IGF1R Gene

IGF1R Gene

Introduction

Igf1R Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@girnita2007]
<div class="infobox-header">IGF1R</div> [@russo2009]
<div class="infobox-content"> [@bondy1992]
<table> [@fernandez2012]
<tr><th>Full Name</th><td>IGF1R (Insulin-like Growth Factor 1 Receptor)</td></tr> [@labandeiragarcia2017]
<tr><th>Chromosome</th><td>chr15</td></tr> [@xie2019]
<tr><th>Location</th><td>15q26.3</td></tr> [@bassil2021]
<tr><th>NCBI Gene ID</th><td>[3480](https://www.ncbi.nlm.nih.gov/gene/3480)</td></tr>
<tr><th>OMIM</th><td>[147370](https://www.omim.org/entry/147370)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000140443](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000140443)</td></tr>
<tr><th>UniProt</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
<tr><th>Protein Class</th><td>Receptor Tyrosine Kinase</td></tr>
<tr><th>Expression</th><td>Ubiquitous, high in brain</td></tr>
</table>
</div>
</div>

Pathway Diagram

IGF1R Gene

Introduction

Igf1R Gene is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

<div class="infobox infobox-gene"> [@girnita2007]
<div class="infobox-header">IGF1R</div> [@russo2009]
<div class="infobox-content"> [@bondy1992]
<table> [@fernandez2012]
<tr><th>Full Name</th><td>IGF1R (Insulin-like Growth Factor 1 Receptor)</td></tr> [@labandeiragarcia2017]
<tr><th>Chromosome</th><td>chr15</td></tr> [@xie2019]
<tr><th>Location</th><td>15q26.3</td></tr> [@bassil2021]
<tr><th>NCBI Gene ID</th><td>[3480](https://www.ncbi.nlm.nih.gov/gene/3480)</td></tr>
<tr><th>OMIM</th><td>[147370](https://www.omim.org/entry/147370)</td></tr>
<tr><th>Ensembl</th><td>[ENSG00000140443](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000140443)</td></tr>
<tr><th>UniProt</th><td>[P08069](https://www.uniprot.org/uniprotkb/P08069/entry)</td></tr>
<tr><th>Associated Diseases</th><td>Alzheimer's Disease, Parkinson's Disease, ALS, Cancer, Laron Syndrome</td></tr>
<tr><th>Protein Class</th><td>Receptor Tyrosine Kinase</td></tr>
<tr><th>Expression</th><td>Ubiquitous, high in brain</td></tr>
</table>
</div>
</div>

Pathway Diagram

Overview

IGF1R (Insulin-like Growth Factor 1 Receptor) is a heterotetrameric receptor tyrosine kinase that binds IGF1 and IGF2 with high affinity. It is essential for normal brain development, neuronal survival, synaptic plasticity, and overall nervous system function. IGF1R is widely expressed throughout the brain, with particularly high levels in the [hippocampus](/brain-regions/hippocampus), [cortex](/brain-regions/cortex), and olfactory bulb during development. As the primary mediator of IGF1's neuroprotective effects, IGF1R activates the PI3K/Akt and MAPK/ERK signaling cascades that promote cell survival, growth, and differentiation. Dysregulation of IGF1R signaling has been implicated in neurodegenerative diseases, making it an important therapeutic target.

Gene Structure

The IGF1R gene is located on chromosome 15q26.3 and spans approximately 100 kb. The gene consists of 21 exons and produces a single major transcript encoding the precursor protein. The gene promoter contains multiple transcription factor binding sites, allowing regulation by growth factors, hormones, and cellular stress:

• Exon 1-2: 5' UTR and signal peptide
• Exons 3-11: α-subunit (extracellular ligand-binding domain)
• Exons 12-21: β-subunit (transmembrane and intracellular domains)
• Alternative splicing: Produces variants with tissue-specific expression

Protein Structure

The mature IGF1R is a heterotetramer consisting of two α-subunits and two β-subunits:

• α-Subunit (706 aa each): Extracellular ligand-binding domain containing multiple cysteine-rich repeats
• β-Subunit (626 aa each): Single transmembrane helix and intracellular tyrosine kinase domain
• Disulfide bonds: Link the two α- and two β-subunits

Key Domains

• Cysteine-rich region: Ligand binding
• Fibronectin type III repeats: Structural
• Tyrosine kinase domain: Catalytic activity
• C-terminal tail: Multiple phosphorylation sites

Normal Function

Receptor Activation

PI3K/Akt Pathway

• Akt phosphorylation inhibits pro-apoptotic proteins
• mTORC1 activation promotes protein synthesis
• [GSK-3β](/entities/gsk3-beta) inhibition affects [tau](/proteins/tau) phosphorylation
• FOXO transcription factor regulation

MAPK/ERK Pathway

• Ras/Raf/MEK/ERK cascade activation
• Gene transcription
• Cell growth and proliferation
• Synaptic plasticity modulation

