H2BW1

Summary

H2BW1 (H2B.W histone 1, HGNC:27252) is a protein-coding gene on chromosome Xq22.2, encoding Histone H2B type W-T (Q7Z2G1). Atypical histone H2B that can form nucleosomes structurally and dynamically indistinguishable from those containing conventional H2B.

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 that is specifically expressed in sperm nuclei. A polymorphism in the 5’ UTR of this gene is associated with male infertility.

Source: NCBI Gene 158983 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total — 2 pathogenic
• MANE Select transcript: NM_001002916

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:27252
Approved symbol	H2BW1
Name	H2B.W histone 1
Location	Xq22.2
Locus type	gene with protein product
Status	Approved
Aliases	TH2B-175
Ensembl gene	ENSG00000123569
Ensembl biotype	protein_coding
OMIM	300507
Entrez	158983

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000217926

RefSeq mRNA: 1 — MANE Select: NM_001002916 NM_001002916

CCDS: CCDS35362

Canonical transcript exons

ENST00000217926 — 3 exons

Exon	Start	End
ENSE00000674142	104013170	104013708
ENSE00001520302	104011147	104011463
ENSE00001632622	104012690	104012748

Expression profiles

Bgee: expression breadth broad, 13 present calls, max score 86.77.

Top tissues by expression

119 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	86.77	gold quality
cortical plate	UBERON:0005343	41.54	gold quality
right testis	UBERON:0004534	38.36	gold quality
placenta	UBERON:0001987	37.49	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
testis	UBERON:0000473	35.44	gold quality
skeletal muscle tissue	UBERON:0001134	34.98	gold quality
left testis	UBERON:0004533	34.95	gold quality
right coronary artery	UBERON:0001625	33.01	gold quality
muscle tissue	UBERON:0002385	32.23	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
prefrontal cortex	UBERON:0000451	31.10	silver quality
sural nerve	UBERON:0015488	30.93	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
tonsil	UBERON:0002372	29.77	silver quality
superior frontal gyrus	UBERON:0002661	28.25	silver quality
duodenum	UBERON:0002114	28.14	gold quality
liver	UBERON:0002107	28.04	gold quality
lymph node	UBERON:0000029	27.57	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
leukocyte	CL:0000738	26.35	gold quality
monocyte	CL:0000576	26.23	gold quality
blood	UBERON:0000178	26.04	silver quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
cerebellum	UBERON:0002037	25.88	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

18 targeting H2BW1, 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-576-5P	99.84	70.46	2582
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6848-3P	99.64	66.49	885
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-578	99.46	68.36	1787
HSA-MIR-103A-1-5P	99.39	67.78	1545
HSA-MIR-103A-2-5P	99.39	67.72	1577
HSA-MIR-6843-3P	99.26	66.42	915
HSA-MIR-3191-5P	99.24	66.52	1722
HSA-MIR-4727-5P	99.23	67.55	1154
HSA-MIR-593-3P	99.22	67.28	1327
HSA-MIR-3149	98.77	67.13	1639
HSA-MIR-518C-5P	98.53	69.20	1640
HSA-MIR-676-5P	98.49	68.87	1492
HSA-MIR-6834-3P	98.16	65.77	551
HSA-MIR-4433B-5P	95.91	66.56	727

Literature-anchored findings (GeneRIF, showing 6)

• Data indicate that the polymorphism -9C>T and 368A>G in H2BFWT gene are associated with male infertility with idiopathic azoospermia or oligozoospermia, suggesting susceptibility of H2BFWT gene to spermatogenesis impairment in Chinese population. (PMID:22509975)
• It is concluded that H2BFWT gene c.-9C>T and c.368A>G polymorphisms might be genetic risk factors for idiopathic male infertility. (PMID:28370107)
• the association of -9C>T and 368A>G polymorphisms in H2BFWT gene with male infertility risk was assessed through a case-control and meta-analysis (PMID:29453813)
• Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2. (PMID:33440036)
• Impact of tobacco smoking in association with H2BFWT, PRM1 and PRM2 genes variants on male infertility. (PMID:36217675)
• H2BFWT Variations in Sperm DNA and Its Correlation to Pregnancy. (PMID:38892236)

Cross-species orthologs

1 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2bw2	ENSMUSG00000048155

Paralogs (21): H2BW2 (ENSG00000101812), 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 W-T — Q7Z2G1 (reviewed: Q7Z2G1)

Alternative names: H2B histone family member W testis-specific, H2B.W histone 1

All UniProt accessions (1): Q7Z2G1

UniProt curated annotations — full annotation on UniProt →

Function. Atypical histone H2B that can form nucleosomes structurally and dynamically indistinguishable from those containing conventional H2B. 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. However, unlike conventional H2B, does not recruit chromosome condensation factors and does not participate in the assembly of mitotic chromosomes. May be important for telomere function and play a role in spermatogenesis.

Subunit / interactions. Can replace the conventional histone H2B in the nucleosome. 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 membrane. Chromosome. Telomere.

Tissue specificity. Testis-specific (at protein level).

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

Similarity. Belongs to the histone H2B family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q7Z2G1-2	2	yes
Q7Z2G1-1	1
Q7Z2G1-3	3

RefSeq proteins (1): NP_001002916* (*=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 (19 total): modified residue 7, helix 4, splice variant 2, sequence variant 2, compositionally biased region 2, chain 1, region of interest 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8JCD	ELECTRON MICROSCOPY	3.14
8JCC	ELECTRON MICROSCOPY	3.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q7Z2G1-F1	76.73	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 (7): 138, 26, 26, 35, 107, 130, 130

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 32 (showing top): GOBP_CHROMOSOME_ORGANIZATION, GOBP_CHROMOSOME_CONDENSATION, GOBP_ORGANELLE_FISSION, GOBP_MITOTIC_NUCLEAR_DIVISION, GOBP_MITOTIC_CELL_CYCLE, GOBP_NUCLEAR_CHROMOSOME_SEGREGATION, GOBP_MITOTIC_CHROMOSOME_CONDENSATION, GOCC_NUCLEAR_ENVELOPE, GOCC_CHROMOSOMAL_REGION, GOCC_PROTEIN_DNA_COMPLEX, GOCC_CHROMOSOME_TELOMERIC_REGION, GOCC_NUCLEAR_MEMBRANE, GOBP_CELL_CYCLE_PROCESS, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY

GO Biological Process (0):

GO Molecular Function (4): DNA binding (GO:0003677), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)

GO Cellular Component (6): chromosome, telomeric region (GO:0000781), nucleosome (GO:0000786), nucleus (GO:0005634), nuclear membrane (GO:0031965), chromosome (GO:0005694), membrane (GO:0016020)

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
binding	1
chromosomal region	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
nucleus	1
nuclear envelope	1
organelle membrane	1
intracellular membraneless organelle	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1724 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2BW1	PLG	P00747	867
H2BW1	RNF20	Q5VTR2	843
H2BW1	H3-5	Q6NXT2	816
H2BW1	H3C1	P02295	816
H2BW1	H3-4	Q16695	816
H2BW1	H3C14	Q71DI3	815
H2BW1	H3-7	Q5TEC6	815
H2BW1	H3-3A	P06351	813
H2BW1	RNF40	O75150	772
H2BW1	H4C7	Q99525	746
H2BW1	H4C16	P02304	743
H2BW1	H2AC20	Q16777	743
H2BW1	H2AC19	P20670	743
H2BW1	USP22	Q9UPT9	728
H2BW1	DET1	Q7L5Y6	727

IntAct

7 interactions, top by confidence:

A	B	Type	Score
H2BW1	PPP1R2B	psi-mi:“MI:0915”(physical association)	0.560
CEP78	H2BW1	psi-mi:“MI:0915”(physical association)	0.400
H2BW1	MACROH2A1	psi-mi:“MI:0914”(association)	0.350
H2BW1	PPP1R2B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (15): PPP1R2P3 (Two-hybrid), HSPG2 (Affinity Capture-MS), TRO (Affinity Capture-MS), XPC (Affinity Capture-MS), KPNB1 (Affinity Capture-MS), ZC3H18 (Affinity Capture-MS), SUPT16H (Affinity Capture-MS), ARHGEF40 (Affinity Capture-MS), HIST1H2AG (Affinity Capture-MS), NAP1L3 (Affinity Capture-MS), H2AFY (Affinity Capture-MS), C18orf25 (Affinity Capture-MS), MDM2 (Affinity Capture-MS), MAP1S (Affinity Capture-MS), HIST2H2AB (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”	H2BW1	“translation regulation”
“MSL acetyltransferase”	“down-regulates activity”	H2BW1	monoubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	0
Uncertain significance	43
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
150913	GRCh38/hg38 Xq22.2(chrX:103772099-104048812)x3	Pathogenic
4683032	GRCh37/hg19 Xq22.2(chrX:102988399-103291789)x3	Pathogenic

SpliceAI

511 predictions. Top by Δscore:

Variant	Effect	Δscore
X:104011899:T:TA	donor_gain	1.0000
X:104012767:C:CT	acceptor_gain	1.0000
X:104012768:A:T	acceptor_gain	1.0000
X:104012771:C:CT	acceptor_gain	1.0000
X:104012773:C:CT	acceptor_gain	1.0000
X:104012774:A:T	acceptor_gain	1.0000
X:104012780:A:AC	acceptor_gain	1.0000
X:104012787:A:T	acceptor_gain	1.0000
X:104011870:A:AC	donor_gain	0.9900
X:104011890:A:AC	donor_gain	0.9900
X:104011891:C:CC	donor_gain	0.9900
X:104011895:AAATT:A	donor_gain	0.9900
X:104012685:GTTA:G	donor_loss	0.9900
X:104012686:TTAC:T	donor_loss	0.9900
X:104012687:TACCT:T	donor_loss	0.9900
X:104012689:CCT:C	donor_loss	0.9900
X:104012689:CCTTG:C	donor_gain	0.9900
X:104012763:C:CT	acceptor_gain	0.9900
X:104012767:C:T	acceptor_gain	0.9900
X:104012780:A:C	acceptor_gain	0.9900
X:104012786:C:CT	acceptor_gain	0.9900
X:104013165:TGTAC:T	donor_loss	0.9900
X:104013166:GTAC:G	donor_loss	0.9900
X:104013168:ACC:A	donor_loss	0.9900
X:104013169:CC:C	donor_loss	0.9900
X:104011464:C:CC	acceptor_gain	0.9800
X:104011837:T:C	donor_gain	0.9800
X:104011912:AATC:A	donor_gain	0.9800
X:104011962:C:CC	acceptor_gain	0.9800
X:104012764:A:T	acceptor_gain	0.9800

AlphaMissense

1120 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:104013418:G:C	F81L	0.964
X:104013418:G:T	F81L	0.964
X:104013420:A:G	F81L	0.964
X:104013406:G:C	F85L	0.877
X:104013406:G:T	F85L	0.877
X:104013408:A:G	F85L	0.877
X:104013300:C:G	A121P	0.819
X:104013357:C:G	A102P	0.794
X:104013263:A:G	I133T	0.760
X:104013419:A:C	F81C	0.755
X:104013287:G:T	A125D	0.744
X:104013421:G:C	S80R	0.741
X:104013421:G:T	S80R	0.741
X:104013423:T:G	S80R	0.741
X:104013251:T:A	E137V	0.727
X:104013314:C:G	R116P	0.725
X:104013365:G:A	S99F	0.724
X:104013239:G:T	A141D	0.722
X:104013309:C:G	A118P	0.719
X:104013343:C:A	M106I	0.713
X:104013343:C:G	M106I	0.713
X:104013343:C:T	M106I	0.713
X:104013323:A:T	I113K	0.703
X:104013200:G:T	A154D	0.700
X:104013263:A:C	I133S	0.699
X:104013308:G:T	A118D	0.690
X:104013240:C:G	A141P	0.684
X:104013299:G:T	A121D	0.680
X:104013419:A:G	F81S	0.678
X:104013332:A:T	V110D	0.676

dbSNP variants (sampled 300 via entrez): RS1000081745 (X:104014665 A>G), RS1003947912 (X:104015626 G>A,C), RS1003980744 (X:104015348 G>A), RS1014156760 (X:104014201 C>A), RS1015277200 (X:104014907 A>G), RS1029501237 (X:104015309 C>T), RS1032813108 (X:104014256 A>G), RS1033968159 (X:104015446 C>A), RS1042340075 (X:104015201 C>T), RS1042391951 (X:104014593 G>A), RS1051345105 (X:104015593 A>C), RS1054298436 (X:104015517 C>G,T), RS1056977142 (X:104014571 T>A,C), RS111263150 (X:104013041 C>A), RS113217714 (X:104011869 T>C)

Disease associations

OMIM: gene MIM:300507 | disease phenotypes: MIM:312080

GenCC curated gene-disease

Mondo (1): Pelizaeus-Merzbacher spectrum disorder (MONDO:0010714)

Orphanet (1): Pelizaeus-Merzbacher disease (Orphanet:702)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D020371	Pelizaeus-Merzbacher Disease	C10.228.140.163.100.362.775; C10.228.140.695.625.775; C10.314.400.775; C16.320.322.906; C16.320.565.189.362.775; C18.452.132.100.362.775; C18.452.648.189.362.775

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

7 total (human), top 7 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, decreases methylation	1
Resveratrol	affects cotreatment, decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Benzo(a)pyrene	affects methylation	1
Endosulfan	decreases expression	1
Plant Extracts	decreases expression, affects cotreatment	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT07382739	PHASE2	RECRUITING	A Phase 2 Study of Radiotherapy-induced Immune Priming to Enhance Elranatamab (Elra) in Relapsed Refractory Multiple Myeloma (RRMM) With Extramedullary Disease (EMD) and Paramedullary Disease (PMD) PRIME-EMD-PMD
NCT01005004	PHASE1	COMPLETED	Study of Human Central Nervous System (CNS) Stem Cells Transplantation in Pelizaeus-Merzbacher Disease (PMD) Subjects
NCT02254863	PHASE1	RECRUITING	UCB Transplant of Inherited Metabolic Diseases With Administration of Intrathecal UCB Derived Oligodendrocyte-Like Cells
NCT06150716	PHASE1	RECRUITING	Orbit Study: A Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Intrathecally Administered ION356 in Participants With Pelizaeus Merzbacher Disease (PMD)
NCT01391637	Not specified	COMPLETED	Long-Term Follow-Up Study of Human Stem Cells Transplanted in Subjects With Connatal Pelizaeus-Merzbacher Disease (PMD)
NCT02699190	Not specified	COMPLETED	LeukoSEQ: Whole Genome Sequencing as a First-Line Diagnostic Tool for Leukodystrophies
NCT03047369	Not specified	RECRUITING	The Myelin Disorders Biorepository Project
NCT03333200	Not specified	RECRUITING	Longitudinal Study of Neurodegenerative Disorders
NCT05659901	Not specified	RECRUITING	Rocket Study: A Study to Characterize Biomarkers and Disease Progression in Participants With Pelizaeus-Merzbacher Disease