CBX8

Summary

CBX8 (chromobox 8, HGNC:15962) is a protein-coding gene on chromosome 17q25.3, encoding Chromobox protein homolog 8 (Q9HC52). Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development.

Enables methylated histone binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in chromatin and nucleoplasm. Part of PRC1 complex. Biomarker of esophagus squamous cell carcinoma and glioblastoma.

Source: NCBI Gene 57332 — RefSeq curated summary.

At a glance

• Gene–disease (curated): schizophrenia (No Known Disease Relationship, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 57 total
• Druggable target: yes
• MANE Select transcript: NM_020649

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15962
Approved symbol	CBX8
Name	chromobox 8
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	RC1, HPC3, PC3
Ensembl gene	ENSG00000141570
Ensembl biotype	protein_coding
OMIM	617354
Entrez	57332

Gene structure

Transcript identifiers

Ensembl transcripts: 4 — 3 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000269385, ENST00000413392, ENST00000427800, ENST00000485449

RefSeq mRNA: 1 — MANE Select: NM_020649 NM_020649

CCDS: CCDS11765

Canonical transcript exons

ENST00000269385 — 5 exons

Exon	Start	End
ENSE00001311523	79792132	79795558
ENSE00001318720	79796930	79797077
ENSE00003571677	79796057	79796123
ENSE00003587407	79796497	79796540
ENSE00003638013	79796250	79796315

Expression profiles

Bgee: expression breadth ubiquitous, 169 present calls, max score 90.87.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 5.7956 / max 42.8450, expressed in 1601 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168576	5.7956	1601

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right uterine tube	UBERON:0001302	90.87	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.94	gold quality
stromal cell of endometrium	CL:0002255	79.76	gold quality
right testis	UBERON:0004534	79.30	gold quality
ganglionic eminence	UBERON:0004023	78.48	gold quality
left testis	UBERON:0004533	77.62	gold quality
gluteal muscle	UBERON:0002000	77.54	gold quality
cortical plate	UBERON:0005343	77.46	gold quality
triceps brachii	UBERON:0001509	77.32	gold quality
ventricular zone	UBERON:0003053	77.31	gold quality
embryo	UBERON:0000922	76.28	gold quality
apex of heart	UBERON:0002098	76.14	gold quality
testis	UBERON:0000473	75.38	gold quality
granulocyte	CL:0000094	74.56	gold quality
right lobe of liver	UBERON:0001114	72.98	gold quality
pituitary gland	UBERON:0000007	72.78	gold quality
adenohypophysis	UBERON:0002196	72.69	gold quality
right adrenal gland	UBERON:0001233	72.53	gold quality
monocyte	CL:0000576	72.49	gold quality
leukocyte	CL:0000738	72.21	gold quality
right adrenal gland cortex	UBERON:0035827	72.07	gold quality
metanephros cortex	UBERON:0010533	72.01	gold quality
mononuclear cell	CL:0000842	71.97	gold quality
cervix squamous epithelium	UBERON:0006922	71.17	gold quality
heart left ventricle	UBERON:0002084	71.16	gold quality
mucosa of transverse colon	UBERON:0004991	70.82	gold quality
cardiac ventricle	UBERON:0002082	70.66	gold quality
left adrenal gland	UBERON:0001234	70.64	gold quality
omental fat pad	UBERON:0010414	70.48	gold quality
peritoneum	UBERON:0002358	70.40	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	1.14

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
ARID3A
ARID3B
CDKN1A	Repression
IRF4

miRNA regulators (miRDB)

43 targeting CBX8, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4779	99.86	66.50	1583
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-92A-2-5P	99.75	67.01	2164
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-8061	99.63	69.44	1411
HSA-MIR-1260A	99.61	66.67	1098
HSA-MIR-1260B	99.61	66.67	1098
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-6752-5P	99.59	67.32	1243
HSA-MIR-203A-3P	99.49	70.56	2806

Literature-anchored findings (GeneRIF, showing 30)

