HMGB4

Summary

HMGB4 (high mobility group box 4, HGNC:24954) is a protein-coding gene on chromosome 1p35.1, encoding High mobility group protein B4 (Q8WW32).

Predicted to enable DNA binding activity, bending. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleus.

Source: NCBI Gene 127540 — RefSeq curated summary.

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 4 total
• MANE Select transcript: NM_001379301

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24954
Approved symbol	HMGB4
Name	high mobility group box 4
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	FLJ40388
Ensembl gene	ENSG00000176256
Ensembl biotype	protein_coding
OMIM	617285
Entrez	127540

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000425537, ENST00000458277, ENST00000519684, ENST00000522796, ENST00000681531

RefSeq mRNA: 3 — MANE Select: NM_001379301 NM_001352984, NM_001379301, NM_145205

CCDS: CCDS30668

Canonical transcript exons

ENST00000681531 — 1 exons

Exon	Start	End
ENSE00003912429	33864079	33864791

Expression profiles

Bgee: expression breadth ubiquitous, 122 present calls, max score 99.36.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4871 / max 375.0524, expressed in 9 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2060	0.4818	8
201461	0.0052	4

Top tissues by expression

249 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	99.36	gold quality
left testis	UBERON:0004533	99.25	gold quality
adult organism	UBERON:0007023	98.65	gold quality
sperm	CL:0000019	97.96	gold quality
testis	UBERON:0000473	96.34	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.25	gold quality
pancreatic ductal cell	CL:0002079	78.65	silver quality
buccal mucosa cell	CL:0002336	63.15	gold quality
vena cava	UBERON:0004087	59.42	gold quality
epithelial cell of pancreas	CL:0000083	56.91	gold quality
cauda epididymis	UBERON:0004360	56.28	gold quality
myocardium	UBERON:0002349	56.09	gold quality
endothelial cell	CL:0000115	55.23	gold quality
right coronary artery	UBERON:0001625	55.19	gold quality
cardiac muscle of right atrium	UBERON:0003379	54.34	gold quality
left ventricle myocardium	UBERON:0006566	54.23	gold quality
kidney epithelium	UBERON:0004819	53.93	gold quality
upper arm skin	UBERON:0004263	53.52	gold quality
caput epididymis	UBERON:0004358	53.48	gold quality
lower lobe of lung	UBERON:0008949	52.72	silver quality
upper leg skin	UBERON:0004262	52.30	silver quality
trabecular bone tissue	UBERON:0002483	52.21	gold quality
parotid gland	UBERON:0001831	51.79	gold quality
corpus epididymis	UBERON:0004359	49.84	gold quality
tibialis anterior	UBERON:0001385	49.51	silver quality
metanephros cortex	UBERON:0010533	49.23	gold quality
ectocervix	UBERON:0012249	48.70	gold quality
medial globus pallidus	UBERON:0002477	48.56	gold quality
deltoid	UBERON:0001476	48.34	gold quality
cerebellar vermis	UBERON:0004720	48.32	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-134144	yes	7694.00
E-GEOD-124263	yes	5258.10
E-HCAD-38	yes	2830.11
E-ANND-3	yes	2.79

Regulation

Is transcription factor: no

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
danio_rerio	ubtf	ENSDARG00000035066
danio_rerio	ubtfl	ENSDARG00000038780
mus_musculus	Hmgb4	ENSMUSG00000048686
rattus_norvegicus	LOC103694587	ENSRNOG00000065461
rattus_norvegicus	Hmgb4l2	ENSRNOG00000067113
rattus_norvegicus	LOC120099313	ENSRNOG00000069692
rattus_norvegicus	Hmgb4l6	ENSRNOG00000070469
rattus_norvegicus	Hmgb4	ENSRNOG00000071968
rattus_norvegicus		ENSRNOG00000072252
rattus_norvegicus		ENSRNOG00000073930
rattus_norvegicus		ENSRNOG00000075877
rattus_norvegicus		ENSRNOG00000076772
rattus_norvegicus		ENSRNOG00000077096
rattus_norvegicus		ENSRNOG00000079515
rattus_norvegicus		ENSRNOG00000079946
rattus_norvegicus		ENSRNOG00000080046
rattus_norvegicus		ENSRNOG00000082635
rattus_norvegicus		ENSRNOG00000083046
rattus_norvegicus		ENSRNOG00000085671
rattus_norvegicus		ENSRNOG00000085712
rattus_norvegicus		ENSRNOG00000089850
caenorhabditis_elegans	hmg-3	WBGENE00001973
caenorhabditis_elegans		WBGENE00001974

Paralogs (20): HMGB3 (ENSG00000029993), HMG20B (ENSG00000064961), SP100 (ENSG00000067066), SMARCE1 (ENSG00000073584), SP140 (ENSG00000079263), TOX4 (ENSG00000092203), HMGXB4 (ENSG00000100281), TOX3 (ENSG00000103460), TFAM (ENSG00000108064), UBTF (ENSG00000108312), HMGB1P1 (ENSG00000124097), TOX2 (ENSG00000124191), SP110 (ENSG00000135899), HMG20A (ENSG00000140382), SSRP1 (ENSG00000149136), HMGB2 (ENSG00000164104), SP140L (ENSG00000185404), HMGB1 (ENSG00000189403), TOX (ENSG00000198846), UBTFL1 (ENSG00000255009)

Protein

Protein identifiers

High mobility group protein B4 — Q8WW32 (reviewed: Q8WW32)

All UniProt accessions (1): Q8WW32

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus. Chromosome.

Similarity. Belongs to the HMGB family.

RefSeq proteins (3): NP_001339913, NP_001366230, NP_660206 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR009071	HMG_box_dom	Domain
IPR036910	HMG_box_dom_sf	Homologous_superfamily
IPR050342	HMGB	Family

Pfam: PF00505, PF09011

UniProt features (8 total): sequence variant 3, DNA-binding region 2, chain 1, region of interest 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8WW32-F1	88.21	0.59

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 22 (showing top): ATF3_Q6, GOBP_CHROMATIN_REMODELING, chr1p35, MMEF2_Q6, CDC5_01, MARTENS_TRETINOIN_RESPONSE_UP, GSE13306_TREG_VS_TCONV_UP, GSE13493_DP_VS_CD4INTCD8POS_THYMOCYTE_UP, AMEF2_Q6, TGACAGNY_MEIS1_01, GSE17721_CTRL_VS_LPS_2H_BMDC_DN, GSE17721_POLYIC_VS_PAM3CSK4_2H_BMDC_DN, MEF2C_TARGET_GENES, GSE29615_CTRL_VS_DAY3_LAIV_IFLU_VACCINE_PBMC_DN, GSE29615_CTRL_VS_LAIV_FLU_VACCINE_PBMC_DN

GO Biological Process (1): chromatin remodeling (GO:0006338)

GO Molecular Function (2): DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1132 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMGB4	SOX4	Q06945	633
HMGB4	SRY	Q05066	621
HMGB4	FNDC8	Q8TC99	432
HMGB4	SCP2D1	Q9UJQ7	364
HMGB4	IQCF1	Q8N6M8	359
HMGB4	SPTAN1	Q13813	353
HMGB4	RD3	Q7Z3Z2	351
HMGB4	SEPTIN7	Q16181	351
HMGB4	SPTA1	P02549	351
HMGB4	ENTHD1	Q8IYW4	347
HMGB4	CAPZA3	Q96KX2	340
HMGB4	ANKRD9	Q96BM1	338
HMGB4	TMCO2	Q7Z6W1	330
HMGB4	CCDC187	A0A096LP49	326
HMGB4	CCDC181	Q5TID7	325
HMGB4	TSACC	Q96A04	325

IntAct

11 interactions, top by confidence:

A	B	Type	Score
CEP70	HMGB4	psi-mi:“MI:0915”(physical association)	0.720
HMGB4	CEP70	psi-mi:“MI:0915”(physical association)	0.720
HMGB4	KRTAP12-4	psi-mi:“MI:0915”(physical association)	0.560
KRTAP12-4	HMGB4	psi-mi:“MI:0915”(physical association)	0.560
HMGB4	IQCF5	psi-mi:“MI:0915”(physical association)	0.400
HMGB4	CEP70	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (8): HMGB4 (Two-hybrid), KRTAP12-4 (Two-hybrid), HMGB4 (Reconstituted Complex), HMGB4 (Two-hybrid), HMGB4 (Proximity Label-MS), HMGB4 (Cross-Linking-MS (XL-MS)), SOAT1 (Cross-Linking-MS (XL-MS)), APP (Reconstituted Complex)

