IGF2BP3

Chr 7

insulin like growth factor 2 mRNA binding protein 3

Also known as: CT98, IMP-3, IMP3, KOC, KOC1, VICKZ3

NCBI Gene: 10643ENSG00000136231UniProt: O00425

The protein encoded by this gene is primarily found in the nucleolus, where it can bind to the 5' UTR of the insulin-like growth factor II leader 3 mRNA and may repress translation of insulin-like growth factor II during late development. The encoded protein contains several KH domains, which are important in RNA binding and are known to be involved in RNA synthesis and metabolism. A pseudogene exists on chromosome 7, and there are putative pseudogenes on other chromosomes. [provided by RefSeq, Jul 2008]

94
ClinVar variants
31
Pathogenic / LP
1.00
pLI score· haploinsufficient
1
Active trials
Clinical Summary— IGF2BP3
⚡
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
31 Pathogenic / Likely Pathogenic· 61 VUS of 94 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

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.
0.10LOEUF
pLI 1.000
Z-score 5.20
OE 0.00 (0.00–0.10)
Highly constrained

Among the most LoF-intolerant genes (~top 3%)

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.
2.12Z-score
OE missense 0.67 (0.60–0.75)
218 obs / 325.4 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.0.00 (0.00–0.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.60–0.75)
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.1.09
0≤1.21.6
LoF obs/exp: 0 / 31.4Missense obs/exp: 218 / 325.4Syn Z: -0.74

ClinVar Variant Classifications

94 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic29
Likely Pathogenic2
VUS61
Likely Benign1
Benign1
29
Pathogenic
2
Likely Pathogenic
61
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
29
0
29
Likely Pathogenic
0
0
2
0
2
VUS
0
56
5
0
61
Likely Benign
0
0
1
0
1
Benign
0
0
1
0
1
Total05638094

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

View in ClinVar →

Protein Context — Lollipop Plot

IGF2BP3 · 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
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
METTL3/IGF2BP3 axis inhibits tumor immune surveillance by upregulating N(6)-methyladenosine modification of PD-L1 mRNA in breast cancer.
Wan W et al.·Mol Cancer
2022
N(6)-methyladenosine regulates glycolysis of cancer cells through PDK4.
Li Z et al.·Nat Commun
2020
Comprehensive proteogenomic characterization of rare kidney tumors.
Li GX et al.·Cell Rep Med
2024
Demethylase ALKBH5 suppresses invasion of gastric cancer via PKMYT1 m6A modification.
Hu Y et al.·Mol Cancer
2022
N6-methyladenosine-modified SENP1, identified by IGF2BP3, is a novel molecular marker in acute myeloid leukemia and aggravates progression by activating AKT signal via de-SUMOylating HDAC2.
Wen D et al.·Mol Cancer
2024
m(6) A-Dependent Modulation via IGF2BP3/MCM5/Notch Axis Promotes Partial EMT and LUAD Metastasis.
Yang X et al.·Adv Sci (Weinh)
2023
Kupffer cell diversity maintains liver function in alcohol-associated liver disease.
Sasaki K et al.·Hepatology
2025
METTL3-mediated m(6)A modification of HDGF mRNA promotes gastric cancer progression and has prognostic significance.
Wang Q et al.·Gut
2020
Multi-omics analysis unveils the predictive value of IGF2BP3/SPHK1 signaling in cancer stem cells for prognosis and immunotherapeutic response in muscle-invasive bladder cancer.
Wang Y et al.·J Transl Med
2024
Targeting GPX4 to Induce Ferroptosis Overcomes Chemoresistance Mediated by the PAX8-AS1/GPX4 Axis in Intrahepatic Cholangiocarcinoma.
Chen ZW et al.·Adv Sci (Weinh)
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
Behavior Change

Evaluation of Report-Back Strategies for Long-term and Short-term Exposure Information in Rural Tribal Populations

NOT YET RECRUITING
NCT06593340Phase NAUniversity of UtahStarted 2026-10
Messenger 1Messenger 2Format 1

External Resources

Links to major genomics databases and tools