HMGA2

Chr 12

high mobility group AT-hook 2

Also known as: BABL, HMGI-C, HMGIC, LIPO, SRS5, STQTL9

NCBI Gene: 8091 ENSG00000149948 UniProt: P52926

HMGA2 encodes a transcriptional regulator that controls cell cycle progression and positively regulates IGF2 expression. Mutations cause Silver-Russell syndrome 5, a growth disorder characterized by prenatal and postnatal growth restriction, with autosomal dominant inheritance. The gene is highly constrained against loss-of-function variants, indicating intolerance to complete protein loss.

GeneReviews ResearchSummary from OMIM, UniProt

This gene encodes a protein that belongs to the non-histone chromosomal high mobility group (HMG) protein family. HMG proteins function as architectural factors and are essential components of the enhancesome. This protein contains structural DNA-binding domains and may act as a transcriptional regulating factor. Identification of the deletion, amplification, and rearrangement of this gene that are associated with myxoid liposarcoma suggests a role in adipogenesis and mesenchymal differentiation. A gene knock out study of the mouse counterpart demonstrated that this gene is involved in diet-induced obesity. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtSilver-Russell syndrome 5

Clinical highlights

Gene-disease validity (ClinGen)

Silver-Russell syndrome 5 · ADDefinitivesufficient evidence for diagnostic panels

Interpreting a novel variant

Loss of function is the curated mechanism (Gene2Phenotype) and the gene is intolerant of it in the population — truncating, frameshift and canonical splice variants carry more prior weight here than missense.Curated gene-level mechanism — a prior for triage, not a per-variant call.

Active trials

243

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

0.45

LOEUF

LOF

Mechanism· G2P

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