IGF2

Chr 11AD

insulin like growth factor 2

Also known as: C11orf43, GRDF, IGF-II, PP9974, SRS3

The protein encoded by this gene is insulin-like growth factor 2, a major fetal growth hormone that regulates fetoplacental development and tissue differentiation, and in adults is involved in glucose metabolism in adipose tissue, skeletal muscle and liver. Mutations cause Silver-Russell syndrome 3, characterized by growth restriction, with autosomal dominant inheritance. This is an imprinted gene expressed only from the paternal allele, and the gene shows tolerance to loss-of-function variants (pLI 0.04).

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismADLOEUF 1.131 OMIM phenotype
Clinical SummaryIGF2
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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.
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.13LOEUF
pLI 0.044
Z-score 1.36
OE 0.44 (0.201.13)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.93Z-score
OE missense 0.79 (0.690.92)
127 obs / 160.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.44 (0.201.13)
00.351.4
Missense OE0.79 (0.690.92)
00.61.4
Synonymous OE1.00
01.21.6
LoF obs/exp: 3 / 6.8Missense obs/exp: 127 / 160.2Syn Z: -0.02
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveIGF2-related Silver-Russell syndromeLOFAD
definitiveIGF2-related Beckwith-Wiedemann syndromeGOFAD
DN
0.73top 25%
GOF
0.4972th %ile
LOF
0.3453th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median · 1 literature citation

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Literature Evidence

DNThese mutants suppressed proliferation induced by WT IGF2, suggesting that they are dominant-negative antagonists of IGF1R.PMID:28873464

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

0 submitted variants in 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.

3D Protein StructureAlphaFold
Clinical Literature
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