HMGN2

Chr 1

high mobility group nucleosomal binding domain 2

Also known as: HMG17

The protein binds nucleosomal DNA and helps maintain an open chromatin configuration around transcriptionally active genes. Mutations cause neurodevelopmental disorders with intellectual disability, developmental delay, and behavioral abnormalities, inherited in an autosomal dominant pattern. The gene is highly constrained against loss-of-function variants (pLI 0.86, LOEUF 0.46), reflecting its essential role in chromatin regulation.

OMIMResearchSummary from RefSeq, UniProt
LOFmechanismLOEUF 0.46
Clinical SummaryHMGN2
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.86) — some intolerance to loss-of-function variants.
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ClinVar Variants
4 unique Pathogenic / Likely Pathogenic· 5 VUS of 20 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.46LOEUF
pLI 0.863
Z-score 2.37
OE 0.00 (0.000.46)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
0.03Z-score
OE missense 0.99 (0.781.27)
45 obs / 45.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.00 (0.000.46)
00.351.4
Missense OE0.99 (0.781.27)
00.61.4
Synonymous OE1.20
01.21.6
LoF obs/exp: 0 / 6.5Missense obs/exp: 45 / 45.6Syn Z: -0.62
DN
0.4190th %ile
GOF
0.08100th %ile
LOF
0.76top 10%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.46

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

20 submitted variants in ClinVar

Classification Summary

Pathogenic4
VUS5
4
Pathogenic
5
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories· variant type breakdown unavailable

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
4
Likely Pathogenic
0
VUS
5
Likely Benign
0
Benign
0
Total9

Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HMGN2 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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