IGF2

insulin like growth factor 2, the group of Neuropeptides|MicroRNA protein coding host genes

Basic information

Region (hg38): 11:2129112-2158391

Previous symbols: [ "C11orf43" ]

Links

ENSG00000167244 ∙ NCBI:3481 ∙ OMIM:147470 ∙ HGNC:5466 ∙ Uniprot:P01344 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Silver-Russell syndrome 1 (Definitive), mode of inheritance: Autosomal dominant inheritance with maternal imprinting HP:0012275
• Beckwith-Wiedemann syndrome (Definitive), mode of inheritance: Autosomal dominant inheritance with maternal imprinting HP:0012275
• Silver-Russell syndrome 3 (Strong), mode of inheritance: AD
• Silver-Russell syndrome 3 (Definitive), mode of inheritance: AD
• Silver-Russell syndrome 1 (Definitive), mode of inheritance: AD
• Beckwith-Wiedemann syndrome (Definitive), mode of inheritance: AD
• Silver-Russell syndrome 3 (Definitive), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Silver-Russell syndrome 3	AD	Cardiovascular; Endocrine	Among other findings, response to growth hormone therapy has been described, and awareness may allow early diagnosis and management of this issue; The condition can involve congenital cardiac anomalies, and awareness may allow early management	Cardiovascular; Craniofacial; Endocrine; Genitourinary; Musculoskeletal; Neurologic	26154720; 28489339; 28796236; 28848601; 30400067; 30152198; 31544945
Imprinting has been implicated in the inheritance pattern

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the IGF2 gene.

• not provided (4 variants)
• Silver-Russell syndrome 3 (4 variants)
• Silver-Russell syndrome 1 (1 variants)
• Inborn genetic diseases (1 variants)
• IGF2-related disorder (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the IGF2 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				27	4	31
missense	2	3	46	1	1	53
nonsense	2	4		1		7
start loss			1			1
frameshift	2	3	4			9
inframe indel						0
splice donor/acceptor (+/-2bp)	2					2
splice region	1		2	1		4
non coding			3	2	1	6
Total	8	10	54	31	6

Variants in IGF2

This is a list of pathogenic ClinVar variants found in the IGF2 region.

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

Position	Type	Phenotype	Significance	ClinVar
11-2133009-T-G		IGF2-related disorder	Uncertain significance (Feb 26, 2024)
11-2133009-T-TG		Colorectal cancer	Pathogenic (-)
11-2133011-T-TG			Uncertain significance (Nov 28, 2023)
11-2133012-G-A		Inborn genetic diseases	Uncertain significance (Dec 16, 2022)
11-2133013-G-A			Uncertain significance (Nov 03, 2022)
11-2133017-G-T		not specified	Likely benign (Jan 23, 2024)
11-2133020-GC-G		not specified	Uncertain significance (Feb 19, 2024)
11-2133025-C-A		Inborn genetic diseases	Conflicting classifications of pathogenicity (Nov 18, 2023)
11-2133025-C-G		Inborn genetic diseases	Uncertain significance (Dec 19, 2021)
11-2133026-G-A			Likely benign (Sep 10, 2023)
11-2133027-T-G		Inborn genetic diseases	Uncertain significance (Jun 30, 2021)
11-2133031-C-A		Inborn genetic diseases	Uncertain significance (Jul 27, 2023)
11-2133034-G-T		IGF2-related disorder	Uncertain significance (Sep 16, 2024)
11-2133035-G-C		Inborn genetic diseases	Uncertain significance (Aug 20, 2023)
11-2133040-G-A			Likely pathogenic (Feb 01, 2021)
11-2133050-A-G		IGF2-related disorder	Likely benign (Oct 13, 2023)
11-2133057-AG-A			Uncertain significance (Jul 25, 2023)
11-2133063-C-T			Benign (Jan 28, 2024)
11-2133064-G-A		Inborn genetic diseases	Uncertain significance (Jan 07, 2022)
11-2133070-G-A			Uncertain significance (Jan 27, 2024)
11-2133086-C-T			Likely benign (Mar 02, 2022)
11-2133089-C-T			Benign (Aug 30, 2023)
11-2133091-C-G			Uncertain significance (Apr 14, 2023)
11-2133091-C-T		Inborn genetic diseases	Conflicting classifications of pathogenicity (Jan 08, 2024)
11-2133092-G-A			Likely benign (Oct 16, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
IGF2	protein_coding	protein_coding	ENST00000434045	4	20492

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0441	0.859	0	0	0	0	0.00

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.931	127	160	0.793	0.0000104	1509
Missense in Polyphen		41	55.948	0.73283		492
Synonymous	-0.0161	66	65.8	1.00	0.00000448	503
Loss of Function	1.36	3	6.84	0.439	2.91e-7	81

