H2AB1

Summary

H2AB1 (H2A.B variant histone 1, HGNC:22516) is a protein-coding gene on chromosome Xq28, encoding Histone H2A-Bbd type 1 (P0C5Y9). Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing.

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 encodes a replication-independent histone that is a member of the histone H2A family. This gene is part of a region that is repeated three times on chromosome X, once in intron 22 of the F8 gene and twice closer to the Xq telomere. This record represents the most centromeric copy which is in intron 22 of the F8 gene.

Source: NCBI Gene 474382 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001017990

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22516
Approved symbol	H2AB1
Name	H2A.B variant histone 1
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	H2A.B.2
Ensembl gene	ENSG00000274183
Ensembl biotype	protein_coding
OMIM	301037
Entrez	474382

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000620016

RefSeq mRNA: 1 — MANE Select: NM_001017990 NM_001017990

CCDS: CCDS35458

Canonical transcript exons

ENST00000620016 — 1 exons

Exon	Start	End
ENSE00003719914	154884972	154885558

Expression profiles

Bgee: expression breadth ubiquitous, 118 present calls, max score 96.98.

Top tissues by expression

133 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	96.98	gold quality
lower esophagus mucosa	UBERON:0035834	69.03	gold quality
apex of heart	UBERON:0002098	63.94	gold quality
right testis	UBERON:0004534	58.24	gold quality
left testis	UBERON:0004533	53.76	gold quality
cortical plate	UBERON:0005343	53.21	gold quality
testis	UBERON:0000473	53.02	gold quality
ganglionic eminence	UBERON:0004023	50.54	gold quality
blood	UBERON:0000178	46.68	gold quality
duodenum	UBERON:0002114	44.93	gold quality
hindlimb stylopod muscle	UBERON:0004252	44.02	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	43.97	gold quality
bone marrow	UBERON:0002371	42.77	gold quality
cortex of kidney	UBERON:0001225	42.14	gold quality
superior frontal gyrus	UBERON:0002661	42.03	gold quality
right lobe of liver	UBERON:0001114	39.66	gold quality
smooth muscle tissue	UBERON:0001135	39.46	gold quality
lymph node	UBERON:0000029	38.64	gold quality
tonsil	UBERON:0002372	38.63	silver quality
liver	UBERON:0002107	37.92	gold quality
metanephros cortex	UBERON:0010533	37.74	gold quality
muscle tissue	UBERON:0002385	37.24	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
muscle of leg	UBERON:0001383	36.98	gold quality
left uterine tube	UBERON:0001303	36.93	gold quality
skeletal muscle tissue	UBERON:0001134	36.84	silver quality
gastrocnemius	UBERON:0001388	36.82	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
vermiform appendix	UBERON:0001154	35.46	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting H2AB1, 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-4493	99.90	66.48	977
HSA-MIR-3151-5P	99.86	63.83	1069
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-3136-3P	99.57	66.59	781
HSA-MIR-7155-3P	99.57	66.48	794
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-363-5P	99.46	64.51	1015
HSA-MIR-128-1-5P	99.33	60.46	332
HSA-MIR-128-2-5P	99.33	60.83	311
HSA-MIR-7109-5P	99.18	66.13	1057
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-661	99.09	65.94	2062
HSA-MIR-4260	98.78	65.37	848
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-6887-5P	98.56	68.49	1295
HSA-MIR-6795-5P	98.52	68.51	1277
HSA-MIR-6742-5P	96.32	64.01	869
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-2861	95.24	65.47	1056
HSA-MIR-6781-5P	94.61	59.49	155
HSA-MIR-492	94.02	64.46	413

Literature-anchored findings (GeneRIF, showing 2)

• Structural basis of nucleosome dynamics modulation by histone variants H2A.B and H2A.Z.2.2. (PMID:33073403)
• H2A.B is a cancer/testis factor involved in the activation of ribosome biogenesis in Hodgkin lymphoma. (PMID:34350706)

Cross-species orthologs

24 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2ab1	ENSMUSG00000067441
mus_musculus	H2ab2	ENSMUSG00000082482
mus_musculus	H2ab3	ENSMUSG00000083616
rattus_norvegicus	H2ab3	ENSRNOG00000029736
drosophila_melanogaster	His2A:CG31618	FBGN0051618
drosophila_melanogaster	His2A:CG33808	FBGN0053808
drosophila_melanogaster	His2A:CG33814	FBGN0053814
drosophila_melanogaster	His2A:CG33817	FBGN0053817
drosophila_melanogaster	His2A:CG33820	FBGN0053820
drosophila_melanogaster	His2A:CG33823	FBGN0053823
drosophila_melanogaster	His2A:CG33826	FBGN0053826
drosophila_melanogaster	His2A:CG33829	FBGN0053829
drosophila_melanogaster	His2A:CG33832	FBGN0053832
drosophila_melanogaster	His2A:CG33835	FBGN0053835
drosophila_melanogaster	His2A:CG33838	FBGN0053838
drosophila_melanogaster	His2A:CG33841	FBGN0053841
drosophila_melanogaster	His2A:CG33844	FBGN0053844
drosophila_melanogaster	His2A:CG33847	FBGN0053847
drosophila_melanogaster	His2A:CG33850	FBGN0053850
drosophila_melanogaster	His2A:CG33853	FBGN0053853
drosophila_melanogaster	His2A:CG33856	FBGN0053856
drosophila_melanogaster	His2A:CG33859	FBGN0053859
drosophila_melanogaster	His2A:CG33862	FBGN0053862
drosophila_melanogaster	His2A:CG33865	FBGN0053865

Paralogs (27): MACROH2A2 (ENSG00000099284), H2AZ2 (ENSG00000105968), MACROH2A1 (ENSG00000113648), H2AZ1 (ENSG00000164032), H2AC1 (ENSG00000164508), H2AC6 (ENSG00000180573), H2AC25 (ENSG00000181218), H2AC20 (ENSG00000184260), H2AC21 (ENSG00000184270), H2AX (ENSG00000188486), H2AC13 (ENSG00000196747), H2AC11 (ENSG00000196787), H2AC7 (ENSG00000196866), H2AL3 (ENSG00000229674), H2AJ (ENSG00000246705), H2AL1Q (ENSG00000249467), H2AC12 (ENSG00000274997), H2AC15 (ENSG00000275221), H2AC14 (ENSG00000276368), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A-Bbd type 1 — P0C5Y9 (reviewed: P0C5Y9)

Alternative names: H2A Barr body-deficient

All UniProt accessions (1): P0C5Y9

UniProt curated annotations — full annotation on UniProt →

Function. Atypical histone H2A which can replace conventional H2A in some nucleosomes and is associated with active transcription and mRNA processing. 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. Nucleosomes containing this histone are less rigid and organize less DNA than canonical nucleosomes in vivo. They are enriched in actively transcribed genes and associate with the elongating form of RNA polymerase. They associate with spliceosome components and are required for mRNA splicing.

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. May be incorporated into a proportion of nucleosomes, replacing one or more H2A molecules.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Present in mature sperm.

Domain organisation. The docking domain is responsible for the weaker heterodimerization with H2B.

Miscellaneous. In contrast to other H2A histones, it does not contain the conserved residues that are the target of post-translational modifications.

Similarity. Belongs to the histone H2A family.

RefSeq proteins (1): NP_001017990* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR009072	Histone-fold	Homologous_superfamily

UniProt features (4 total): region of interest 2, chain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C5Y9-F1	87.90	0.76

Function

Pathways and Gene Ontology

Reactome pathways

47 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-3214858	RMTs methylate histone arginines
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-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-73728	RNA Polymerase I Promoter Opening
R-HSA-73772	RNA Polymerase I Promoter Escape
R-HSA-8936459	RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function
R-HSA-8939236	RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-9018519	Estrogen-dependent gene expression
R-HSA-912446	Meiotic recombination

MSigDB gene sets: 111 (showing top): REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, REACTOME_DNA_REPAIR, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PROTEIN_DNA_COMPLEX, REACTOME_REGULATION_OF_T_CELL_ACTIVATION_BY_CD28_FAMILY, GOCC_EUCHROMATIN

GO Biological Process (3): nucleosome assembly (GO:0006334), mRNA processing (GO:0006397), heterochromatin formation (GO:0031507)

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

GO Cellular Component (4): nucleosome (GO:0000786), euchromatin (GO:0000791), nucleus (GO:0005634), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-13 pathways:

Category	Pathways
Cellular Senescence	3
Depyrimidination	2
Depurination	2
Epigenetic regulation of gene expression	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
Chromatin modifying enzymes	1
Gene Silencing by RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin	3
chromatin organization	1
nucleosome organization	1
protein-DNA complex assembly	1
RNA processing	1
mRNA metabolic process	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
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

1320 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AB1	H2BC21	Q16778	708
H2AB1	H3Y1	P0DPK2	606
H2AB1	H3Y2	P0DPK5	590
H2AB1	CENPA	P49450	561
H2AB1	CD74	P04233	528
H2AB1	H1-0	P07305	481
H2AB1	IL33	O95760	460
H2AB1	H2BC1	Q96A08	451
H2AB1	H1-7	Q75WM6	415
H2AB1	H2AP	O75409	373
H2AB1	H1-6	P22492	370
H2AB1	H1-8	Q8IZA3	367
H2AB1	H3C1	P02295	361
H2AB1	H3-4	Q16695	346
H2AB1	H4C7	Q99525	339

IntAct

3 interactions, top by confidence:

A	B	Type	Score
H2AB1	UBB	psi-mi:“MI:0914”(association)	0.350
H2AB1	NRDC	psi-mi:“MI:0914”(association)	0.350

