HMGA2

Chr 12AD

high mobility group AT-hook 2

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

NCBI Gene: 8091ENSG00000149948UniProt: P52926

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]

Primary Disease Associations & Inheritance

Silver-Russell syndrome 5MIM #618908
AD
0
ClinVar variants
0
Pathogenic / LP
0.87
pLI score
1
Active trials
Clinical Summary— HMGA2
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Gene-Disease Validity (ClinGen)
Silver-Russell syndrome 5 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.87) — some intolerance to loss-of-function variants.
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

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

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.45LOEUF
pLI 0.870
Z-score 2.39
OE 0.00 (0.00–0.45)
Moderately constrained

More LoF-intolerant than ~75% of genes

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.
1.34Z-score
OE missense 0.48 (0.35–0.67)
25 obs / 52.1 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.0.00 (0.00–0.45)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.48 (0.35–0.67)
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.1.78
0≤1.21.6
LoF obs/exp: 0 / 6.7Missense obs/exp: 25 / 52.1Syn Z: -2.63

ClinVar Variant Classifications

0 submitted variants in ClinVar

ClinVar

Protein Context — Lollipop Plot

HMGA2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

HMGA2-related Silver-Russell-like syndrome

strong
ADLoss Of FunctionDecreased Gene Product Level
Dev. Disorders
G2P ↗
splice donor variantframeshift variantstop lostmissense variantintron variantstop gained NMD escapingwhole partial gene deletion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Silver-Russell syndrome 5

MIM #618908

Molecular basis of disorder known

Autosomal dominant
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Updated Salivary Gland Immunohistochemistry: A Review.
Swid MA et al.·Arch Pathol Lab Med
2023Review
Approach to the Patient With Suspected Silver-Russell Syndrome.
Kurup U et al.·J Clin Endocrinol Metab
2024Review
HMGA2 facilitates colorectal cancer progression via STAT3-mediated tumor-associated macrophage recruitment.
Wang X et al.·Theranostics
2022
KRAS-G12D mutation drives immune suppression and the primary resistance of anti-PD-1/PD-L1 immunotherapy in non-small cell lung cancer.
Liu C et al.·Cancer Commun (Lond)
2022
HMGA2-WIF1 Rearrangements Characterize a Distinctive Subset of Salivary Pleomorphic Adenomas With Prominent Trabecular (Canalicular Adenoma-like) Morphology.
Agaimy A et al.·Am J Surg Pathol
2022
Deficient H2A.Z deposition is associated with genesis of uterine leiomyoma.
Berta DG et al.·Nature
2021
Keratin-positive giant cell-rich tumor review.
Chrisinger JSA et al.·Semin Diagn Pathol
2025Review
HMGA2 as a prognostic and immune biomarker in hepatocellular carcinoma: Comprehensive analysis of the HMG family and experiments validation.
Zhong Q et al.·PLoS One
2024
Oncological role of HMGA2 (Review).
Zhang S et al.·Int J Oncol
2019Review
Papillary thyroid carcinoma variants.
Lloyd RV et al.·Head Neck Pathol
2011Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov
Obesity and Obesity-related Medical ConditionsCardiovascular RiskGenetics

Cardiometabolic Risk of Obese Subjects: Cross-sectional Study

RECRUITING
NCT06714058IRCCS Azienda Ospedaliero-Universitaria di BolognaStarted 2024-11-30

External Resources

Links to major genomics databases and tools