ESM2 similar proteins: A3QMD7, B2RPK0, C7U331, O04608, O49597, P07746, P0CY16, P0CY17, P17480, P25976, P25977, P25979, P25980, P26586, P40628, P40644, P87057, Q03435, Q08747, Q09390, Q196Z2, Q32L34, Q3USZ2, Q42344, Q59PR9, Q5U1X0, Q61CX7, Q6AYK9, Q6C5G5, Q6P8W9, Q6PGY5, Q6WRX6, Q84XV2, Q8LDF9, Q8WW32, Q93ZG9, Q941D1, Q94234, Q9FT54, Q9LG02

Diamond homologs: A9RA84, B0CM99, B1MTB0, B2RPK0, O01683, O04235, O15347, O15405, O49595, O49596, O49597, O54879, O64702, O94842, O94900, P07156, P07746, P09429, P0CO24, P0CO25, P10103, P11632, P11633, P11873, P12682, P17741, P23497, P26583, P26584, P26585, P26586, P27347, P30681, P40618, P40619, P40620, P40621, P40622, P40623, P40632

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

4 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	4
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

371 predictions. Top by Δscore:

Variant	Effect	Δscore
1:33862863:A:AG	acceptor_gain	0.9800
1:33862864:G:GG	acceptor_gain	0.9800
1:33862864:GAA:G	acceptor_gain	0.9800
1:33861307:T:TG	donor_gain	0.9700
1:33860508:T:G	donor_gain	0.9600
1:33861305:T:TA	donor_gain	0.9500
1:33861333:GTT:G	donor_gain	0.9500
1:33861334:TTT:T	donor_gain	0.9500
1:33862864:GA:G	acceptor_gain	0.9500
1:33861299:A:AG	donor_gain	0.9400
1:33861299:A:G	donor_gain	0.9400
1:33860579:G:GT	donor_gain	0.9300
1:33862859:TTACA:T	acceptor_loss	0.9300
1:33862860:TACAG:T	acceptor_loss	0.9300
1:33862861:ACAG:A	acceptor_loss	0.9300
1:33862862:CA:C	acceptor_loss	0.9300
1:33862863:A:AC	acceptor_loss	0.9300
1:33862864:G:A	acceptor_loss	0.9300
1:33863034:TC:T	donor_gain	0.9300
1:33860579:G:T	donor_gain	0.9200
1:33861306:T:A	donor_gain	0.9100
1:33862936:C:T	donor_gain	0.9100
1:33863027:GCT:G	donor_gain	0.9100
1:33860499:GCT:G	donor_gain	0.9000
1:33862857:TTTTA:T	acceptor_loss	0.8900
1:33862858:TTTAC:T	acceptor_loss	0.8900
1:33861304:GTTT:G	donor_gain	0.8800
1:33860502:G:GG	donor_gain	0.8700
1:33860507:G:GG	donor_gain	0.8700
1:33862864:GAAGA:G	acceptor_gain	0.8500

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000455122 (1:33862573 G>C), RS1001379989 (1:33859571 A>G), RS1002234808 (1:33864391 A>T), RS1002952576 (1:33861473 A>C), RS1003016296 (1:33860861 T>C), RS1003456753 (1:33861150 TTAAG>T), RS1003584231 (1:33860259 T>A,G), RS1003956108 (1:33862856 C>T), RS1004726589 (1:33864998 G>A,T), RS1005086632 (1:33862072 G>A), RS1005321301 (1:33864658 A>T), RS1006734928 (1:33863351 A>G), RS1007023735 (1:33861381 G>A,C), RS1007574160 (1:33860206 C>T), RS1008140387 (1:33862452 T>C,G)

Disease associations

OMIM: gene MIM:617285 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

2 associations (top):

Study	Trait	p-value
GCST002755_5	Depressive symptoms (SSRI exposure interaction)	1.000000e-06
GCST010206_2	Anorectal malformation	5.000000e-18

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007006	depressive symptom measurement
EFO:0007010	drug use measurement
EFO:0007011	SSRI use measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Acetaminophen	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Gold Compounds	increases expression	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.