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)	0.00	0.00
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: The insulin-like growth factors possess growth-promoting activity. Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF-II is influenced by placental lactogen. Also involved in tissue differentiation. Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation (By similarity). In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver (Probable). Acts as a ligand for integrin which is required for IGF2 signaling (PubMed:28873464). {ECO:0000250|UniProtKB:P09535, ECO:0000269|PubMed:28873464, ECO:0000305|PubMed:24593700}.
• Disease: DISEASE: Silver-Russell syndrome (SRS) [MIM:180860]: A clinically heterogeneous condition characterized by severe intrauterine growth retardation, poor postnatal growth, craniofacial features such as a triangular shaped face and a broad forehead, body asymmetry, and a variety of minor malformations. The phenotypic expression changes during childhood and adolescence, with the facial features and asymmetry usually becoming more subtle with age. {ECO:0000269|PubMed:19066168}. Note=The gene represented in this entry is involved in disease pathogenesis. Most of the cases of Silver-Russell syndrome are caused by the epigenetic changes of DNA hypomethylation at the telomeric imprinting control region (ICR1) on chromosome 11p15, involving the H19 and IGF2 genes.; DISEASE: Growth restriction, severe, with distinctive facies (GRDF) [MIM:616489]: A disease characterized by severe prenatal and postnatal growth restriction, facial dysmorphism, and short stature in the presence of normal or slightly elevated growth hormone levels. {ECO:0000269|PubMed:26154720}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: PI3K-Akt signaling pathway - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Ras signaling pathway - Homo sapiens (human);MAPK signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);IGF-Core;Cardiac Progenitor Differentiation;Apoptosis;JAK-STAT;MECP2 and Associated Rett Syndrome;Apoptotic Signaling Pathway;PI3K-Akt Signaling Pathway;Endochondral Ossification;Signal Transduction;Metabolism of proteins;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs);GPCR signaling-G alpha s Epac and ERK;Platelet degranulation ;Response to elevated platelet cytosolic Ca2+;Platelet activation, signaling and aggregation;GPCR signaling-G alpha s PKA and ERK;Hemostasis;Posttranslational regulation of adherens junction stability and dissassembly;GPCR signaling-G alpha i;SHC-related events triggered by IGF1R;IRS-related events triggered by IGF1R;IGF1R signaling cascade;Signaling by Receptor Tyrosine Kinases;Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) (Consensus)

Intolerance Scores

• loftool: 0.0504
• rvis_EVS: -0.27
• rvis_percentile_EVS: 34.32

Haploinsufficiency Scores

• pHI: 0.964
• hipred: N
• hipred_score: 0.285
• ghis: 0.630

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.999

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Igf2
• Phenotype: limbs/digits/tail 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); digestive/alimentary phenotype; vision/eye phenotype; immune system phenotype; skeleton phenotype; renal/urinary system phenotype; embryo phenotype; liver/biliary system phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); 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); hematopoietic 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); endocrine/exocrine gland phenotype; muscle phenotype; craniofacial 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

Zebrafish Information Network

• Gene name: igf2a
• Affected structure: spinal cord neural keel
• Phenotype tag: abnormal
• Phenotype quality: apoptotic

Gene ontology

• Biological process: negative regulation of transcription by RNA polymerase II;skeletal system development;osteoblast differentiation;in utero embryonic development;embryonic placenta development;positive regulation of protein phosphorylation;platelet degranulation;glucose metabolic process;regulation of gene expression by genetic imprinting;regulation of transcription, DNA-templated;multicellular organism development;positive regulation of cell population proliferation;insulin receptor signaling pathway;animal organ morphogenesis;regulation of signaling receptor activity;exocrine pancreas development;regulation of histone modification;insulin receptor signaling pathway via phosphatidylinositol 3-kinase;positive regulation of multicellular organism growth;positive regulation of activated T cell proliferation;positive regulation of catalytic activity;positive regulation of MAPK cascade;cellular protein metabolic process;positive regulation of glycogen biosynthetic process;positive regulation of mitotic nuclear division;positive regulation of transcription by RNA polymerase II;positive regulation of insulin receptor signaling pathway;positive regulation of peptidyl-tyrosine phosphorylation;striated muscle cell differentiation;regulation of muscle cell differentiation;positive regulation of cell division;positive regulation of protein kinase B signaling;embryonic placenta morphogenesis;positive regulation of protein serine/threonine kinase activity;positive regulation of glycogen (starch) synthase activity
• Cellular component: extracellular region;extracellular space;platelet alpha granule lumen
• Molecular function: insulin receptor binding;insulin-like growth factor receptor binding;integrin binding;hormone activity;protein binding;growth factor activity;protein serine/threonine kinase activator activity;receptor ligand activity