Brain-Specific Functions

• Neurogenesis regulation
• Neuronal survival
• Synaptic plasticity and [LTP](/mechanisms/long-term-potentiation)
• Myelination support
• Astrocyte function

Disease Associations

Alzheimer's Disease

• Decreased IGF1R expression in hippocampus and cortex
• Impaired downstream signaling (PI3K/Akt deficits)
• Reduced IRS-1/2 function (insulin resistance)
• Therapeutic potential of IGF1R modulation

Parkinson's Disease

• IGF1R protects dopaminergic neurons
• Reduced signaling in substantia nigra
• Therapeutic delivery of IGF1 shows promise
• Receptor as drug target

Amyotrophic Lateral Sclerosis (ALS)

• Motor neurons vulnerable to IGF1R deficits
• Gene therapy approaches targeting IGF1R
• Neuroprotective effects demonstrated
• Clinical trials ongoing

Cancer

• Promotes tumor growth and metastasis
• Resistance to chemotherapy
• Therapeutic targeting with antibodies and small molecules
• Dual targeting with IGF1R/IR inhibitors

Laron Syndrome

• IGF1R mutations cause GH insensitivity
• Severe growth deficiency
• Neurodevelopmental consequences

Expression Pattern

IGF1R exhibits widespread expression:

• Highest Expression: Embryonic brain, adult hippocampus (CA1-CA3), cortex, olfactory bulb
• Moderate Expression: Cerebellum, basal ganglia, thalamus
• Cell Types: [Neurons](/entities/neurons), [astrocytes](/entities/astrocytes), oligodendrocytes, [microglia](/entities/microglia)

Molecular Mechanisms

Tyrosine Kinase Activation

• Tyrosine 1131: Major activation site
• Tyrosine 1135/1136: Kinase domain
• Tyrosine 1250/1251: Docking sites

Adapter Protein Recruitment

• IRS-1/2: PI3K/Akt pathway
• Shc: MAPK/ERK pathway
• Grb10: Negative regulation

Cross-talk with Other Receptors

• Insulin Receptor (IR): Hybrid receptors
• Integrins: Cell adhesion signaling
• Other growth factor receptors

Negative Regulation

• Protein tyrosine phosphatases (PTPs)
• SOCS proteins
• Endocytosis and degradation

Therapeutic Implications

Receptor Agonists

• Recombinant IGF1: Mecasermin
• IGF1 mimetics: Selective activation
• Allosteric modulators

Receptor Antagonists

• Blocking antibodies: Picropodophyllin
• Small molecule inhibitors: NVP-AEW541
• IGF1/IGF2 neutralizers

Gene Therapy

• AAV-IGF1R modulation
• CRISPR approaches
• siRNA targeting

Combination Strategies

• IGF1R + PI3K modulators
• IGF1R + neurotrophic factors
• Targeted delivery to brain

Animal Models

Knockout Mice

• Complete KO: Embryonic lethal, growth deficiency
• Neuron-specific KO: Learning/memory deficits
• Conditional KO: Age-related phenotypes

Transgenic Models

• Overexpression: Enhanced neurogenesis
• Disease models: AD, PD, HD
• Reporter lines

Research Directions

• Brain-penetrant IGF1R modulators
• Selective agonists vs. antagonists
• Delivery across [BBB](/entities/blood-brain-barrier)
• Biomarker development
• Clinical translation

See Also

• [Alzheimer's Disease](/diseases/alzheimers-disease)
• [Parkinson's Disease](/diseases/parkinsons-disease)
• [Neurotrophic Factors](/therapeutics/neurotrophic-factor-therapy-neurodegeneration)
• [IGF1 Gene](/proteins/igf1-protein)
• [PI3K/Akt Pathway](/mechanisms/pi3k-akt-pathway)

External Links

• [NCBI Gene: IGF1R](https://www.ncbi.nlm.nih.gov/gene/3480)
• [UniProt: IGF1R](https://www.uniprot.org/uniprotkb/P08069/entry)
• [Ensembl: IGF1R](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000140443)
• [OMIM: IGF1R](https://www.omim.org/entry/147370)

Background

The study of Igf1R Gene has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Allen Brain Atlas Resources

• Allen Human Brain Atlas: [IGF1R gene expression](https://human.brain-map.org/microarray/search/show?search_term=IGF1R)
• Allen Mouse Brain Atlas: [IGF1R expression](https://mouse.brain-map.org/search/index.html?query=IGF1R)
• Allen Cell Type Atlas: [Transcriptomic cell type reference](https://portal.brain-map.org/atlases-and-data/rnaseq)
• BrainSpan Atlas: [IGF1R developmental expression](https://www.brainspan.org/rnaseq/search/index.html?search_term=IGF1R)

References

Pathway Diagram

The following diagram shows the key molecular relationships involving IGF1R Gene discovered through SciDEX knowledge graph analysis: