H4C8
gene geneOn this page
Also known as H4/h
Summary
H4C8 (H4 clustered histone 8, HGNC:4788) is a protein-coding gene on chromosome 6p22.2, encoding Histone H4 (P62805). Core component of nucleosome.
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 H4 family. Transcripts from this gene lack polyA tails but instead contain a palindromic termination element. This gene is found in the large histone gene cluster on chromosome 6.
Source: NCBI Gene 8365 — RefSeq curated summary.
At a glance
- GWAS associations: 23
- Clinical variants (ClinVar): 17 total
- Druggable target: yes — 1 molecules with ChEMBL bioactivity
- MANE Select transcript:
NM_003543
Identifiers
Gene identifiers
| Field | Value |
|---|---|
| HGNC ID | HGNC:4788 |
| Approved symbol | H4C8 |
| Name | H4 clustered histone 8 |
| Location | 6p22.2 |
| Locus type | gene with protein product |
| Status | Approved |
| Aliases | H4/h |
| Ensembl gene | ENSG00000158406 |
| Ensembl biotype | protein_coding |
| OMIM | 602828 |
| Entrez | 8365 |
Gene structure
Transcript identifiers
Ensembl transcripts: 3 — 2 nonsense_mediated_decay, 1 protein_coding
ENST00000377727, ENST00000634560, ENST00000634956
RefSeq mRNA: 1 — MANE Select: NM_003543
NM_003543
CCDS: CCDS4604
Canonical transcript exons
ENST00000377727 — 1 exons
| Exon | Start | End |
|---|---|---|
| ENSE00001474963 | 26285126 | 26285534 |
Expression profiles
Bgee: expression breadth ubiquitous, 224 present calls, max score 96.02.
FANTOM5 (CAGE): breadth ubiquitous, TPM avg 232.2769 / max 2844.3084, expressed in 1823 samples.
FANTOM5 promoters (1 alternative TSS)
| Promoter ID | TPM avg | Samples expressed |
|---|---|---|
| 72343 | 232.2769 | 1823 |
Top tissues by expression
275 total, by Bgee expression score (0-100, higher = more expressed):
| Tissue | Anatomy ID | Expression score | Quality |
|---|---|---|---|
| adrenal tissue | UBERON:0018303 | 96.02 | gold quality |
| calcaneal tendon | UBERON:0003701 | 95.80 | gold quality |
| colonic epithelium | UBERON:0000397 | 92.55 | gold quality |
| gastrocnemius | UBERON:0001388 | 87.66 | gold quality |
| monocyte | CL:0000576 | 87.39 | gold quality |
| mononuclear cell | CL:0000842 | 87.04 | gold quality |
| muscle of leg | UBERON:0001383 | 86.97 | gold quality |
| leukocyte | CL:0000738 | 86.09 | gold quality |
| bone marrow cell | CL:0002092 | 85.71 | gold quality |
| amniotic fluid | UBERON:0000173 | 85.22 | gold quality |
| hindlimb stylopod muscle | UBERON:0004252 | 84.89 | gold quality |
| sperm | CL:0000019 | 82.50 | gold quality |
| muscle organ | UBERON:0001630 | 81.70 | gold quality |
| primordial germ cell in gonad | CL:0000670 ∩ UBERON:0000991 | 81.32 | gold quality |
| blood | UBERON:0000178 | 81.30 | gold quality |
| corpus callosum | UBERON:0002336 | 81.06 | gold quality |
| C1 segment of cervical spinal cord | UBERON:0006469 | 80.72 | gold quality |
| tonsil | UBERON:0002372 | 80.35 | gold quality |
| buccal mucosa cell | CL:0002336 | 80.02 | gold quality |
| male germ cell | CL:0000015 | 79.78 | gold quality |
| lower esophagus mucosa | UBERON:0035834 | 79.71 | gold quality |
| mucosa of transverse colon | UBERON:0004991 | 79.68 | gold quality |
| apex of heart | UBERON:0002098 | 79.24 | gold quality |
| esophagus squamous epithelium | UBERON:0006920 | 78.66 | gold quality |
| spinal cord | UBERON:0002240 | 78.42 | gold quality |
| heart left ventricle | UBERON:0002084 | 78.07 | gold quality |
| cardiac ventricle | UBERON:0002082 | 77.67 | gold quality |
| tendon | UBERON:0000043 | 77.65 | gold quality |
| male germ line stem cell (sensu Vertebrata) in testis | CL:0000089 ∩ UBERON:0000473 | 76.67 | gold quality |
| bone marrow | UBERON:0002371 | 76.63 | gold quality |
Single-cell (SCXA)
Detected in 1 experiment(s), a significant marker in 1.
| Experiment | Marker? | Max mean expression |
|---|---|---|
| E-ANND-3 | yes | 3.10 |
Regulation
Is transcription factor: no
Upstream regulators (CollecTRI, top): E2F1
Cross-species orthologs
0 orthologs
Paralogs (14): H4C3 (ENSG00000197061), H4C11 (ENSG00000197238), H4C16 (ENSG00000197837), H4C15 (ENSG00000270276), H4C14 (ENSG00000270882), H4C12 (ENSG00000273542), H4C6 (ENSG00000274618), H4C13 (ENSG00000275126), H4C7 (ENSG00000275663), H4C9 (ENSG00000276180), H4C5 (ENSG00000276966), H4C4 (ENSG00000277157), H4C1 (ENSG00000278637), H4C2 (ENSG00000278705)
Protein
Protein identifiers
Histone H4 — P62805 (reviewed: P62805)
All UniProt accessions (2): P62805, B2R4R0
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. Found in a co-chaperone complex with DNJC9, MCM2 and histone H3.3-H4 dimers. Within the complex, interacts with DNJC9 (via C-terminus); the interaction is direct. Interacts with NASP; NASP is a histone chaperone that stabilizes and maintains a soluble pool of Histone H3-H4 dimers.
Subcellular location. Nucleus. Chromosome.
Post-translational modifications. Acetylation at Lys-6 (H4K5ac), Lys-9 (H4K8ac), Lys-13 (H4K12ac) and Lys-17 (H4K16ac) occurs in coding regions of the genome but not in heterochromatin. Acetylated as part of spermatogenesis progression prior to histone-to-protamine exchange. Citrullination at Arg-4 (H4R3ci) by PADI4 impairs methylation. Monomethylation and asymmetric dimethylation at Arg-4 (H4R3me1 and H4R3me2a, respectively) by PRMT1 favors acetylation at Lys-9 (H4K8ac) and Lys-13 (H4K12ac). Demethylation is performed by JMJD6. Symmetric dimethylation on Arg-4 (H4R3me2s) by the PRDM1/PRMT5 complex may play a crucial role in the germ-cell lineage. Monomethylated, dimethylated or trimethylated at Lys-21 (H4K20me1, H4K20me2, H4K20me3). Monomethylation is performed by KMT5A/SET8. Dimethylation and trimethylation is performed by KMT5B and KMT5C and induces gene silencing. Monomethylated at Lys-13 (H4K12me1) by N6AMT1; H4K12me1 modification is present at the promoters of numerous genes encoding cell cycle regulators. H4K20me2 and H4K20me3 are demethylated into monomethyl (H4K20me1) by RSBN1. H4K20me1, H4K20me2 and H4K20me3 are demethylated by RAD23A and RAD23B. H4K20me1 is demethylated by PHF8. Acetyl-methylated at Lys-6 and Lys-13 (H4K5acme and H4K12acme, respectively), acetyl-methylation is an epigenetic mark of active chromatin associated with increased transcriptional initiation. Acetyl-methylation is formed by acetylation by EP300/p300 of lysine residues that are already monomethylated on the same side chain. H4K5acme and H4K12acme marks specifically bind BRD2. Phosphorylated by PAK2 at Ser-48 (H4S47ph). This phosphorylation increases the association of H3.3-H4 with the histone chaperone HIRA, thus promoting nucleosome assembly of H3.3-H4 and inhibiting nucleosome assembly of H3.1-H4. Ubiquitinated by the CUL4-DDB-RBX1 complex in response to ultraviolet irradiation. This may weaken the interaction between histones and DNA and facilitate DNA accessibility to repair proteins. Monoubiquitinated at Lys-92 of histone H4 (H4K91ub1) in response to DNA damage. The exact role of H4K91ub1 in DNA damage response is still unclear but it may function as a licensing signal for additional histone H4 post-translational modifications such as H4 Lys-21 methylation (H4K20me). Ubiquitinated; by PHF7. Ufmylated; monofmylated by UFL1 at Lys-32 (H4K31Ufm1) in response to DNA damage. Sumoylated, which is associated with transcriptional repression. 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. Butyrylation of histones marks active promoters and competes with histone acetylation. Glutarylation at Lys-92 (H4K91glu) destabilizes nucleosomes by promoting dissociation of the H2A-H2B dimers from nucleosomes. Lactylated in macrophages by EP300/P300 by using lactoyl-CoA directly derived from endogenous or exogenous lactate, leading to stimulates gene transcription. Delactylated by SIRT3 at Lys-17 (H4K16la).
Disease relevance. Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 1 (TEBIVANED1) [MIM:619758] An autosomal dominant disorder with onset in infancy, characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, poor or absent speech, and characteristic dysmorphic facial features, including hypertelorism and abnormal nose. Other variable neurologic and systemic features may also occur. The disease is caused by variants affecting the gene represented in this entry. TEBIVANED1 is caused by variants in H4C3. Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 2 (TEBIVANED2) [MIM:619759] An autosomal dominant disorder characterized by poor overall growth, microcephaly, hypotonia, profound global developmental delay, impaired intellectual development, absent speech, and characteristic dysmorphic facial features, including hypertelorism, abnormal nose, and wide mouth. The disease is caused by variants affecting the gene represented in this entry. TEBIVANED2 is caused by variants in H4C11. Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 3 (TEBIVANED3) [MIM:619950] An autosomal dominant disorder characterized by global developmental delay with poor overall growth, impaired intellectual development, and speech difficulties. More variable features include hypotonia, microcephaly, and dysmorphic facies. The disease is caused by variants affecting the gene represented in this entry. TEBIVANED3 is caused by variants in H4C5. Tessadori-Bicknell-Van Haaften neurodevelopmental syndrome 4 (TEBIVANED4) [MIM:619951] An autosomal dominant disorder characterized by global developmental delay with poor overall growth, variably impaired intellectual development, learning difficulties, distal skeletal anomalies, and dysmorphic facies. Some patients have visual or hearing deficits. The disease is caused by variants affecting the gene represented in this entry. TEBIVANED4 is caused by variants in H4C9. Chromosomal aberrations involving HISTONE H4 is a cause of B-cell non-Hodgkin lymphomas (B-cell NHL). Translocation t(3;6)(q27;p21), with BCL6.
Similarity. Belongs to the histone H4 family.
RefSeq proteins (1): NP_003534* (*=MANE)
Domains & families (InterPro)
| ID | Name | Type |
|---|---|---|
| IPR001951 | Histone_H4 | Family |
| IPR004823 | TAF_TATA-bd_Histone-like_dom | Domain |
| IPR009072 | Histone-fold | Homologous_superfamily |
| IPR019809 | Histone_H4_CS | Conserved_site |
| IPR035425 | CENP-T/H4_C | Domain |
Pfam: PF15511
UniProt features (138 total): modified residue 94, sequence variant 17, cross-link 8, strand 4, helix 4, mutagenesis site 2, sequence conflict 2, turn 2, initiator methionine 1, chain 1, DNA-binding region 1, region of interest 1, compositionally biased region 1
Structure
Experimental structures (PDB)
626 structures, top 30 by resolution.
| PDB | Method | Resolution (Å) |
|---|---|---|
| 3F9X | X-RAY DIFFRACTION | 1.25 |
| 8PEF | X-RAY DIFFRACTION | 1.28 |
| 5TEG | X-RAY DIFFRACTION | 1.3 |
| 3UVW | X-RAY DIFFRACTION | 1.37 |
| 8UK5 | X-RAY DIFFRACTION | 1.4 |
| 1ZKK | X-RAY DIFFRACTION | 1.45 |
| 4YY6 | X-RAY DIFFRACTION | 1.45 |
| 3F9Y | X-RAY DIFFRACTION | 1.5 |
| 3QZT | X-RAY DIFFRACTION | 1.5 |
| 4YYI | X-RAY DIFFRACTION | 1.5 |
| 4YYM | X-RAY DIFFRACTION | 1.5 |
| 5FFW | X-RAY DIFFRACTION | 1.5 |
| 2BQZ | X-RAY DIFFRACTION | 1.5 |
| 4YYD | X-RAY DIFFRACTION | 1.52 |
| 8B5C | X-RAY DIFFRACTION | 1.58 |
| 6RXS | X-RAY DIFFRACTION | 1.6 |
| 3F9W | X-RAY DIFFRACTION | 1.6 |
| 3F9Z | X-RAY DIFFRACTION | 1.6 |
| 6VO5 | X-RAY DIFFRACTION | 1.6 |
| 7M98 | X-RAY DIFFRACTION | 1.6 |
| 2IG0 | X-RAY DIFFRACTION | 1.7 |
| 3O36 | X-RAY DIFFRACTION | 1.7 |
| 4QUT | X-RAY DIFFRACTION | 1.7 |
| 5YE3 | X-RAY DIFFRACTION | 1.7 |
| 4YYH | X-RAY DIFFRACTION | 1.74 |
| 8TGP | X-RAY DIFFRACTION | 1.76 |
| 4YYK | X-RAY DIFFRACTION | 1.79 |
| 5YE4 | X-RAY DIFFRACTION | 1.8 |
| 3QZS | X-RAY DIFFRACTION | 1.8 |
| 4QUU | X-RAY DIFFRACTION | 1.8 |
Predicted structure (AlphaFold)
| Model | pLDDT | Fraction very-high |
|---|---|---|
| AF-P62805-F1 | 90.90 | 0.75 |
Antibody-complex structures (SAbDab): 21 — 5YE3, 5YE4, 6E0C, 6E0P, 7K5X, 7K5Y, 7K60, 7K61, 7K63, 7U0G, 7U0I, 7U0J, 8DK5, 8EVG, 8EVH, 8EVI, 8EVJ, 8SPS, 8SPU, 8SYP, 8VFX
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 (102): 4, 21, 32, 32, 60, 80, 92, 92, 6, 6, 6, 6, 6, 6, 6, 6, 9, 9, 9, 9 …
Mutagenesis-validated functional residues (2):
| Position | Phenotype |
|---|---|
| 13 | impaired methylation by n6amt1. |
| 32 | abolished ufmylation. |
Function
Pathways and Gene Ontology
Reactome pathways
60 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-3214841 | PKMTs methylate histone lysines |
| R-HSA-3214842 | HDMs demethylate 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-4551638 | SUMOylation of chromatin organization proteins |
| 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-5693565 | Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks |
| R-HSA-5693571 | Nonhomologous End-Joining (NHEJ) |
| R-HSA-5693607 | Processing of DNA double-strand break ends |
MSigDB gene sets: 310 (showing top):
GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_UP, GOBP_MYELOID_CELL_DIFFERENTIATION, REACTOME_MEIOTIC_RECOMBINATION, RNGTGGGC_UNKNOWN, GOBP_CHROMOSOME_ORGANIZATION, REACTOME_DNA_REPLICATION, REACTOME_SIGNALING_BY_NOTCH, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, BERTUCCI_MEDULLARY_VS_DUCTAL_BREAST_CANCER_DN, REACTOME_MEIOTIC_SYNAPSIS, FISCHER_G1_S_CELL_CYCLE, REACTOME_G2_M_DNA_DAMAGE_CHECKPOINT, GOZGIT_ESR1_TARGETS_DN, GOBP_TELOMERE_ORGANIZATION, MOLENAAR_TARGETS_OF_CCND1_AND_CDK4_UP
GO Biological Process (5): chromatin organization (GO:0006325), nucleosome assembly (GO:0006334), telomere organization (GO:0032200), negative regulation of megakaryocyte differentiation (GO:0045653), protein localization to CENP-A containing chromatin (GO:0061644)
GO Molecular Function (5): DNA binding (GO:0003677), RNA binding (GO:0003723), structural constituent of chromatin (GO:0030527), protein heterodimerization activity (GO:0046982), protein binding (GO:0005515)
GO Cellular Component (10): chromosome, telomeric region (GO:0000781), nucleosome (GO:0000786), extracellular region (GO:0005576), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), protein-containing complex (GO:0032991), CENP-A containing nucleosome (GO:0043505), extracellular exosome (GO:0070062), chromosome (GO:0005694)
Reactome top-level categories
Rollup of top-12 pathways:
| Category | Pathways |
|---|---|
| Chromatin modifying enzymes | 5 |
| Cellular Senescence | 3 |
| Depyrimidination | 2 |
| Depurination | 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 |
| Negative epigenetic regulation of rRNA expression | 1 |
| Positive epigenetic regulation of rRNA expression | 1 |
GO top-level categories
Rollup of top GO terms by namespace:
| Category | Terms |
|---|---|
| cellular anatomical structure | 3 |
| nucleic acid binding | 2 |
| chromatin | 2 |
| cellular component organization | 1 |
| chromatin organization | 1 |
| nucleosome organization | 1 |
| protein-DNA complex assembly | 1 |
| chromosome organization | 1 |
| megakaryocyte differentiation | 1 |
| negative regulation of myeloid cell differentiation | 1 |
| regulation of megakaryocyte differentiation | 1 |
| protein localization to chromatin | 1 |
| protein localization to chromosome, centromeric region | 1 |
| structural molecule activity | 1 |
| protein dimerization activity | 1 |
| binding | 1 |
| chromosomal region | 1 |
| protein-DNA complex | 1 |
| intracellular membrane-bounded organelle | 1 |
| nuclear lumen | 1 |
| cellular_component | 1 |
| nucleosome | 1 |
| CENP-A containing chromatin | 1 |
| extracellular vesicle | 1 |
| intracellular membraneless organelle | 1 |
Protein interactions and networks
STRING
0 interactions, top by confidence (×1000):
IntAct
672 interactions, top by confidence:
| A | B | Type | Score |
|---|---|---|---|
| ASF1A | H4C16 | psi-mi:“MI:0915”(physical association) | 0.950 |
| H4C16 | ASF1A | psi-mi:“MI:0915”(physical association) | 0.950 |
| ASF1A | H4C16 | psi-mi:“MI:0914”(association) | 0.950 |
| H3C1 | H4C16 | psi-mi:“MI:0915”(physical association) | 0.890 |
| H4C16 | H3C1 | psi-mi:“MI:0407”(direct interaction) | 0.890 |
| ASF1A | MCM2 | psi-mi:“MI:0915”(physical association) | 0.890 |
| ASF1A | MCM2 | psi-mi:“MI:0914”(association) | 0.890 |
| TP53BP1 | H4C16 | psi-mi:“MI:0407”(direct interaction) | 0.870 |
| H3-3A | H4C16 | psi-mi:“MI:0915”(physical association) | 0.860 |
| H3-3A | H4C16 | psi-mi:“MI:0914”(association) | 0.860 |
| H3-3A | H4C16 | psi-mi:“MI:0407”(direct interaction) | 0.860 |
| H2AC4 | H2BC11 | psi-mi:“MI:0915”(physical association) | 0.850 |
BioGRID (3544): RBBP4 (Affinity Capture-Western), HIST1H4A (Affinity Capture-Western), HIST4H4 (Biochemical Activity), HIST4H4 (Affinity Capture-MS), HIST2H4B (Affinity Capture-MS), HIST4H4 (Two-hybrid), ASF1A (Two-hybrid), HIST4H4 (Biochemical Activity), HIST4H4 (Biochemical Activity), HIST1H4I (Affinity Capture-RNA), HIST1H4E (Affinity Capture-RNA), HIST1H4I (Affinity Capture-RNA), HIST1H4E (Affinity Capture-RNA), HIST1H4E (Affinity Capture-RNA), HIST1H4A (Biochemical Activity)
ESM2 similar proteins: P02309, P08436, P09322, P0CG89, P23750, P23751, P27996, P35057, P35059, P50566, P59259, P62785, P62786, P62787, P62788, P62794, P62797, P62798, P62799, P62800, P62801, P62802, P62803, P62805, P62806, P62887, Q27443, Q27765, Q43083, Q4R362, Q5RCS7, Q6LAF1, Q6LAF3, Q6PMI5, Q6V9I2, Q6WV72, Q6WV73, Q6WV90, Q6WZ83, Q71V09
Diamond homologs: P02309, P04914, P04915, P08436, P09322, P0CG89, P23750, P23751, P27996, P35057, P35059, P50566, P59259, P62776, P62777, P62778, P62779, P62780, P62781, P62782, P62783, P62784, P62785, P62786, P62787, P62788, P62790, P62791, P62792, P62793, P62794, P62795, P62796, P62797, P62798, P62799, P62800, P62801, P62802, P62803
SIGNOR signaling
27 interactions.
| A | Effect | B | Mechanism |
|---|---|---|---|
| TP53BP1 | unknown | H4C1 | binding |
| MAML1 | “down-regulates activity” | H4C1 | acetylation |
| “Integrator complex” | “down-regulates quantity by repression” | H4C1 | “transcriptional regulation” |
| KAT5 | “down-regulates activity” | H4C1 | acetylation |
| H4C1 | “up-regulates activity” | BRD2 | relocalization |
| H4C1 | “up-regulates activity” | BRD4 | relocalization |
| H4C1 | “up-regulates activity” | BRDT | relocalization |
| H4C1 | “form complex” | “Nucleosome_H3.3 variant” | binding |
| “MSL acetyltransferase” | “down-regulates activity” | H4C1 | acetylation |
| UFL1 | “up-regulates activity” | H4C1 | ubiquitination |
| SLBP | “up-regulates quantity by expression” | H4C1 | “translation regulation” |
| “NSL histone acetyltransferase” | “down-regulates activity” | H4C1 | acetylation |
| “NuA4 complex” | “down-regulates activity” | H4C1 | acetylation |
| DTX3L | “down-regulates activity” | H4C1 | monoubiquitination |
| “BRCA1-BARD1 complex” | “up-regulates activity” | H4C1 | ubiquitination |
| H4C1 | “form complex” | “CENP-A nucleosome” | binding |
| H4C1 | “form complex” | “Nucleosome_H2A.Z.2 variant” | binding |
| H4C1 | “form complex” | “Nucleosome_H2A.Z.1 variant” | binding |
| H4C1 | “form complex” | “Nucleosome_H3.1 variant” | binding |
| H4C1 | “form complex” | “Nucleosome_H3.1t variant” | binding |
| HAT1 | “down-regulates activity” | H4C1 | acetylation |
| H4C1 | “form complex” | Nucleosome | binding |
| KMT5C | “down-regulates activity” | H4C1 | methylation |
| KMT5B | “down-regulates activity” | H4C1 | methylation |
Enriched among interaction partners
Reactome pathways and GO biological processes over-represented among this gene’s 107 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 |
|---|---|---|---|
| Formation of Senescence-Associated Heterochromatin Foci (SAHF) | 5 | 40.5× | 1e-06 |
| Notch-HLH transcription pathway | 6 | 29.5× | 6e-07 |
| NOTCH1 Intracellular Domain Regulates Transcription | 8 | 22.9× | 3e-08 |
| ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression | 12 | 22.0× | 3e-11 |
| Packaging Of Telomere Ends | 8 | 21.2× | 7e-08 |
| FXIIa activates plasma kallikrein-kinin system | 10 | 20.9× | 2e-09 |
| Condensation of Prophase Chromosomes | 11 | 20.7× | 3e-10 |
| NuRD complex assembly | 12 | 20.4× | 7e-11 |
GO biological processes:
| GO term | Partners | Fold | FDR |
|---|---|---|---|
| negative regulation of gene expression, epigenetic | 6 | 25.3× | 2e-05 |
| nucleosome assembly | 16 | 23.6× | 5e-15 |
| heterochromatin formation | 8 | 21.5× | 1e-06 |
| epigenetic regulation of gene expression | 5 | 20.2× | 3e-04 |
| chromatin organization | 12 | 12.5× | 9e-08 |
| antimicrobial humoral immune response mediated by antimicrobial peptide | 5 | 8.5× | 1e-02 |
| chromatin remodeling | 11 | 8.4× | 1e-05 |
| DNA damage response | 10 | 5.6× | 6e-04 |
Disease & clinical
Clinical variants and AI predictions
ClinVar
17 variants total. Per-class counts are floors (≥ shown; pagination cap):
| Classification | Count (floor) |
|---|---|
| Pathogenic | 0 |
| Likely pathogenic | 0 |
| Uncertain significance | 17 |
| Likely benign | 0 |
| Benign | 0 |
Top pathogenic / likely-pathogenic (0)
SpliceAI
459 predictions. Top by Δscore:
| Variant | Effect | Δscore |
|---|---|---|
| 6:26281583:CAGAA:C | acceptor_gain | 1.0000 |
| 6:26281588:C:CC | acceptor_gain | 1.0000 |
| 6:26285190:AG:A | donor_gain | 1.0000 |
| 6:26285215:T:TA | donor_gain | 1.0000 |
| 6:26285216:C:A | donor_gain | 1.0000 |
| 6:26281584:AGAA:A | acceptor_gain | 0.9900 |
| 6:26281585:GAA:G | acceptor_gain | 0.9900 |
| 6:26281585:GAAC:G | acceptor_loss | 0.9900 |
| 6:26281586:AA:A | acceptor_gain | 0.9900 |
| 6:26281587:AC:A | acceptor_loss | 0.9900 |
| 6:26281588:CTA:C | acceptor_loss | 0.9900 |
| 6:26281589:T:A | acceptor_loss | 0.9900 |
| 6:26284587:G:GA | donor_gain | 0.9900 |
| 6:26285181:AGGAG:A | donor_gain | 0.9900 |
| 6:26285188:TTAGC:T | donor_gain | 0.9900 |
| 6:26285189:TAGCC:T | donor_gain | 0.9900 |
| 6:26285190:AGCCA:A | donor_gain | 0.9900 |
| 6:26285243:T:TA | donor_gain | 0.9900 |
| 6:26284585:C:CT | donor_gain | 0.9800 |
| 6:26284586:T:TT | donor_gain | 0.9800 |
| 6:26284667:A:AC | donor_gain | 0.9800 |
| 6:26284668:C:CC | donor_gain | 0.9800 |
| 6:26285190:AGC:A | donor_gain | 0.9800 |
| 6:26285191:G:C | donor_gain | 0.9800 |
| 6:26285192:C:CT | donor_gain | 0.9800 |
| 6:26285193:C:CT | donor_gain | 0.9800 |
| 6:26284668:CG:C | donor_gain | 0.9700 |
| 6:26285190:A:AC | donor_gain | 0.9700 |
| 6:26285198:AAG:A | donor_gain | 0.9600 |
| 6:26283897:G:C | donor_gain | 0.9500 |
AlphaMissense
0 scored. Top likely-pathogenic:
dbSNP variants (sampled 300 via entrez): RS1000196206 (6:26286542 G>A,C), RS1001252156 (6:26284900 C>G), RS1003250123 (6:26286529 A>C,G), RS1003716764 (6:26286505 A>G,T), RS1005612712 (6:26285067 C>A,G,T), RS1005667442 (6:26286276 T>G), RS1006265256 (6:26286691 A>C,G), RS1007318575 (6:26285716 CTTGCAA>C), RS1007701087 (6:26285608 G>A), RS1007980339 (6:26287274 C>G), RS1008363548 (6:26287083 C>T), RS1010345523 (6:26285092 G>A,C), RS1011351239 (6:26285650 G>A), RS1014381008 (6:26284750 C>T), RS1016728496 (6:26286590 C>G,T)
Disease associations
OMIM: gene MIM:602828 | disease phenotypes:
GenCC curated gene-disease
Mondo (0):
Orphanet (0):
HPO phenotypes
0 total (0 of 0 shown, HPO-id order):
GWAS associations
23 associations (top):
| Study | Trait | p-value |
|---|---|---|
| GCST004521_113 | Autism spectrum disorder or schizophrenia | 3.000000e-19 |
| GCST004521_142 | Autism spectrum disorder or schizophrenia | 2.000000e-09 |
| GCST004521_169 | Autism spectrum disorder or schizophrenia | 4.000000e-14 |
| GCST004521_69 | Autism spectrum disorder or schizophrenia | 8.000000e-24 |
| GCST004521_83 | Autism spectrum disorder or schizophrenia | 1.000000e-13 |
| GCST004748_56 | Lung cancer | 1.000000e-10 |
| GCST004749_63 | Lung cancer in ever smokers | 1.000000e-07 |
| GCST004750_81 | Squamous cell lung carcinoma | 1.000000e-10 |
| GCST005830_120 | Hand grip strength | 3.000000e-10 |
| GCST007294_143 | Body fat distribution (trunk fat ratio) | 5.000000e-29 |
| GCST007294_82 | Body fat distribution (trunk fat ratio) | 1.000000e-48 |
| GCST007295_120 | Body fat distribution (leg fat ratio) | 2.000000e-46 |
| GCST007295_91 | Body fat distribution (leg fat ratio) | 1.000000e-26 |
| GCST007576_156 | Chronotype | 7.000000e-10 |
| GCST010002_50 | Refractive error | 4.000000e-34 |
| GCST010043_138 | Asthma | 6.000000e-14 |
| GCST010141_1 | Beef consumption | 7.000000e-13 |
| GCST010989_261 | Body size at age 10 | 1.000000e-18 |
| GCST012227_896 | Hip circumference adjusted for BMI | 6.000000e-15 |
| GCST90000047_117 | Age at first sexual intercourse | 2.000000e-10 |
| GCST90020028_815 | Hip circumference adjusted for BMI | 5.000000e-36 |
| GCST90020028_938 | Hip circumference adjusted for BMI | 1.000000e-28 |
| GCST90020028_939 | Hip circumference adjusted for BMI | 1.000000e-30 |
EFO canonical traits (7, from GWAS)
| EFO ID | Trait name |
|---|---|
| EFO:0006941 | grip strength measurement |
| EFO:0004341 | body fat distribution |
| EFO:0008328 | chronotype measurement |
| EFO:0008111 | diet measurement |
| EFO:0009819 | comparative body size at age 10, self-reported |
| EFO:0008039 | BMI-adjusted hip circumference |
| EFO:0009749 | age at first sexual intercourse measurement |
Drugs & pharmacology
Drug and pharmacology data
Is drug target: yes
ChEMBL targets (1): CHEMBL5876 (SINGLE PROTEIN)
Molecules with ChEMBL bioactivity
1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 312 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).
| Molecule | Name | Phase | Patents |
|---|---|---|---|
| CHEMBL3919831 | AMREDOBRESIB | 2 | 312 |
PharmGKB: 1 entry (VIP=true, CPIC=false)
Binding affinities (BindingDB)
78 measured of 78 human assays (78 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.
| Ligand | Measure | Value | Patent |
|---|---|---|---|
| 6-[1-[(5-fluoro-2-pyridinyl)methyl]-6-morpholin-4-ylimidazo[4,5-c]pyridin-2-yl]-3-methyl-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 1 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-[1-benzyl-2-[8-[[1-(2-methoxyethyl)piperidin-4-yl]amino]-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzimidazol-5-yl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one | IC50 | 3 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-morpholin-4-yl-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 3 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-morpholin-4-yl-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 3 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzyl-5-methyl-4-phenylimidazol-2-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 4 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-morpholin-4-yl-1-(pyridin-3-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 4 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-[1-benzyl-2-[3-methyl-8-(methylamino)-[1,2,4]triazolo[4,3-a]pyrazin-6-yl]benzimidazol-5-yl]-4-methyl-4,5-dihydro-1H-pyridazin-6-one | IC50 | 5 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-morpholin-4-yl-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 5 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-morpholin-4-yl-1-(pyridin-3-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 5 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzylbenzimidazol-2-yl)-3-methyl-N-(1-methylpiperidin-4-yl)-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 7 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzyl-6-morpholin-4-ylbenzimidazol-2-yl)-N-[1-(2-methoxyethyl)piperidin-4-yl]-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 7 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[6-(dimethylamino)-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-3-methyl-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 7 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1,5-dimethyl-4-phenoxypyrazol-3-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 8 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzylbenzimidazol-2-yl)-N-[1-(2-methoxyethyl)piperidin-4-yl]-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 8 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-(4-methylpiperazin-1-yl)-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 8 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-(4-methylpiperazin-1-yl)-1-(pyridin-3-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 8 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-[(4-fluorophenyl)methyl]benzimidazol-2-yl]-N-[1-(2-methoxyethyl)piperidin-4-yl]-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-[(3,4-difluorophenyl)methyl]benzimidazol-2-yl]-N-[1-(2-methoxyethyl)piperidin-4-yl]-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-benzyl-6-(4-methylpiperazin-1-yl)imidazo[4,5-c]pyridin-2-yl]-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[9-benzyl-2-(4-methylpiperazin-1-yl)purin-8-yl]-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-benzyl-6-(4-methylpiperazin-1-yl)benzimidazol-2-yl]-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-[(3R)-3-methylmorpholin-4-yl]-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-[(3S)-3-methylmorpholin-4-yl]-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 9 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzyl-6-morpholin-4-ylbenzimidazol-2-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 10 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-morpholin-4-yl-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 10 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[5-(oxan-4-yl)-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 11 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-(4-methylpiperazin-1-yl)-1-(pyridin-3-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 12 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| N,3-dimethyl-6-[6-(4-methylpiperazin-1-yl)-1-(pyridin-4-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 12 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-methoxyacetamide | IC50 | 12.8 nM | US-9125915: Antitumor agent |
| N,3-dimethyl-6-[6-(4-methylpiperazin-1-yl)-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 13 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[6-(dimethylamino)-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-3-methyl-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 13 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-morpholin-4-yl-1-(pyridin-3-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-[(3R)-oxolan-3-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 13 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-benzyl-6-(4-methylpiperazin-1-yl)imidazo[4,5-c]pyridin-2-yl]-3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyrazine | IC50 | 14 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-N-propan-2-yl-6-[1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 14 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzyl-4,5-dimethylimidazol-2-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 15 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-methyl-1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 15 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-benzyl-6-(4-methylpiperazin-1-yl)imidazo[4,5-c]pyridin-2-yl]-N-ethyl-3-methyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 17 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[1-[(6-methyl-2-pyridinyl)methyl]-6-morpholin-4-ylimidazo[4,5-c]pyridin-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 17 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 2-[7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-methylacetamide | IC50 | 17.3 nM | US-9125915: Antitumor agent |
| 6-(4-benzyl-1,5-dimethylpyrazol-3-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 18 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(3-benzylimidazo[4,5-b]pyridin-2-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 18 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-N-propan-2-yl-6-[6-propan-2-yl-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 18 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| methyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate | IC50 | 18.2 nM | US-9125915: Antitumor agent |
| 3-methyl-6-[6-morpholin-4-yl-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-[(3R)-oxolan-3-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 20 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-N-propan-2-yl-6-[1-(pyridin-2-ylmethyl)benzimidazol-2-yl]-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 20 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 2-[7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(2-hydroxyethyl)acetamide | IC50 | 21 nM | US-9125915: Antitumor agent |
| 6-(1-benzylbenzimidazol-2-yl)-N,3-dimethyl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 22 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-[1-benzyl-6-(4-methylpiperazin-1-yl)imidazo[4,5-c]pyridin-2-yl]-3-methyl-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 26 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 3-methyl-6-[6-methyl-1-(pyridin-2-ylmethyl)imidazo[4,5-c]pyridin-2-yl]-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine | IC50 | 28 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
| 6-(1-benzyl-4,5-dimethylimidazol-2-yl)-3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyrazine | IC50 | 31 nM | US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors |
ChEMBL bioactivities
65 potent at pChembl≥5 of 66 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).
PubChem BioAssay actives
2 with measured affinity, of 108 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.
| Compound | Assay | Type | Value | Unit |
|---|---|---|---|---|
| 4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148510: Binding affinity to human HIST1H4A incubated for 45 mins by Kinobead based pull down assay | kd | 0.0099 | uM |
| 4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide | 2148510: Binding affinity to human HIST1H4A incubated for 45 mins by Kinobead based pull down assay | kd | 4.0927 | uM |
CTD chemical–gene interactions
73 total (human), top 30 by PubMed support.
| Chemical | Actions (top 5) | PubMed papers |
|---|---|---|
| Benzo(a)pyrene | decreases expression, increases expression, increases methylation | 4 |
| sodium arsenite | decreases expression, increases expression | 3 |
| (+)-JQ1 compound | decreases expression, increases expression | 3 |
| Silicon Dioxide | decreases expression, increases expression | 3 |
| Air Pollutants | increases expression, decreases expression, increases abundance | 2 |
| Cisplatin | decreases expression, affects cotreatment | 2 |
| Doxorubicin | affects expression, increases expression | 2 |
| Tetrachlorodibenzodioxin | increases expression | 2 |
| Cyclosporine | decreases expression | 2 |
| aristolochic acid I | increases expression | 1 |
| bisphenol F | affects cotreatment, increases expression | 1 |
| sotorasib | affects cotreatment, increases expression | 1 |
| propionaldehyde | decreases expression | 1 |
| bisphenol A | decreases expression | 1 |
| perfluorooctanoic acid | increases expression | 1 |
| 2,3-bis(3’-hydroxybenzyl)butyrolactone | affects cotreatment, decreases expression | 1 |
| versicolorin A | decreases expression | 1 |
| hydroquinone | decreases expression | 1 |
| picene | increases expression | 1 |
| perfluorooctane sulfonic acid | increases expression | 1 |
| cylindrospermopsin | increases expression | 1 |
| CGP 52608 | affects binding, increases reaction | 1 |
| abrine | increases expression | 1 |
| Grape Seed Proanthocyanidins | affects cotreatment, increases expression | 1 |
| 2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine | increases expression, increases response to substance | 1 |
| bisphenol S | affects cotreatment, increases expression | 1 |
| jinfukang | affects cotreatment, decreases expression | 1 |
| incobotulinumtoxinA | increases expression | 1 |
| NSC 689534 | affects binding, increases expression | 1 |
| trametinib | affects cotreatment, increases expression | 1 |
ChEMBL screening assays
14 unique, capped per target: 14 binding
Representative assays (with source publication via chembl_document):
| Assay ID | Type | Description | Source paper |
|---|---|---|---|
| CHEMBL2175621 | Binding | Binding affinity to fluorescein-labeled Histone H4(1-20) by spectrofluorometry | Pharmacophore-based virtual screening and biological evaluation of small molecule inhibitors for protein arginine methylation. — J Med Chem |
Clinical trials (associated diseases)
0 trials via MONDO — disease-level, not drug-specific.
Related Atlas pages
No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.