H2AC20

Summary

H2AC20 (H2A clustered histone 20, HGNC:4738) is a protein-coding gene on chromosome 1q21.2, encoding Histone H2A type 2-C (Q16777). Core component of nucleosome. It is a common-essential gene (DepMap: required in 93.7% of cancer cell lines).

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 is intronless and encodes a replication-dependent histone that is a member of the histone H2A family.

Source: NCBI Gene 8338 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 6 total
• Cancer dependency (DepMap): dependent in 93.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_003517

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4738
Approved symbol	H2AC20
Name	H2A clustered histone 20
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	H2A/q
Ensembl gene	ENSG00000184260
Ensembl biotype	protein_coding
OMIM	602797
Entrez	8338

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000331380

RefSeq mRNA: 1 — MANE Select: NM_003517 NM_003517

CCDS: CCDS937

Canonical transcript exons

ENST00000331380 — 1 exons

Exon	Start	End
ENSE00001316918	149886918	149887411

Expression profiles

Bgee: expression breadth ubiquitous, 133 present calls, max score 99.62.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 1222.4654 / max 35759.3114, expressed in 1825 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5035	1222.1357	1825
201718	0.3297	172

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	99.62	gold quality
bone marrow cell	CL:0002092	99.21	gold quality
colonic epithelium	UBERON:0000397	97.04	gold quality
corpus callosum	UBERON:0002336	96.80	gold quality
sural nerve	UBERON:0015488	95.49	gold quality
adrenal tissue	UBERON:0018303	94.57	gold quality
bone marrow	UBERON:0002371	91.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.65	silver quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.69	gold quality
blood	UBERON:0000178	83.04	gold quality
tonsil	UBERON:0002372	80.37	gold quality
uterine cervix	UBERON:0000002	75.66	gold quality
granulocyte	CL:0000094	75.45	gold quality
monocyte	CL:0000576	75.10	gold quality
leukocyte	CL:0000738	74.64	gold quality
mucosa of transverse colon	UBERON:0004991	72.70	gold quality
ectocervix	UBERON:0012249	72.35	gold quality
adrenal gland	UBERON:0002369	71.65	gold quality
hindlimb stylopod muscle	UBERON:0004252	71.10	gold quality
right adrenal gland	UBERON:0001233	70.49	gold quality
left adrenal gland cortex	UBERON:0035825	70.22	gold quality
left ovary	UBERON:0002119	70.01	gold quality
mucosa of stomach	UBERON:0001199	69.95	gold quality
right lung	UBERON:0002167	69.75	gold quality
lower esophagus mucosa	UBERON:0035834	69.74	gold quality
left adrenal gland	UBERON:0001234	69.62	gold quality
ovary	UBERON:0000992	69.56	gold quality
right adrenal gland cortex	UBERON:0035827	69.56	gold quality
liver	UBERON:0002107	69.16	gold quality
thoracic mammary gland	UBERON:0005200	69.14	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-7052	yes	68.18
E-MTAB-9467	yes	32.16
E-MTAB-9689	no	123.81
E-MTAB-6911	no	70.84
E-ANND-3	no	2.64

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 93.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 14)

• deiminated residues were present in H2A (1-56) and H4 (1-52) (PMID:15823041)
• Monoubiquitinated histone H2A in native chromatin coimmunoprecipitates with the endogenous DDB1-CUL4A(DDB2) complex in response to UV irradiation. (PMID:16473935)
• The 2 MDa GCN5 HAT-containing metazoan TFTC/STAGA complexes contain a histone H2A and H2B deubiquitinase activity. (PMID:18206972)
• DDB1-CUL4B(DDB2) is more efficient than DDB1-CUL4A(DDB2) in monoubiquitinating histone H2A in vitro. (PMID:18593899)
• The change in nucleosome core particle conformation induced by global histone acetylation is dependent on H2A/H2A.Z acetylation. (PMID:19385636)
• Study demonstrated that RNF168 is endowed with ubiquitin ligase activity both in vitro and in vivo, which targets histones H2A and H2AX, but not H2B, forming K63 polyubiquitin chains. (PMID:19500350)
• Results demonstrate the potential of C-terminal truncated H2A to contribute to the process of carcinogenesis through epigenetic mechanisms. (PMID:19667409)
• AT1R modify the composition of histone H2A and post-translational modifications. (PMID:20838438)
• L3MBTL2-specific RNAi resulted in increased expression of target genes that exhibited a significant reduction in H2A lysine 119 monoubiquitination. (PMID:21596310)
• Aurora-B-dependent phosphorylation of condensin promotes its association with histone H2A and H2A.Z, which we identify as conserved chromatin ‘receptors’ of condensin (PMID:21633354)
• Our results provide mechanistic insight into how post-translational modification of H2A at the site of a photolesion initiates the repair process and directly affects the stability of the human genome. (PMID:22334663)
• Glycated-H2A histone is better bound by serum anti-DNA autoantibodies in systemic lupus erythematosus patients, and could be a likely trigger for the disease. (PMID:25065453)
• we found an excess of mutations in genes encoding histone H2A and H2B, as well as significant amplification of the segment of chromosome 6p harboring the histone gene cluster containing these genes.We also found frequent deletions of the genes TP53 and MBD3 (a member with CHD4 of the nucleosome remodeling deacetylase complex). (PMID:27791010)
• HIV-Infected Patients: Cross Site-Specific Hydrolysis of H2a and H2b Histones and Myelin Basic Protein with Antibodies against These Three Proteins. (PMID:33143355)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
		ENSDARG00000098739
mus_musculus	H2ac20	ENSMUSG00000068855
rattus_norvegicus		ENSRNOG00000085068
caenorhabditis_elegans		WBGENE00014240

Paralogs (27): MACROH2A2 (ENSG00000099284), H2AZ2 (ENSG00000105968), MACROH2A1 (ENSG00000113648), H2AZ1 (ENSG00000164032), H2AC1 (ENSG00000164508), H2AC6 (ENSG00000180573), H2AC25 (ENSG00000181218), 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), H2AB2 (ENSG00000277858), H2AC4 (ENSG00000278463), H2AC17 (ENSG00000278677), H2AC18 (ENSG00000288825), H2AC19 (ENSG00000288859)

Protein

Protein identifiers

Histone H2A type 2-C — Q16777 (reviewed: Q16777)

Alternative names: H2A-clustered histone 20, Histone H2A-GL101, Histone H2A/q

All UniProt accessions (1): Q16777

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.

Post-translational modifications. Deiminated on Arg-4 in granulocytes upon calcium entry. Monoubiquitination of Lys-120 (H2AK119Ub) by RING1, TRIM37 and RNF2/RING2 complex gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. It is involved in the initiation of both imprinted and random X inactivation. Ubiquitinated H2A is enriched in inactive X chromosome chromatin. Ubiquitination of H2A functions downstream of methylation of ‘Lys-27’ of histone H3 (H3K27me). H2AK119Ub by RNF2/RING2 can also be induced by ultraviolet and may be involved in DNA repair. Monoubiquitination of Lys-120 (H2AK119Ub) by TRIM37 may promote transformation of cells in a number of breast cancers. Following DNA double-strand breaks (DSBs), it is ubiquitinated through ‘Lys-63’ linkage of ubiquitin moieties by the E2 ligase UBE2N and the E3 ligases RNF8 and RNF168, leading to the recruitment of repair proteins to sites of DNA damage. Ubiquitination at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) in response to DNA damage is initiated by RNF168 that mediates monoubiquitination at these 2 sites, and ‘Lys-63’-linked ubiquitin are then conjugated to monoubiquitin; RNF8 is able to extend ‘Lys-63’-linked ubiquitin chains in vitro. Deubiquitinated by USP51 at Lys-14 and Lys-16 (H2AK13Ub and H2AK15Ub, respectively) after damaged DNA is repaired. H2AK119Ub and ionizing radiation-induced ‘Lys-63’-linked ubiquitination (H2AK13Ub and H2AK15Ub) are distinct events. Phosphorylation on Ser-2 (H2AS1ph) is enhanced during mitosis. Phosphorylation on Ser-2 by RPS6KA5/MSK1 directly represses transcription. Acetylation of H3 inhibits Ser-2 phosphorylation by RPS6KA5/MSK1. Phosphorylation at Thr-121 (H2AT120ph) by DCAF1 is present in the regulatory region of many tumor suppresor genes and down-regulates their transcription. Symmetric dimethylation on Arg-4 by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. Glutamine methylation at Gln-105 (H2AQ104me) by FBL is specifically dedicated to polymerase I. It is present at 35S ribosomal DNA locus and impairs binding of the FACT complex. Crotonylation (Kcr) is specifically present in male germ cells and marks testis-specific genes in post-meiotic cells, including X-linked genes that escape sex chromosome inactivation in haploid cells. Crotonylation marks active promoters and enhancers and confers resistance to transcriptional repressors. It is also associated with post-meiotically activated genes on autosomes. Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription.

Similarity. Belongs to the histone H2A family.

RefSeq proteins (1): NP_003508* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002119	Histone_H2A	Family
IPR007125	H2A/H2B/H3	Domain
IPR009072	Histone-fold	Homologous_superfamily
IPR032454	Histone_H2A_C	Domain
IPR032458	Histone_H2A_CS	Conserved_site

Pfam: PF00125, PF16211

UniProt features (55 total): modified residue 36, helix 5, cross-link 3, strand 3, turn 3, initiator methionine 1, chain 1, region of interest 1, compositionally biased region 1, mutagenesis site 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
7U0G	ELECTRON MICROSCOPY	2.6
7U0I	ELECTRON MICROSCOPY	2.6
8SYP	ELECTRON MICROSCOPY	2.6
8EVI	ELECTRON MICROSCOPY	2.64
7U0J	ELECTRON MICROSCOPY	2.7
8DK5	ELECTRON MICROSCOPY	2.71
8EVG	ELECTRON MICROSCOPY	2.75
8SPU	ELECTRON MICROSCOPY	2.8
8EVH	ELECTRON MICROSCOPY	2.85
8SPS	ELECTRON MICROSCOPY	3
6Y5E	ELECTRON MICROSCOPY	3.15
8EVJ	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16777-F1	91.30	0.80

Antibody-complex structures (SAbDab): 11 — 7U0G, 7U0I, 7U0J, 8DK5, 8EVG, 8EVH, 8EVI, 8EVJ, 8SPS, 8SPU, 8SYP

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 (39): 10, 10, 10, 10, 10, 14, 14, 16, 37, 37, 37, 37, 75, 76, 96, 96, 96, 96, 96, 100 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
2	blocks the inhibition of transcription by rps6ka5/msk1.

Function

Pathways and Gene Ontology

Reactome pathways

55 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-3214815	HDACs deacetylate histones
R-HSA-3214847	HATs acetylate histones
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-5689603	UCH proteinases
R-HSA-5689880	Ub-specific processing proteases
R-HSA-5689901	Metalloprotease DUBs
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

MSigDB gene sets: 189 (showing top): REACTOME_MEIOTIC_RECOMBINATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_MEIOTIC_SYNAPSIS, FISCHER_G1_S_CELL_CYCLE, GGGTGGRR_PAX4_03, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, DEBIASI_APOPTOSIS_BY_REOVIRUS_INFECTION_UP, CREB_Q3, FISCHER_DREAM_TARGETS, NOUZOVA_TRETINOIN_AND_H4_ACETYLATION, REACTOME_DNA_REPAIR, OCT1_B

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 (4): nucleosome (GO:0000786), nucleus (GO:0005634), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
Cellular Senescence	3
Chromatin modifying enzymes	3
Depyrimidination	2
Depurination	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
Epigenetic regulation of gene expression	1
Mitotic Prophase	1

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
extracellular vesicle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

3578 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
H2AC20	H4C16	P02304	999
H2AC20	H3C1	P02295	999
H2AC20	H2BC21	Q16778	999
H2AC20	H4C7	Q99525	999
H2AC20	H3-3A	P06351	998
H2AC20	H3-4	Q16695	998
H2AC20	H3-7	Q5TEC6	998
H2AC20	H3-5	Q6NXT2	998
H2AC20	H3C14	Q71DI3	998
H2AC20	H1-0	P07305	995
H2AC20	H1-1	Q02539	994
H2AC20	TP53BP1	Q12888	991
H2AC20	H1-5	P16401	989
H2AC20	RCC1	P18754	968
H2AC20	CENPA	P49450	956

IntAct

143 interactions, top by confidence:

A	B	Type	Score
CHUK	IKBKB	psi-mi:“MI:0914”(association)	0.960
VSX1	USP12	psi-mi:“MI:0914”(association)	0.730
OPG044	DDX3X	psi-mi:“MI:0914”(association)	0.730
ALDH3A1	RCCD1	psi-mi:“MI:0914”(association)	0.640
CAPZA2	CNOT1	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
THOC1	DDX39A	psi-mi:“MI:0914”(association)	0.640
LACC1	DUSP14	psi-mi:“MI:0914”(association)	0.530
ULK3	AIP	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
RPS2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
BLOC1S5	SNAPIN	psi-mi:“MI:0914”(association)	0.530
P/V/C	KPNA3	psi-mi:“MI:0914”(association)	0.530
TOMM20	TPP1	psi-mi:“MI:0914”(association)	0.480
PPM1G	H2BC12	psi-mi:“MI:0914”(association)	0.420
H2AC20	H1-1	psi-mi:“MI:0915”(physical association)	0.400
H2AC20	H2BC9	psi-mi:“MI:0915”(physical association)	0.400
H2AC20	H3-4	psi-mi:“MI:0915”(physical association)	0.400
H3C13	H2AC20	psi-mi:“MI:0915”(physical association)	0.400
RAB37	H2AC20	psi-mi:“MI:0915”(physical association)	0.400
Itsn2	EIF3F	psi-mi:“MI:0914”(association)	0.350
Mta2	MTA3	psi-mi:“MI:0914”(association)	0.350
MAPK8		psi-mi:“MI:0914”(association)	0.350
NEK4	E2F8	psi-mi:“MI:0914”(association)	0.350
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350

BioGRID (499): HIST2H2AC (Biochemical Activity), HIST2H2AC (Reconstituted Complex), HIST2H2AC (Biochemical Activity), HIST2H2AC (Biochemical Activity), HIST2H2AC (Affinity Capture-Western), HIST2H2AC (Affinity Capture-Western), HIST2H2AC (Biochemical Activity), HIST2H2AC (Biochemical Activity), HIST2H2AC (Biochemical Activity), HIST2H2AC (Biochemical Activity), HIST2H2AC (Reconstituted Complex), HIST2H2AC (Affinity Capture-MS), HIST2H2AC (Affinity Capture-MS), HIST2H2AC (Biochemical Activity), HIST2H2AC (Reconstituted Complex)

ESM2 similar proteins: A1A4R1, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, P02262, P02263, P02270, P04908, P06897, P0C0S8, P0C0S9, P0C169, P0C170, P0CC09, P13912, P19178, P20671, P21896, P27325, P35061, P35062, P70082, P84052, Q07135, Q16777, Q3ZBX9, Q4FZT6, Q4R3X5, Q64522, Q64523, Q64598, Q6FI13, Q6GSS7

Diamond homologs: A0A097I1R9, A0A097I2B5, A0A0D2UG83, A1A4R1, A1CJ10, A1D8G8, A3LXE7, A3LZZ0, A5DBG4, A5DJJ2, A5DWF1, A5DXC6, A9UMV8, C0HKE1, C0HKE2, C0HKE3, C0HKE4, C0HKE5, C0HKE6, C0HKE7, C0HKE8, C0HKE9, L7HZV6, O74268, P02262, P02263, P02264, P04908, P04909, P04910, P04911, P04912, P06897, P07793, P08844, P0C0S8, P0C0S9, P0C169, P0C170, P0C952

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SLBP	“up-regulates quantity by expression”	H2AC20	“translation regulation”
DZIP3	“up-regulates activity”	H2AC20	monoubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 191 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Packaging Of Telomere Ends	7	12.3×	2e-04
Recognition and association of DNA glycosylase with site containing an affected pyrimidine	8	11.8×	8e-05
Cleavage of the damaged pyrimidine	8	11.8×	8e-05
Recognition and association of DNA glycosylase with site containing an affected purine	7	11.4×	2e-04
Cleavage of the damaged purine	7	11.4×	2e-04
SIRT1 negatively regulates rRNA expression	8	10.9×	1e-04
DNA Damage/Telomere Stress Induced Senescence	8	10.4×	1e-04
Meiotic synapsis	9	10.2×	8e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of macroautophagy	5	16.1×	5e-03
energy homeostasis	6	9.9×	7e-03
heterochromatin formation	6	9.3×	8e-03
nucleosome assembly	8	6.8×	7e-03
protein phosphorylation	15	6.2×	2e-05
chromatin organization	10	6.0×	4e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	6
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

67 predictions. Top by Δscore:

Variant	Effect	Δscore
1:149887062:C:T	donor_gain	0.8700
1:149887088:C:T	donor_gain	0.8700
1:149887087:GCAAC:G	donor_gain	0.8300
1:149887138:TCCTC:T	donor_gain	0.7700
1:149887001:C:T	donor_gain	0.7300
1:149887199:G:GT	donor_gain	0.7300
1:149886997:G:GT	donor_gain	0.6800
1:149887091:C:G	donor_gain	0.5600
1:149887051:TCCCG:T	donor_loss	0.5100
1:149887052:CCCGG:C	donor_loss	0.5100
1:149887053:CCG:C	donor_loss	0.5100
1:149887054:CG:C	donor_loss	0.5100
1:149887055:GGTAG:G	donor_loss	0.5100
1:149887056:GTAGG:G	donor_loss	0.5100
1:149887057:T:A	donor_loss	0.5100
1:149887058:A:C	donor_loss	0.5000
1:149887059:G:GC	donor_loss	0.4700
1:149887252:A:T	donor_gain	0.4500
1:149887060:G:C	donor_loss	0.4000
1:149887056:G:GG	donor_gain	0.3800
1:149887251:G:GT	donor_gain	0.3700
1:149887050:TTCCC:T	donor_loss	0.3600
1:149887054:C:A	donor_gain	0.3500
1:149887059:G:A	donor_gain	0.3500
1:149887102:G:A	donor_gain	0.3500
1:149887229:GCT:G	acceptor_gain	0.3400
1:149887061:G:T	donor_gain	0.3300
1:149887228:A:AG	acceptor_gain	0.3200
1:149887229:G:GG	acceptor_gain	0.3200
1:149887107:G:A	donor_gain	0.3100

AlphaMissense

814 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:149887045:T:A	L24H	1.000
1:149887123:T:A	V50D	1.000
1:149887135:C:A	A54E	1.000
1:149887146:T:C	Y58H	1.000
1:149887150:T:C	L59P	1.000
1:149887155:G:C	A61P	1.000
1:149887156:C:A	A61D	1.000
1:149887159:A:T	E62V	1.000
1:149887165:T:C	L64P	1.000
1:149887167:G:A	E65K	1.000
1:149887171:T:C	L66P	1.000
1:149887174:C:A	A67E	1.000
1:149887176:G:C	G68R	1.000
1:149887176:G:T	G68C	1.000
1:149887177:G:A	G68D	1.000
1:149887177:G:T	G68V	1.000
1:149887185:G:C	A71P	1.000
1:149887186:C:A	A71D	1.000
1:149887191:G:C	D73H	1.000
1:149887192:A:T	D73V	1.000
1:149887210:T:A	I79N	1.000
1:149887218:C:A	R82S	1.000
1:149887231:T:C	L86P	1.000
1:149887234:C:A	A87D	1.000
1:149887240:G:C	R89P	1.000
1:149887245:G:C	D91H	1.000
1:149887246:A:C	D91A	1.000
1:149887246:A:G	D91G	1.000
1:149887246:A:T	D91V	1.000
1:149887255:T:C	L94P	1.000

dbSNP variants (sampled 300 via entrez): RS1002085119 (1:149885572 G>A), RS1004208294 (1:149886803 C>T), RS1005621517 (1:149885489 G>C), RS1008980388 (1:149887855 C>T), RS1014554334 (1:149887856 G>A), RS1015832667 (1:149886687 G>A,C), RS1016899751 (1:149885510 G>C), RS1020749141 (1:149886077 T>A,C), RS1020781430 (1:149885606 G>A), RS1025322852 (1:149885130 T>C), RS1025523015 (1:149887031 G>A,C), RS1028575428 (1:149887381 C>T), RS1028635793 (1:149887522 A>C,G), RS1029622454 (1:149886527 G>A), RS1033866495 (1:149886839 A>C,G)

Disease associations

OMIM: gene MIM:602797 | 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

49 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression	4
bisphenol F	increases expression, affects cotreatment	2
bisphenol A	decreases expression, affects cotreatment, increases expression	2
sodium arsenite	decreases expression, increases expression	2
Acetaminophen	increases expression	2
Valproic Acid	decreases expression, decreases methylation	2
Aflatoxin B1	decreases expression, decreases methylation	2
Copper Sulfate	increases expression, decreases expression	2
afuresertib	decreases expression	1
TAK-243	decreases sumoylation	1
propionaldehyde	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
arsenite	affects binding, increases reaction	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
ferrous chloride	increases expression	1
hydroquinone	decreases expression	1
chloropicrin	decreases expression	1
nickel acetate	decreases ubiquitination, increases ubiquitination	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	increases expression	1
Benztropine	increases expression	1
Cannabidiol	increases expression	1

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A2Q8	SEES3-1V human HIST2H2AC, clone1	Embryonic stem cell	Male
CVCL_A2Q9	SEES3-1V human HIST2H2AC, clone2	Embryonic stem cell	Male
CVCL_A2R0	SEES3-1V human HIST2H2AC, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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