IRS2

insulin receptor substrate 2, the group of Pleckstrin homology domain containing

Basic information

Region (hg38): 13:109752694-109786583

Links

ENSG00000185950 ∙ NCBI:8660 ∙ OMIM:600797 ∙ HGNC:6126 ∙ Uniprot:Q9Y4H2 ∙ 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 IRS2 gene.

• Inborn genetic diseases (41 variants)
• not provided (20 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IRS2 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				10	6	16
missense			40	3	2	45
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	40	13	8

Variants in IRS2

This is a list of pathogenic ClinVar variants found in the IRS2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
13-109782071-T-C			Uncertain significance (-)
13-109782120-C-T		not specified	Uncertain significance (May 17, 2023)
13-109782129-G-A		not specified	Uncertain significance (Oct 12, 2021)
13-109782266-C-A			Benign (Dec 31, 2019)
13-109782296-T-C		not specified	Uncertain significance (Jan 29, 2024)
13-109782382-C-G		not specified	Uncertain significance (Mar 14, 2023)
13-109782389-G-A		not specified	Uncertain significance (May 18, 2022)
13-109782391-G-C			Likely benign (May 24, 2018)
13-109782404-C-T		not specified	Uncertain significance (May 03, 2023)
13-109782442-T-G		IRS2-related disorder	Benign (Jun 02, 2019)
13-109782475-G-A			Likely benign (May 09, 2018)
13-109782489-C-T		not specified	Uncertain significance (Sep 07, 2022)
13-109782530-G-A		not specified	Uncertain significance (Aug 23, 2021)
13-109782602-G-A		not specified	Uncertain significance (Jun 06, 2022)
13-109782727-G-T		not specified	Uncertain significance (May 27, 2022)
13-109782782-G-T		not specified	Uncertain significance (Jun 08, 2022)
13-109782840-A-G		not specified	Uncertain significance (Dec 28, 2022)
13-109782884-C-T		DIABETES, TYPE II, SUSCEPTIBILITY TO • IRS2-related disorder	Benign (Oct 17, 2019)
13-109782908-G-A		not specified	Uncertain significance (Dec 26, 2023)
13-109782929-T-G		not specified	Uncertain significance (Feb 21, 2024)
13-109782945-C-T		not specified	Uncertain significance (Nov 02, 2023)
13-109782955-T-C		IRS2-related disorder	Benign/Likely benign (Dec 31, 2019)
13-109782957-G-C		not specified	Uncertain significance (Aug 16, 2022)
13-109782961-C-T			Benign (Dec 31, 2019)
13-109782992-G-C		not specified	Uncertain significance (Apr 07, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IRS2	protein_coding	protein_coding	ENST00000375856	2	32732

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.990	0.00968	123480	0	9	123489	0.0000364

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.53	541	734	0.737	0.0000493	8303
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000202	0.000193
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000482	0.0000451
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.000175	0.000165

dbNSFP

Source: dbNSFP

• Function: FUNCTION: May mediate the control of various cellular processes by insulin.
• Pathway: 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);Longevity regulating pathway - multiple species - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);FoxO signaling pathway - Homo sapiens (human);AMPK signaling pathway - Homo sapiens (human);Longevity regulating pathway - Homo sapiens (human);MicroRNAs in cancer - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Insulin signaling pathway - Homo sapiens (human);Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics;Leucine Stimulation on Insulin Signaling;Insulin Signalling;IGF-Core;Prolactin Signaling Pathway;Adipogenesis;Brain-Derived Neurotrophic Factor (BDNF) signaling pathway;Alpha 6 Beta 4 signaling pathway;JAK-STAT;Farnesoid X Receptor Pathway;Nuclear Receptors Meta-Pathway;Transcription factor regulation in adipogenesis;IL-4 Signaling Pathway;Angiopoietin Like Protein 8 Regulatory Pathway;Focal Adhesion-PI3K-Akt-mTOR-signaling pathway;Leptin Insulin Overlap;Insulin Signaling;EPO Receptor Signaling;Interferon type I signaling pathways;Developmental Biology;Disease;Signal Transduction;Growth hormone receptor signaling;Cytokine Signaling in Immune system;Alpha6Beta4Integrin;IRS activation;Signal attenuation;PI3K Cascade;SOS-mediated signalling;IRS-mediated signalling;Insulin receptor signalling cascade;Signaling by Insulin receptor;Immune System;insulin Mam;Signaling by NTRK1 (TRKA);Signaling by NTRKs;BDNF;EGFR1;PI3K/AKT activation;RAF/MAP kinase cascade;MAPK1/MAPK3 signaling;MAPK family signaling cascades;PIP3 activates AKT signaling;IL2;Signaling by Leptin;Signaling events regulated by Ret tyrosine kinase;IL2-mediated signaling events;PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling;Negative regulation of the PI3K/AKT network;IL4;EPO signaling pathway;RET signaling;Axon guidance;Leptin;Constitutive Signaling by Aberrant PI3K in Cancer;PI3K/AKT Signaling in Cancer;IRS-related events triggered by IGF1R;IGF1R signaling cascade;IL-7;Signaling by Receptor Tyrosine Kinases;Intracellular signaling by second messengers;Diseases of signal transduction;IGF1 pathway;IL4-mediated signaling events;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R);IL-13 signaling;insulin (Consensus)

Recessive Scores

• pRec: 0.753

Haploinsufficiency Scores

• pHI: 0.623
• ghis: 0.424

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: S
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.901

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Irs2
• 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); endocrine/exocrine gland phenotype; cellular phenotype; homeostasis/metabolism phenotype; muscle phenotype; normal 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); reproductive system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); pigmentation phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); liver/biliary system phenotype; immune system phenotype; renal/urinary system phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Gene ontology

• Biological process: MAPK cascade;positive regulation of mesenchymal cell proliferation;negative regulation of B cell apoptotic process;glucose metabolic process;signal transduction;axon guidance;brain development;cell population proliferation;positive regulation of cell population proliferation;insulin receptor signaling pathway;response to glucose;negative regulation of plasma membrane long-chain fatty acid transport;positive regulation of glucose metabolic process;positive regulation of phosphatidylinositol 3-kinase signaling;regulation of lipid metabolic process;positive regulation of cell migration;mammary gland development;positive regulation of B cell proliferation;positive regulation of fatty acid beta-oxidation;positive regulation of insulin secretion;cellular response to insulin stimulus;negative regulation of kinase activity;phosphatidylinositol-3-phosphate biosynthetic process;interleukin-7-mediated signaling pathway;positive regulation of glycogen biosynthetic process;positive regulation of glucose import;positive regulation of Ras protein signal transduction;phosphatidylinositol phosphorylation;phosphatidylinositol-mediated signaling;positive regulation of protein kinase B signaling;lipid homeostasis;cellular response to glucose stimulus
• Cellular component: cytosol;plasma membrane;protein-containing complex
• Molecular function: Ras guanyl-nucleotide exchange factor activity;insulin receptor binding;protein binding;1-phosphatidylinositol-3-kinase activity;protein kinase binding;protein phosphatase binding;protein domain specific binding;phosphatidylinositol 3-kinase binding;phosphatidylinositol-4,5-bisphosphate 3-kinase activity;14-3-3 protein binding