HMGN4

Summary

HMGN4 (high mobility group nucleosomal binding domain 4, HGNC:4989) is a protein-coding gene on chromosome 6p22.2, encoding High mobility group nucleosome-binding domain-containing protein 4 (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.

Source: NCBI Gene 10473 — RefSeq curated summary.

At a glance

• GWAS associations: 24
• Clinical variants (ClinVar): 14 total
• MANE Select transcript: NM_006353

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4989
Approved symbol	HMGN4
Name	high mobility group nucleosomal binding domain 4
Location	6p22.2
Locus type	gene with protein product
Status	Approved
Aliases	NHC
Ensembl gene	ENSG00000182952
Ensembl biotype	protein_coding
Entrez	10473

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 23 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000377575, ENST00000477243, ENST00000895803, ENST00000895804, ENST00000895805, ENST00000895806, ENST00000895807, ENST00000895808, ENST00000895809, ENST00000895810, ENST00000916006, ENST00000916007, ENST00000916008, ENST00000916009, ENST00000916010, ENST00000916011, ENST00000916012, ENST00000916013, ENST00000916014, ENST00000916015, ENST00000916016, ENST00000954641, ENST00000954642, ENST00000954643

RefSeq mRNA: 1 — MANE Select: NM_006353 NM_006353

CCDS: CCDS4615

Canonical transcript exons

ENST00000377575 — 2 exons

Exon	Start	End
ENSE00001474414	26545127	26546933
ENSE00001474420	26538366	26538501

Expression profiles

Bgee: expression breadth ubiquitous, 294 present calls, max score 98.51.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 53.0012 / max 302.5516, expressed in 1824 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
66535	51.8385	1824
66536	0.7131	450
66534	0.4496	159

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.51	gold quality
germinal epithelium of ovary	UBERON:0001304	97.87	gold quality
choroid plexus epithelium	UBERON:0003911	97.77	gold quality
epithelium of nasopharynx	UBERON:0001951	97.46	gold quality
parietal pleura	UBERON:0002400	97.37	gold quality
endothelial cell	CL:0000115	97.11	gold quality
granulocyte	CL:0000094	97.05	gold quality
pleura	UBERON:0000977	97.05	gold quality
superficial temporal artery	UBERON:0001614	97.01	gold quality
endometrium	UBERON:0001295	96.97	gold quality
smooth muscle tissue	UBERON:0001135	96.75	gold quality
rectum	UBERON:0001052	96.70	gold quality
visceral pleura	UBERON:0002401	96.62	gold quality
hair follicle	UBERON:0002073	96.56	gold quality
blood vessel layer	UBERON:0004797	96.54	gold quality
epithelial cell of pancreas	CL:0000083	96.45	gold quality
seminal vesicle	UBERON:0000998	96.43	gold quality
lymph node	UBERON:0000029	96.39	gold quality
cauda epididymis	UBERON:0004360	96.34	gold quality
jejunal mucosa	UBERON:0000399	96.30	gold quality
thymus	UBERON:0002370	96.23	gold quality
caput epididymis	UBERON:0004358	96.15	gold quality
mucosa of sigmoid colon	UBERON:0004993	96.10	gold quality
vermiform appendix	UBERON:0001154	96.07	gold quality
leukocyte	CL:0000738	96.05	gold quality
palpebral conjunctiva	UBERON:0001812	96.04	gold quality
urethra	UBERON:0000057	96.02	gold quality
mononuclear cell	CL:0000842	95.95	gold quality
uterus	UBERON:0000995	95.93	gold quality
monocyte	CL:0000576	95.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.85
E-GEOD-110499	no	996.22

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

57 targeting HMGN4, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-8075	99.97	67.20	962
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-205-3P	99.92	69.92	3165
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917
HSA-MIR-30E-3P	99.87	69.68	2942
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-5003-3P	99.85	69.29	2517
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-2052	99.79	69.37	2031
HSA-MIR-34B-5P	99.78	67.56	1175
HSA-MIR-449C-5P	99.78	67.63	1168
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-2682-5P	99.73	67.38	1055
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3714	99.71	70.74	2671
HSA-MIR-7-5P	99.67	70.53	1809

Literature-anchored findings (GeneRIF, showing 2)

• HMGN4 may serve as an additional diagnostic marker. (PMID:28186538)
• HMGN4 plays a key role in STAT3-mediated oncogenesis of triple-negative breast cancer. (PMID:35792800)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
danio_rerio	hmgn2	ENSDARG00000099572

Paralogs (3): HMGN3 (ENSG00000118418), HMGN2 (ENSG00000198830), HMGN1 (ENSG00000205581)

Protein

Protein identifiers

High mobility group nucleosome-binding domain-containing protein 4 — O00479 (reviewed: O00479)

Alternative names: Non-histone chromosomal protein HMG-17-like 3

All UniProt accessions (1): O00479

UniProt curated annotations — full annotation on UniProt →

Subcellular location. Nucleus.

Similarity. Belongs to the HMGN family.

RefSeq proteins (1): NP_006344* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000079	HMGN_fam	Family

Pfam: PF01101

UniProt features (7 total): modified residue 3, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00479-F1	65.41	0.00

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (3): 29, 80, 82

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 157 (showing top): MORF_HDAC2, MODULE_16, TOMLINS_PROSTATE_CANCER_DN, PUJANA_CHEK2_PCC_NETWORK, YORDY_RECIPROCAL_REGULATION_BY_ETS1_AND_SP100_UP, CREIGHTON_ENDOCRINE_THERAPY_RESISTANCE_1, WATANABE_RECTAL_CANCER_RADIOTHERAPY_RESPONSIVE_UP, MORF_PRKDC, SCHLOSSER_SERUM_RESPONSE_DN, MORF_RAP1A, WANG_CISPLATIN_RESPONSE_AND_XPC_DN, TANAKA_METHYLATED_IN_ESOPHAGEAL_CARCINOMA, CAIRO_HEPATOBLASTOMA_UP, MODULE_98, SASAKI_ADULT_T_CELL_LEUKEMIA

GO Biological Process (1): chromatin organization (GO:0006325)

GO Molecular Function (4): chromatin binding (GO:0003682), nucleosomal DNA binding (GO:0031492), DNA binding (GO:0003677), protein binding (GO:0005515)

GO Cellular Component (2): chromatin (GO:0000785), nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular component organization	1
chromatin DNA binding	1
nucleosome binding	1
nucleic acid binding	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3004 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HMGN4	HMGN1	P05114	571
HMGN4	POM121L2	Q96KW2	472
HMGN4	HMGN5	P82970	453
HMGN4	CCL19	Q99731	385
HMGN4	ESF1	Q9H501	376
HMGN4	MXD3	Q9BW11	376
HMGN4	ZNF184	Q99676	369
HMGN4	PNCK	Q6P2M8	368
HMGN4	YARS1	P54577	349
HMGN4	VARS1	P26640	349
HMGN4	PRSS16	Q9NQE7	346
HMGN4	DENND11	A4D1U4	317
HMGN4	ZNF322	Q6U7Q0	315
HMGN4	ABT1	Q9ULW3	313
HMGN4	MARS1	P56192	312

IntAct

22 interactions, top by confidence:

A	B	Type	Score
HMGN4	TERF2IP	psi-mi:“MI:0915”(physical association)	0.510
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
HMGN4	NPM1	psi-mi:“MI:0915”(physical association)	0.400
HMGN4	TERF1	psi-mi:“MI:0915”(physical association)	0.370
HMGN4	TERF2	psi-mi:“MI:0915”(physical association)	0.370
HMGN4	SMO	psi-mi:“MI:0915”(physical association)	0.370
EWSR1	HMGN4	psi-mi:“MI:0915”(physical association)	0.370
APP	ESYT2	psi-mi:“MI:0914”(association)	0.350
ARHGAP39	HMGN4	psi-mi:“MI:0914”(association)	0.350
TOP3B	HMGN4	psi-mi:“MI:0914”(association)	0.350
rep	HMGN4	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
HMGN4	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
HMGN4	RRP8	psi-mi:“MI:0914”(association)	0.350
LIAS	HMGN4	psi-mi:“MI:0914”(association)	0.350
SMARCB1	KIF2A	psi-mi:“MI:2364”(proximity)	0.270
SMARCB1	FAM186A	psi-mi:“MI:2364”(proximity)	0.270
HMGN4	TERF2IP	psi-mi:“MI:0915”(physical association)	0.000
	HMGN4	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (122): HMGN4 (Proximity Label-MS), HMGN4 (Biochemical Activity), HMGN4 (Reconstituted Complex), HMGN4 (Proximity Label-MS), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS), NPM1 (Proximity Label-MS), HMGN4 (Proximity Label-MS), HMGN4 (Two-hybrid), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS), HMGN4 (Affinity Capture-MS)