• CBX8 is an essential component of one of the polycomb repressive complexes, which directly regulate the expression of numerous target genes, including the INK4A-ARF locus, involved in cell-fate decisions. (PMID:17332741)
• CBX8 plays an essential role in MLL-AF9 transcriptional regulation and leukemogenesis. (PMID:22094252)
• CBX8 cooperated with SIRT1 for suppressing p53 acetylation induced by Sirtinol and etoposide/TSA. Upon ectopic expression, CBX8 or SIRT1 repressed the expression of p21(WAF1) by inhibiting p53 binding to the promoter. (PMID:23474493)
• Interaction with CBX8 precludes AF9-DOT1L binding. (PMID:23891621)
• The presence of CBX8-GFP in the same focus had a minor impact on BMI1 and RING1 recovery kinetics. (PMID:24460908)
• CBX8 might emerge as an oncogene for promoting the proliferation of tumor cells and raising the resistance of neoplasms to chemotherapy. (PMID:25197352)
• Low CBX8 expression was associated with distant metastasis in colorectal cancer. (PMID:25360999)
• IGF1 can promote the colon cancer cell line, HCT116 cell, proliferation via promoting Cbx8 expression (PMID:25398592)
• These data suggest that CBX8 modulates SIPS through the RB-E2F1 pathway in CML cells and provide important insight into its application in CML treatment. (PMID:26718407)
• The difference in the SUZ12 and CBX8 genes expression were significantly divergent between tumors and their marginal tissues. (PMID:26837964)
• CBX8 binds to H3K27me3 at bivalent promoters during germinal center formation, and recruits a novel PRC1-BCOR complex at BCL6 binding sites to specifically silence genes in the germinal center and promote lymphomagenesis (PMID:27505670)
• CBX8 plates roles in epigenetic regulation in DNA damage response. (PMID:27555324)
• The data suggest that high expression of CBX8 plays a critical oncogenic role in aggressiveness of urothelial carcinoma cells of the bladder through promoting cancer cell proliferation by repressing the p53 pathway, and CBX8 could be used as a novel predictor for muscle invasive bladder cancer patients. (PMID:28837252)
• CBX8 binds with the Snai1 promoter, represses Snai1 transcription and suppresses esophageal carcinoma metastasis. (PMID:28912889)
• CBX8 functions as an oncogene to upregulate EGR1 and miR-365-3p to stimulate the AKT/beta-catenin pathway in hepatocellular carcinoma.CBX8 expression is increased and associated with poor outcomes in hepatocellular carcinoma. (PMID:29066512)
• PIM1 can phosphorylate CBX8 to promote its degradation, thereby up-regulating p16, during PIM1-induced cell senescence. (PMID:29763603)
• Circular RNA circ_0005230 was proved to be a sponge of miR-618, and expression of miR-618 could regulate CBX8 expression via targeting the 3’UTR of CBX8. (PMID:30504704)
• function of the CBX8 chromodomain (CD) in vitro and in vivo; the CD is in fact a major driver of CBX8 chromatin association and this is driven by both histone and previously unrecognized DNA binding activity; characterization of the structural basis of histone and DNA binding and determine how they integrate on multiple levels (PMID:30597065)
• Results establish CBX8 as a critical driver of HCC stem cell-like and metastatic behaviors and characterize its role in modulating BMP4 expression. (PMID:30718464)
• Report shows that CBX8 is upregulated in esophageal squamous cell carcinoma (ESCC) tissues and cells and serves as an indicator of poor prognosis for ESCC patients. CBX8 knockdown inhibits cell proliferation, colony formation capability, DNA repair and promotes cell apoptosis. (PMID:31255735)
• Chromobox homolog 8 (CBX8) Interacts with Y-Box binding protein 1 (YBX1) to promote cellular proliferation in hepatocellular carcinoma cells. (PMID:31495785)
• Optimization of Ligands Using Focused DNA-Encoded Libraries To Develop a Selective, Cell-Permeable CBX8 Chromodomain Inhibitor. (PMID:31755685)
• CBX8 acts as an independent RNA-binding protein to regulate the maturation of miR-378a-3p in colon cancer cells. (PMID:33417156)
• KPNA2 interaction with CBX8 contributes to the development and progression of bladder cancer by mediating the PRDM1/c-FOS pathway. (PMID:33731128)
• hsamiR429 targets CBX8 to promote cell apoptosis in diffuse large Bcell lymphoma. (PMID:34651663)
• High Expression of a Cancer Stemness-Related Gene, Chromobox 8 (CBX8), in Normal Tissue Adjacent to the Tumor (NAT) Is Associated with Poor Prognosis of Colorectal Cancer Patients. (PMID:35681547)
• CBX8 Promotes Cell Proliferation and Metastasis and Leads to Radiotherapy Tolerance of Glioma Cells. (PMID:35713250)
• CBX8 Together with SET Facilitates Ovarian Carcinoma Growth and Metastasis by Suppressing the Transcription of SUSD2. (PMID:35894945)
• CBX8 promotes lung adenocarcinoma growth and metastasis through transcriptional repression of CDKN2C and SCEL. (PMID:37733753)
• CBX8 Promotes Epithelial-mesenchymal Transition, Migration, and Invasion of Lung Cancer through Wnt/beta-catenin Signaling Pathway. (PMID:38265409)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbx8a	ENSDARG00000087327
danio_rerio	cbx8b	ENSDARG00000098771
mus_musculus	Cbx8	ENSMUSG00000025578
rattus_norvegicus	Cbx8	ENSRNOG00000048113
caenorhabditis_elegans		WBGENE00001995
caenorhabditis_elegans		WBGENE00007615

Paralogs (8): CBX5 (ENSG00000094916), CBX7 (ENSG00000100307), CBX1 (ENSG00000108468), CBX3 (ENSG00000122565), CBX4 (ENSG00000141582), CBX2 (ENSG00000173894), CBX6 (ENSG00000183741), NPTXR (ENSG00000221890)

Protein

Protein identifiers

Chromobox protein homolog 8 — Q9HC52 (reviewed: Q9HC52)

Alternative names: Polycomb 3 homolog, Rectachrome 1

All UniProt accessions (3): C9J6K3, C9JM54, Q9HC52

UniProt curated annotations — full annotation on UniProt →

Function. Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A ‘Lys-119’, rendering chromatin heritably changed in its expressibility.

Subunit / interactions. Component of a PRC1-like complex. Interacts with RING1 RNF2, PCGF1, PCGF2, PCGF3, BMI1, PCGF5 and PCGF6. Interacts with MLLT3 and histone H3. Interacts with PHC2.

Subcellular location. Nucleus.

Miscellaneous. The human orthologuous proteins of Drosophila Polycomb group protein Pc, CBX2, CBX4, CBX6, CBX7 and CBX8, show distinct nuclear localizations, contribute differently to transcriptional repression, and appear to be part of distinct PRC1-like protein complexes. The hPRC-H complex purification reported by PubMed:12167701 probably presents a mixture of different complexes.

RefSeq proteins (1): NP_065700* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023779	Chromodomain_CS	Conserved_site
IPR023780	Chromo_domain	Domain
IPR033773	CBX7_C	Conserved_site
IPR052458	PcG_PRC1-like_component	Family

Pfam: PF00385, PF17218

UniProt features (23 total): modified residue 8, strand 5, helix 4, region of interest 2, chain 1, domain 1, sequence variant 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
5EQ0	X-RAY DIFFRACTION	1.18
3I91	X-RAY DIFFRACTION	1.55
2N4Q	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HC52-F1	63.27	0.18

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 (8): 311, 332, 352, 110, 130, 191, 256, 265

Function

Pathways and Gene Ontology

Reactome pathways

24 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3108214	SUMOylation of DNA damage response and repair proteins
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-4551638	SUMOylation of chromatin organization proteins
R-HSA-4570464	SUMOylation of RNA binding proteins
R-HSA-4655427	SUMOylation of DNA methylation proteins
R-HSA-8939243	RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1257604	PIP3 activates AKT signaling
R-HSA-162582	Signal Transduction
R-HSA-212436	Generic Transcription Pathway
R-HSA-2262752	Cellular responses to stress
R-HSA-2559583	Cellular Senescence
R-HSA-2990846	SUMOylation
R-HSA-3108232	SUMO E3 ligases SUMOylate target proteins
R-HSA-392499	Metabolism of proteins
R-HSA-597592	Post-translational protein modification
R-HSA-6807070	PTEN Regulation
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878171	Transcriptional regulation by RUNX1
R-HSA-8953897	Cellular responses to stimuli
R-HSA-9006925	Intracellular signaling by second messengers

MSigDB gene sets: 155 (showing top): ATF_B, BENPORATH_ES_WITH_H3K27ME3, AREB6_03, GRAESSMANN_APOPTOSIS_BY_SERUM_DEPRIVATION_DN, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, CREBP1_Q2, GGGTGGRR_PAX4_03, PAX2_01, CTCTAGA_MIR526C_MIR518F_MIR526A, CREB_Q4, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MYOD_01, ATF1_Q6, WTGAAAT_UNKNOWN, E4F1_Q6

GO Biological Process (6): negative regulation of transcription by RNA polymerase II (GO:0000122), positive regulation of cell population proliferation (GO:0008284), positive regulation of collagen biosynthetic process (GO:0032967), positive regulation of DNA repair (GO:0045739), cellular response to hydrogen peroxide (GO:0070301), chromatin organization (GO:0006325)

GO Molecular Function (5): chromatin binding (GO:0003682), single-stranded RNA binding (GO:0003727), histone H3K27me3 reader activity (GO:0061628), ubiquitin-protein transferase activator activity (GO:0097027), protein binding (GO:0005515)

GO Cellular Component (6): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), PcG protein complex (GO:0031519), PRC1 complex (GO:0035102)

Reactome top-level categories

Rollup of top-14 pathways:

Category	Pathways
SUMO E3 ligases SUMOylate target proteins	5
Cellular Senescence	1
Transcriptional regulation by RUNX1	1
PTEN Regulation	1
Differentiation of T cells	1
Intracellular signaling by second messengers	1
RNA Polymerase II Transcription	1
Cellular responses to stimuli	1
Cellular responses to stress	1
Post-translational protein modification	1
SUMOylation	1
Metabolism of proteins	1
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
positive regulation of biosynthetic process	1
positive regulation of collagen metabolic process	1
collagen biosynthetic process	1
regulation of collagen biosynthetic process	1
DNA repair	1
regulation of DNA repair	1
positive regulation of response to stimulus	1
positive regulation of DNA metabolic process	1
cellular response to reactive oxygen species	1
response to hydrogen peroxide	1
cellular component organization	1
RNA binding	1
histone H3 reader activity	1
ubiquitin-protein transferase activity	1
enzyme activator activity	1
ubiquitin-protein transferase regulator activity	1
chromosome	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1

Protein interactions and networks

STRING

1393 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBX8	RING1	Q06587	987
CBX8	CBX2	Q14781	980
CBX8	BMI1	P35226	977
CBX8	R4GMX3	R4GMX3	977
CBX8	CBX4	O00257	966
CBX8	PHC2	Q8IXK0	944
CBX8	CBX7	O95931	941
CBX8	PHC3	Q8NDX5	921
CBX8	CBX6	O95503	920
CBX8	RNF2	Q99496	824
CBX8	PCGF2	P35227	803
CBX8	PHC1	P78364	797
CBX8	RYBP	Q8N488	787
CBX8	WDR5	P61964	783
CBX8	KMT2B	Q9UMN6	766

IntAct

466 interactions, top by confidence:

A	B	Type	Score
BMI1	CBX7	psi-mi:“MI:0914”(association)	0.940
RING1	CBX8	psi-mi:“MI:0915”(physical association)	0.920
CBX8	RING1	psi-mi:“MI:0915”(physical association)	0.920
RNF2	CBX8	psi-mi:“MI:0407”(direct interaction)	0.920
PCGF1	BCOR	psi-mi:“MI:0914”(association)	0.880
PHC2	CBX8	psi-mi:“MI:0915”(physical association)	0.840
CBX8	PHC2	psi-mi:“MI:0915”(physical association)	0.840
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
FSD2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
ZBTB14	CBX8	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
CBX8	TFCP2	psi-mi:“MI:0915”(physical association)	0.720
CBX8	TRAF2	psi-mi:“MI:0915”(physical association)	0.720
CBX8	CALCOCO2	psi-mi:“MI:0915”(physical association)	0.720
KRT40	CBX8	psi-mi:“MI:0915”(physical association)	0.720
CBX8	HMBOX1	psi-mi:“MI:0915”(physical association)	0.720
KCTD9	CBX8	psi-mi:“MI:0915”(physical association)	0.720
CBX8	GPRASP2	psi-mi:“MI:0915”(physical association)	0.720
LZTS2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
MID2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
PNMA2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
TFCP2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
TRAF2	CBX8	psi-mi:“MI:0915”(physical association)	0.720
CALCOCO2	CBX8	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (400): CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid), CBX8 (Two-hybrid)

ESM2 similar proteins: A2WXR5, A2XTW9, A2Y0Q2, A2Y4R8, A9LMC0, B8ADZ3, B8AMA8, B8B8C5, B8B8I3, B8BJV8, O19132, O81488, P29475, P29476, P58268, P58269, P58270, Q14106, Q27571, Q29498, Q2R837, Q40359, Q567C6, Q5XEM9, Q60DW3, Q61103, Q66650, Q6EPZ2, Q6IEK5, Q6IEN1, Q6YTY3, Q6Z7F4, Q75IR6, Q7F2Z1, Q7XUW3, Q84TV4, Q8H383, Q8LA16, Q8S8M9, Q8UVR5

Diamond homologs: G5EDE2, G5EET5, O43463, O54864, O95503, P23198, P45973, P83916, P83917, Q13185, Q2NL30, Q339W7, Q5F3W5, Q5R6X7, Q5RB81, Q61686, Q6AYK9, Q6DGD3, Q6NRE8, Q7JXA8, Q8N8U2, Q944N1, Q946J8, Q9D5D8, Q9DBY5, Q9EQQ0, Q9HC52, Q9QXV1, Q9WTK2, Q9Y232, Q9Y6F7, Q9Y6F8, O00257, O55187, O95931, P05205, P26017, P30658, P34618, P60889

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 105 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
SUMOylation of DNA methylation proteins	7	87.1×	1e-10
Transcriptional Regulation by E2F6	8	43.4×	1e-09
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	7	39.0×	3e-08
SUMOylation of transcription cofactors	7	31.5×	1e-07
SUMOylation of RNA binding proteins	7	30.8×	1e-07
Regulation of PTEN gene transcription	8	26.4×	4e-08
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	9	24.4×	9e-09
SUMOylation of chromatin organization proteins	8	23.5×	8e-08

GO biological processes:

GO term	Partners	Fold	FDR
intermediate filament organization	5	12.8×	5e-03
chromatin remodeling	11	8.5×	1e-05
chromatin organization	8	8.4×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	48
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

459 predictions. Top by Δscore:

Variant	Effect	Δscore
17:79795558:CCT:C	acceptor_loss	1.0000
17:79795559:C:CC	acceptor_gain	1.0000
17:79796055:A:AC	donor_gain	1.0000
17:79796056:C:CC	donor_gain	1.0000
17:79796246:GTACC:G	donor_loss	1.0000
17:79796247:TA:T	donor_loss	1.0000
17:79796248:A:AG	donor_loss	1.0000
17:79796249:C:CT	donor_loss	1.0000
17:79796253:T:A	donor_gain	1.0000
17:79796316:CT:C	acceptor_loss	1.0000
17:79796491:A:AC	donor_gain	1.0000
17:79796492:C:CC	donor_gain	1.0000
17:79796492:CTTA:C	donor_gain	1.0000
17:79796493:TTA:T	donor_loss	1.0000
17:79796494:TACT:T	donor_loss	1.0000
17:79796495:A:AC	donor_gain	1.0000
17:79796495:ACT:A	donor_loss	1.0000
17:79796496:C:CC	donor_gain	1.0000
17:79796496:C:G	donor_loss	1.0000
17:79796496:CTT:C	donor_gain	1.0000
17:79796927:TA:T	donor_loss	1.0000
17:79796928:A:AC	donor_gain	1.0000
17:79796928:ACTT:A	donor_loss	1.0000
17:79796928:ACTTT:A	donor_gain	1.0000
17:79796929:C:CA	donor_gain	1.0000
17:79796929:CT:C	donor_gain	1.0000
17:79796929:CTT:C	donor_gain	1.0000
17:79796929:CTTT:C	donor_gain	1.0000
17:79796929:CTTTC:C	donor_gain	1.0000
17:79796932:T:A	donor_gain	1.0000

AlphaMissense

2489 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:79794650:A:C	F385L	1.000
17:79794650:A:T	F385L	1.000
17:79794651:A:C	F385C	1.000
17:79794651:A:G	F385S	1.000
17:79794652:A:C	F385V	1.000
17:79794652:A:G	F385L	1.000
17:79794652:A:T	F385I	1.000
17:79794653:A:C	F384L	1.000
17:79794653:A:T	F384L	1.000
17:79794654:A:C	F384C	1.000
17:79794654:A:G	F384S	1.000
17:79794655:A:G	F384L	1.000
17:79794658:C:G	G383R	1.000
17:79794671:A:C	S378R	1.000
17:79794671:A:T	S378R	1.000
17:79794673:T:G	S378R	1.000
17:79794674:T:A	E377D	1.000
17:79794674:T:G	E377D	1.000
17:79794675:T:A	E377V	1.000
17:79794676:C:T	E377K	1.000
17:79794677:C:A	K376N	1.000
17:79794677:C:G	K376N	1.000
17:79794681:A:C	I375S	1.000
17:79794681:A:G	I375T	1.000
17:79794681:A:T	I375N	1.000
17:79794684:G:A	T374I	1.000
17:79794685:T:G	T374P	1.000
17:79794687:A:T	V373D	1.000
17:79794690:G:A	T372I	1.000
17:79794705:G:A	T367I	1.000

dbSNP variants (sampled 300 via entrez): RS1000095911 (17:79795790 A>T), RS1000589411 (17:79791887 G>A), RS1000645033 (17:79797600 A>C,G,T), RS1001049861 (17:79796702 C>T), RS1001500874 (17:79796932 T>C,G), RS1002218411 (17:79797211 G>A,C), RS1002403065 (17:79792002 G>A), RS1002842865 (17:79792240 T>C), RS1003219622 (17:79798544 A>G), RS1003275679 (17:79796403 C>CATTGT), RS1003439689 (17:79793564 G>A), RS1003563138 (17:79792721 G>C), RS1003815000 (17:79793299 A>C), RS1004584864 (17:79796375 G>A,C), RS1005550693 (17:79797231 G>A)

Disease associations

OMIM: gene MIM:617354 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
schizophrenia	No Known Disease Relationship	Unknown

Mondo (2): spastic cerebral palsy (MONDO:0000396), schizophrenia (MONDO:0005090)

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST007323_26	Risk-taking tendency (4-domain principal component model)	1.000000e-08
GCST007325_136	General risk tolerance (MTAG)	9.000000e-11
GCST007327_52	Smoking status (ever vs never smokers)	1.000000e-08
GCST010703_16	Brain morphology (MOSTest)	1.000000e-09
GCST011011_34	Youthful appearance (self-reported)	3.000000e-08
GCST90002400_235	Plateletcrit	4.000000e-09

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour
EFO:0004318	smoking behavior
EFO:0004346	neuroimaging measurement
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL3232684 (SINGLE PROTEIN), CHEMBL5739545 (PROTEIN-PROTEIN INTERACTION)

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

ChEMBL bioactivities

41 potent at pChembl≥5 of 55 total, top 40 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.92	Kd	120	nM	CHEMBL4635096
6.34	Kd	458	nM	CHEMBL5715919
6.32	Kd	480	nM	CHEMBL3559502
6.30	Kd	500	nM	CHEMBL5715922
6.21	Kd	624	nM	CHEMBL3780251
6.16	IC50	700	nM	CHEMBL3905193
6.16	Kd	700	nM	CHEMBL4643012
6.16	Kd	700	nM	CHEMBL5715922
6.10	Kd	800	nM	CHEMBL5715922
6.05	Kd	890	nM	CHEMBL4647581
6.02	Kd	960	nM	CHEMBL4640223
6.01	IC50	980	nM	CHEMBL3898460
6.00	Kd	1000	nM	CHEMBL3780712
6.00	Kd	1000	nM	CHEMBL3780251
6.00	IC50	1000	nM	CHEMBL3889586
5.92	Kd	1200	nM	CHEMBL3939958
5.89	IC50	1300	nM	CHEMBL3939958
5.89	IC50	1300	nM	CHEMBL3972289
5.82	Kd	1500	nM	CHEMBL3234188
5.82	IC50	1500	nM	CHEMBL3953637
5.82	IC50	1500	nM	CHEMBL3958557
5.77	IC50	1700	nM	CHEMBL3916023
5.77	Kd	1700	nM	CHEMBL4637043
5.75	Kd	1780	nM	CHEMBL3234442
5.72	Kd	1890	nM	CHEMBL3234443
5.72	IC50	1900	nM	CHEMBL3934881
5.70	IC50	2000	nM	CHEMBL3933207
5.68	IC50	2100	nM	CHEMBL3942693
5.62	IC50	2400	nM	CHEMBL3987134
5.58	Kd	2600	nM	CHEMBL4640186
5.52	IC50	3000	nM	CHEMBL3973366
5.48	IC50	3300	nM	CHEMBL3937936
5.46	IC50	3500	nM	CHEMBL3969494
5.42	IC50	3800	nM	CHEMBL4646032
5.35	Kd	4500	nM	CHEMBL4646516
5.32	IC50	4800	nM	CHEMBL3935965
5.32	IC50	4800	nM	CHEMBL3925993
5.32	IC50	4800	nM	CHEMBL3943850
5.29	IC50	5100	nM	CHEMBL3944916
5.22	Kd	6000	nM	CHEMBL3780489

PubChem BioAssay actives

36 with measured affinity, of 76 total; 34 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
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]butanoyl]amino]-2-cyclopentylacetyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.1200	uM
[(5S)-6-(2-aminoethylamino)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-2-cyclopentylacetyl]amino]-6-oxohexyl]-trimethylazanium	1129998: Binding affinity to CBX8 (unknown origin) by isothermal titration calorimetry assay	kd	0.4800	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.6240	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	0.7000	uM
[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]butanoyl]amino]-2-cyclopentylacetyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.7000	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.8900	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]butanoyl]amino]-3-phenylpropanoyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.9600	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]butanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	0.9800	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]butanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1288274: Binding affinity to N-terminal His6-tagged human CBX8 (8 to 61 residues) expressed in Escherichia coli BL21 using FITC-peptide-3 as competitive binding probe by fluorescence polarization assay	kd	1.0000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-[ethyl(propan-2-yl)amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.0000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319528: Binding affinity to human N-terminal his-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS by ITC method	kd	1.2000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-[propan-2-yl(propyl)amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.3000	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-ethylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.5000	uM
[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-6-oxohexyl]-trimethylazanium	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.5000	uM
[(5S)-6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]-trimethylazanium	1129998: Binding affinity to CBX8 (unknown origin) by isothermal titration calorimetry assay	kd	1.5000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-[4-[[(2-methylpropan-2-yl)oxycarbonylamino]methyl]phenyl]propanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.7000	uM
[(5S)-6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[3-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]propanoylamino]-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	1.7000	uM
[(5S)-6-[[(2R)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-cyclopentyl-2-[[(2S)-2-[[(2S)-2-[(4-methoxycarbonylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]acetyl]amino]-6-oxohexyl]-trimethylazanium	1129998: Binding affinity to CBX8 (unknown origin) by isothermal titration calorimetry assay	kd	1.7800	uM
[(5S)-5-[[(2S)-2-cyclopentyl-2-[[(2S)-2-[[(2S)-2-[(4-methoxycarbonylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]acetyl]amino]-6-(1,3-dihydroxypropan-2-ylamino)-6-oxohexyl]-trimethylazanium	1129998: Binding affinity to CBX8 (unknown origin) by isothermal titration calorimetry assay	kd	1.8900	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-4-methyl-2-[[(2S)-2-[[(2S)-3-phenyl-2-[(4-propan-2-ylbenzoyl)amino]propanoyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	1.9000	uM
(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-tert-butylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoic acid	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	2.0000	uM
4-tert-butyl-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-(diethylamino)-1-[[(2S)-1-(dimethylamino)-3-hydroxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	2.1000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-3-[4-(aminomethyl)phenyl]-2-[(4-tert-butylbenzoyl)amino]propanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	2.4000	uM
[(5S)-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	2.6000	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-4-methyl-2-[[(2S)-2-[[(2S)-3-phenyl-2-[[4-(trifluoromethyl)benzoyl]amino]propanoyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	3.0000	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-methoxybenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	3.3000	uM
4-tert-butyl-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-(diethylamino)-1-(2-hydroxyethylamino)-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]benzamide	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	3.5000	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-amino-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]butanoyl]amino]-2-cyclopentylacetyl]amino]-6-oxohexyl]-trimethylazanium	1650082: Inhibition of CBX8 (unknown origin) assessed as inhibition of CBX4 disruption by competitive FP assay	ic50	3.8000	uM
[(5S)-6-[[(2S)-1-amino-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[3-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]propanoylamino]-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-oxohexyl]-trimethylazanium	1650079: Binding affinity to CBX8 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	4.5000	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-4-methyl-2-[[(2S)-2-[[(2S)-2-[(4-methylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	4.8000	uM
methyl 4-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-(diethylamino)-1-[[(2S)-3-hydroxy-1-methoxy-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]carbamoyl]benzoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	4.8000	uM
methyl (2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-benzamido-3-phenylpropanoyl]amino]propanoyl]amino]-4-methylpentanoyl]amino]-6-(diethylamino)hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	4.8000	uM
methyl (2S)-2-[[(2S)-6-(diethylamino)-2-[[(2S)-4-methyl-2-[[(2S)-2-[[(2S)-2-[(3-methylbenzoyl)amino]-3-phenylpropanoyl]amino]propanoyl]amino]pentanoyl]amino]hexanoyl]amino]-3-hydroxypropanoate	1319523: Antagonist activity at recombinant human N-terminal His-tagged CBX8 chromodomain (8 to 61 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS using biotin-labeled H3K9me3 measured after 30 mins by AlphaScreen assay	ic50	5.1000	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-1-amino-6-[[3-carboxy-4-(3-hydroxy-6-oxoxanthen-9-yl)phenyl]carbamothioylamino]-1-oxohexan-2-yl]amino]-4-carboxy-1-oxobutan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-5-[[(2S)-2-[[(2S)-2-[[(2S)-2-[(4-bromobenzoyl)amino]-3-phenylpropanoyl]amino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1288274: Binding affinity to N-terminal His6-tagged human CBX8 (8 to 61 residues) expressed in Escherichia coli BL21 using FITC-peptide-3 as competitive binding probe by fluorescence polarization assay	kd	6.0000	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases methylation	1
arsenite	increases methylation	1
cypermethrin	decreases expression	1
sodium arsenite	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	affects phosphorylation	1
Cannabidiol	increases expression	1
Dexamethasone	affects cotreatment, increases expression	1
Folic Acid	increases expression	1
Indomethacin	affects cotreatment, increases expression	1
Lipopolysaccharides	decreases expression, affects response to substance, increases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	increases methylation	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
Okadaic Acid	decreases expression	1
Copper Sulfate	decreases expression	1

