7-155302843-T-C			Benign (Aug 16, 2018)

GnomAD

Source: gnomAD

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: dbNSFP

• 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