ESM2 similar proteins: A0A1B0GTR3, O00479, O14598, P02313, P02314, P02315, P02316, P05114, P05204, P09602, P0DPH9, P10156, P12274, P12902, P18437, P18608, P22058, P49342, P80272, Q04504, Q15651, Q29026, Q2YDK4, Q32N87, Q32PF3, Q3ZBV4, Q4VC05, Q5FVI4, Q5R715, Q5RAA0, Q5RCI9, Q5XXA9, Q5ZIR5, Q5ZM33, Q66H40, Q6P8I4, Q711A6, Q80XU3, Q8C551, Q8N111

Diamond homologs: O00479, P02313, P02314, P05204, P09602, P12902, P18437, P80272, Q15651, Q2YDK4, Q3ZBV4, Q5R715, Q5RAA0, Q66H40, Q711A6, Q9DCB1, P02316, P05114, P12274, P18608, P82970, Q5ZIR5

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	13
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

553 predictions. Top by Δscore:

Variant	Effect	Δscore
6:26538500:GG:G	donor_gain	1.0000
6:26538501:GG:G	donor_gain	1.0000
6:26538502:G:GG	donor_gain	1.0000
6:26538502:GTAA:G	donor_loss	1.0000
6:26538497:CTCGG:C	donor_gain	0.9900
6:26538498:TCGG:T	donor_gain	0.9900
6:26538499:CGG:C	donor_gain	0.9900
6:26538500:GGG:G	donor_gain	0.9900
6:26542821:T:TA	acceptor_gain	0.9900
6:26542832:ATGT:A	acceptor_gain	0.9900
6:26542833:T:G	acceptor_gain	0.9900
6:26545126:GAC:G	acceptor_gain	0.9900
6:26545126:GACA:G	acceptor_gain	0.9900
6:26542828:T:TA	acceptor_gain	0.9800
6:26542832:ATGTG:A	acceptor_gain	0.9800
6:26545123:A:AG	acceptor_gain	0.9800
6:26545124:A:G	acceptor_gain	0.9800
6:26545125:A:AG	acceptor_gain	0.9800
6:26545126:G:GG	acceptor_gain	0.9800
6:26542817:ATTTT:A	acceptor_gain	0.9700
6:26542832:A:AG	acceptor_gain	0.9700
6:26545126:GACAT:G	acceptor_gain	0.9700
6:26542822:G:A	acceptor_gain	0.9600
6:26545122:TAAA:T	acceptor_loss	0.9600
6:26545126:GA:G	acceptor_gain	0.9600
6:26542835:T:TA	acceptor_gain	0.9500
6:26542832:AT:A	acceptor_gain	0.9400
6:26544850:G:GT	acceptor_gain	0.9400
6:26545119:T:A	acceptor_gain	0.9300
6:26538502:G:T	donor_gain	0.9100

AlphaMissense

576 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:26545275:G:C	R23S	0.958
6:26545275:G:T	R23S	0.958
6:26545278:A:C	R24S	0.953
6:26545278:A:T	R24S	0.953
6:26545218:A:C	R4S	0.932
6:26545218:A:T	R4S	0.932
6:26545274:G:T	R23M	0.914
6:26545277:G:C	R24T	0.884
6:26545274:G:C	R23T	0.872
6:26545286:G:C	R27P	0.838
6:26545217:G:C	R4T	0.827
6:26545215:G:C	K3N	0.821
6:26545215:G:T	K3N	0.821
6:26545217:G:T	R4I	0.815
6:26545277:G:T	R24I	0.810
6:26545211:C:A	P2H	0.801
6:26545273:A:G	R23G	0.794
6:26545276:A:G	R24G	0.790
6:26545273:A:T	R23W	0.788
6:26545280:C:T	S25L	0.782
6:26545211:C:T	P2L	0.765
6:26545221:G:C	K5N	0.761
6:26545221:G:T	K5N	0.761
6:26545286:G:T	R27L	0.752
6:26545285:C:G	R27G	0.722
6:26545289:T:G	L28W	0.721
6:26545292:C:T	S29F	0.709
6:26545214:A:T	K3M	0.698
6:26545211:C:G	P2R	0.674
6:26545289:T:C	L28S	0.673

dbSNP variants (sampled 300 via entrez): RS1000055525 (6:26538047 T>C,G), RS1000385579 (6:26539338 A>G), RS1000728839 (6:26540179 C>G), RS1000756525 (6:26538772 C>A,T), RS1001050671 (6:26546524 A>G,T), RS1002091220 (6:26541591 A>G), RS1002320430 (6:26542488 CAA>C,CA), RS1002632214 (6:26545793 T>C), RS1002775010 (6:26542259 G>C), RS1002829858 (6:26538132 T>C), RS1002842237 (6:26538049 A>C,G), RS1003346538 (6:26545030 A>G), RS1003361388 (6:26543417 T>C), RS1003556814 (6:26537759 C>G,T), RS1003821962 (6:26537942 G>A)

Disease associations

OMIM: gene `` | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

24 associations (top):

Study	Trait	p-value
GCST004521_113	Autism spectrum disorder or schizophrenia	3.000000e-19
GCST004521_208	Autism spectrum disorder or schizophrenia	5.000000e-17
GCST004521_215	Autism spectrum disorder or schizophrenia	5.000000e-13
GCST004521_301	Autism spectrum disorder or schizophrenia	1.000000e-08
GCST004521_69	Autism spectrum disorder or schizophrenia	8.000000e-24
GCST004746_1	Small cell lung carcinoma	1.000000e-06
GCST004749_65	Lung cancer in ever smokers	6.000000e-07
GCST006269_503	General cognitive ability	2.000000e-17
GCST006269_681	General cognitive ability	8.000000e-10
GCST010002_50	Refractive error	4.000000e-34
GCST010142_16	Fish- and plant-related diet	2.000000e-10
GCST010142_19	Fish- and plant-related diet	4.000000e-10
GCST010142_34	Fish- and plant-related diet	7.000000e-09
GCST010142_35	Fish- and plant-related diet	8.000000e-09
GCST010142_42	Fish- and plant-related diet	1.000000e-08
GCST010142_7	Fish- and plant-related diet	3.000000e-12
GCST010142_74	Fish- and plant-related diet	9.000000e-09
GCST010142_82	Fish- and plant-related diet	3.000000e-08
GCST010702_75	Subcortical volume (MOSTest)	3.000000e-11
GCST010703_272	Brain morphology (MOSTest)	7.000000e-16
GCST90000514_4	Gastroesophageal reflux disease	2.000000e-13
GCST90020025_993	Waist-to-hip ratio adjusted for BMI	1.000000e-09
GCST90020027_750	Waist-hip index	8.000000e-09
GCST90020028_823	Hip circumference adjusted for BMI	3.000000e-11

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008039	BMI-adjusted hip circumference

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

21 total (human), top 21 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
dicrotophos	decreases expression	1
bisphenol A	increases expression	1
methylselenic acid	increases expression	1
sodium arsenite	decreases expression	1
potassium chromate(VI)	decreases expression	1
beta-methylcholine	affects expression	1
di-n-butylphosphoric acid	affects expression	1
K 7174	increases expression	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Air Pollutants	increases abundance, decreases expression	1
Doxorubicin	decreases expression	1
Methyl Methanesulfonate	decreases expression	1
Urethane	increases expression	1
Cyclosporine	increases expression	1
Antirheumatic Agents	decreases expression	1
Cadmium Chloride	decreases expression	1
Particulate Matter	decreases expression, increases abundance	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_B1TR	Abcam HeLa HMGN4 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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