IRS2
protein-codinginsulin receptor substrate 2, the group of Pleckstrin homology domain containing
Gene summary
This gene encodes the insulin receptor substrate 2, a cytoplasmic signaling molecule that mediates effects of insulin, insulin-like growth factor 1, and other cytokines by acting as a molecular adaptor between diverse receptor tyrosine kinases and downstream effectors. The product of this gene is phosphorylated by the insulin receptor tyrosine kinase upon receptor stimulation, as well as by an interleukin 4 receptor-associated kinase in response to IL4 treatment. [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 ~33.9 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 IRS2 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_003749.3. 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 | 3 | 11 | 8 | 22 | ||
| missense | 122 | 4 | 2 | 128 | ||
| nonsense | 3 | 3 | ||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| Total | 0 | 0 | 129 | 15 | 10 | 154 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_003740.2 | 2 | MANE Select | |
| Ensembl | ENSP00000365016.3 | 2 | MANE Select | |
| Ensembl | ENSP00000810604.1 | 2 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Regulation of lipolysis in adipocytes - Homo sapiens (human)
- Adipocytokine signaling pathway - Homo sapiens (human)
- Type II diabetes mellitus - Homo sapiens (human)
- Insulin resistance - Homo sapiens (human)
- Non-alcoholic fatty liver disease (NAFLD) - Homo sapiens (human)
Biological Process
- MAPK cascade
- positive regulation of mesenchymal cell proliferation
- negative regulation of B cell apoptotic process
- glucose metabolic process
- signal transduction
Molecular Function
- Ras guanyl-nucleotide exchange factor activity
- insulin receptor binding
- protein binding
- 1-phosphatidylinositol-3-kinase activity
- protein kinase binding
Cellular Component
- cytosol
- plasma membrane
- protein-containing complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000375856
- Coding exons
- 2
- Length
- 32732
- Individuals with no LoFs
- 123480
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 9
- Defined
- 123489
- p
- 0.0000364
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.53 | 541 | 734 | 0.737 | 0.0000493 | 8303 |
| Missense (PolyPhen) | 158 | 297.51 | 0.53108 | 3244 | ||
| Synonymous | -0.780 | 387 | 368 | 1.05 | 0.0000293 | 2948 |
| Loss of Function | 4.30 | 3 | 27.2 | 0.110 | 0.00000136 | 313 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00020 | 0.00019 | rare |
| 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) | 0.000048 | 0.000045 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0.00018 | 0.00017 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: May mediate the control of various cellular processes by insulin.;
Recessive Scores
- pRec
- 0.753
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- S
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.901
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |