HMGA2, variants, traits, and what the research shows

HMGA2 - what this gene does

HMGA2 (High Mobility Group AT-hook 2, also known as HMGIC), located at chromosomal region 12q14.3 on chromosome 12, appears in research spanning rare diseases, cardiovascular biology, immune function, metabolism, and pharmacogenomics (the study of how genetic variants influence responses to drugs and other substances).

Key takeaways

• The strongest supported finding for this gene is an association with intracranial volume (the total space inside the skull), reaching genome-wide significance in a study of nearly 16,000 people.
• Multiple variants carry high evidence scores for rare disease associations.
• Associations also span immune function, metabolism, and pharmacogenomics, though detailed summaries are not yet available for all.
• All intracranial volume evidence to date comes from European ancestry populations, limiting generalizability.
• These are population-level statistical signals, not predictions for any individual.

Notable variants

The best-documented variant, rs10784502, is associated with intracranial volume at genome-wide significance (the standard statistical threshold used in genetics research, here P = 1.12 x 10^-12) in a meta-analysis (a study that pools results from multiple independent cohorts) of approximately 15,782 people. The alternative allele at this position is also linked to reduced gene expression in cultured fibroblasts (connective tissue cells commonly used as a model system in lab research). Five variants - rs1114167319, rs1114167320, rs1876803958, rs2120807666, and rs2498933809 - each carry a magnitude score of 5.50 under the rare disease category, placing them among the highest-ranked signals in this dataset. A sixth rare disease variant, rs2498929809, follows at magnitude 5.0. Separate variants are catalogued for immune (rs147005466), metabolic (rs7138102), and pharmacogenomic (rs76456255) trait categories, though detailed research summaries are not yet available for these.

Trait associations

The best-grounded trait link is intracranial volume, supported by rs10784502 across a large multi-cohort meta-analysis. Rare diseases represent the most frequently appearing category in this gene's variant list, with six variants - rs1114167319, rs1114167320, rs1876803958, rs2120807666, rs2498933809, and rs2498929809 - carrying the highest magnitude scores in the dataset. Additional rare disease variants appear at lower magnitudes, including rs1241586108, rs1876805546, rs2498929974, and rs2498945771. Immune, metabolic, and pharmacogenomic signals are each represented by at least one variant - rs147005466, rs7138102, and rs76456255 respectively - but no published summaries are available for these in this dataset.

Evidence quality

The intracranial volume signal from rs10784502 is the most robustly supported finding here: it met genome-wide significance (P = 1.12 x 10^-12) in a meta-analysis of approximately 15,782 individuals, with a supporting molecular finding of reduced gene expression in fibroblasts. The key limitation is that all evidence for this association comes from European ancestry populations, so its applicability to other groups is not established. The rare disease variants carry high magnitude scores but lack detailed published summaries in this dataset, so the specific conditions and underlying evidence behind them cannot be characterized here. The immune, metabolic, and pharmacogenomic variants are similarly uncharacterized in the available data. This gene has 71 variants on file but detailed editorial content for only a small subset, so the full trait picture remains incomplete.

What this is NOT

These variants are population-level statistical signals - the result of comparing large groups - and do not deterministically predict any outcome for any individual. Nothing in this entry constitutes medical advice, a diagnosis, or a recommendation to take any action.