H2AB2

Summary

H2AB2 (H2A.B variant histone 2, HGNC:18298) is a protein-coding gene on chromosome Xq28, encoding Histone H2A-Bbd type 2/3 (P0C5Z0). 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 middle copy.

Source: NCBI Gene 474381 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total — 2 pathogenic
• MANE Select transcript: NM_001017991

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18298
Approved symbol	H2AB2
Name	H2A.B variant histone 2
Location	Xq28
Locus type	gene with protein product
Status	Approved
Aliases	H2A.B.1
Ensembl gene	ENSG00000277858
Ensembl biotype	protein_coding
OMIM	301038
Entrez	474381

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000354514

RefSeq mRNA: 1 — MANE Select: NM_001017991 NM_001017991

CCDS: CCDS35461

Canonical transcript exons

ENST00000354514 — 1 exons

Exon	Start	End
ENSE00001744885	155380709	155381299

Expression profiles

Bgee: expression breadth ubiquitous, 113 present calls, max score 82.64.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.64	gold quality
left testis	UBERON:0004533	72.35	gold quality
testis	UBERON:0000473	71.56	gold quality
granulocyte	CL:0000094	70.69	gold quality
right testis	UBERON:0004534	70.68	gold quality
mucosa of transverse colon	UBERON:0004991	68.36	gold quality
bone marrow cell	CL:0002092	57.91	gold quality
right uterine tube	UBERON:0001302	53.27	gold quality
mucosa of stomach	UBERON:0001199	53.06	gold quality
primary visual cortex	UBERON:0002436	50.85	gold quality
endocervix	UBERON:0000458	49.85	gold quality
right adrenal gland cortex	UBERON:0035827	49.79	gold quality
spleen	UBERON:0002106	49.74	gold quality
blood	UBERON:0000178	49.33	gold quality
bone marrow	UBERON:0002371	48.65	gold quality
right coronary artery	UBERON:0001625	48.32	gold quality
colonic epithelium	UBERON:0000397	47.62	gold quality
right adrenal gland	UBERON:0001233	47.42	gold quality
sural nerve	UBERON:0015488	46.58	silver quality
cortical plate	UBERON:0005343	46.47	gold quality
fundus of stomach	UBERON:0001160	46.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	46.05	gold quality
cerebellar cortex	UBERON:0002129	45.65	gold quality
cerebellum	UBERON:0002037	45.51	gold quality
cerebellar hemisphere	UBERON:0002245	45.42	gold quality
lower esophagus muscularis layer	UBERON:0035833	45.10	gold quality
lower esophagus	UBERON:0013473	44.90	gold quality
leukocyte	CL:0000738	44.88	gold quality
transverse colon	UBERON:0001157	44.80	gold quality
ganglionic eminence	UBERON:0004023	44.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

21 targeting H2AB2, 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-4447	99.85	67.81	2900
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6745	99.74	65.33	1321
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1915-3P	99.58	66.79	1988
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-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-6762-5P	96.55	64.62	972
HSA-MIR-6845-5P	96.55	64.65	969
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 1)

• Changes in exon inclusion rates and increased presence of intronic sequences in mRNA products upon H2A.Bbd depletion. (PMID:22795134)

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), H2AB1 (ENSG00000274183), H2AC12 (ENSG00000274997), H2AC15 (ENSG00000275221), H2AC14 (ENSG00000276368), H2AC16 (ENSG00000276903), H2AC8 (ENSG00000277075), H2AB3 (ENSG00000277745), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A-Bbd type 2/3 — P0C5Z0 (reviewed: P0C5Z0)

Alternative names: H2A Barr body-deficient

All UniProt accessions (1): P0C5Z0

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. May participate in spermatogenesis.

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_001017991* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR009072	Histone-fold	Homologous_superfamily

UniProt features (12 total): helix 5, strand 4, region of interest 2, chain 1

Structure

Experimental structures (PDB)

4 structures.

PDB	Method	Resolution (Å)
6A7U	X-RAY DIFFRACTION	2.6
6M4G	ELECTRON MICROSCOPY	2.8
9II7	ELECTRON MICROSCOPY	3.5
6M4H	ELECTRON MICROSCOPY	3.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P0C5Z0-F1	87.38	0.76

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 47 (showing top): GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PROTEIN_DNA_COMPLEX, GOCC_EUCHROMATIN, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, chrXq28, GOBP_NUCLEOSOME_ORGANIZATION, GOBP_MRNA_PROCESSING, MIR494_3P, MIR4260

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

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

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
binding	1
protein-DNA complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

920 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AB2	H4C7	Q99525	664
H2AB2	H4C16	P02304	640
H2AB2	CENPA	P49450	610
H2AB2	H3Y2	P0DPK5	587
H2AB2	H2BC21	Q16778	587
H2AB2	H3Y1	P0DPK2	584
H2AB2	H1-0	P07305	510
H2AB2	H3C1	P02295	451
H2AB2	H2BC1	Q96A08	439
H2AB2	H1-8	Q8IZA3	418
H2AB2	H1-7	Q75WM6	406
H2AB2	H3-4	Q16695	402
H2AB2	GMCL2	Q8NEA9	390
H2AB2	H3-3A	P06351	389
H2AB2	H1-6	P22492	388

IntAct

12 interactions, top by confidence:

A	B	Type	Score
H2BC13	H2AB2	psi-mi:“MI:0915”(physical association)	0.560
H2AB2	H2BC15	psi-mi:“MI:0915”(physical association)	0.560
H2AB2	H2BC13	psi-mi:“MI:0915”(physical association)	0.560
H2AB2	MESD	psi-mi:“MI:0915”(physical association)	0.560
SLC16A11	H2AB2	psi-mi:“MI:0914”(association)	0.530
H2AB2	H2BC15	psi-mi:“MI:0915”(physical association)	0.000
H2AB2	MESD	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (242): H2AFB3 (Affinity Capture-MS), H2AFB3 (Two-hybrid), H2AFB2 (Two-hybrid), H2AFB3 (Two-hybrid), H2AFB2 (Two-hybrid), H2AFB3 (Two-hybrid), H2AFB2 (Two-hybrid), SRRM1 (Affinity Capture-MS), CDK13 (Affinity Capture-MS), DKC1 (Affinity Capture-MS), FTSJ3 (Affinity Capture-MS), UTP3 (Affinity Capture-MS), PAIP2B (Affinity Capture-MS), ZCCHC6 (Affinity Capture-MS), GNL3 (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”	H2AB2	“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	2
Likely pathogenic	0
Uncertain significance	0
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
4819213	Single allele	Pathogenic
816416	GRCh37/hg19 Xq28(chrX:154120620-154617577)x3	Pathogenic

SpliceAI

91 predictions. Top by Δscore:

Variant	Effect	Δscore
X:155380961:GTTAT:G	donor_gain	0.8900
X:155380962:TTATT:T	donor_gain	0.8900
X:155380965:T:TG	donor_gain	0.8600
X:155380986:TCCTG:T	donor_gain	0.7600
X:155380963:TATTG:T	donor_gain	0.7500
X:155380964:ATTGA:A	donor_gain	0.7500
X:155380890:T:TA	donor_gain	0.7300
X:155380891:G:GA	donor_gain	0.7300
X:155380795:G:GT	donor_gain	0.7200
X:155380798:G:GT	donor_gain	0.7100
X:155380969:G:GG	donor_gain	0.7100
X:155380968:A:AG	donor_gain	0.7000
X:155380924:GCGCC:G	donor_gain	0.6500
X:155381023:A:T	donor_gain	0.6500
X:155380926:GCC:G	donor_gain	0.6400
X:155381074:GCTAC:G	donor_gain	0.6300
X:155380907:G:T	donor_gain	0.6200
X:155380987:C:A	donor_gain	0.6000
X:155380824:C:CG	donor_gain	0.5900
X:155380906:G:GT	donor_gain	0.5800
X:155380892:GA:G	donor_gain	0.5500
X:155380928:C:G	donor_gain	0.5500
X:155381059:G:GA	donor_gain	0.5500
X:155380879:A:AG	acceptor_gain	0.5300
X:155380880:G:GG	acceptor_gain	0.5300
X:155380928:C:CG	donor_gain	0.5300
X:155380959:C:CA	acceptor_gain	0.5200
X:155380965:T:G	donor_gain	0.5100
X:155380973:C:G	donor_gain	0.5100
X:155380884:G:GT	donor_gain	0.5000

AlphaMissense

720 scored. Top likely-pathogenic:

dbSNP variants (sampled 34 via entrez): RS1209944426 (X:155381727 C>G), RS1466632844 (X:155381766 C>G), RS1557324776 (X:155380185 C>T), RS1557324777 (X:155380509 A>C), RS1557324781 (X:155380877 T>C), RS1557324782 (X:155380927 CCT>C), RS1557324783 (X:155380989 T>C), RS1557324784 (X:155381078 C>T), RS1557324786 (X:155381091 T>G), RS1557324788 (X:155381681 G>T), RS1557324790 (X:155381692 T>G), RS1557324793 (X:155381693 A>G), RS1557324795 (X:155381701 C>G), RS1557324798 (X:155381728 C>T), RS1569561481 (X:155381701 CGGGGGGGG>C,CGG,CGGGGGGG)

Disease associations

OMIM: gene MIM:301038 | disease phenotypes: MIM:300271

GenCC curated gene-disease

Mondo (1): intellectual disability, X-linked 72 (MONDO:0010289)

Orphanet (1): X-linked non-syndromic intellectual disability (Orphanet:777)

HPO phenotypes

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

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C564547	Mental Retardation, X-Linked 72 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
chromium hexavalent ion	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	increases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

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