BioGRID (24): CHCHD2 (Affinity Capture-MS), TEX10 (Affinity Capture-MS), H2AFB1 (Affinity Capture-MS), UBB (Affinity Capture-MS), NOL9 (Affinity Capture-MS), RAB15 (Affinity Capture-MS), SENP3 (Affinity Capture-MS), H2AFB1 (Affinity Capture-MS), C1QBP (Affinity Capture-MS), MDM2 (Affinity Capture-MS), BAG1 (Affinity Capture-MS), PELP1 (Affinity Capture-MS), CYBA (Affinity Capture-MS), NRD1 (Affinity Capture-MS), MDC1 (Affinity Capture-MS)

ESM2 similar proteins: A0A1W2PP81, A0A1W2PPE2, A0A1W2PPH5, A0A1W2PPL8, A0A1W2PR64, A0A1W2PRV1, A0A3B3IU63, A4QVR2, A5DQL2, A9UMV8, F4HR03, O35216, P06898, P0C1H6, P0C5Y9, P0C5Z0, P0DW11, P0DW12, P0DW13, P0DW14, P0DW85, P35061, P48003, P49450, Q00728, Q3SZB8, Q3ZBX9, Q4IMD1, Q5M8Q2, Q5TKR9, Q64522, Q64598, Q7Z2G1, Q803H4, Q873G4, Q8BRB7, Q8BZ21, Q8CGP5, Q8IUE6, Q8R1M2

Diamond homologs: A0A3B3IU63, A1A4R1, A2WQG7, A5DBG4, A5DJJ2, A5DXS8, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, P02262, P02263, P02264, P02269, P02270, P02273, P02274, P02276, P02277, P04908, P06897, P07793, P09588, P0C0S8, P0C0S9, P0C169, P0C170, P0C5Y9, P0C5Z0, P0CC09, P0CN98, P0CN99, P13630, P13912

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2AB1	“translation regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

138 predictions. Top by Δscore:

Variant	Effect	Δscore
X:154885058:G:GT	donor_gain	0.9200
X:154885061:G:GT	donor_gain	0.9200
X:154885224:GTTAT:G	donor_gain	0.8700
X:154885225:TTATT:T	donor_gain	0.8700
X:154885228:T:TG	donor_gain	0.8100
X:154885226:TATTG:T	donor_gain	0.7100
X:154885227:ATTGA:A	donor_gain	0.7100
X:154885275:C:T	acceptor_gain	0.7100
X:154885142:A:AG	acceptor_gain	0.7000
X:154885143:G:GG	acceptor_gain	0.7000
X:154885087:C:CG	donor_gain	0.6800
X:154885153:T:TA	donor_gain	0.6800
X:154885154:G:GA	donor_gain	0.6800
X:154885275:C:CT	acceptor_gain	0.6800
X:154885337:GCTAC:G	donor_gain	0.6400
X:154885249:TCCCG:T	donor_gain	0.6300
X:154885187:GCGCC:G	donor_gain	0.6200
X:154885170:G:T	donor_gain	0.6100
X:154885232:G:GG	donor_gain	0.6100
X:154884986:C:G	donor_gain	0.5900
X:154885040:AACGC:A	donor_gain	0.5900
X:154885169:G:GT	donor_gain	0.5900
X:154885231:A:AG	donor_gain	0.5900
X:154885143:GTGA:G	acceptor_gain	0.5600
X:154885148:C:T	donor_gain	0.5500
X:154885189:GCC:G	donor_gain	0.5500
X:154885322:G:GA	donor_gain	0.5500
X:154884985:ACT:A	donor_gain	0.5300
X:154885142:AGT:A	acceptor_gain	0.5300
X:154885143:GTG:G	acceptor_gain	0.5300

AlphaMissense

721 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:154885137:T:C	F30L	0.918
X:154885139:T:A	F30L	0.918
X:154885139:T:G	F30L	0.918
X:154885353:T:C	F102L	0.767
X:154885355:C:A	F102L	0.767
X:154885355:C:G	F102L	0.767
X:154885221:G:C	A58P	0.592
X:154885194:A:C	S49R	0.581
X:154885196:T:A	S49R	0.581
X:154885196:T:G	S49R	0.581
X:154885297:T:C	I83T	0.581

dbSNP variants (sampled 300 via entrez): RS113683431 (X:154886026 G>C), RS1156675377 (X:154885705 G>A), RS1161854920 (X:154884962 G>T), RS1163080636 (X:154885354 T>G), RS1166099089 (X:154885159 G>A), RS1166324509 (X:154885500 A>T), RS1166720558 (X:154885829 G>A), RS1167468518 (X:154885964 CGGGGGGGGG>C,CGG,CGGGGG,CGGGGGG,CGGGGGGG,CGGGGGGGG,CGGGGGGGGGG,CGGGGGGGGGGG), RS1171881100 (X:154885629 G>C), RS1175661281 (X:154885555 G>A), RS1179806735 (X:154885650 G>A), RS1183187239 (X:154885718 G>A,C), RS1184863941 (X:154885983 C>A), RS1187041935 (X:154885182 G>A), RS1188443344 (X:154885862 G>A,C)

Disease associations

OMIM: gene MIM:301037 | 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

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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