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insulin-like growth factor 2 OKDB#: 864
 Symbols: IGF2 Species: human
 Synonyms: IGF-II, PP9974, C11orf43  Locus: 11p15.5 in Homo sapiens

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General Comment Insulin-like growth factors I and II, also known as somatomedin C and somatomedin A, respectively, are single chain polypeptides which share an amino acid sequence homology of about 47% with insulin and about 31% with relaxin and with them comprise the insulin family of polypeptide growth factors. Their functions include mediation of growth hormone action, stimulation of growth of cultured cells, stimulation of the action of insulin, and involvement in development and growth. They appear to be autocrine regulators of cell proliferation.

NCBI Summary: This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]
General function Ligand, Growth factor
Comment IGF2 is a mitogen for many cell types and an important modulator of muscle growth and differentiation. The gene is widely expressed during prenatal development and its activity is regulated by genomic imprinting, the gene being inactive on the chromosome inherited from the mother in most normal tissues.
Cellular localization Secreted
Ovarian function Follicle development, Preantral follicle growth, Antral follicle growth, Follicle atresia, Steroid metabolism, Luteinization, Oogenesis
Comment Poretsky L, et al. reviewed the insulin-related ovarian regulatory system in health and disease. Giudice LC. reviewed the growth factor action on ovarian function in polycystic ovary syndrome. Yuan W, et al. reported that insulin-like growth factor-II mediates the steroidogenic and growth promoting actions of follicle stimulating hormone on human ovarian pre-antral follicles cultured in vitro.
Expression regulated by FSH, LH
Comment FSH Regulates IGF2 Expression in Human Granulosa Cells in an AKT-dependent Manner. Baumgarten SC et al. (2015) IGF2 is highly expressed in the granulosa cells of human dominant ovarian follicles; however, little is known about the regulation of the IGF2 gene or the interaction of IGF2 and FSH during follicle development. To examine the mechanisms involved in the regulation of the IGF2 gene by FSH and the interplay between FSH and IGF2 during granulosa cell differentiation. Design, Setting, Patients, and Interventions: Cumulus granulosa cells were separated from cumulus-oocyte-complexes isolated from the follicular aspirates of IVF patients and cultured for in vitro studies. Protein and mRNA levels of IGF2 and CYP19A1 (aromatase) were quantified using Western blot and quantitative real-time PCR. IGF2 promoter-specific activation was determined by the amplification of alternative exons by PCR. Cell proliferation was assessed after treatment with FSH and/or IGF2. FSH significantly enhanced IGF2 expression after 8 hours of treatment and at low doses (1 ng/ml). Reciprocally, IGF2 synergized with FSH to increase cell proliferation and the expression of CYP19A1. When IGF2 activity was blocked, FSH was no longer able to stimulate CYP19A1 expression. Determination of IGF2 promoter usage in human cumulus cells showed that the IGF2 gene is driven by promoters P3 and P4. However, FSH exclusively increased P3 promoter derived transcripts. Moreover, the FSH-induced stimulation of P3-driven IGF2 transcripts was blocked by co-treatment with inhibitors of AKT or IGF1R. The inhibitory effect of the IGF1R inhibitor on FSH-induced IGF2 mRNA accumulation was reversed by overexpression of a constitutively active AKT construct. FSH is a potent enhancer of IGF2 expression in human granulosa cells. In return, IGF2 activation of the IGF1R and AKT is required for FSH to stimulate CYP19A1 expression and proliferation of granulosa cells. These findings suggest a positive loop interaction between FSH and IGF2 that is critical for human granulosa cell proliferation and differentiation.//////////////////
Ovarian localization Granulosa, Theca, Luteal cells
Comment el-Roeiy A, et al. reported the expression of the genes encoding the insulin-like growth factors (IGF-I and II), the IGF and insulin receptors, and IGF-binding proteins-1-6 and the localization of their gene products in normal and polycystic ovary syndrome ovaries.
Follicle stages Secondary, Antral, Preovulatory, Corpus luteum
Mutations 2 mutations

Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: DeChiara et al. (1991) produced targeted disruption of the Igf2 gene in mice by homologous recombination in ES cells. Transmission of this mutation through the male germline resulted in heterozygous progeny that were growth deficient. In contrast, when the disrupted gene was transmitted maternally, the heterozygous offspring were phenotypically normal. Homozygous mutants were indistinguishable in appearance from growth-deficient heterozygous sibs.

Species: mouse
Mutation name: None
type: targeted overexpression
fertility: embryonic lethal
Comment: Sun et al. (1997) introduced Igf2 transgenes into the mouse genome by using embryonic stem (ES) cells and thereby caused transactivation of the endogenous Igf2 gene. The consequent overexpression of Igf2 resulted in most of the symptoms of Beckwith-Wiedemann syndrome (BWS), including prenatal overgrowth, polyhydramnios, fetal and neonatal lethality, disproportionate organ overgrowth including tongue enlargement, and skeletal abnormalities. This was presented as evidence that IGF2 overexpression is a key determinant of BWS.

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created: Feb. 19, 2000, midnight by: Giudice   email:
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last update: June 15, 2015, 11:03 a.m. by: hsueh    email:

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