HMGB1

Chr 13

high mobility group box 1

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

NCBI Gene: 3146ENSG00000189403UniProt: P09429

This gene encodes a protein that belongs to the High Mobility Group-box superfamily. The encoded non-histone, nuclear DNA-binding protein regulates transcription, and is involved in organization of DNA. This protein plays a role in several cellular processes, including inflammation, cell differentiation and tumor cell migration. Multiple pseudogenes of this gene have been identified. Alternative splicing results in multiple transcript variants that encode the same protein. [provided by RefSeq, Sep 2015]

GeneReviewsResearchGenerating clinical summary…

Clinical highlights

Gene-disease validity (ClinGen)
HMGB1-related brachyphalangy, polydactyly and tibial aplasia syndrome · ADModerateconsider for supplementary testing
Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Curated gene-level mechanism — a prior for triage, not a per-variant call.
5
Active trials
1634
Pubs (1 yr)
—
P/LP submissions
—
P/LP missense
0.47
LOEUF
—
Mechanism
📖
GeneReview available — HMGB1
Authoritative clinical overview · Recommended first read
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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

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 OE?0.10 (0.03–0.47)
0≤0.351.4
Missense OE?0.27 (0.20–0.37)
0≤0.61.4
Synonymous OE?1.13
0≤1.21.6
LoF obs/exp: 1 / 10.0Missense obs/exp: 30 / 109.2Syn Z: -0.62

ClinVar Variant Classifications

0 submitted variants in ClinVar

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.

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