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H3-4

gene
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Also known as H3tH3/gH3.4H3C16

Summary

H3-4 (H3.4 histone, cluster member, HGNC:4778) is a protein-coding gene on chromosome 1q42.13, encoding Histone H3.1t (Q16695). Core component of nucleosome.

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 is intronless and encodes a replication-dependent histone that is a member of the histone H3 family. Transcripts from this gene lack polyA tails; instead, they contain a palindromic termination element. This gene is located separately from the other H3 genes that are in the histone gene cluster on chromosome 6p22-p21.3.

Source: NCBI Gene 8290 — RefSeq curated summary.

At a glance

  • Gene–disease (curated): neurodevelopmental disorder (Limited, GenCC)
  • GWAS associations: 1
  • Clinical variants (ClinVar): 51 total
  • MANE Select transcript: NM_003493

Identifiers

Gene identifiers

FieldValue
HGNC IDHGNC:4778
Approved symbolH3-4
NameH3.4 histone, cluster member
Location1q42.13
Locus typegene with protein product
StatusApproved
AliasesH3t, H3/g, H3.4, H3C16
Ensembl geneENSG00000168148
Ensembl biotypeprotein_coding
OMIM602820
Entrez8290

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000366696

RefSeq mRNA: 1 — MANE Select: NM_003493 NM_003493

CCDS: CCDS1572

Canonical transcript exons

ENST00000366696 — 1 exons

ExonStartEnd
ENSE00001442338228424845228425360

Expression profiles

Bgee: expression breadth broad, 89 present calls, max score 92.02.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.5600 / max 474.6942, expressed in 32 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter IDTPM avgSamples expressed
178410.560032

Top tissues by expression

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

TissueAnatomy IDExpression scoreQuality
male germ line stem cell (sensu Vertebrata) in testisCL:0000089 ∩ UBERON:000047392.02gold quality
right testisUBERON:000453461.66gold quality
left testisUBERON:000453360.66gold quality
testisUBERON:000047360.49gold quality
right coronary arteryUBERON:000162551.37gold quality
granulocyteCL:000009450.59silver quality
ectocervixUBERON:001224949.56gold quality
endocervixUBERON:000045847.45gold quality
mucosa of transverse colonUBERON:000499146.34gold quality
uterine cervixUBERON:000000245.46gold quality
right uterine tubeUBERON:000130245.07silver quality
right ovaryUBERON:000211844.70gold quality
right hemisphere of cerebellumUBERON:001489044.15silver quality
colonic epitheliumUBERON:000039743.54silver quality
mucosa of stomachUBERON:000119943.51silver quality
cerebellar hemisphereUBERON:000224542.48silver quality
cerebellumUBERON:000203742.41silver quality
cerebellar cortexUBERON:000212942.37silver quality
stromal cell of endometriumCL:000225542.31silver quality
urinary bladderUBERON:000125541.65gold quality
body of uterusUBERON:000985341.55gold quality
vaginaUBERON:000099640.69gold quality
small intestine Peyer’s patchUBERON:000345438.84silver quality
transverse colonUBERON:000115738.82gold quality
bone marrow cellCL:000209238.63gold quality
ascending aortaUBERON:000149638.59gold quality
small intestineUBERON:000210838.08silver quality
thoracic aortaUBERON:000151537.88gold quality
myometriumUBERON:000129637.84gold quality
lower esophagus muscularis layerUBERON:003583337.57gold quality

Single-cell (SCXA)

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

ExperimentMarker?Max mean expression
E-ANND-3no0.00

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 40)

  • These results define H3 phosphorylation as a key to hTERT transactivation induced by proliferation and reveal a fundamental mechanism for telomerase regulation in both normal human cells and transformed T cells. (PMID:16354694)
  • Results indicate that single bromodomains bind specific acetyl-lysine sites within the histone 3 tail with sub-micromolar affinity. (PMID:17320048)
  • JARID1B was identified as a demethylase capable of removing three methyl groups from histone H3 lysine 4 and up-regulated in prostate cancer. (PMID:18048344)
  • Human Nap2 promotes nucleosome assembly with H3t/H4. (PMID:18281699)
  • Cooperative H3 modification provides a mechanistic basis for GCN5L association with cdk8-Mediator and also identifies a biochemical means by which cdk8 can indirectly activate gene expression. (PMID:18418385)
  • These results suggest that the histone H3 di-methylation at lysine 9, as well as acetylation at lysine 9/14, may be indispensable for coordinated induction of the GLUT5 gene by p44/42 MAP kinase inhibition and the glucocorticoid hormone. (PMID:18439419)
  • Dynamic changes in the levels of acetylated, methylated, and phosphorylated histone H3 occur during the initiation of DNA replication at the two human origin loci examined (lamin B2 and hOrs8). (PMID:19585526)
  • These results suggest that PELP1 is a reader of H3 methylation marks and has a crucial role in modulating the histone code at the ERalpha target genes. (PMID:20448663)
  • crystal structure of the H3T nucleosome revealed structural differences in the H3T regions on both ends of the central alpha2 helix, as compared to those of H3.1. (PMID:20498094)
  • Discovery of a subgroup of genes linked to T cell functions displaying high levels of H3K4me2 within their gene body. (PMID:20841431)
  • The ataxia telangiectasia, mutated and Rad3-related-Chk1 axis regulates H3-pThr 11 dephosphorylation on DNA damage, at least in part by the activation of PP1gamma through Chk1-dependent inhibition of cyclin dependent kinases. (PMID:20948546)
  • laryngeal cancer is characterized by high proliferative potential mediated by increase in cyclin D1 and H3 mRNAs expression. (PMID:21193919)
  • Deacetylation of histone H3 occurs in the early stages of multiple sclerosis, its efficiency decreasing with disease duration. (PMID:21368055)
  • Trimethylation of lysine 27 on histone H3 expression, as examined by immunohistochemistry, has the potential to be used as an immunomarker to predict nasopharyngeal carcinoma chemoradiotherapy response and patient prognosis. (PMID:21738951)
  • aberration of the global H3K9me2 level is an important epigenetic event in colorectal tumorigenesis and carcinogenesis (PMID:21917293)
  • Studies indicate that in Th17 cells, activated STAT3 by IL-6 positively regulates H3K4me3 deposition in the Il17 locus. (PMID:21977994)
  • Studies identified a physical and functional interaction between RUNX1 (AML1) and MLL and show that both are required to maintain the histone lysine 4 trimethyl mark (H3K4me3) at 2 critical regulatory regions of the AML1 target gene PU.1. (PMID:22012064)
  • NSD2 links dimethylation of histone H3 at lysine 36 to oncogenic programming. (PMID:22099308)
  • HAT1 differentially impacts nucleosome assembly of H3.1-H4 and H3.3-H4. (PMID:22228774)
  • our data suggest that global histone H3 and H4 modification patterns are potential markers of tumor recurrence and disease-free survival in non-small cell lung cancer (PMID:22360506)
  • O-GlcNAcylation regulates mitosis-specific phosphorylations on H3, providing a mechanistic switch that orchestrates the G2-M transition of the cell cycle. (PMID:22371497)
  • Increased levels of decondensed chromatin in both normal progenitor cells and cancer cells are associated with global loss of H3K27me3, which is linked to MYC overexpression. (PMID:22713676)
  • The levels of H3K4me3 and H3K27me3 show dynamic changes during human oocyte maturation and preimplantation embryonic development. (PMID:22818287)
  • 17beta-estradiol stimulation induces the recruitment of PAD2 to target promoters by ERalpha, whereby PAD2 then citrullinates H3R26, which leads to local chromatin decondensation and transcriptional activation. (PMID:22853951)
  • Elongated telomeres show increased trimethylated histone H3 Lys9 (H3K9me3)density. (PMID:22922742)
  • Histone H3 is increased during amino acid response that is associated with active transcription. (PMID:22978410)
  • Histone H3 Ser-10 phosphorylation can be designated a new ‘apoptotic histone code’ mediated by PKCdelta. (PMID:22984491)
  • These data suggest that the tandem of plant homeodomain 1/2 fingers play a role in MOZ and MORF histone acetyltransferase association with histon H3 regions enriched in acetylated marks. (PMID:23063713)
  • Data using recombinant proteins in cell-free lysates suggest that interaction of survivin with phosphorylated histone 3 (H3T3-Phos; a mitotic biological marker appearing during cell division) is abolished by trimethylation at neighboring lysine. (PMID:23281010)
  • The SUV39H1 chromodomain was shown to recognize histone H3K9me2/3 specifically. (PMID:23285239)
  • histone H3 lysine 79 dimethylation (H3K79me2) and a novel identified site, H2bK5 monomethylation (H2bK5me1), were completely absent in individuals with Neural tube defects (PMID:23376398)
  • Study shows that H3K4me3-TAF3 interactions direct global TFIID recruitment to active genes, some of which are p53 targets. Further analyses show that H3K4me3 enhances p53-dependent transcription by stimulating preinitiation complex formation. (PMID:23452851)
  • PRAME expression in leukaemic cell lines is upregulated by IFN gamma and LPS, suggesting a possible role in immune responses. Nuclear PRAME interacts with Histone H3, suggesting a role in gene regulation in the nucleus. (PMID:23460923)
  • Results suggest that histone modification in H3K27 detected using immunohistochemistry can be successfully used as an independent prognostic factor for colorectal cancer patients with metachronous liver metastasis. (PMID:23523318)
  • Histone H3.3. mutations drive pediatric glioblastoma through upregulation of MYCN. (PMID:23539269)
  • Results suggest that GLP may play a significant role in the maintenance of HIV-1 latency by catalyzing dimethylation of H3K9. (PMID:23541084)
  • C-kinase-activated protein phosphatase (CPI)-17 inhibitor knockdown in human pancreatic cancer cells results in dephosphorylation of histone H3. (PMID:23541585)
  • Data indicate that S6 kinase 2 (S6K2) can phosphorylate histone H3 at position Thr45, which may play a role during cell proliferation and/or differentiation. (PMID:23564320)
  • Menin-dependent transcriptional repression of histone H3 lysine 9 methylation might play an important role in preventing tumors. (PMID:23579270)
  • Disruption of neocortical histone H3 homeostasis by soluble Abeta implicates Alzheimer’s disease. (PMID:23582659)

Cross-species orthologs

24 orthologs

OrganismSymbolGene ID
danio_reriozgc:173552ENSDARG00000051737
danio_reriosi:ch1073-153i20.2ENSDARG00000105345
danio_reriozgc:173552ENSDARG00000110909
danio_reriosi:ch211-113a14.27ENSDARG00000111396
danio_reriosi:ch211-113a14.20ENSDARG00000112131
danio_reriozgc:173552ENSDARG00000112175
danio_reriosi:ch211-113a14.23ENSDARG00000114334
mus_musculusH3f4ENSMUSG00000080152
drosophila_melanogasterHis3:CG33812FBGN0053812
caenorhabditis_elegansWBGENE00001876
caenorhabditis_elegansWBGENE00001880
caenorhabditis_elegansWBGENE00001883
caenorhabditis_elegansWBGENE00001887
caenorhabditis_elegansWBGENE00001891
caenorhabditis_elegansWBGENE00001899
caenorhabditis_elegansWBGENE00001901
caenorhabditis_elegansWBGENE00001906
caenorhabditis_elegansWBGENE00001914
caenorhabditis_elegansWBGENE00001916
caenorhabditis_elegansWBGENE00001919
caenorhabditis_elegansWBGENE00001923
caenorhabditis_elegansWBGENE00001929
caenorhabditis_elegansWBGENE00001933
caenorhabditis_elegansWBGENE00001937

Paralogs (20): CENPA (ENSG00000115163), H3-3B (ENSG00000132475), H3-3A (ENSG00000163041), H3C13 (ENSG00000183598), H3-5 (ENSG00000188375), H3C12 (ENSG00000197153), H3C4 (ENSG00000197409), H3C14 (ENSG00000203811), H3C15 (ENSG00000203852), H3Y2 (ENSG00000268799), H3Y1 (ENSG00000269466), H3-7 (ENSG00000273213), H3C8 (ENSG00000273983), H3C6 (ENSG00000274750), H3C11 (ENSG00000275379), H3C1 (ENSG00000275714), H3C7 (ENSG00000277775), H3C10 (ENSG00000278828), H3C2 (ENSG00000286522), H3C3 (ENSG00000287080)

Protein

Protein identifiers

Histone H3.1t — Q16695 (reviewed: Q16695)

Alternative names: H3/g, Histone H3.4

All UniProt accessions (1): Q16695

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. Interacts with TONSL; CHAF1A and CHAF1B.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in testicular cells.

Post-translational modifications. Acetylation is generally linked to gene activation. Acetylation on Lys-10 (H3K9ac) impairs methylation at Arg-9 (H3R8me2s). Acetylation on Lys-19 (H3K18ac) and Lys-24 (H3K24ac) favors methylation at Arg-18 (H3R17me). Acetylation at Lys-123 (H3K122ac) by EP300/p300 plays a central role in chromatin structure: localizes at the surface of the histone octamer and stimulates transcription, possibly by promoting nucleosome instability. Citrullination at Arg-9 (H3R8ci) and/or Arg-18 (H3R17ci) by PADI4 impairs methylation and represses transcription. Asymmetric dimethylation at Arg-18 (H3R17me2a) by CARM1 is linked to gene activation. Symmetric dimethylation at Arg-9 (H3R8me2s) by PRMT5 is linked to gene repression. Asymmetric dimethylation at Arg-3 (H3R2me2a) by PRMT6 is linked to gene repression and is mutually exclusive with H3 Lys-5 methylation (H3K4me2 and H3K4me3). H3R2me2a is present at the 3’ of genes regardless of their transcription state and is enriched on inactive promoters, while it is absent on active promoters. Methylation at Lys-5 (H3K4me), Lys-37 (H3K36me) and Lys-80 (H3K79me) are linked to gene activation. Methylation at Lys-5 (H3K4me) facilitates subsequent acetylation of H3 and H4. Methylation at Lys-80 (H3K79me) is associated with DNA double-strand break (DSB) responses and is a specific target for TP53BP1. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are linked to gene repression. Methylation at Lys-10 (H3K9me) is a specific target for HP1 proteins (CBX1, CBX3 and CBX5) and prevents subsequent phosphorylation at Ser-11 (H3S10ph) and acetylation of H3 and H4. Methylation at Lys-5 (H3K4me) and Lys-80 (H3K79me) require preliminary monoubiquitination of H2B at ‘Lys-120’. Methylation at Lys-10 (H3K9me) and Lys-28 (H3K27me) are enriched in inactive X chromosome chromatin. Monomethylation at Lys-57 (H3K56me1) by EHMT2/G9A in G1 phase promotes interaction with PCNA and is required for DNA replication. Phosphorylated at Thr-4 (H3T3ph) by HASPIN during prophase and dephosphorylated during anaphase. Phosphorylation at Ser-11 (H3S10ph) by AURKB is crucial for chromosome condensation and cell-cycle progression during mitosis and meiosis. In addition phosphorylation at Ser-11 (H3S10ph) by RPS6KA4 and RPS6KA5 is important during interphase because it enables the transcription of genes following external stimulation, like mitogens, stress, growth factors or UV irradiation and result in the activation of genes, such as c-fos and c-jun. Phosphorylation at Ser-11 (H3S10ph), which is linked to gene activation, prevents methylation at Lys-10 (H3K9me) but facilitates acetylation of H3 and H4. Phosphorylation at Ser-11 (H3S10ph) by AURKB mediates the dissociation of HP1 proteins (CBX1, CBX3 and CBX5) from heterochromatin. Phosphorylation at Ser-11 (H3S10ph) is also an essential regulatory mechanism for neoplastic cell transformation. Phosphorylated at Ser-29 (H3S28ph) by MAP3K20 isoform 1, RPS6KA5 or AURKB during mitosis or upon ultraviolet B irradiation. Phosphorylation at Thr-7 (H3T6ph) by PRKCB is a specific tag for epigenetic transcriptional activation that prevents demethylation of Lys-5 (H3K4me) by LSD1/KDM1A. At centromeres, specifically phosphorylated at Thr-12 (H3T11ph) from prophase to early anaphase, by DAPK3 and PKN1. Phosphorylation at Thr-12 (H3T11ph) by PKN1 or isoform M2 of PKM (PKM2) is a specific tag for epigenetic transcriptional activation that promotes demethylation of Lys-10 (H3K9me) by KDM4C/JMJD2C. Phosphorylation at Tyr-42 (H3Y41ph) by JAK2 promotes exclusion of CBX5 (HP1 alpha) from chromatin. Ubiquitinated. Lysine deamination at Lys-5 (H3K4all) to form allysine is mediated by LOXL2. Allysine formation by LOXL2 only takes place on H3K4me3 and results in gene repression. Butyrylation of histones marks active promoters and competes with histone acetylation. It is present during late spermatogenesis. Succinylation at Lys-80 (H3K79succ) by KAT2A takes place with a maximum frequency around the transcription start sites of genes. It gives a specific tag for epigenetic transcription activation. Desuccinylation at Lys-123 (H3K122succ) by SIRT7 in response to DNA damage promotes chromatin condensation and double-strand breaks (DSBs) repair. Serine ADP-ribosylation constitutes the primary form of ADP-ribosylation of proteins in response to DNA damage. Serine ADP-ribosylation at Ser-11 (H3S10ADPr) is mutually exclusive with phosphorylation at Ser-11 (H3S10ph) and impairs acetylation at Lys-10 (H3K9ac).

Similarity. Belongs to the histone H3 family.

RefSeq proteins (1): NP_003484* (*=MANE)

Domains & families (InterPro)

IDNameType
IPR000164Histone_H3/CENP-AFamily
IPR007125H2A/H2B/H3Domain
IPR009072Histone-foldHomologous_superfamily

Pfam: PF00125

UniProt features (124 total): modified residue 110, helix 5, cross-link 3, strand 2, initiator methionine 1, chain 1, turn 1, region of interest 1

Structure

Experimental structures (PDB)

13 structures.

PDBMethodResolution (Å)
3MO8X-RAY DIFFRACTION1.69
6WAUX-RAY DIFFRACTION1.75
6WATX-RAY DIFFRACTION1.8
4V2WX-RAY DIFFRACTION1.81
3T6RX-RAY DIFFRACTION1.95
4V2VX-RAY DIFFRACTION2
2YBPX-RAY DIFFRACTION2.02
6OIEX-RAY DIFFRACTION2.08
2YBSX-RAY DIFFRACTION2.32
3A6NX-RAY DIFFRACTION2.7
8Z50X-RAY DIFFRACTION2.8
2V1DX-RAY DIFFRACTION3.1
8VMIELECTRON MICROSCOPY3.1

Predicted structure (AlphaFold)

ModelpLDDTFraction very-high
AF-Q16695-F186.990.71

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 (113): 5, 80, 81, 87, 108, 116, 116, 123, 123, 123, 123, 5, 123, 123, 123, 15, 19, 24, 5, 5 …

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

IDPathway
R-HSA-110328Recognition and association of DNA glycosylase with site containing an affected pyrimidine
R-HSA-110329Cleavage of the damaged pyrimidine
R-HSA-110330Recognition and association of DNA glycosylase with site containing an affected purine
R-HSA-110331Cleavage of the damaged purine
R-HSA-1221632Meiotic synapsis
R-HSA-171306Packaging Of Telomere Ends
R-HSA-201722Formation of the beta-catenin:TCF transactivating complex
R-HSA-2299718Condensation of Prophase Chromosomes
R-HSA-2559586DNA Damage/Telomere Stress Induced Senescence
R-HSA-5693565Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-5693571Nonhomologous End-Joining (NHEJ)
R-HSA-5693607Processing of DNA double-strand break ends
R-HSA-69473G2/M DNA damage checkpoint
R-HSA-912446Meiotic recombination
R-HSA-9670095Inhibition of DNA recombination at telomere

MSigDB gene sets: 105 (showing top): REACTOME_MEIOTIC_RECOMBINATION, REACTOME_MEIOTIC_SYNAPSIS, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, HELLER_HDAC_TARGETS_SILENCED_BY_METHYLATION_UP, TATA_C, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEIN_DNA_COMPLEX_ORGANIZATION, REACTOME_DNA_REPAIR, GOBP_CHROMATIN_REMODELING, GOBP_HETEROCHROMATIN_ORGANIZATION, TTTNNANAGCYR_UNKNOWN, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, REACTOME_CELL_CYCLE_CHECKPOINTS

GO Biological Process (6): chromatin organization (GO:0006325), nucleosome assembly (GO:0006334), DNA replication-dependent chromatin assembly (GO:0006335), spermatogonial cell division (GO:0007284), regulation of cell differentiation (GO:0045595), heterochromatin organization (GO:0070828)

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 (8): chromosome, telomeric region (GO:0000781), nucleosome (GO:0000786), heterochromatin (GO:0000792), condensed nuclear chromosome (GO:0000794), nucleus (GO:0005634), nucleoplasm (GO:0005654), extracellular exosome (GO:0070062), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-11 pathways:

CategoryPathways
Depyrimidination2
Depurination2
Meiosis2
Telomere Maintenance2
TCF dependent signaling in response to WNT1
Mitotic Prophase1
Cellular Senescence1
DNA Double Strand Break Response1
DNA Double-Strand Break Repair1
HDR through Homologous Recombination (HRR) or Single Strand Annealing (SSA)1
G2/M Checkpoints1

GO top-level categories

Rollup of top GO terms by namespace:

CategoryTerms
chromatin organization3
chromatin3
cellular component organization1
nucleosome organization1
protein-DNA complex assembly1
spermatogenesis1
cell division1
cell differentiation1
regulation of developmental process1
regulation of cellular process1
nucleic acid binding1
structural molecule activity1
protein dimerization activity1
binding1
chromosomal region1
protein-DNA complex1
nuclear chromosome1
condensed chromosome1
nucleus1
intracellular membrane-bounded organelle1
nuclear lumen1
cellular anatomical structure1
extracellular vesicle1
intracellular membraneless organelle1

Protein interactions and networks

STRING

8670 interactions, top by confidence (×1000):

Protein AProtein BPartner UniProtScore
H3-4H4C16P02304998
H3-4H2AC20Q16777998
H3-4H2AC19P20670998
H3-4H2BC21Q16778998
H3-4H4C7Q99525998
H3-4WDR5P61964997
H3-4CBX5P45973995
H3-4DNMT3LQ9UJW3994
H3-4CBX3Q13185991
H3-4BRD4O60885990
H3-4DNMT3AQ9Y6K1987
H3-4RAG2P55895978
H3-4DNMT1P26358973
H3-4CBX1P23197973
H3-4HDAC1Q13547964

IntAct

218 interactions, top by confidence:

ABTypeScore
H2AC4H2BC11psi-mi:“MI:0915”(physical association)0.850
KDM1Apsi-mi:“MI:0915”(physical association)0.700
H3-4H4C16psi-mi:“MI:0407”(direct interaction)0.680
H3-4H4C16psi-mi:“MI:0915”(physical association)0.680
H3-4H2AXpsi-mi:“MI:0915”(physical association)0.640
KDM4AH3-4psi-mi:“MI:0871”(demethylation reaction)0.620
KDM4AH3-4psi-mi:“MI:0407”(direct interaction)0.620
H3-4H2AC4psi-mi:“MI:0915”(physical association)0.590
H3-4CBX5psi-mi:“MI:0915”(physical association)0.560
NASPH3-4psi-mi:“MI:0915”(physical association)0.560
RIPPLY1H3-4psi-mi:“MI:0915”(physical association)0.560
H3-4AURKBpsi-mi:“MI:0217”(phosphorylation reaction)0.540
AURKBH3-4psi-mi:“MI:0217”(phosphorylation reaction)0.540
AURKBH3-4psi-mi:“MI:0915”(physical association)0.540
CBX6IGF2BP3psi-mi:“MI:0914”(association)0.530
CBX1KPNA3psi-mi:“MI:0914”(association)0.530
CBX5KPNA3psi-mi:“MI:0914”(association)0.530
VRK1H3-4psi-mi:“MI:0217”(phosphorylation reaction)0.440
H3-4KDM1Apsi-mi:“MI:0915”(physical association)0.400

BioGRID (659): HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), UHRF1 (Protein-peptide), HIST3H3 (Protein-peptide), HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), HIST3H3 (Biochemical Activity), WDR5 (Affinity Capture-MS), WDR5 (Reconstituted Complex), ASH2L (Reconstituted Complex), RBP5 (Reconstituted Complex), HIST3H3 (Affinity Capture-Western)

ESM2 similar proteins: A1CP80, A1D240, A2QRR5, A2XHJ3, A4RCX7, O15819, P06902, P07041, P15512, P22843, P23753, P41353, P59169, P61832, P61834, P61835, P68431, P68432, P68433, P69149, P69150, P69244, P69245, P80553, P90543, Q0D0E8, Q0JCT1, Q0UY45, Q16695, Q1E225, Q22RG7, Q2UCQ0, Q3C2E5, Q4IER8, Q55BN9, Q55BP0, Q5DWI3, Q6C0C4, Q6DL03, Q6LBF0

Diamond homologs: A2XHJ3, A2Y533, A5DWE2, A5PK61, C0HL66, C0HL67, P02299, P02301, P02302, P06352, P08437, P08898, P08903, P09988, P22843, P50564, P59169, P59226, P68427, P68428, P68429, P68430, P68431, P68432, P68433, P69071, P69072, P69073, P69074, P69075, P69076, P69077, P69078, P69079, P69244, P69245, P69246, P69248, P80553, P84227

SIGNOR signaling

42 interactions.

AEffectBMechanism
KDM4C“down-regulates activity”H3-4demethylation
SETDB2“up-regulates activity”H3-4methylation
KDM5A“up-regulates activity”H3-4demethylation
KDM5B“up-regulates activity”H3-4demethylation
KDM5C“up-regulates activity”H3-4demethylation
KDM5D“up-regulates activity”H3-4demethylation
“Set1-Ash2 HMT complex”“down-regulates activity”H3-4methylation
CBX5“up-regulates activity”H3-4binding
CBX1“up-regulates activity”H3-4binding
CBX3“up-regulates activity”H3-4binding
KDM1A“up-regulates activity”H3-4demethylation
PHF2“up-regulates activity”H3-4demethylation
PHF2“down-regulates activity”H3-4demethylation
JMJD1C“down-regulates activity”H3-4demethylation
SLBP“up-regulates quantity by expression”H3-4“translation regulation”
SETD1B“down-regulates activity”H3-4methylation
BAZ2B“down-regulates activity”H3-4binding
Sin3B_complex“down-regulates activity”H3-4binding
DOT1LunknownH3-4methylation
“MLL2 complex”“down-regulates activity”H3-4methylation
“MLL1 complex”“down-regulates activity”H3-4methylation
“MLL3 complex”“down-regulates activity”H3-4methylation
KAT2A“down-regulates activity”H3-4acetylation
KAT2B“down-regulates activity”H3-4acetylation
“SAGA complex”“down-regulates activity”H3-4acetylation
KDM3A“up-regulates activity”H3-4demethylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 186 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:

PathwayPartnersFoldFDR
Formation of Senescence-Associated Heterochromatin Foci (SAHF)631.7×3e-07
ChAHP complex assembly1623.2×3e-15
Packaging Of Telomere Ends1322.5×5e-13
Replacement of protamines by nucleosomes in the male pronucleus1021.4×3e-10
Recognition and association of DNA glycosylase with site containing an affected purine1320.9×1e-12
Cleavage of the damaged purine1320.9×1e-12
FXIIa activates plasma kallikrein-kinin system1520.4×7e-14
RNA Polymerase I Promoter Opening1420.3×4e-13

GO biological processes:

GO termPartnersFoldFDR
negative regulation of DNA recombination640.6×1e-06
chromosome condensation735.5×2e-07
heterochromatin formation1218.5×9e-10
nucleosome assembly1815.2×1e-13
negative regulation of translation78.3×3e-03
chromatin organization127.2×2e-05
chromatin remodeling114.8×3e-03
DNA damage response123.9×9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

ClassificationCount (floor)
Pathogenic0
Likely pathogenic0
Uncertain significance49
Likely benign2
Benign0

Top pathogenic / likely-pathogenic (0)

SpliceAI

105 predictions. Top by Δscore:

VariantEffectΔscore
1:228425157:T:TAdonor_gain0.9100
1:228425184:C:CTdonor_gain0.8300
1:228425185:C:CTdonor_gain0.8300
1:228425089:AAAGT:Adonor_gain0.7900
1:228425134:G:Adonor_gain0.7900
1:228425250:C:CTdonor_gain0.7200
1:228425251:C:CTdonor_gain0.7200
1:228425191:G:Adonor_gain0.6700
1:228425283:TGCC:Tdonor_gain0.6200
1:228425093:T:TAdonor_gain0.6100
1:228425249:G:Cdonor_gain0.6000
1:228425042:T:TAdonor_gain0.5900
1:228425149:A:ACdonor_gain0.5900
1:228425142:G:Cdonor_gain0.5500
1:228425247:GAGC:Gdonor_gain0.5400
1:228425299:G:Adonor_gain0.5400
1:228425039:G:Adonor_gain0.5300
1:228425285:C:CTdonor_gain0.5300
1:228425035:G:Adonor_gain0.5100
1:228425037:ACG:Adonor_gain0.5000
1:228425038:CGC:Cdonor_gain0.5000
1:228425129:A:ATdonor_gain0.5000
1:228425246:CGAG:Cdonor_gain0.4900
1:228425090:AAGT:Adonor_gain0.4800
1:228425117:CG:Cacceptor_gain0.4800
1:228425023:C:CTdonor_gain0.4700
1:228425024:A:Tdonor_gain0.4700
1:228425145:G:Cdonor_gain0.4700
1:228425033:TCG:Tdonor_gain0.4500
1:228425034:CGC:Cdonor_gain0.4500

AlphaMissense

863 scored. Top likely-pathogenic:

VariantProtein changeam_pathogenicity
1:228425071:G:CF85L0.946
1:228425071:G:TF85L0.946
1:228425073:A:GF85L0.946
1:228425158:C:AQ56H0.932
1:228425158:C:GQ56H0.932
1:228425122:G:CF68L0.930
1:228425122:G:TF68L0.930
1:228425124:A:GF68L0.930
1:228424956:C:GD124H0.905
1:228424954:G:CD124E0.904
1:228424954:G:TD124E0.904
1:228424934:A:GI131T0.899
1:228424937:C:GR130P0.897
1:228425007:C:GD107H0.897
1:228425117:C:GR70P0.894
1:228425311:C:AK5N0.894
1:228425311:C:GK5N0.894
1:228424955:T:GD124A0.888
1:228424940:C:GR129P0.882
1:228425192:C:TG45D0.881
1:228425169:G:TR53S0.876
1:228425171:A:GI52T0.876
1:228425168:C:GR53P0.871
1:228425072:A:GF85S0.869
1:228425089:A:CF79L0.869
1:228425089:A:TF79L0.869
1:228425091:A:GF79L0.869
1:228425177:C:GR50P0.869
1:228424993:A:CC111W0.867
1:228424955:T:AD124V0.864

dbSNP variants (sampled 300 via entrez): RS1000042512 (1:228425096 T>C,G), RS1001475235 (1:228425492 T>A), RS1001607156 (1:228425038 C>A,G,T), RS1003379877 (1:228426947 C>G), RS1003801489 (1:228425091 AG>A), RS1004441593 (1:228425242 C>G,T), RS1004558692 (1:228426565 A>G), RS1004774038 (1:228426083 C>A,G), RS1005550583 (1:228425578 T>A), RS1006964069 (1:228426686 T>A), RS1006993745 (1:228426416 A>G), RS1007963297 (1:228425394 C>A,G,T), RS1010342755 (1:228426878 T>A,C), RS1010372872 (1:228426707 GA>G), RS1011382656 (1:228425434 G>C,T)

Disease associations

OMIM: gene MIM:602820 | disease phenotypes:

GenCC curated gene-disease

DiseaseClassificationInheritance
neurodevelopmental disorderLimitedAutosomal recessive

Mondo (1): neurodevelopmental disorder (MONDO:0700092)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

StudyTraitp-value
GCST006276_1Non-Richardson’s syndrome vs Richardson’s syndrome in progressive supranuclear palsy2.000000e-09

MeSH disease descriptors (1)

DescriptorNameTree numbers
D065886Neurodevelopmental DisordersF03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

ChemicalActions (top 5)PubMed papers
trichostatin Aaffects expression, affects binding, increases reaction, increases acetylation, affects acetylation (+4 more)13
Decitabineaffects acetylation, affects expression, affects methylation, decreases methylation, increases reaction (+4 more)11
sodium arseniteaffects acetylation, affects methylation, decreases methylation, increases expression, increases methylation (+2 more)4
Butyratesincreases acetylation4
Valproic Acidaffects cotreatment, decreases methylation, increases acetylation, increases methylation4
Tetrachlorodibenzodioxinaffects cotreatment, decreases methylation, increases acetylation, increases expression3
nickel chloridedecreases acetylation, increases methylation2
romidepsinincreases acetylation, increases reaction2
entinostatincreases acetylation, affects cotreatment2
Benzo(a)pyreneaffects cotreatment, decreases methylation, decreases expression2
Ironaffects cotreatment, decreases methylation, increases activity, increases methylation2
Nickelincreases acetylation, increases methylation, affects cotreatment2
Polyaminesaffects methylation, increases methylation2
Tretinoinincreases acetylation, affects cotreatment, affects methylation, affects binding, affects reaction2
4-biphenylamineaffects cotreatment, decreases methylation1
4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanoneincreases expression1
perfluorooctanoic acidaffects cotreatment, decreases expression1
fludarabineaffects cotreatment, increases acetylation1
potassium chromate(VI)increases methylation1
nickel sulfateincreases methylation1
3-deazaneplanocinaffects acetylation, affects cotreatment, affects expression, affects methylation1
2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridineaffects cotreatment, decreases methylation1
perfluorooctane sulfonic acidaffects cotreatment, decreases expression1
CGP 52608affects binding, increases reaction1
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-onedecreases acetylation, decreases reaction1
monomethylarsonous acidaffects acetylation, affects methylation1
pyrazolanthronedecreases reaction, increases phosphorylation1
perfluorohexanesulfonic acidaffects cotreatment, decreases expression1
15-deoxyprostaglandin J2decreases reaction, increases acetylation1
5-((4-methylphenyl)methylene)-2-(phenylamino)-4(5H)-thiazoloneincreases phosphorylation1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

CellosaurusNameCategorySex
CVCL_A656MZ-CRC-1Cancer cell lineFemale

Clinical trials (associated diseases)

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

TrialPhaseStatusTitle
NCT04586348PHASE4UNKNOWNPrenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115PHASE4UNKNOWNDouble-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102PHASE3COMPLETEDDexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079PHASE3COMPLETEDStudy of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480PHASE3RECRUITINGReducing Missed Appointments
NCT07377032PHASE3RECRUITINGTAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959PHASE2COMPLETEDSulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348PHASE2RECRUITINGSertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372PHASE2COMPLETEDSafety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191PHASE1COMPLETEDNeuroModulation Technique Treatment of Autism
NCT04475848PHASE1COMPLETEDA Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398PHASE1COMPLETEDIAMA-6 Oral Dose Study in Healthy Adults
NCT01783041PHASE2/PHASE3COMPLETEDEffect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385PHASE2/PHASE3RECRUITINGFetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098EARLY_PHASE1NOT_YET_RECRUITINGCentral Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783Not specifiedCOMPLETEDCYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504Not specifiedRECRUITINGStudying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784Not specifiedUNKNOWNHigh Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791Not specifiedCOMPLETEDNutrition and Pregnancy Intervention Study
NCT01942525Not specifiedUNKNOWNInfluence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170Not specifiedCOMPLETEDEtiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649Not specifiedACTIVE_NOT_RECRUITINGEnhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191Not specifiedTERMINATEDBiomarkers, Neurodevelopment and Preterm Infants
NCT02690675Not specifiedCOMPLETEDIron Supplement Effect on Child Development
NCT02694003Not specifiedCOMPLETEDBetter Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894Not specifiedCOMPLETEDFamily Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674Not specifiedUNKNOWNGood Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157Not specifiedCOMPLETEDAnalyzing Retinal Microanatomy in ROP
NCT02898298Not specifiedCOMPLETEDPositive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780Not specifiedUNKNOWNIntroduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293Not specifiedCOMPLETEDn-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644Not specifiedCOMPLETEDImproving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991Not specifiedUNKNOWNEarly Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189Not specifiedTERMINATEDEffect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028Not specifiedCOMPLETEDDevelopmental Origins of Mental Health Disorders
NCT03148782Not specifiedCOMPLETEDBrain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104Not specifiedCOMPLETEDNeurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375Not specifiedRECRUITINGSQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928Not specifiedCOMPLETEDClinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489Not specifiedUNKNOWNStudy for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
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BioBTree
v2.0.2

Sources 75

This page pulls from 75 datasets indexed by BioBTree:

alphafoldalphamissenseantibodybgeebgee_evidencebindingdbbiogrid_interactionbrendabrenda_kineticsccdscellosauruschembl_activitychembl_targetciviccivic_evidenceclingen_dosageclingen_gene_validityclinical_trialsclinvarcollectrictd_gene_interactiondbsnpdepmapdiamond_similarityefoensemblentrezesm2_similarityexonfantom5_genefantom5_promotergenccgenerifgogoparentgtopdbgwasgwas_studyhgnchpointactinterprointogenjasparmeshmimmirdbmondomsigdborphanetorthologparalogpdbpfampharmgkb_clinicalpharmgkb_genepharmgkb_guidelinepharmgkb_variantpubchempubchem_activitypubchem_assaypubmedreactomereactomeparentrefseqrhearnacentralscxa_expressionscxa_gene_experimentsignorspliceaistring_interactiontranscriptufeatureuniprot