insulin like growth factor 1 receptor
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Diagnostic Grade (Green)
DDG2P
BOTH monoallelic and biallelic, autosomal or pseudoautosomalFetal anomalies
BOTH monoallelic and biallelic, autosomal or pseudoautosomalIntellectual disability
BIALLELIC, autosomal or pseudoautosomalIUGR and IGF abnormalities
BOTH monoallelic and biallelic, autosomal or pseudoautosomalMonogenic short stature
BOTH monoallelic and biallelic, autosomal or pseudoautosomalSevere microcephaly
BOTH monoallelic and biallelic, autosomal or pseudoautosomalSilver Russell syndrome
BOTH monoallelic and biallelic, autosomal or pseudoautosomalRare syndromic craniosynostosis or isolated multisuture synostosis
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growth delay due to insulin-like growth factor I resistance
Abnormality of the skeletal system
Graves ophthalmopathy
neurodegenerative disease
hereditary disease
Growth delay
gout
type 2 diabetes mellitus
atrial fibrillation
prostate carcinoma
Score is the Open Targets composite evidence score (0-1). Higher = stronger gene-disease association.
Insulin-like growth factor 1 receptor
Receptor tyrosine kinase which mediates actions of insulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K-driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R
IGF1R · P08069
Mean pLDDT
78.0/ 100
Confident
1,367 residues
Confidence breakdown
AlphaFold (Jumper et al., 2021) · CC BY 4.0
