H2AL3

Summary

H2AL3 (H2A.L variant histone 3, HGNC:53960) is a protein-coding gene on chromosome Xp11.4, encoding Histone H2A-like 3 (A0A3B3IU63). Core component of nucleosome.

Predicted to be a structural constituent of chromatin. Predicted to be involved in heterochromatin formation. Predicted to be located in chromosome. Predicted to be part of nucleosome. Predicted to be active in nucleus.

Source: NCBI Gene 115482686 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 2 total
• MANE Select transcript: NM_001395555

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:53960
Approved symbol	H2AL3
Name	H2A.L variant histone 3
Location	Xp11.4
Locus type	gene with protein product
Status	Approved
Aliases	H2A.L.3
Ensembl gene	ENSG00000229674
Ensembl biotype	protein_coding
Entrez	115482686

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000448797

RefSeq mRNA: 1 — MANE Select: NM_001395555 NM_001395555

CCDS: CCDS94587

Canonical transcript exons

ENST00000448797 — 1 exons

Exon	Start	End
ENSE00003978222	37994272	37994904

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 63.48.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	63.48	gold quality
left testis	UBERON:0004533	62.61	gold quality
testis	UBERON:0000473	62.59	gold quality
sural nerve	UBERON:0015488	54.79	silver quality
mucosa of transverse colon	UBERON:0004991	47.98	gold quality
granulocyte	CL:0000094	39.70	gold quality
hypothalamus	UBERON:0001898	38.39	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
bone marrow	UBERON:0002371	33.21	gold quality
gall bladder	UBERON:0002110	33.08	gold quality
islet of Langerhans	UBERON:0000006	33.02	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
adenohypophysis	UBERON:0002196	31.64	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
putamen	UBERON:0001874	30.27	gold quality
nucleus accumbens	UBERON:0001882	30.11	silver quality
pituitary gland	UBERON:0000007	30.08	silver quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.44	gold quality
caudate nucleus	UBERON:0001873	29.32	silver quality
endometrium	UBERON:0001295	28.99	gold quality
pancreas	UBERON:0001264	28.49	gold quality
transverse colon	UBERON:0001157	28.32	gold quality
duodenum	UBERON:0002114	28.14	gold quality
lymph node	UBERON:0000029	27.57	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.29

Regulation

Is transcription factor: no

Cross-species orthologs

38 orthologs

Organism	Symbol	Gene ID
mus_musculus	H2al1o	ENSMUSG00000061065
mus_musculus	H2al2a	ENSMUSG00000062651
mus_musculus	H2al1j	ENSMUSG00000069038
mus_musculus	H2al1n	ENSMUSG00000078346
mus_musculus	H2al2c	ENSMUSG00000094881
mus_musculus	H2al1d	ENSMUSG00000094904
mus_musculus	H2al1e	ENSMUSG00000095413
mus_musculus	H2al1i	ENSMUSG00000095445
mus_musculus	H2al2b	ENSMUSG00000095573
mus_musculus	H2al1f	ENSMUSG00000095655
mus_musculus	H2al1g	ENSMUSG00000095662
mus_musculus	H2al1c	ENSMUSG00000096097
mus_musculus	H2al1h	ENSMUSG00000099443
mus_musculus	H2al1m	ENSMUSG00000100200
mus_musculus	H2al1k	ENSMUSG00000100448
mus_musculus	H2al1a	ENSMUSG00000100626
mus_musculus	H2al1b	ENSMUSG00000101819
rattus_norvegicus	H2al3	ENSRNOG00000079918
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), H2AJ (ENSG00000246705), H2AL1Q (ENSG00000249467), H2AB1 (ENSG00000274183), 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-like 3 — A0A3B3IU63 (reviewed: A0A3B3IU63)

All UniProt accessions (1): A0A3B3IU63

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.

Similarity. Belongs to the histone H2A family.

RefSeq proteins (1): NP_001382484* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR009072	Histone-fold	Homologous_superfamily

UniProt features (3 total): chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A0A3B3IU63-F1	77.18	0.42

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 17 (showing top): GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, SCHLINGEMANN_SKIN_CARCINOGENESIS_TPA_UP, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOCC_PROTEIN_DNA_COMPLEX, GOMF_PROTEIN_HETERODIMERIZATION_ACTIVITY, GOMF_PROTEIN_DIMERIZATION_ACTIVITY, GOMF_STRUCTURAL_MOLECULE_ACTIVITY, chrXp11, BILANGES_SERUM_SENSITIVE_VIA_TSC2, RB_P130_DN.V1_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION, GOCC_NUCLEOSOME, GOMF_STRUCTURAL_CONSTITUENT_OF_CHROMATIN

GO Biological Process (1): 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 (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
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

706 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AL3	CENPT	Q96BT3	375
H2AL3	TRAM1L1	Q8N609	370
H2AL3	BHLHA9	Q7RTU4	327
H2AL3	ASCL5	Q7RTU5	311
H2AL3	FERD3L	Q96RJ6	277
H2AL3	ARL11	Q969Q4	271
H2AL3	PCDH11X	Q9BZA7	269
H2AL3	PCDHB4	Q9Y5E5	262
H2AL3	PCDHB10	Q9UN67	262
H2AL3	NPBWR2	P48146	253
H2AL3	PCDHB7	Q9Y5E2	248
H2AL3	CDK5R2	Q13319	247
H2AL3	H1-0	P07305	245
H2AL3	PCDHB3	Q9Y5E6	242
H2AL3	BHLHE23	Q8NDY6	242

IntAct

0 interactions, top by confidence:

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

0 interactions.

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	0
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

25 predictions. Top by Δscore:

Variant	Effect	Δscore
X:37994499:T:A	acceptor_gain	0.6600
X:37994713:G:GT	donor_gain	0.5400
X:37994689:G:GT	donor_gain	0.5300
X:37994374:AGGAG:A	acceptor_gain	0.5200
X:37994716:G:GT	donor_gain	0.4600
X:37994865:T:TA	donor_gain	0.4400
X:37994727:G:GA	donor_gain	0.3900
X:37994695:G:GT	donor_gain	0.3400
X:37994495:T:TA	acceptor_gain	0.3300
X:37994726:T:TA	donor_gain	0.3300
X:37994884:C:G	donor_gain	0.3300
X:37994900:A:G	donor_gain	0.3200
X:37994686:G:GT	donor_gain	0.3000
X:37994704:G:GT	donor_gain	0.3000
X:37994399:GAA:G	acceptor_gain	0.2900
X:37994373:TAGGA:T	acceptor_gain	0.2700
X:37994663:TAG:T	donor_gain	0.2500
X:37994664:AGA:A	donor_gain	0.2500
X:37994641:G:GT	donor_gain	0.2300
X:37994698:G:GT	donor_gain	0.2300
X:37994399:GAAGA:G	acceptor_gain	0.2200
X:37994701:G:GT	donor_gain	0.2200
X:37994894:GT:G	donor_gain	0.2200
X:37994611:GA:G	donor_gain	0.2100
X:37994367:TAGG:T	acceptor_gain	0.2000

AlphaMissense

977 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
X:37994491:T:C	F50L	0.938
X:37994493:C:A	F50L	0.938
X:37994493:C:G	F50L	0.938
X:37994416:T:C	F25L	0.907
X:37994418:T:A	F25L	0.907
X:37994418:T:G	F25L	0.907
X:37994521:G:C	A60P	0.792
X:37994417:T:C	F25S	0.782
X:37994417:T:G	F25C	0.777
X:37994492:T:C	F50S	0.746
X:37994576:T:C	I78T	0.730
X:37994516:T:C	L58P	0.727
X:37994511:G:C	E56D	0.692
X:37994511:G:T	E56D	0.692
X:37994504:T:A	V54D	0.685
X:37994510:A:T	E56V	0.685
X:37994423:T:A	V27D	0.665
X:37994473:A:C	S44R	0.657
X:37994475:C:A	S44R	0.657
X:37994475:C:G	S44R	0.657
X:37994576:T:G	I78S	0.645
X:37994438:G:C	R32P	0.642
X:37994599:G:C	A86P	0.637
X:37994492:T:G	F50C	0.633
X:37994501:G:A	G53D	0.626
X:37994507:T:A	L55H	0.626
X:37994576:T:A	I78N	0.626
X:37994603:T:C	L87P	0.623
X:37994498:C:A	A52D	0.613
X:37994512:T:C	Y57H	0.611

dbSNP variants (sampled 300 via entrez): RS1000949566 (X:37993535 A>G), RS1001001752 (X:37993160 C>T), RS1001346865 (X:37994043 C>A,T), RS1004127988 (X:37992300 G>A), RS1005539599 (X:37994465 G>A,C), RS1007855995 (X:37994213 G>A), RS1008308646 (X:37993380 C>A), RS1008323756 (X:37993685 G>A), RS1008914156 (X:37995251 G>A), RS1010767404 (X:37995216 A>G), RS1012037107 (X:37994568 G>A), RS10127316 (X:37993793 G>C,T), RS1013662480 (X:37993058 C>T), RS1013973393 (X:37992822 C>G,T), RS1015307269 (X:37993708 C>A)

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)

Clinical trials (associated diseases)

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