ChEMBL screening assays

15 unique, capped per target: 14 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3242417	Binding	Binding affinity to CBX8 (unknown origin) by isothermal titration calorimetry assay	Chromodomain antagonists that target the polycomb-group methyllysine reader protein chromobox homolog 7 (CBX7). — J Med Chem
CHEMBL5723172	Functional	Affinity Biochemical interaction: (Fluorescence polarisation (fluorescein conjugated)) EUB0002326a CBX8	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0L6	SEES3-1V human CBX8, clone1	Embryonic stem cell	Male
CVCL_A0L7	SEES3-1V human CBX8, clone2	Embryonic stem cell	Male
CVCL_A0L8	SEES3-1V human CBX8, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00000374	PHASE4	COMPLETED	Treatment for First-Episode Schizophrenia
NCT00001656	PHASE4	COMPLETED	Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
NCT00007774	PHASE4	COMPLETED	To Determine if Olanzapine is More Cost Effective Than Haloperidol for the Treatment of Schizophrenia
NCT00014001	PHASE4	COMPLETED	CATIE- Schizophrenia Trial
NCT00018668	PHASE4	COMPLETED	Antipsychotic Response in Schizophrenia
NCT00034801	PHASE4	COMPLETED	Olanzapine Versus Active Comparator in the Treatment of Depression in Patients With Schizophrenia
NCT00034905	PHASE4	COMPLETED	A Comparison of Seroquel vs. Risperidone in Schizophrenia
NCT00036088	PHASE4	COMPLETED	Olanzapine Versus An Active Comparator in the Treatment of Schizophrenia
NCT00044187	PHASE4	COMPLETED	The Assessment of a Weight-Gain Agent for the Treatment of Olanzapine-Associated Anti-Obesity Agent in Patients With Schizophrenia, Schizophreniform Disorder, Schizoaffective Disorder, and Bipolar I Disorder
NCT00044655	PHASE4	COMPLETED	Switching Medication to Treat Schizophrenia
NCT00048828	PHASE4	COMPLETED	Treating Drug-Resistant Childhood Schizophrenia
NCT00053703	PHASE4	COMPLETED	Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
NCT00056498	PHASE4	COMPLETED	Risperidone Treatment in Schizophrenia Patients Who Are Currently Taking Clozapine
NCT00061802	PHASE4	COMPLETED	Efficacy and Safety of Two Atypical Antipsychotics vs. Placebo in Patients With an Acute Exacerbation of Either Schizophrenia or Schizoaffective Disorder
NCT00080327	PHASE4	COMPLETED	Study of Three Doses of Aripiprazole in Patients With Acute Schizophrenia
NCT00088049	PHASE4	COMPLETED	Study of Olanzapine vs. Aripiprazole in the Treatment of Schizophrenia
NCT00090012	PHASE4	COMPLETED	Comparison of Continuing Olanzapine to Switching to Quetiapine in Overweight or Obese Patients With Schizophrenia and Schizoaffective Disorder
NCT00100776	PHASE4	COMPLETED	Efficacy of High Dose Olanzapine for the Treatment of Schizophrenia and Schizoaffective Disorder
NCT00103571	PHASE4	COMPLETED	Olanzapine Versus Aripiprazole in the Treatment of Acutely Ill Patients With Schizophrenia
NCT00108368	PHASE4	COMPLETED	The Effects of Risperidone and Olanzapine on Thinking
NCT00114595	PHASE4	COMPLETED	Ethyl-Eicosapentaenoic Acid and Tardive Dyskinesia
NCT00130923	PHASE4	COMPLETED	Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder
NCT00137020	PHASE4	COMPLETED	Clinical Effect Of Cross Titration Of Antipsychotics With Ziprasidone In Schizophrenia Or Schizoaffective Disorder
NCT00140166	PHASE4	COMPLETED	Treatment of Acute Schizophrenia With Vitamin Therapy
NCT00145847	PHASE4	COMPLETED	Naltrexone Treatment of Alcohol Abuse in Schizophrenia
NCT00148564	PHASE4	COMPLETED	Energy Homeostasis Under Treatment With Atypical Antipsychotics
NCT00156715	PHASE4	COMPLETED	Efficacy of Quetiapine in the Treatment of Patients With Schizophrenia and a Comorbid Substance Use Disorder
NCT00158223	PHASE4	COMPLETED	Effectiveness of Pimozide in Augmenting the Effects of Clozapine in the Treatment of Schizophrenia
NCT00159081	PHASE4	COMPLETED	One Year Drug Treatment in First-Episode Schizophrenia
NCT00159120	PHASE4	COMPLETED	Maintenance Treatment vs. Stepwise Drug Discontinuation in First-Episode Schizophrenia
NCT00159133	PHASE4	COMPLETED	Prodrome-Based Early Intervention With Antipsychotics vs. Benzodiazepines in First-Episode Schizophrenia
NCT00159757	PHASE4	TERMINATED	12 Week Open, Non-Comparative Switch Study Of Oral Ziprazidone In Previously Treated Schizophrenic Patients
NCT00167817	PHASE4	COMPLETED	Effect of Switch to Aripiprazole on Health and Smoking Parameters in Patients With Schizophrenia: A Pilot Study
NCT00169026	PHASE4	TERMINATED	Alcoholism and Schizophrenia: Effects of Clozapine
NCT00169039	PHASE4	TERMINATED	Clozapine Versus Chlorpromazine for Treatment-Unresponsive Schizophrenia
NCT00169065	PHASE4	COMPLETED	Effectiveness of Clozapine Versus Olanzapine for Treatment-resistant Schizophrenia
NCT00169091	PHASE4	TERMINATED	Clozapine Versus Haloperidol for Treating the First Episode of Schizophrenia
NCT00176423	PHASE4	COMPLETED	Efficacy Study of Galantamine for Cognitive Impairments in Schizophrenia
NCT00176436	PHASE4	COMPLETED	Atomoxetine for Treatment of Weight Gain in Olanzapine or Clozapine Patients
NCT00177008	PHASE4	COMPLETED	Aripiprazole for the Treatment of Schizophrenia With Co-Morbid Social Anxiety