IGF1R

Chr 15ADAR

insulin like growth factor 1 receptor

Also known as: CD221, IGFIR, IGFR, JTK13

NCBI Gene: 3480ENSG00000140443UniProt: P08069

This receptor binds insulin-like growth factor with a high affinity. It has tyrosine kinase activity. The insulin-like growth factor I receptor plays a critical role in transformation events. Cleavage of the precursor generates alpha and beta subunits. It is highly overexpressed in most malignant tissues where it functions as an anti-apoptotic agent by enhancing cell survival. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene. [provided by RefSeq, May 2014]

Primary Disease Associations & Inheritance

Insulin-like growth factor I, resistance toMIM #270450
ADAR
152
ClinVar variants
20
Pathogenic / LP
0.97
pLI score· haploinsufficient
0
Active trials
Clinical Summary— IGF1R
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
20 Pathogenic / Likely Pathogenic· 102 VUS of 152 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.31LOEUF
pLI 0.968
Z-score 5.99
OE 0.19 (0.12–0.31)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
2.73Z-score
OE missense 0.73 (0.69–0.78)
609 obs / 830.3 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.19 (0.12–0.31)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.73 (0.69–0.78)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.14
0≤1.21.6
LoF obs/exp: 12 / 63.6Missense obs/exp: 609 / 830.3Syn Z: -2.08

ClinVar Variant Classifications

152 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic11
Likely Pathogenic9
VUS102
Likely Benign30
11
Pathogenic
9
Likely Pathogenic
102
VUS
30
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
1
7
0
11
Likely Pathogenic
3
2
4
0
9
VUS
0
95
5
2
102
Likely Benign
0
0
4
26
30
Benign
0
0
0
0
0
Total6982028152

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

IGF1R · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

IGF1R-related insulin-like growth factor I, resistance to

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

IGF1R-related insulin-like growth factor I, resistance to

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Insulin-like growth factor I, resistance to

MIM #270450

Molecular basis of disorder known

Autosomal dominantAutosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Graves disease: latest understanding of pathogenesis and treatment options.
Lanzolla G et al.·Nat Rev Endocrinol
2024Review
Clinical and genomic landscape of gastric cancer with a mesenchymal phenotype.
Oh SC et al.·Nat Commun
2018
Metabolic Induction of Trained Immunity through the Mevalonate Pathway.
Bekkering S et al.·Cell
2018
Increasing knowledge in IGF1R defects: lessons from 35 new patients.
Giabicani E et al.·J Med Genet
2020Cohort
Hepatocyte Ninjurin2 promotes hepatic stellate cell activation and liver fibrosis through the IGF1R/EGR1/PDGF-BB signaling pathway.
Wang Y et al.·Metabolism
2023
Targeting IGF1R signaling enhances the sensitivity of cisplatin by inhibiting proline and arginine metabolism in oesophageal squamous cell carcinoma under hypoxia.
Fang K et al.·J Exp Clin Cancer Res
2023
IGFBPL1 is a master driver of microglia homeostasis and resolution of neuroinflammation in glaucoma and brain tauopathy.
Pan L et al.·Cell Rep
2023
POU2F3 is a master regulator of a tuft cell-like variant of small cell lung cancer.
Huang YH et al.·Genes Dev
2018
The Rare and Atypical Diabetes Network (RADIANT) Study: Design and Early Results.
RADIANT Study Group·Diabetes Care
2023
Cixutumumab.
McKian KP et al.·Expert Opin Investig Drugs
2009Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools