IGF2

Chr 11AD

insulin like growth factor 2

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

NCBI Gene: 3481 ENSG00000167244 UniProt: P01344 OMIM: 147470

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).

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a member of the insulin family of polypeptide growth factors, which are involved in development and growth. It is an imprinted gene, expressed only from the paternal allele, and epigenetic changes at this locus are associated with Wilms tumour, Beckwith-Wiedemann syndrome, rhabdomyosarcoma, and Silver-Russell syndrome. A read-through INS-IGF2 gene exists, whose 5' region overlaps the INS gene and the 3' region overlaps this gene. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2010]

GeneReviews OMIM ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

Silver-Russell syndrome 3MIM #616489

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · Silver-Russell syndrome 3 · AD · ClinGen 2023

Interpreting a novel variant

Curated mechanisms (Gene2Phenotype) include both loss of function and gain of function. Which applies is variant-dependent — do not assume a null variant is, or isn’t, the pathogenic class without checking the specific variant.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

317

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

—

LOEUF

Multiple*

Mechanism· G2P

📖

GeneReview available — IGF2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

gnomad: Error: gnomAD API error: 400

Population Genetics & Constraint

gnomAD

Constraint data not available from gnomAD.

Background carrier burden — how many people carry a rare variant somewhere in IGF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 270

301 rare PASS variants

Rare truncating (LoF)

1 in 2,800

28 rare PASS variants

Rare synonymous (reference)

1 in 190

138 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for IGF2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 260	1 in 2,800
South Asian	~43k	1 in 110	1 in 6,000
Remaining (unassigned)	~30k	1 in 310	1 in 380
European (Finnish)	~27k	1 in 730	1 in 1,600
Admixed American	~22k	1 in 290	1 in 470
African / African American	~21k	1 in 210	1 in 670
East Asian	~20k	1 in 200	1 in 2,800
Ashkenazi Jewish	~13k	1 in 910	1 in 860
Middle Eastern	~2,884	1 in 260	≈ 1 in 1,400

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 3 coding exons well covered in gnomAD exomes and genomes.? see exons ↓