HMGB1

Chr 13

high mobility group box 1

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.

OMIMResearchSummary from RefSeq, UniProt
LOEUF 0.47
Clinical SummaryHMGB1
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.82) — some intolerance to loss-of-function variants.
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Clinical Trials
4 active or recruiting trials — potential therapeutic options may be available
Some data sources returned errors (1)

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.47LOEUF
pLI 0.820
Z-score 2.64
OE 0.10 (0.030.47)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.69Z-score
OE missense 0.27 (0.200.37)
30 obs / 109.2 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.10 (0.030.47)
00.351.4
Missense OE0.27 (0.200.37)
00.61.4
Synonymous OE1.13
01.21.6
LoF obs/exp: 1 / 10.0Missense obs/exp: 30 / 109.2Syn Z: -0.62

ClinVar Variant Classifications

0 submitted variants 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
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