IGF1 (Insulin-Like Growth Factor 1 (Somatomedin C))

2013-11-01   Nicholas D Panayi , Randy Burd 

Department of Nutritional Sciences, College of Medicine, University of Arizona, Tucson, AZ 85721, USA




Atlas Image
Illustrates IGF-1 splice sites and isoform variants (adapted from Mills et al., 2007).


Genomic size: 84779 bp. The IGF-1 Gene is composed of 6 different exons. Exons 1 and 2 determine the class of the protein and functionally represent the signal peptide for cellular localization post-translation. Exons 3 and 4 will primarily encode the IGF-1 mature peptide; ultimately becoming the receptor binding ligand. Exons 5 and 6 will primarily represent the E domain peptide; with exon six providing the different polyadenylating signals. These parts of the transcript give a functional distinction to the 6 isoforms produced (although such distinctions have yet to be definitively identified) (Adapted from Mills et al., 2007; Philippou et al., 2007).


Six different heterogeneous mRNA are transcribed using alternate promoters, alternate splice sites and varying polyadenylation signals. Class one and two are derived from the exon one and two promoter respectively; both are differentially spliced to the common three exon. Each class can be variably spliced to the fifth and sixth exons, producing a total of six different isoforms (Philippou et al., 2007).
Class one isoforms predominate in the extrahepatic tissues and are secreted in a paracrine/autocrine fashion.
Class two isoforms predominate in the liver and are secreted in an endocrine fashion. They are also more sensitive or responsive to growth hormone relative to class 1 (Mills et al., 2007).
Individual isoforms may be more favorably translated depending on the tissue type, the available binding proteins and the physiological context.
Researchers are discovering evidence that suggest certain isoforms may be preferentially expressed under varying amounts of mechanical pressure in skeletal muscle (Philippou et al., 2007). The advantages of one isoform or another, in varying contexts of stress, inflammation, regeneration and hypertrophy are yet to be elucidated.


Not reported.



Single polypeptide chain protein consisting of 70 amino acids and three disulfide bridges.


It is primarily produced and secreted in endocrine fashion by the liver. It is also produced and secreted in autocrine or paracrine fashion in a wide range of extra-hepatic tissues. Tissues produce IGF-1 protein in response to growth hormone during periods of pre/post-natal development, exercise and injury. Inhibited in undernourished states, low protein, growth hormone deficiency and growth hormone receptor insensitivity (Cheng et al., 2006).


The protein is post-translationally modified by protease cleavage of the signal and E-peptide. The mature protein subsequently binds to one of six binding proteins and is then secreted form the tissue of origin (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, IGFBP6). IGFBP3 predominates, binding to 80% of the available IGF-1. The binding proteins increase the half life of IGF, preventing renal clearance and inactivation. IGFBP (1,3,4,6) are growth promoting; IGFBP-(2,5) bind IGF-1 and limit IGFR/IGF-1 interaction; a growth inhibiting effect.


Important for growth/development in children and adults. Vital role in anabolic processes in general. Important functions in osteogenesis, axonal generation in nerves, nerve regeneration after ischemic insult, muscle repair and hypertrophy after trauma or exercise (Cheng et al., 2006). Although still under investigation, studies suggest that individual isotype/binding protein combinations manifest in response to specific environmental interactions or physiological demands. In addition, the binding proteins are critical for maintaining the bioavailability of the IGF-1. The unique IGF-1/IGF-1 receptor complex will then signal the protein cascade necessary for tissue metabolism or regeneration. Ischemic damage to the brain illustrates how this concept materializes. Cytotoxic edema and inflammatory markers induce the transcription of a specific isotype; which then binds to a tissue specific binding protein; protecting the integrity of the protein and preventing its renal clearance. The distinctive IGF-1/IGF-1R complex will then activate the protein kinase cascade necessary for axonal regeneration.
Cellular/molecular effects: Upon binding, the tyrosine kinase receptor, IGF-1/IGF-1R complex activates the PI3K/AKT/mTOR and RAS/RAF/MAPK protein cascades. Both interfere with apoptosis and are pro-cell survival; the latter additionally promotes cellular differentiation, metabolism, growth and repair. Given its integral utility in tissue growth, repair and cell cycle regulation, IGF-1 receptors are found ubiquitously throughout the body and include: muscle, bone, cartilage, kidney, liver, lung and nervous tissue (Schiaffino et al., 2011).
It is speculated that binding proteins may not only enhance or subdue IGF-1/IGF-1R interaction but help specify which isoform should predominate.
Biotech and Clinical Application: Recombinant IGF-1 expressed in e. Coli is being tested either for symptomatic relief, tissue regeneration or penetrance reduction in the following diseases or conditions:
- Larons Dwarfism
- Duchennes Muscular Dystrophy
- Amyotrophic Lateral Sclerosis
- Post ischemic damage to brain (stroke)
- Diabetes and Insulin Insensitivity


