H2BC26

Summary

H2BC26 (H2B clustered histone 26, HGNC:20514) is a protein-coding gene on chromosome 1q42.13, encoding Histone H2B type 3-B (Q8N257). Core component of nucleosome.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones (H2A, H2B, H3, and H4). The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. This gene is intronless and encodes a replication-dependent histone that is a member of the histone H2B family. Transcripts from this gene contain a palindromic termination element.

Source: NCBI Gene 128312 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 21 total
• MANE Select transcript: NM_175055

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:20514
Approved symbol	H2BC26
Name	H2B clustered histone 26
Location	1q42.13
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000196890
Ensembl biotype	protein_coding
OMIM	615046
Entrez	128312

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000620438, ENST00000690378, ENST00000693095

RefSeq mRNA: 1 — MANE Select: NM_175055 NM_175055

CCDS: CCDS1574

Canonical transcript exons

ENST00000647549 — 0 exons

Expression profiles

Bgee: expression breadth ubiquitous, 119 present calls, max score 76.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 63.2815 / max 1825.3523, expressed in 1654 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
8949	63.2815	1654

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	76.83	gold quality
right uterine tube	UBERON:0001302	71.02	gold quality
cerebellum	UBERON:0002037	70.63	gold quality
cerebellar hemisphere	UBERON:0002245	70.61	gold quality
cerebellar cortex	UBERON:0002129	70.58	gold quality
right hemisphere of cerebellum	UBERON:0014890	69.91	gold quality
ganglionic eminence	UBERON:0004023	66.61	gold quality
ventricular zone	UBERON:0003053	63.01	gold quality
bone marrow	UBERON:0002371	62.18	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	61.84	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	61.47	gold quality
prefrontal cortex	UBERON:0000451	59.98	gold quality
blood	UBERON:0000178	59.61	gold quality
vagina	UBERON:0000996	59.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	59.08	gold quality
lower esophagus mucosa	UBERON:0035834	58.66	gold quality
frontal cortex	UBERON:0001870	56.94	gold quality
right adrenal gland	UBERON:0001233	56.76	gold quality
cortical plate	UBERON:0005343	56.48	gold quality
right adrenal gland cortex	UBERON:0035827	56.32	gold quality
tonsil	UBERON:0002372	56.07	gold quality
granulocyte	CL:0000094	55.81	gold quality
left adrenal gland cortex	UBERON:0035825	55.62	gold quality
brain	UBERON:0000955	55.53	gold quality
colonic epithelium	UBERON:0000397	55.25	gold quality
left adrenal gland	UBERON:0001234	55.22	gold quality
skin of abdomen	UBERON:0001416	55.21	gold quality
esophagus mucosa	UBERON:0002469	55.09	gold quality
adrenal gland	UBERON:0002369	55.07	gold quality
nucleus accumbens	UBERON:0001882	54.85	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-MTAB-6379	no	178.72
E-ANND-3	no	0.86

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 5)

• Histone H2B represents a regulated plasminogen receptor, which contributes significantly to the plasminogen binding capacity of cells. (PMID:16878981)
• infertile men have a higher proportion of spermatozoa with diffuse histone H2B (PMID:18958350)
• USP7 can stimulate EBNA1-DNA interactions and EBNA1 can alter histone modification at oriP through recruitment of USP7. (PMID:19834552)
• The present findings provide evidence indicating that the extrachromosomal histone H2B is engaged in the signaling pathway initiated by dsDNA to trigger antiviral innate immune responses. (PMID:19906922)
• ATM-dependent monoubiquitylation of histone H2B is required for timely repair of DNA double-strand breaks (PMID:21362549)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bc26	ENSMUSG00000080712
rattus_norvegicus	H2bu1	ENSRNOG00000085593

Paralogs (21): H2BW2 (ENSG00000101812), H2BW1 (ENSG00000123569), H2BC11 (ENSG00000124635), H2BC1 (ENSG00000146047), H2BC5 (ENSG00000158373), H2BC4 (ENSG00000180596), H2BC21 (ENSG00000184678), H2BC13 (ENSG00000185130), H2BC12 (ENSG00000197903), H2BC18 (ENSG00000203814), H2BC15 (ENSG00000233822), H2BC12L (ENSG00000234289), H2BC14 (ENSG00000273703), H2BC8 (ENSG00000273802), H2BC6 (ENSG00000274290), H2BC17 (ENSG00000274641), H2BC9 (ENSG00000275713), H2BC3 (ENSG00000276410), H2BC7 (ENSG00000277224), H2BC10 (ENSG00000278588), H2BK1 (ENSG00000285480)

Protein

Protein identifiers

Histone H2B type 3-B — Q8N257 (reviewed: Q8N257)

Alternative names: H2B type 12, H2B-clustered histone 26, H2B.U histone 1

All UniProt accessions (1): Q8N257

UniProt curated annotations — full annotation on UniProt →

Function. Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

Subunit / interactions. The nucleosome is a histone octamer containing two molecules each of H2A, H2B, H3 and H4 assembled in one H3-H4 heterotetramer and two H2A-H2B heterodimers. The octamer wraps approximately 147 bp of DNA.

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Monoubiquitination at Lys-35 (H2BK34Ub) by the MSL1/MSL2 dimer is required for histone H3 ‘Lys-4’ (H3K4me) and ‘Lys-79’ (H3K79me) methylation and transcription activation at specific gene loci, such as HOXA9 and MEIS1 loci. Similarly, monoubiquitination at Lys-121 (H2BK120Ub) by the RNF20/40 complex gives a specific tag for epigenetic transcriptional activation and is also prerequisite for histone H3 ‘Lys-4’ and ‘Lys-79’ methylation. It also functions cooperatively with the FACT dimer to stimulate elongation by RNA polymerase II. H2BK120Ub also acts as a regulator of mRNA splicing: deubiquitination by USP49 is required for efficient cotranscriptional splicing of a large set of exons. Phosphorylation at Ser-37 (H2BS36ph) by AMPK in response to stress promotes transcription. Phosphorylated on Ser-15 (H2BS14ph) by STK4/MST1 during apoptosis; which facilitates apoptotic chromatin condensation. Also phosphorylated on Ser-15 in response to DNA double strand breaks (DSBs), and in correlation with somatic hypermutation and immunoglobulin class-switch recombination. GlcNAcylation at Ser-113 promotes monoubiquitination of Lys-121. It fluctuates in response to extracellular glucose, and associates with transcribed genes. ADP-ribosylated by PARP1 or PARP2 on Ser-7 (H2BS6ADPr) in response to DNA damage. H2BS6ADPr promotes recruitment of CHD1L. Poly ADP-ribosylation on Glu-36 (H2BE35ADPr) by PARP1 regulates adipogenesis: it inhibits phosphorylation at Ser-37 (H2BS36ph), thereby blocking expression of pro-adipogenetic genes. Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.

Similarity. Belongs to the histone H2B family.

RefSeq proteins (1): NP_778225* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000558	Histone_H2B	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR055333	HISTONE_H2B_site	Conserved_site

Pfam: PF00125

UniProt features (99 total): modified residue 90, cross-link 4, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
6BIZ	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8N257-F1	87.46	0.68

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 (94): 6, 6, 6, 7, 12, 12, 12, 12, 12, 12, 13, 13, 13, 15, 16, 16, 16, 16, 17, 17 …

Glycosylation sites (1): 113

Function

Pathways and Gene Ontology

Reactome pathways

57 pathways

ID	Pathway
R-HSA-110328	Recognition and association of DNA glycosylase with site containing an affected pyrimidine
R-HSA-110329	Cleavage of the damaged pyrimidine
R-HSA-110330	Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331	Cleavage of the damaged purine
R-HSA-1221632	Meiotic synapsis
R-HSA-171306	Packaging Of Telomere Ends
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-201722	Formation of the beta-catenin:TCF transactivating complex
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2299718	Condensation of Prophase Chromosomes
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-2559582	Senescence-Associated Secretory Phenotype (SASP)
R-HSA-2559586	DNA Damage/Telomere Stress Induced Senescence
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214847	HATs acetylate histones
R-HSA-427359	SIRT1 negatively regulates rRNA expression
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-427413	NoRC negatively regulates rRNA expression
R-HSA-5250924	B-WICH complex positively regulates rRNA expression
R-HSA-5334118	DNA methylation
R-HSA-5578749	Transcriptional regulation by small RNAs
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571	Nonhomologous End-Joining (NHEJ)
R-HSA-5693607	Processing of DNA double-strand break ends
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-68616	Assembly of the ORC complex at the origin of replication
R-HSA-69473	G2/M DNA damage checkpoint

MSigDB gene sets: 176 (showing top): REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, CCAWYNNGAAR_UNKNOWN, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_INNATE_IMMUNE_RESPONSE_IN_MUCOSA, GOBP_HUMORAL_IMMUNE_RESPONSE, CREB_Q3, REACTOME_DNA_REPAIR

GO Biological Process (0):

GO Molecular Function (3): DNA binding (GO:0003677), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982)

GO Cellular Component (5): nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Cellular Senescence	3
Depyrimidination	2
Depurination	2
Epigenetic regulation of gene expression	2
Chromatin modifying enzymes	2
Negative epigenetic regulation of rRNA expression	2
Positive epigenetic regulation of rRNA expression	2
Meiosis	1
Telomere Maintenance	1
Pre-NOTCH Expression and Processing	1
TCF dependent signaling in response to WNT	1
Mitotic Prophase	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
cellular anatomical structure	2
nucleic acid binding	1
structural molecule activity	1
protein dimerization activity	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cytoplasm	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2310 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BC26	PLG	P00747	867
H2BC26	RNF20	Q5VTR2	843
H2BC26	H3C1	P02295	816
H2BC26	H3C14	Q71DI3	815
H2BC26	H3-4	Q16695	814
H2BC26	H3-7	Q5TEC6	814
H2BC26	H3-3A	P06351	813
H2BC26	H3-5	Q6NXT2	813
H2BC26	RNF40	O75150	772
H2BC26	H4C16	P02304	747
H2BC26	H2AC20	Q16777	745
H2BC26	H2AC19	P20670	745
H2BC26	H4C7	Q99525	745
H2BC26	USP22	Q9UPT9	728
H2BC26	DET1	Q7L5Y6	727

IntAct

27 interactions, top by confidence:

A	B	Type	Score
MAP4K4	STRN	psi-mi:“MI:0914”(association)	0.530
MED27	POLR2D	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
TNIP1	COCH	psi-mi:“MI:0914”(association)	0.350
HAUS8	ATP5PD	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
LIN28A	MEX3A	psi-mi:“MI:0914”(association)	0.350
	PSMD3	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
H1-0	SMARCA5	psi-mi:“MI:0914”(association)	0.350
H2BC21	SMCHD1	psi-mi:“MI:0914”(association)	0.350
NCK1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
NECAP1	SMARCA5	psi-mi:“MI:0914”(association)	0.350
NUMA1	SHANK3	psi-mi:“MI:0914”(association)	0.350
PARP1	KPNA3	psi-mi:“MI:0914”(association)	0.350
PPM1G	SRP14	psi-mi:“MI:0914”(association)	0.350
SSRP1	DDX39A	psi-mi:“MI:0914”(association)	0.350
SCRIB	CHD2	psi-mi:“MI:0914”(association)	0.350
LZTS3	SIPA1L1	psi-mi:“MI:0914”(association)	0.350
H2AZ1	PPM1G	psi-mi:“MI:0914”(association)	0.350
NS	IGF2BP3	psi-mi:“MI:0914”(association)	0.350
US11		psi-mi:“MI:0914”(association)	0.350
VP35		psi-mi:“MI:0914”(association)	0.350

BioGRID (361): HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-RNA), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Affinity Capture-MS), HIST3H2BB (Synthetic Lethality)

ESM2 similar proteins: A0A2R8Y619, O97484, P02284, P02285, P02286, P02287, P02288, P04255, P04913, P07794, P07795, P0C1H4, P16888, P16889, P16890, P19374, P21897, P23527, P27326, P30757, P33778, P35067, P35068, P35069, P48557, P57053, P62807, P62808, P70696, P83863, Q00715, Q00729, Q16778, Q27894, Q32L48, Q5QNW6, Q5R893, Q5RCP8, Q64475, Q64478

Diamond homologs: A0A2R8Y619, A2WKT1, A2WKT4, A2WWU2, A2XF66, A2YWI3, A3AGM4, O22582, O60814, O65819, P02281, P02283, P02284, P02285, P02286, P02287, P02288, P02289, P02290, P04255, P06145, P06899, P06900, P07794, P07795, P0C1H3, P0C1H4, P0C1H5, P10853, P10854, P14001, P16888, P16889, P16890, P17271, P19374, P21897, P23527, P27326, P27807

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2BU1	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BU1	monoubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	21
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

264 predictions. Top by Δscore:

Variant	Effect	Δscore
1:228458507:G:GG	donor_gain	0.9900
1:228458592:GGT:G	donor_gain	0.9700
1:228458589:AAGG:A	donor_gain	0.9600
1:228458587:TG:T	donor_gain	0.9300
1:228458485:TCACC:T	donor_gain	0.9200
1:228458593:GT:G	donor_gain	0.9100
1:228458594:TT:T	donor_gain	0.9100
1:228460340:A:G	acceptor_gain	0.9000
1:228458594:T:G	donor_gain	0.8900
1:228458492:G:GG	donor_gain	0.8300
1:228458588:GAAG:G	donor_gain	0.8300
1:228460011:G:GC	acceptor_gain	0.8300
1:228458494:ACACC:A	donor_gain	0.8200
1:228458491:A:AG	donor_gain	0.8000
1:228458569:A:T	donor_gain	0.7900
1:228458596:AT:A	donor_gain	0.7800
1:228459877:A:AG	acceptor_gain	0.7700
1:228459878:G:GG	acceptor_gain	0.7700
1:228459441:T:TA	acceptor_gain	0.7100
1:228458506:A:AG	donor_gain	0.6900
1:228458590:AGGGT:A	donor_gain	0.6600
1:228459608:C:G	donor_gain	0.6500
1:228458512:G:T	donor_gain	0.6400
1:228459485:GAGGA:G	acceptor_gain	0.6400
1:228458511:G:GT	donor_gain	0.6300
1:228459177:A:G	acceptor_gain	0.6300
1:228459481:C:CA	acceptor_gain	0.6300
1:228459482:CGGGA:C	acceptor_gain	0.6300
1:228459483:GGGAG:G	acceptor_gain	0.6300
1:228459484:GGAGG:G	acceptor_gain	0.6300

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000238442 (1:228458768 T>A,C), RS1001050817 (1:228458095 C>A,G,T), RS1002053230 (1:228457187 CTGT>C), RS1002084351 (1:228457042 G>T), RS1003133451 (1:228457383 C>A,G,T), RS1003629686 (1:228456512 C>A,T), RS1003893672 (1:228457092 T>C,G), RS1003987150 (1:228456898 T>C), RS1005427562 (1:228458307 A>G), RS1007247054 (1:228458986 C>A,T), RS1007334703 (1:228458782 C>T), RS1008061056 (1:228457805 C>T), RS1008341408 (1:228457993 C>A,T), RS1009178635 (1:228456552 T>C), RS1009875224 (1:228456843 G>A)

Disease associations

OMIM: gene MIM:615046 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

27 total (human), top 27 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
decabromobiphenyl ether	affects expression	1
trichostatin A	affects expression	1
nickel chloride	decreases acetylation, increases ubiquitination	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
lei gong teng	increases expression	1
epigallocatechin gallate	decreases expression	1
nickel acetate	decreases methylation, decreases ubiquitination, increases methylation, increases ubiquitination	1
abrine	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Cisplatin	decreases expression	1
Curcumin	increases expression	1
Folic Acid	decreases expression	1
Hydrogen Peroxide	affects expression	1
Lipopolysaccharides	affects response to substance, increases expression	1
Nickel	decreases methylation, decreases ubiquitination, increases methylation, increases ubiquitination	1
Oxygen	decreases expression	1
Silicon Dioxide	increases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
Cadmium Chloride	decreases expression	1
Copper Sulfate	increases expression	1
Lactic Acid	increases expression	1
Vitamin K 3	affects expression	1

Clinical trials (associated diseases)

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