IGF2R

Chr 6

insulin like growth factor 2 receptor

Also known as: CD222, CI-M6PR, CIMPR, M6P-R, M6P/IGF2R, MPR 300, MPR1, MPR300

NCBI Gene: 3482ENSG00000197081UniProt: P11717

This gene encodes a receptor for both insulin-like growth factor 2 and mannose 6-phosphate. The binding sites for each ligand are located on different segments of the protein. This receptor has various functions, including in the intracellular trafficking of lysosomal enzymes, the activation of transforming growth factor beta, and the degradation of insulin-like growth factor 2. Mutation or loss of heterozygosity of this gene has been association with risk of hepatocellular carcinoma. The orthologous mouse gene is imprinted and shows exclusive expression from the maternal allele; however, imprinting of the human gene may be polymorphic, as only a minority of individuals showed biased expression from the maternal allele (PMID:8267611). [provided by RefSeq, Nov 2015]

Primary Disease Associations & Inheritance

Hepatocellular carcinoma, somaticMIM #114550
361
ClinVar variants
29
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— IGF2R
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
29 Pathogenic / Likely Pathogenic· 281 VUS of 361 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.
0.21LOEUF
pLI 1.000
Z-score 8.71
OE 0.14 (0.10–0.21)
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.
2.07Z-score
OE missense 0.85 (0.81–0.89)
1203 obs / 1422.2 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.0.14 (0.10–0.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.85 (0.81–0.89)
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.1.07
0≤1.21.6
LoF obs/exp: 17 / 120.0Missense obs/exp: 1203 / 1422.2Syn Z: -1.33

ClinVar Variant Classifications

361 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic26
Likely Pathogenic3
VUS281
Likely Benign35
Benign16
26
Pathogenic
3
Likely Pathogenic
281
VUS
35
Likely Benign
16
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
2
24
0
26
Likely Pathogenic
1
1
1
0
3
VUS
1
272
6
2
281
Likely Benign
0
18
0
17
35
Benign
0
9
2
5
16
Total23023324361

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

View in ClinVar →

Protein Context — Lollipop Plot

IGF2R · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Hepatocellular carcinoma, somatic

MIM #114550

Molecular basis of disorder known

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Genetics of hepatocellular tumors.
Laurent-Puig P et al.·Oncogene
2006Review
Secreted Clever-1 modulates T cell responses and impacts cancer immunotherapy efficacy.
Prince S et al.·Theranostics
2025Clinical trial
A minireview of E4BP4/NFIL3 in heart failure.
Velmurugan BK et al.·J Cell Physiol
2018Review
Hormonal regulation of fetal growth.
Gicquel C et al.·Horm Res
2006Review
Clinical epigenetics and acute/chronic rejection in solid organ transplantation: An update.
Vasco M et al.·Transplant Rev (Orlando)
2021Review
Molecular pharmacology and therapeutic advances of monoterpene perillyl alcohol.
Zhang L et al.·Phytomedicine
2024Review
Oncogenic cholesterol rewires lipid metabolism in hepatocellular carcinoma via the CSNK2A1-IGF2R Ser2484 axis.
Su RY et al.·J Adv Res
2025
The mannose 6-phosphate/insulin-like growth factor 2 receptor (M6P/IGF2R), a putative breast tumor suppressor gene.
Oates AJ et al.·Breast Cancer Res Treat
1998Review
CD34(+)CLDN5(+) tumor associated senescent endothelial cells through IGF2-IGF2R signaling increased cholangiocellular phenotype in hepatocellular carcinoma.
Zhu XY et al.·J Adv Res
2025
SorCS3 suppresses adrenocortical carcinoma progression by enhancing IGF2R-mediated endocytic trafficking and signaling attenuation.
Zhang Y et al.·J Transl Med
2025
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