Shares some sequence homology to insulin and has a relatively weak affinity to insulin receptors.

Implicated in

Entity name
Various cancers
No specific mutations of IGF-1 have been connected to genetically acquired diseases. Despite this fact, certain haplotypes of IGF-1 have been implicated in the survival of solid tumors. It is postulated that IGF-1 has tumor promoting effects when its cellular growth/anti-apoptotic functions become dysregulated (see oncogenesis below). Additionally it plays a critical role in the clinical sequelae of Larons dwarfism (see below).
High levels implicated in the survival of solid tumors and Acromegaly. Low levels of IGF-1/IGFBP3 consistently found in Larons Dwarfism; An Autosomal recessive disease caused by a mutation in the growth hormone receptor; causing poor ligand interaction with growth hormone and subsequent low levels of IGF-1.
Individuals with Larons are dwarfs with characteristic facial and anatomical anomalies (flat nasal bridge, prominent forehead, obesity, small mandible and phallus). They also exhibit seizures secondary to hypoglycemia. Unlike Achondroplasia, Larons Dwarfism does not respond to GH. Laron Dwarfs have a greater resistance to diabetes, cancer and age progression; underscoring the function of IGF-1 and its critical role in cellular metabolism and cell cycle maintenance (Melnik et al., 2011).
Atlas Image
IGF-1 mediated signal transduction (adapted from Schiaffino, S. et. al, 2011).
IGF-1 signaling through RAS/RAF/MAPK and has been demonstrated to promote breast cancer and prostate tumorigenesis. IGF-1/IGF-R interaction induces the transcription of survival/ growth enhancing genes. Signaling through these pathways results in increased cellular proliferation and anti-apoptotic effects; promoting a favorable environment for tumor growth. In General, high levels of IGF-1 are found in solid tumors (particularly breast and prostate). Certain SNPs and IGF-1 haplotypes have been associated with increased risk of colon, pancreatic, prostate and breast cancer. It is likely that specific haplotypes in combination with other variables can create a more favorable tumorigenic environment. i.e. Individuals with a BMI>25, containing specific IGF-1 haplotypes may have a greater risk of developing pancreatic cancer (Cheng et al., 2006).


Pubmed IDLast YearTitleAuthors
164185152006Common genetic variation in IGF1 and prostate cancer risk in the Multiethnic Cohort.Cheng I et al
216997362011Over-stimulation of insulin/IGF-1 signaling by western diet may promote diseases of civilization: lessons learnt from laron syndrome.Melnik BC et al
178455602007A synthetic mechano growth factor E Peptide enhances myogenic precursor cell transplantation success.Mills P et al
173546132007The role of the insulin-like growth factor 1 (IGF-1) in skeletal muscle physiology.Philippou A et al
217980822011Regulation of skeletal muscle growth by the IGF1-Akt/PKB pathway: insights from genetic models.Schiaffino S et al

Other Information

Locus ID:

NCBI: 3479
MIM: 147440
HGNC: 5464
Ensembl: ENSG00000017427


dbSNP: 3479
ClinVar: 3479
TCGA: ENSG00000017427


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
p53 signaling pathwayKEGGko04115
mTOR signaling pathwayKEGGko04150
Focal adhesionKEGGko04510
Long-term depressionKEGGko04730
Progesterone-mediated oocyte maturationKEGGko04914
Prostate cancerKEGGko05215
p53 signaling pathwayKEGGhsa04115
mTOR signaling pathwayKEGGhsa04150
Focal adhesionKEGGhsa04510
Long-term depressionKEGGhsa04730
Pathways in cancerKEGGhsa05200
Prostate cancerKEGGhsa05215
Hypertrophic cardiomyopathy (HCM)KEGGko05410
Hypertrophic cardiomyopathy (HCM)KEGGhsa05410
Progesterone-mediated oocyte maturationKEGGhsa04914
Dilated cardiomyopathyKEGGko05414
Dilated cardiomyopathyKEGGhsa05414
Oocyte meiosisKEGGko04114
Oocyte meiosisKEGGhsa04114
Aldosterone-regulated sodium reabsorptionKEGGko04960
Aldosterone-regulated sodium reabsorptionKEGGhsa04960
Transcriptional misregulation in cancerKEGGko05202
Transcriptional misregulation in cancerKEGGhsa05202
PI3K-Akt signaling pathwayKEGGhsa04151
PI3K-Akt signaling pathwayKEGGko04151
HIF-1 signaling pathwayKEGGhsa04066
Proteoglycans in cancerKEGGhsa05205
Proteoglycans in cancerKEGGko05205
Ovarian steroidogenesisKEGGhsa04913
Ovarian steroidogenesisKEGGko04913
Ras signaling pathwayKEGGhsa04014
Rap1 signaling pathwayKEGGhsa04015
Rap1 signaling pathwayKEGGko04015
FoxO signaling pathwayKEGGhsa04068
Inflammatory mediator regulation of TRP channelsKEGGhsa04750
Inflammatory mediator regulation of TRP channelsKEGGko04750
AMPK signaling pathwayKEGGhsa04152
AMPK signaling pathwayKEGGko04152
Signaling pathways regulating pluripotency of stem cellsKEGGhsa04550
Signaling pathways regulating pluripotency of stem cellsKEGGko04550
Metabolism of proteinsREACTOMER-HSA-392499
Peptide hormone metabolismREACTOMER-HSA-2980736
Synthesis, secretion, and deacylation of GhrelinREACTOMER-HSA-422085
Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)REACTOMER-HSA-381426
Platelet activation, signaling and aggregationREACTOMER-HSA-76002
Response to elevated platelet cytosolic Ca2+REACTOMER-HSA-76005
Platelet degranulationREACTOMER-HSA-114608
Signal TransductionREACTOMER-HSA-162582
Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)REACTOMER-HSA-2404192
IGF1R signaling cascadeREACTOMER-HSA-2428924
SHC-related events triggered by IGF1RREACTOMER-HSA-2428933
IRS-related events triggered by IGF1RREACTOMER-HSA-2428928
Longevity regulating pathwayKEGGhsa04211
Longevity regulating pathway - multiple speciesKEGGko04213
Longevity regulating pathway - multiple speciesKEGGhsa04213
EGFR tyrosine kinase inhibitor resistanceKEGGko01521
Endocrine resistanceKEGGko01522
EGFR tyrosine kinase inhibitor resistanceKEGGhsa01521
Endocrine resistanceKEGGhsa01522
Breast cancerKEGGko05224
Breast cancerKEGGhsa05224

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
183167252008Functionally significant insulin-like growth factor I receptor mutations in centenarians.282
227292832012Matrix IGF-1 maintains bone mass by activation of mTOR in mesenchymal stem cells.164
120620942002The IGF-1/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt.152
189486172008IGF-1-overexpressing mesenchymal stem cells accelerate bone marrow stem cell mobilization via paracrine activation of SDF-1alpha/CXCR4 signaling to promote myocardial repair.137
187573222008Insulin-like growth factor-I activates gene transcription programs strongly associated with poor breast cancer prognosis.114
18003755200825-hydroxyvitamin D, IGF-1, and metabolic syndrome at 45 years of age: a cross-sectional study in the 1958 British Birth Cohort.112
121221012002Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 as predictors of advanced-stage prostate cancer.103
128431792003Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control.103


Nicholas D Panayi ; Randy Burd


Atlas Genet Cytogenet Oncol Haematol. 2013-11-01

Online version: http://atlasgeneticsoncology.org/gene/40927/igf1