H2BW2

Summary

H2BW2 (H2B.W histone 2, HGNC:27867) is a protein-coding gene on chromosome Xq22.2, encoding Histone H2B type F-M (P0C1H6). Core component of nucleosome.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Two molecules of each of the four core histones (H2A, H2B, H3, and H4) form an octamer, around which approximately 146 bp of DNA is wrapped in repeating units, called nucleosomes. The linker histone, H1, interacts with linker DNA between nucleosomes and functions in the compaction of chromatin into higher order structures. This gene encodes a replication-independent histone that is a member of the H2B histone family.

Source: NCBI Gene 286436 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 49 total — 2 pathogenic
• MANE Select transcript: NM_001388464

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27867
Approved symbol	H2BW2
Name	H2B.W histone 2
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000101812
Ensembl biotype	protein_coding
Entrez	286436

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 3 protein_coding

ENST00000355016, ENST00000417637, ENST00000675318

RefSeq mRNA: 2 — MANE Select: NM_001388464 NM_001164416, NM_001388464

CCDS: CCDS55468

Canonical transcript exons

ENST00000675318 — 4 exons

Exon	Start	End
ENSE00001766493	104040828	104040886
ENSE00001789673	104042112	104042454
ENSE00003154177	104039956	104040404
ENSE00003902681	104041088	104041106

Expression profiles

Bgee: expression breadth ubiquitous, 153 present calls, max score 83.57.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.0097 / max 9.9239, expressed in 4 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
197126	0.0097	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	83.57	silver quality
cerebellar hemisphere	UBERON:0002245	76.09	gold quality
cerebellar cortex	UBERON:0002129	75.84	gold quality
cortical plate	UBERON:0005343	74.67	gold quality
right hemisphere of cerebellum	UBERON:0014890	74.29	gold quality
ganglionic eminence	UBERON:0004023	74.25	gold quality
cerebellum	UBERON:0002037	73.21	gold quality
right ovary	UBERON:0002118	72.01	gold quality
left ovary	UBERON:0002119	71.12	gold quality
ventricular zone	UBERON:0003053	71.12	gold quality
stromal cell of endometrium	CL:0002255	67.90	gold quality
endocervix	UBERON:0000458	67.32	gold quality
descending thoracic aorta	UBERON:0002345	66.71	gold quality
tibial artery	UBERON:0007610	66.52	gold quality
popliteal artery	UBERON:0002250	66.50	gold quality
right coronary artery	UBERON:0001625	66.45	gold quality
body of uterus	UBERON:0009853	66.24	gold quality
aorta	UBERON:0000947	66.05	gold quality
left coronary artery	UBERON:0001626	65.90	gold quality
thoracic aorta	UBERON:0001515	65.81	gold quality
ascending aorta	UBERON:0001496	65.70	gold quality
ovary	UBERON:0000992	65.53	gold quality
smooth muscle tissue	UBERON:0001135	64.84	gold quality
mucosa of stomach	UBERON:0001199	64.74	gold quality
coronary artery	UBERON:0001621	64.55	gold quality
hypothalamus	UBERON:0001898	63.32	gold quality
left uterine tube	UBERON:0001303	63.10	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	62.92	gold quality
granulocyte	CL:0000094	62.82	gold quality
anterior cingulate cortex	UBERON:0009835	62.61	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

33 targeting H2BW2, 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-9-5P	100.00	72.28	2361
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-545-3P	99.95	70.74	2783
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-576-5P	99.84	70.46	2582
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-12130	99.75	65.47	452
HSA-MIR-5580-3P	99.70	69.41	2052
HSA-MIR-5093	99.67	69.26	2291
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-182-3P	99.57	67.57	825
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-4437	99.52	65.29	1266
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-6505-3P	99.34	67.39	1071
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6765-3P	97.83	64.59	1165
HSA-MIR-192-3P	97.52	67.66	1001
HSA-MIR-4474-3P	96.97	65.87	870
HSA-MIR-656-5P	96.82	67.67	372
HSA-MIR-4701-5P	96.45	68.41	1121
HSA-MIR-588	96.45	68.36	1127
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-5586-5P	96.29	68.02	685

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bw2	ENSMUSG00000048155

Paralogs (21): H2BW1 (ENSG00000123569), H2BC11 (ENSG00000124635), H2BC1 (ENSG00000146047), H2BC5 (ENSG00000158373), H2BC4 (ENSG00000180596), H2BC21 (ENSG00000184678), H2BC13 (ENSG00000185130), H2BC26 (ENSG00000196890), 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 F-M — P0C1H6 (reviewed: P0C1H6)

Alternative names: Histone H2B.s

All UniProt accessions (2): P0C1H6, A9UJN3

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.

Miscellaneous. Gene prediction based on conservation. In contrast to other H2B histones, it does not contain the conserved residue in C-terminus that is the target of monoubiquitination.

Similarity. Belongs to the histone H2B family.

Isoforms (2)

UniProt ID	Names	Canonical?
P0C1H6-1	1	yes
P0C1H6-2	2

RefSeq proteins (2): NP_001157888, NP_001375393* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00125

UniProt features (13 total): modified residue 8, compositionally biased region 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
9JC6	ELECTRON MICROSCOPY	3.34

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C1H6-F1	75.11	0.60

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 (8): 131, 131, 26, 26, 32, 32, 35, 108

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 21 (showing top): GOCC_PROTEIN_DNA_COMPLEX, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, chrXq22, ZWANG_TRANSIENTLY_UP_BY_2ND_EGF_PULSE_ONLY, MIR3915, MIR4437, MEBARKI_HCC_PROGENITOR_FZD8CRD_UP, GSE17974_CTRL_VS_ACT_IL4_AND_ANTI_IL12_0.5H_CD4_TCELL_UP, GOCC_NUCLEOSOME, GOMF_STRUCTURAL_CONSTITUENT_OF_CHROMATIN, GSE2706_R848_VS_LPS_8H_STIM_DC_UP, KEGG_SYSTEMIC_LUPUS_ERYTHEMATOSUS, GSE29615_CTRL_VS_DAY7_LAIV_FLU_VACCINE_PBMC_DN

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 (3): nucleosome (GO:0000786), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	2
nucleic acid binding	1
structural molecule activity	1
protein dimerization activity	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

1712 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BW2	PLG	P00747	867
H2BW2	RNF20	Q5VTR2	843
H2BW2	H3C1	P02295	815
H2BW2	H3C14	Q71DI3	814
H2BW2	H3-5	Q6NXT2	814
H2BW2	H3-4	Q16695	814
H2BW2	H3-7	Q5TEC6	814
H2BW2	H3-3A	P06351	812
H2BW2	RNF40	O75150	772
H2BW2	H4C7	Q99525	746
H2BW2	H4C16	P02304	741
H2BW2	H2AC19	P20670	730
H2BW2	H2AC20	Q16777	729
H2BW2	USP22	Q9UPT9	728
H2BW2	DET1	Q7L5Y6	727

IntAct

0 interactions, top by confidence:

BioGRID (1): H2BFM (Affinity Capture-MS)

ESM2 similar proteins: A0A097I1R9, A0A097I2B5, A0A097I2D0, A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PPW3, A0A1W2PQ09, A0A1W2PR64, A0A1W2PRV1, A6NLC8, O04027, O15819, P06898, P06902, P0C1H6, P0DW11, P0DW12, P0DW13, P0DW14, P27795, P27893, P40284, P40285, P40287, P81195, P81196, P81197, P81198, P81199, P81200, P81201, P81202, Q06196, Q27490, Q2N2K6, Q5M8Q2, Q6CER9, Q6VEU3

Diamond homologs: A0A2R8Y619, A1CJ09, A1D8G9, A2QY49, A3LXE6, A3LZZ1, A5DWF0, O60814, P02281, P02283, P02284, P02285, P02286, P02290, P02293, P04255, P04913, P06899, P06900, P07794, P0C1H3, P0C1H4, P0C1H5, P0C1H6, P10853, P10854, P14001, P16888, P16889, P17271, P19374, P21897, P23527, P23754, P27326, P30757, P33778, P35068, P35069, P48557

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2BW2	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BW2	monoubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	43
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
564880	GRCh37/hg19 Xq22.2(chrX:103032630-103328582)x2	Pathogenic
691845	GRCh37/hg19 Xq22.2(chrX:102615641-103309503)x1	Pathogenic

SpliceAI

546 predictions. Top by Δscore:

Variant	Effect	Δscore
X:104040416:GCAA:G	donor_gain	1.0000
X:104040789:A:AG	acceptor_gain	1.0000
X:104040795:A:AG	acceptor_gain	1.0000
X:104040803:A:AG	acceptor_gain	1.0000
X:104040803:AC:A	acceptor_gain	1.0000
X:104040804:C:CA	acceptor_gain	1.0000
X:104040357:G:GT	donor_gain	0.9900
X:104040357:G:T	donor_gain	0.9900
X:104040366:C:T	donor_gain	0.9900
X:104040400:CTCAG:C	donor_loss	0.9900
X:104040402:CAG:C	donor_loss	0.9900
X:104040403:AG:A	donor_loss	0.9900
X:104040404:GG:G	donor_loss	0.9900
X:104040405:GTA:G	donor_loss	0.9900
X:104040406:T:G	donor_loss	0.9900
X:104040790:C:G	acceptor_gain	0.9900
X:104040796:T:G	acceptor_gain	0.9900
X:104040808:T:TA	acceptor_gain	0.9900
X:104040809:G:A	acceptor_gain	0.9900
X:104040884:AAGG:A	donor_loss	0.9900
X:104040885:AGGTA:A	donor_loss	0.9900
X:104040886:GG:G	donor_loss	0.9900
X:104041224:G:GT	donor_gain	0.9900
X:104040420:G:GG	donor_gain	0.9800
X:104040812:T:TA	acceptor_gain	0.9800
X:104041224:G:T	donor_gain	0.9800
X:104041284:G:GT	donor_gain	0.9800
X:104041285:A:T	donor_gain	0.9800
X:104041677:A:T	donor_gain	0.9800
X:104040882:GCAAG:G	donor_gain	0.9700

AlphaMissense

961 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:104040154:T:C	F60L	0.940
X:104040156:C:A	F60L	0.940
X:104040156:C:G	F60L	0.940
X:104040274:G:C	A100P	0.893
X:104040166:T:C	F64L	0.876
X:104040168:C:A	F64L	0.876
X:104040168:C:G	F64L	0.876
X:104040217:G:C	A81P	0.863
X:104040167:T:C	F64S	0.838
X:104040260:G:C	R95P	0.828
X:104040334:G:C	A120P	0.827
X:104040335:C:A	A120D	0.822
X:104040265:G:C	A97P	0.817
X:104040167:T:G	F64C	0.814
X:104040311:T:G	I112S	0.809
X:104040275:C:A	A100D	0.807
X:104040311:T:C	I112T	0.800
X:104040266:C:A	A97D	0.788
X:104040323:A:G	D116G	0.787
X:104040323:A:C	D116A	0.785
X:104040311:T:A	I112N	0.782
X:104040374:C:A	A133D	0.774
X:104040263:T:G	I96S	0.773
X:104040341:G:C	R122P	0.773
X:104040263:T:A	I96N	0.772
X:104040235:T:C	S87P	0.764
X:104040287:C:A	A104D	0.756
X:104040209:C:T	S78F	0.754
X:104040284:T:C	L103P	0.745
X:104040344:T:C	L123P	0.744

dbSNP variants (sampled 300 via entrez): RS112231653 (X:104040438 G>A,T), RS113466197 (X:104040361 A>C,G), RS113755093 (X:104039913 G>A,C,T), RS1156921632 (X:104038132 G>A), RS1157009640 (X:104039398 C>T), RS1157025638 (X:104041263 T>C), RS1157238504 (X:104040298 A>C,G), RS1157372518 (X:104042264 C>T), RS1157732203 (X:104040718 C>T), RS1157827178 (X:104038930 C>T), RS1158298222 (X:104041735 G>A), RS1159327833 (X:104041632 G>A), RS1159459897 (X:104040598 G>A), RS1159787031 (X:104042829 G>A), RS1161704350 (X:104038719 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: no

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

CTD chemical–gene interactions

6 total (human), top 6 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol F	decreases expression	1
2-palmitoylglycerol	increases expression	1
Berberine	decreases expression	1
Estradiol	decreases expression, affects cotreatment	1
Progesterone	affects cotreatment, decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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