INSIG2

insulin induced gene 2

Basic information

Region (hg38): 2:118088452-118110997

Links

ENSG00000125629

∙ NCBI:51141 ∙ OMIM:608660 ∙ HGNC:20452 ∙ Uniprot:Q9Y5U4 ∙ 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 INSIG2 gene.

not_specified (17 variants)
not_provided (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the INSIG2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000016133.4. Only rare variants are included in the table.

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.

Effect	PathogenicP	Likely pathogenicLP	VUSVUS	Likely benignLB	BenignB	Sum
synonymous					2 clinvar	2
missense			17 clinvar			17
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	17	0	2

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
INSIG2	protein_coding	protein_coding	ENST00000245787	5	22546

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0600	0.925	125731	0	10	125741	0.0000398

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.84	66	123	0.535	0.00000612	1446
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000529	0.0000527
Middle Eastern	0.00	0.00
South Asian	0.000132	0.000131
Other	0.00	0.00

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. Seems to regulate the ubiquitin-mediated proteasomal degradation of HMGCR. {ECO:0000269|PubMed:12242332, ECO:0000269|PubMed:16606821}.;
Pathway: Sterol Regulatory Element-Binding Proteins (SREBP) signalling (Consensus)

Recessive Scores

pRec: 0.205

Intolerance Scores

loftool: 0.235
rvis_EVS: -0.21
rvis_percentile_EVS: 38.28

Haploinsufficiency Scores

pHI: 0.251
hipred: Y
hipred_score: 0.713
ghis: 0.643

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.985

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Insig2
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); liver/biliary system phenotype; homeostasis/metabolism phenotype;

Gene ontology

Biological process: triglyceride metabolic process;cholesterol biosynthetic process;negative regulation of steroid biosynthetic process;response to insulin;SREBP signaling pathway;inner ear morphogenesis;middle ear morphogenesis;negative regulation of fatty acid biosynthetic process;roof of mouth development;cranial suture morphogenesis;response to fatty acid
Cellular component: endoplasmic reticulum membrane;SREBP-SCAP-Insig complex
Molecular function: protein binding;transcription factor binding