HMGN4

Chr 6

high mobility group nucleosomal binding domain 4

Also known as: HMG17L3, NHC

NCBI Gene: 10473ENSG00000182952UniProt: O00479

The protein encoded by this gene, a member of the HMGN protein family, is thought to reduce the compactness of the chromatin fiber in nucleosomes, thereby enhancing transcription from chromatin templates. [provided by RefSeq, Mar 2013]

22
ClinVar variants
4
Pathogenic / LP
0.32
pLI score
0
Active trials
Clinical Summary— HMGN4
⚡
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.00) despite low pLI — interpret in context.
📋
ClinVar Variants
4 Pathogenic / Likely Pathogenic· 18 VUS of 22 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
1.86LOEUF
pLI 0.320
Z-score 0.56
OE 0.00 (0.00–1.86)
Tolerant

Highly tolerant — LoF variants common in population

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.
0.27Z-score
OE missense 0.89 (0.69–1.15)
41 obs / 46.2 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 (0.00–1.86)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.89 (0.69–1.15)
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.0.88
0≤1.21.6
LoF obs/exp: 0 / 0.4Missense obs/exp: 41 / 46.2Syn Z: 0.39

ClinVar Variant Classifications

22 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
VUS18
4
Pathogenic
18
VUS

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
0
0
0
VUS
0
13
5
0
18
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total0139022

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

View in ClinVar →

Protein Context — Lollipop Plot

HMGN4 · protein map & ClinVar variants

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

OMIM — Genotype-Phenotype

OMIM

No OMIM entries found.

Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Lactylation signature identifies liver fibrosis phenotypes and traces fibrotic progression to hepatocellular carcinoma.
Li LN et al.·Front Immunol
2024
Elevated HMGN4 expression potentiates thyroid tumorigenesis.
Kugler J et al.·Carcinogenesis
2017
Spatial and Temporal Expression of High-Mobility-Group Nucleosome-Binding (HMGN) Genes in Brain Areas Associated with Cognition in Individuals with Down Syndrome.
Rodríguez-Ortiz A et al.·Genes (Basel)
2021
Integrative transcriptome analysis identifies a crotonylation gene signature for predicting prognosis and drug sensitivity in hepatocellular carcinoma.
Yang B et al.·J Cell Mol Med
2024
Identification of novel biomarkers for hepatocellular carcinoma using transcriptome analysis.
Xia Q et al.·J Cell Physiol
2019
HMGN4, a newly discovered nucleosome-binding protein encoded by an intronless gene.
Birger Y et al.·DNA Cell Biol
2001
IRX5 Promoted SREBP1-Mediated de Novo Fatty Acid Synthesis via HMGN4 in Hepatocellular Carcinoma.
Zhu L et al.·J Cell Mol Med
2025
HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer.
Mou J et al.·Carcinogenesis
2022
Unveiling the host arsenal: Interactome profiling of ALV-J p32 integrase reveals novel antiviral targets.
Chen L et al.·Int J Biol Macromol
2026
Characterization of a human gene encoding nucleosomal binding protein NSBP1.
King LM et al.·Genomics
2001
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC

No open access results found

Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools