H2BC18

Summary

H2BC18 (H2B clustered histone 18, HGNC:24700) is a protein-coding gene on chromosome 1q21.2, encoding Histone H2B type 2-F (Q5QNW6). Core component of nucleosome. It is a selective cancer dependency (DepMap: 14.7% of cell lines).

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. This structure consists of approximately 146 bp of DNA wrapped around a nucleosome, an 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 encodes a replication-dependent histone that is a member of the histone H2B family and is found in a histone cluster on chromosome 1.

Source: NCBI Gene 440689 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 14 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 14.7% of screened cell lines
• MANE Select transcript: NM_001024599

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:24700
Approved symbol	H2BC18
Name	H2B clustered histone 18
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000203814
Ensembl biotype	protein_coding
Entrez	440689

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 3 protein_coding_CDS_not_defined, 2 protein_coding

ENST00000369167, ENST00000420462, ENST00000469483, ENST00000545683, ENST00000620458

RefSeq mRNA: 2 — MANE Select: NM_001024599 NM_001024599, NM_001161334

CCDS: CCDS30846, CCDS53359

Canonical transcript exons

ENST00000369167 — 1 exons

Exon	Start	End
ENSE00001448939	149811879	149812370

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.00.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.1820 / max 2004.1625, expressed in 1801 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
14253	99.1820	1801

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
bone marrow cell	CL:0002092	98.00	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	93.07	silver quality
adrenal tissue	UBERON:0018303	92.69	gold quality
blood	UBERON:0000178	87.79	gold quality
colonic epithelium	UBERON:0000397	86.71	gold quality
corpus callosum	UBERON:0002336	85.68	gold quality
right uterine tube	UBERON:0001302	85.55	gold quality
lower esophagus mucosa	UBERON:0035834	84.92	gold quality
left ovary	UBERON:0002119	84.07	gold quality
bone marrow	UBERON:0002371	84.00	gold quality
prostate gland	UBERON:0002367	83.92	gold quality
ovary	UBERON:0000992	83.21	gold quality
right hemisphere of cerebellum	UBERON:0014890	82.51	gold quality
cerebellar hemisphere	UBERON:0002245	82.26	gold quality
cerebellar cortex	UBERON:0002129	82.19	gold quality
cerebellum	UBERON:0002037	82.09	gold quality
right ovary	UBERON:0002118	82.00	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	81.75	gold quality
tonsil	UBERON:0002372	81.43	gold quality
vagina	UBERON:0000996	81.19	gold quality
uterine cervix	UBERON:0000002	80.93	gold quality
stomach	UBERON:0000945	79.17	gold quality
calcaneal tendon	UBERON:0003701	79.17	gold quality
endocervix	UBERON:0000458	77.79	gold quality
right lung	UBERON:0002167	77.74	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.42	gold quality
ectocervix	UBERON:0012249	77.23	gold quality
body of stomach	UBERON:0001161	76.83	gold quality
ganglionic eminence	UBERON:0004023	76.23	gold quality
lung	UBERON:0002048	76.12	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.43
E-GEOD-75367	no	153.04

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 14.7% of screened cell lines.

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bc18	ENSMUSG00000105827

Paralogs (21): H2BW2 (ENSG00000101812), H2BW1 (ENSG00000123569), H2BC11 (ENSG00000124635), H2BC1 (ENSG00000146047), H2BC5 (ENSG00000158373), H2BC4 (ENSG00000180596), H2BC21 (ENSG00000184678), H2BC13 (ENSG00000185130), H2BC26 (ENSG00000196890), H2BC12 (ENSG00000197903), 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 2-F — Q5QNW6 (reviewed: Q5QNW6)

Alternative names: H2B-clustered histone 18

All UniProt accessions (1): Q5QNW6

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.

Isoforms (2)

UniProt ID	Names	Canonical?
Q5QNW6-1	1	yes
Q5QNW6-2	2

RefSeq proteins (2): NP_001019770, NP_001154806 (=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 (108 total): modified residue 90, helix 6, cross-link 4, turn 2, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, glycosylation site 1, splice variant 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
10YF	ELECTRON MICROSCOPY	3
6MUP	ELECTRON MICROSCOPY	3.5
6MUO	ELECTRON MICROSCOPY	3.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q5QNW6-F1	87.52	0.67

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

6 pathways

ID	Pathway
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214847	HATs acetylate histones
R-HSA-5689880	Ub-specific processing proteases
R-HSA-9609690	HCMV Early Events
R-HSA-9610379	HCMV Late Events
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 120 (showing top): GOBP_ANTIMICROBIAL_HUMORAL_RESPONSE, GOBP_ORGAN_OR_TISSUE_SPECIFIC_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_OTHER_ORGANISM, GOBP_INNATE_IMMUNE_RESPONSE_IN_MUCOSA, GOBP_HUMORAL_IMMUNE_RESPONSE, GOBP_DEFENSE_RESPONSE_TO_BACTERIUM, chr1q21, GOCC_PROTEIN_DNA_COMPLEX, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, MARSON_BOUND_BY_E2F4_UNSTIMULATED, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOBP_RESPONSE_TO_BACTERIUM, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, REACTOME_POST_TRANSLATIONAL_PROTEIN_MODIFICATION

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 (6): nucleosome (GO:0000786), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Chromatin modifying enzymes	2
HCMV Infection	2
Deubiquitination	1
Dengue Virus Infection	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
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2074 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BC18	PLG	P00747	877
H2BC18	RNF20	Q5VTR2	843
H2BC18	H3C1	P02295	816
H2BC18	H3C14	Q71DI3	814
H2BC18	H3-5	Q6NXT2	812
H2BC18	H3-4	Q16695	812
H2BC18	H3-7	Q5TEC6	812
H2BC18	H3-3A	P06351	809
H2BC18	RNF40	O75150	772
H2BC18	H4C16	P02304	745
H2BC18	H4C7	Q99525	745
H2BC18	H2AC19	P20670	735
H2BC18	H2AC20	Q16777	733
H2BC18	USP22	Q9UPT9	727
H2BC18	DET1	Q7L5Y6	727

IntAct

42 interactions, top by confidence:

A	B	Type	Score
RPL10A	RRP8	psi-mi:“MI:0914”(association)	0.640
MAPK7	PFDN6	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
MECP2	GTPBP10	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
MAP4K4	STRN	psi-mi:“MI:0914”(association)	0.530
MSH6	PCNA	psi-mi:“MI:0914”(association)	0.530
H2BC18	YWHAZ	psi-mi:“MI:0915”(physical association)	0.400
DOK2	MYO1C	psi-mi:“MI:0914”(association)	0.350
ELK4	MYO1C	psi-mi:“MI:0914”(association)	0.350
LCK	UQCRQ	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
M		psi-mi:“MI:0914”(association)	0.350
ATG13	ENAH	psi-mi:“MI:0914”(association)	0.350
ATG3	EMC8	psi-mi:“MI:0914”(association)	0.350
CALM3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
CDC42BPB	H2BC18	psi-mi:“MI:0914”(association)	0.350
EEA1	PARP1	psi-mi:“MI:0914”(association)	0.350
MYO1E	MYO1C	psi-mi:“MI:0914”(association)	0.350
PPM1G	SRP14	psi-mi:“MI:0914”(association)	0.350
RUVBL2	ASDURF	psi-mi:“MI:0914”(association)	0.350
VAPA	ESYT2	psi-mi:“MI:0914”(association)	0.350
VPS8	NUP214	psi-mi:“MI:0914”(association)	0.350
RPL11	ZNF724	psi-mi:“MI:0914”(association)	0.350
H1-2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350

BioGRID (385): HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Proximity Label-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS), HIST2H2BF (Affinity Capture-MS)

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”	H2BC18	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BC18	monoubiquitination

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	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

747 predictions. Top by Δscore:

Variant	Effect	Δscore
1:149782771:TGGGG:T	donor_loss	0.9900
1:149782772:GGG:G	donor_gain	0.9900
1:149782773:GG:G	donor_gain	0.9900
1:149782773:GGG:G	donor_gain	0.9900
1:149782773:GGGTA:G	donor_loss	0.9900
1:149782774:GG:G	donor_gain	0.9900
1:149782775:G:C	donor_loss	0.9900
1:149782775:G:GG	donor_gain	0.9900
1:149782776:T:A	donor_loss	0.9900
1:149783990:A:AG	acceptor_gain	0.9900
1:149790051:TAGAG:T	acceptor_gain	0.9800
1:149791235:A:AG	acceptor_gain	0.9800
1:149791236:G:GG	acceptor_gain	0.9800
1:149790052:A:AG	acceptor_gain	0.9700
1:149790052:AGAGC:A	acceptor_gain	0.9700
1:149790053:G:GG	acceptor_gain	0.9700
1:149791232:TTCA:T	acceptor_loss	0.9700
1:149791235:AGG:A	acceptor_loss	0.9700
1:149791236:G:GC	acceptor_loss	0.9700
1:149790053:GA:G	acceptor_gain	0.9600
1:149790053:GAGCT:G	acceptor_gain	0.9600
1:149791236:GGC:G	acceptor_gain	0.9500
1:149783998:A:G	acceptor_gain	0.9400
1:149791229:T:A	acceptor_gain	0.9400
1:149791235:AG:A	acceptor_gain	0.9400
1:149791236:GG:G	acceptor_gain	0.9400
1:149782770:TTGGG:T	donor_gain	0.9300
1:149783987:T:A	acceptor_gain	0.9300
1:149788443:GA:G	donor_gain	0.9300
1:149790050:TTAGA:T	acceptor_gain	0.9300

AlphaMissense

812 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:149811973:C:A	K117N	1.000
1:149811973:C:G	K117N	1.000
1:149811980:C:T	G115D	1.000
1:149811981:C:A	G115C	1.000
1:149811981:C:G	G115R	1.000
1:149811992:G:T	A111D	1.000
1:149811994:G:C	H110Q	1.000
1:149811994:G:T	H110Q	1.000
1:149811997:C:A	K109N	1.000
1:149811997:C:G	K109N	1.000
1:149812004:A:G	L107P	1.000
1:149812010:C:T	G105D	1.000
1:149812022:A:G	L101P	1.000
1:149812031:G:T	A98D	1.000
1:149812032:C:G	A98P	1.000
1:149812036:C:A	Q96H	1.000
1:149812036:C:G	Q96H	1.000
1:149812187:A:G	L46P	1.000
1:149811968:A:T	V119D	0.999
1:149811972:C:G	A118P	0.999
1:149811974:T:A	K117M	0.999
1:149811975:T:C	K117E	0.999
1:149811977:G:A	T116I	0.999
1:149811980:C:A	G115V	0.999
1:149811981:C:T	G115S	0.999
1:149811984:C:T	E114K	0.999
1:149811986:G:A	S113F	0.999
1:149811987:A:G	S113P	0.999
1:149811993:C:G	A111P	0.999
1:149811995:T:C	H110R	0.999

dbSNP variants (sampled 300 via entrez): RS1050191 (1:149784109 T>C), RS1050204 (1:149791362 G>A), RS1050208 (1:149791405 T>C), RS1050210 (1:149791520 G>A), RS1050211 (1:149791544 C>A,G,T), RS1050212 (1:149791635 G>A), RS10537539 (1:149810388 GAA>G,GA,GAAA), RS10544446 (1:149789418 AATG>A,AATGATG), RS10670379 (1:149785408 GTTTTTTTTTTTTTT>G,GT,GTTT,GTTTTT,GTTTTTT,GTTTTTTT,GTTTTTTTTTTT,GTTTTTTTTTTTT,GTTTTTTTTTTTTT,GTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTT,GTTTTTTTTTTTTTTTTTTTTTT), RS10736382 (1:149796976 T>G), RS10888462 (1:149796806 G>C), RS10888463 (1:149797398 T>A), RS10888464 (1:149800313 G>A), RS10888465 (1:149800489 C>T), RS10888479 (1:149810854 C>T)

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

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4295850 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	increases expression	5
Benzo(a)pyrene	increases expression, increases methylation	3
bisphenol A	decreases expression	2
alpha phellandrene	increases expression	1
2-methyl-4-isothiazolin-3-one	increases expression	1
hydroxyhydroquinone	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
perfluorooctanoic acid	increases expression	1
ferrous chloride	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, affects response to substance, increases expression	1
bisphenol B	increases expression	1
abrine	increases expression	1
Grape Seed Proanthocyanidins	affects cotreatment, increases expression	1
licochalcone B	increases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Air Pollutants	decreases expression	1
Cadmium	decreases expression	1
Catechin	affects cotreatment, increases expression	1
Cisplatin	decreases expression	1
Dichlorodiphenyl Dichloroethylene	decreases expression	1
Gallic Acid	decreases expression	1
Lipopolysaccharides	affects response to substance, increases expression, affects cotreatment	1
N-Nitrosopyrrolidine	decreases expression	1
Oxygen	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Aflatoxin B1	decreases methylation	1
Permethrin	increases expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4118693	Binding	Binding affinity to HIST2H2BF in human NCI-H23 cells at 1 uM by mass spectrometry based pull down assay	Studies of TAK1-centered polypharmacology with novel covalent TAK1 inhibitors. — Bioorg Med Chem

Clinical trials (associated diseases)

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