IGF2

Chr 11AD

insulin like growth factor 2

ENSG00000167244UniProt: P01344

The insulin-like growth factors possess growth-promoting activity (By similarity). Major fetal growth hormone in mammals. Plays a key role in regulating fetoplacental development. IGF2 is influenced by placental lactogen. Also involved in tissue differentiation. In adults, involved in glucose metabolism in adipose tissue, skeletal muscle and liver (Probable). Acts as a ligand for integrin which is required for IGF2 signaling (PubMed:28873464). Positively regulates myogenic transcription factor MYOD1 function by facilitating the recruitment of transcriptional coactivators, thereby controlling muscle terminal differentiation (By similarity). Inhibits myoblast differentiation and modulates metabolism via increasing the mitochondrial respiration rate (By similarity)

Primary Disease Associations & Inheritance

Silver-Russell syndrome 3MIM #616489
AD
0
ClinVar variants
0
Pathogenic / LP
0.04
pLI score
2
Active trials
Clinical Summary— IGF2
🧬
Gene-Disease Validity (ClinGen)
Silver-Russell syndrome 3 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.04) — loss-of-function variants are relatively tolerated in the population.
💊
Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

ncbi: Error: NCBI fetch failed: 429 https://eutils.ncbi.nlm.nih.gov/entrez/eutils/esearch.fcgi

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.13LOEUF
pLI 0.044
Z-score 1.36
OE 0.44 (0.20–1.13)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.93Z-score
OE missense 0.79 (0.69–0.92)
127 obs / 160.2 exp
Tolerant

Mild missense constraint

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.0.44 (0.20–1.13)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.79 (0.69–0.92)
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.1.00
0≤1.21.6
LoF obs/exp: 3 / 6.8Missense obs/exp: 127 / 160.2Syn Z: -0.02

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

IGF2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

IGF2-related Silver-Russell syndrome

definitive
ADLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

IGF2-related Beckwith-Wiedemann syndrome

definitive
ADGain Of FunctionAltered Gene Product Structure
Dev. DisordersSkeletal
G2P ↗

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Silver-Russell syndrome 3

MIM #616489

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Single-cell protein activity analysis reveals aberrant myogenesis and IGF2-PI3K pathway dependencies in MYOD1-mutant rhabdomyosarcoma.
Dermawan JK et al.·Sci Adv
2026🔓 Open Access
Let-7a and miR-34a Interplay Potent Suppressive Roles in Hepatocellular Carcinoma via Co-Targeting FNDC3B, IGF2 and SOX4.
Soliman B et al.·Int J Mol Sci
2026
Methylation profile characteristics in the H19/IGF2:IG-DMR revealed by long-read sequencing analysis in patients with Beckwith-Wiedemann syndrome having defects in the OCT4/SOX2 binding site.
Masubuchi H et al.·Clin Epigenetics
2026🔓 Open AccessCohort
IGF2 in livestock: boosting productivity and enhancing meat quality.
Wang G et al.·Poult Sci
2026🔓 Open Access
Microglial TIA1-mediated stress granules promote neuroinflammation and aggravate neuron loss in mice after ischemic stroke by inhibiting IGF2 signaling.
Qian Y et al.·Theranostics
2026🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Transfusion-dependent Beta-ThalassemiaGene Therapy

Growth and Development-related Outcomes in Children With Transfusion-dependent Beta-thalassemia After Gene Therapy

RECRUITING
NCT05991336Institute of Hematology & Blood Diseases Hospital, ChinaStarted 2023-06-05
Gene therapy
Klinefelter Syndrome

Klinefelter Syndrome and Testosterone Treatment in Puberty

RECRUITING
NCT06294990Phase PHASE4Lise AksglædeStarted 2024-08-15
Testosterone gelPlacebo

External Resources

Links to major genomics databases and tools