HMGB4

protein-coding

high mobility group box 4, the group of Canonical high mobility group

Gene summary

Predicted to enable DNA binding activity. Predicted to be involved in chromatin remodeling. Located in nucleus. [provided by Alliance of Genome Resources, Jun 2026]

MANE transcript

NM_001379301.1

Inheritance

—

ClinVar variants

U:29B:1

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.26

Max pathogenic AF

—

Genomic locus

chr1:33,860,475-33,864,791

External References & Databases

Ensembl (ENSG00000176256)

Transcript & Mutation Effects

hg38 • Region Span ~4.3 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to HMGB4 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 30

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001379301.1. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous						0
missense			29 clinvar	1 clinvar		30
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)						0
Total	0	0	29	1	0	30

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 7 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001379301.1	RefSeq	NP_001366230.1	1	MANE Select
ENST00000681531.1	Ensembl	ENSP00000505691.1	1	MANE Select
NM_001352984.2	RefSeq	NP_001339913.1	1	Standard
NM_145205.6	RefSeq	NP_660206.2	1	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

activation of innate immune response
DNA recombination
chromatin remodeling
regulation of transcription by RNA polymerase II
regulation of signaling receptor activity

Molecular Function

protein binding
transcription factor binding
DNA binding, bending

Cellular Component

nuclear chromatin
nucleus
cytoplasm

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000522796
Coding exons: 1
Length: 4317
Individuals with no LoFs: 125418
Homozygous LoFs: 1
Heterozygous LoFs: 125
Defined: 125544
p: 0.000502

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.216	110	104	1.06	0.00000587	1204
Missense (PolyPhen)		34	37.291	0.91175		469
Synonymous	0.742	35	41.0	0.853	0.00000231	343
Loss of Function	-0.366	3	2.39	1.26	9.92e-8	35

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00025	0.00025	rare
Latino/Admixed American	0.00052	0.00052	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00087	0.00086	rare
South Asian	0.000068	0.000065	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Recessive Scores

pRec: 0.0735

Intolerance Scores

LoFtool: 0.396
RVIS EVS: 0.68
RVIS percentile EVS: 85.04

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.539

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium