HMGB1

Chr 13

high mobility group box 1

Also known as: HMG-1, HMG1, HMG3, SBP-1

NCBI Gene: 3146ENSG00000189403UniProt: P09429

The encoded protein is a multifunctional chromatin-associated non-histone protein that acts as a DNA chaperone involved in transcription, replication, chromatin remodeling, and DNA repair, and also functions as a danger-associated molecular pattern molecule in immune responses. This gene is associated with neurodevelopmental disorders and intellectual disability, with an autosomal dominant inheritance pattern. The gene shows high constraint against loss-of-function variants (pLI 0.82, LOEUF 0.47), indicating that haploinsufficiency is likely not well tolerated.

Summary from RefSeq, UniProt
Research Assistant →
5
Active trials
1125
Pubs (1 yr)
45
P/LP submissions
0%
P/LP missense
0.47
LOEUF
—
Mechanism
Clinical Summary— HMGB1
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
45 unique Pathogenic / Likely Pathogenic· 17 VUS of 83 total submissions
💊
Clinical Trials
5 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →
📖
GeneReview available — HMGB1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.820
Z-score 2.64
OE 0.10 (0.03–0.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.69Z-score
OE missense 0.27 (0.20–0.37)
30 obs / 109.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.03–0.47)
0≤0.351.4
Missense OE0.27 (0.20–0.37)
0≤0.61.4
Synonymous OE1.13
0≤1.21.6
LoF obs/exp: 1 / 10.0Missense obs/exp: 30 / 109.2Syn Z: -0.62

ClinVar Variant Classifications

83 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic39
Likely Pathogenic6
VUS17
Likely Benign5
Benign6
39
Pathogenic
6
Likely Pathogenic
17
VUS
5
Likely Benign
6
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
3
0
36
0
39
Likely Pathogenic
2
0
4
0
6
VUS
2
6
9
0
17
Likely Benign
0
1
1
3
5
Benign
0
0
3
3
6
Total7753673

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HMGB1 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Ma Xing Shi Gan Decoction reduces influenza A virus nucleoprotein levels in association with modulation of lactate-HMGB1 lactylation and autophagosome accumulation.
Ji Y et al.·J Ethnopharmacol
2026
HMGB1-mediated enhancement of glycolysis activates hepatic stellate cells by inhibiting ferroptosis in alcoholic hepatic fibrosis.
Li Y et al.·Stem Cell Res Ther
2026
Attenuation of imidacloprid deleterious effect on hepatic and neural tissues via acetylsalicylic acid: targeting HMGB1/caspase-3 axis and inflammatory pathway.
Ragab AM et al.·Naunyn Schmiedebergs Arch Pharmacol
2026
HMGB1, An Autophagy-Associated Gene, as a Novel Non-Invasive Diagnostic Biomarker: Clinicopathologic Correlation in Urinary Bladder Carcinoma Patients.
Data S et al.·Ann Surg Oncol
2026Cohort
Modulation of the HMGB1/TLR4 pathway by montelukast in PTZ-induced epilepsy: alleviating neuroinflammatory oxidative stress and seizure severity.
Bano A et al.·Int J Neurosci
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients