CBX6

Summary

CBX6 (chromobox 6, HGNC:1556) is a protein-coding gene on chromosome 22q13.1, encoding Chromobox protein homolog 6 (O95503). 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.

Predicted to enable chromatin binding activity and methylated histone binding activity. Involved in negative regulation of transcription by RNA polymerase II. Located in nuclear body. Part of PcG protein complex. Biomarker of glioblastoma.

Source: NCBI Gene 23466 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 64 total
• Druggable target: yes
• MANE Select transcript: NM_014292

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1556
Approved symbol	CBX6
Name	chromobox 6
Location	22q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000183741
Ensembl biotype	protein_coding
OMIM	617438
Entrez	23466

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 retained_intron

ENST00000216083, ENST00000407418, ENST00000469420, ENST00000866240, ENST00000951822

RefSeq mRNA: 2 — MANE Select: NM_014292 NM_001303494, NM_014292

CCDS: CCDS13980, CCDS77675

Canonical transcript exons

ENST00000407418 — 5 exons

Exon	Start	End
ENSE00000654591	38871480	38871546
ENSE00001679462	38861422	38867201
ENSE00001886297	38872122	38872216
ENSE00003515497	38871902	38871945
ENSE00003545492	38871692	38871757

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 98.20.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 58.7239 / max 534.3325, expressed in 1813 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
194252	53.3654	1810
194253	3.8251	1452
194255	0.5462	240
194254	0.5158	147
194251	0.2548	97
194250	0.2165	91

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
Brodmann (1909) area 10	UBERON:0013541	98.20	gold quality
postcentral gyrus	UBERON:0002581	97.97	gold quality
parietal lobe	UBERON:0001872	97.85	gold quality
entorhinal cortex	UBERON:0002728	97.51	gold quality
superior frontal gyrus	UBERON:0002661	97.22	gold quality
endometrium epithelium	UBERON:0004811	97.18	gold quality
cerebellar vermis	UBERON:0004720	97.12	gold quality
CA1 field of hippocampus	UBERON:0003881	96.89	gold quality
type B pancreatic cell	CL:0000169	96.81	silver quality
paraflocculus	UBERON:0005351	96.76	gold quality
frontal pole	UBERON:0002795	96.75	gold quality
temporal lobe	UBERON:0001871	96.31	gold quality
Brodmann (1909) area 46	UBERON:0006483	96.12	gold quality
middle frontal gyrus	UBERON:0002702	95.91	gold quality
frontal cortex	UBERON:0001870	95.83	gold quality
Ammon’s horn	UBERON:0001954	95.70	gold quality
cingulate cortex	UBERON:0003027	95.69	gold quality
anterior cingulate cortex	UBERON:0009835	95.65	gold quality
amygdala	UBERON:0001876	95.59	gold quality
prefrontal cortex	UBERON:0000451	95.57	gold quality
orbitofrontal cortex	UBERON:0004167	95.54	gold quality
middle temporal gyrus	UBERON:0002771	95.52	gold quality
right frontal lobe	UBERON:0002810	95.49	gold quality
occipital lobe	UBERON:0002021	95.43	gold quality
neocortex	UBERON:0001950	95.40	gold quality
cerebral cortex	UBERON:0000956	95.36	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.31	gold quality
olfactory bulb	UBERON:0002264	95.27	silver quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.86	gold quality
saphenous vein	UBERON:0007318	94.81	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-GEOD-135922	yes	25.72
E-GEOD-83139	no	3.09
E-HCAD-31	no	1.93
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

203 targeting CBX6, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6856-5P	100.00	65.47	1298
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-10401-5P	99.99	65.79	948
HSA-MIR-1184	99.99	68.19	1458
HSA-MIR-4514	99.99	67.10	1870
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6825-5P	99.96	69.81	3431

Literature-anchored findings (GeneRIF, showing 5)

• Data show that polycomb-group proteins BMI1, PHC3, CBX6 and CBX7 expression was significantly increased during imatinib treatment. (PMID:26343356)
• our results represent the first evidence that CBX6 contributes to tumor progression and indicate that the protein may serve as a novel prognostic biomarker for hepatocellular carcinoma and as a therapeutic target in the treatment of the disease. (PMID:28122351)
• Data show that USP26 interacts with PRC1 components chromobox (CBX)-containing proteins CBX4 and CBX6. (PMID:28839133)
• CBX6 is negatively regulated by EZH2 and plays a potential tumor suppressor role in breast cancer. (PMID:30655550)
• Proteasomal degradation of polycomb-group protein CBX6 confers MMP-2 expression essential for mesothelioma invasion. (PMID:33028834)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Cbx6	ENSMUSG00000089715
rattus_norvegicus	Cbx6	ENSRNOG00000046955
caenorhabditis_elegans		WBGENE00001995
caenorhabditis_elegans		WBGENE00007615

Paralogs (8): CBX5 (ENSG00000094916), CBX7 (ENSG00000100307), CBX1 (ENSG00000108468), CBX3 (ENSG00000122565), CBX8 (ENSG00000141570), CBX4 (ENSG00000141582), CBX2 (ENSG00000173894), NPTXR (ENSG00000221890)

Protein

Protein identifiers

Chromobox protein homolog 6 — O95503 (reviewed: O95503)

All UniProt accessions (2): B0QXZ6, O95503

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. Possibly contributes to the target selectivity of the PRC1 complex by binding specific regions of chromatin. Recruitment to chromatin might occur in an H3K27me3-independent fashion. May have a PRC1-independent function in embryonic stem cells.

Subunit / interactions. Component of a PRC1-like complex. Distinct PRC1-like core complexes are composed of a RING1 subunit (RING1B or RING1A), one of the six PCGF proteins (PCGF1-6), one PHC protein (PHC1-3) and one of the CBX proteins (CBX2, CBX4, CBX6, CBX7 or CBX8). Interacts with PCGF1, PCGF2, PCGF3, BMI1, PCGF5, PCGF6, RING1 and RNF2. May interact with H3C15 and H3C1. Interacts (via chromodomain) with single-stranded RNA (ssRNA).

Subcellular location. Nucleus. Chromosome.

Post-translational modifications. Ubiquitinated. Ubiquitination regulates the function of the Polycomb group (PcG) multiprotein PRC1-like complex. Deubiquitinated by USP26.

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.

RefSeq proteins (2): NP_001290423, NP_055107* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR017984	Chromo_dom_subgr	Domain
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 (14 total): helix 3, strand 3, region of interest 2, chain 1, domain 1, compositionally biased region 1, modified residue 1, mutagenesis site 1, sequence conflict 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
3GV6	X-RAY DIFFRACTION	1.76
3I90	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O95503-F1	62.15	0.17

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 (1): 107

Mutagenesis-validated functional residues (1):

Position	Phenotype
16	reduced interaction with h3c15 and h3c1.

Function

Pathways and Gene Ontology

Reactome pathways

15 pathways

ID	Pathway
R-HSA-2559580	Oxidative Stress Induced Senescence
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-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: 313 (showing top): PAX4_01, MODULE_151, CMYB_01, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, AP4_Q6, TGACCTY_ERR1_Q2, CAGCTG_AP4_Q5, EFC_Q6, MODULE_66, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GROSS_HYPOXIA_VIA_ELK3_UP, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, GTGTTGA_MIR505, USF_01, HEN1_01

GO Biological Process (2): negative regulation of transcription by RNA polymerase II (GO:0000122), chromatin organization (GO:0006325)

GO Molecular Function (3): chromatin binding (GO:0003682), single-stranded RNA binding (GO:0003727), protein binding (GO:0005515)

GO Cellular Component (8): chromatin (GO:0000785), heterochromatin (GO:0000792), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear body (GO:0016604), PcG protein complex (GO:0031519), PRC1 complex (GO:0035102), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-12 pathways:

Category	Pathways
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
PIP3 activates AKT signaling	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
cellular anatomical structure	2
intracellular membraneless organelle	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
cellular component organization	1
RNA binding	1
chromosome	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nucleoplasm	1
nuclear protein-containing complex	1
nuclear ubiquitin ligase complex	1
PcG protein complex	1

Protein interactions and networks

STRING

819 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CBX6	CBX8	Q9HC52	920
CBX6	RING1	Q06587	900
CBX6	CBX4	O00257	861
CBX6	PHC3	Q8NDX5	796
CBX6	PCGF2	P35227	761
CBX6	RNF2	Q99496	744
CBX6	BMI1	P35226	721
CBX6	R4GMX3	R4GMX3	721
CBX6	PCGF1	Q9BSM1	720
CBX6	PHC2	Q8IXK0	718
CBX6	CBX2	Q14781	714
CBX6	CBX7	O95931	695
CBX6	PHC1	P78364	677
CBX6	PCGF6	Q9BYE7	619
CBX6	YAF2	Q8IY57	603

IntAct

125 interactions, top by confidence:

A	B	Type	Score
BMI1	CBX4	psi-mi:“MI:0914”(association)	0.900
STK25	STRN	psi-mi:“MI:0914”(association)	0.900
CBX6	BMI1	psi-mi:“MI:0915”(physical association)	0.880
BMI1	CBX6	psi-mi:“MI:0407”(direct interaction)	0.880
RNF2	CBX6	psi-mi:“MI:0407”(direct interaction)	0.860
RNF2	CBX6	psi-mi:“MI:0915”(physical association)	0.860
PCGF2	CBX4	psi-mi:“MI:0914”(association)	0.840
CBX6	RING1	psi-mi:“MI:0915”(physical association)	0.810
CBX6	PCGF2	psi-mi:“MI:0407”(direct interaction)	0.810
CBX6	RING1	psi-mi:“MI:0407”(direct interaction)	0.810
PHC1	CBX4	psi-mi:“MI:0914”(association)	0.790
RING1	CBX4	psi-mi:“MI:0914”(association)	0.730
DCAF7	DIAPH1	psi-mi:“MI:0914”(association)	0.730
MOV10	CBX6	psi-mi:“MI:0915”(physical association)	0.670
RNF2	CBX4	psi-mi:“MI:0914”(association)	0.660
PCGF1	CBX6	psi-mi:“MI:0407”(direct interaction)	0.590
GPR173	CBX6	psi-mi:“MI:0915”(physical association)	0.560
KLF11	CBX6	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (369): CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS), CBX6 (Affinity Capture-MS)

ESM2 similar proteins: A2A5K6, A5A763, A7X8B9, A7X8C2, A7X8C4, A7X8C9, A7X8D4, A7XW16, D4A8X0, E9PYH6, E9PZZ1, F1QQA8, G3V893, O08550, O15047, O15156, O43474, O55170, O95503, P16443, P19419, P42580, P50548, P56693, P70459, Q04888, Q14549, Q3B8N7, Q5F293, Q60793, Q62255, Q8CGW4, Q8TDD2, Q8VI67, Q8WUU4, Q91X45, Q924A2, Q96RK0, Q99PV8, Q9BZE0

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 121 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	9	80.6×	1e-13
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	9	36.1×	2e-10
SUMOylation of transcription cofactors	10	32.4×	8e-11
SUMOylation of RNA binding proteins	9	28.6×	2e-09
Transcriptional Regulation by E2F6	7	27.3×	2e-07
Eukaryotic Translation Initiation	6	24.7×	3e-06
Cap-dependent Translation Initiation	6	24.7×	3e-06
SARS-CoV-1 modulates host translation machinery	6	24.7×	3e-06

GO biological processes:

GO term	Partners	Fold	FDR
cytoplasmic translation	8	15.0×	4e-05
translation	9	9.3×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

761 predictions. Top by Δscore:

Variant	Effect	Δscore
22:38870575:CATTT:C	donor_gain	1.0000
22:38871688:TCACT:T	donor_loss	1.0000
22:38871689:CA:C	donor_loss	1.0000
22:38871690:A:AC	donor_gain	1.0000
22:38871691:C:CT	donor_gain	1.0000
22:38871691:CT:C	donor_gain	1.0000
22:38871691:CTT:C	donor_gain	1.0000
22:38871691:CTTT:C	donor_gain	1.0000
22:38871691:CTTTT:C	donor_gain	1.0000
22:38871755:TAC:T	acceptor_gain	1.0000
22:38871755:TACCT:T	acceptor_loss	1.0000
22:38871762:C:CT	acceptor_gain	1.0000
22:38871763:G:T	acceptor_gain	1.0000
22:38871767:C:CT	acceptor_gain	1.0000
22:38871900:A:AC	donor_gain	1.0000
22:38871901:C:CC	donor_gain	1.0000
22:38872117:CTCA:C	donor_loss	1.0000
22:38872118:TCA:T	donor_loss	1.0000
22:38872119:CAC:C	donor_loss	1.0000
22:38872120:A:AC	donor_gain	1.0000
22:38872120:AC:A	donor_gain	1.0000
22:38872121:C:CC	donor_gain	1.0000
22:38872121:C:CT	donor_loss	1.0000
22:38872121:CC:C	donor_gain	1.0000
22:38872121:CCTTT:C	donor_gain	1.0000
22:38870506:C:CA	donor_gain	0.9900
22:38870588:T:TA	donor_gain	0.9900
22:38871687:CTCA:C	donor_gain	0.9900
22:38871753:TGTAC:T	acceptor_gain	0.9900
22:38871756:AC:A	acceptor_gain	0.9900

AlphaMissense

2631 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:38866299:C:A	K383N	1.000
22:38866299:C:G	K383N	1.000
22:38866303:A:C	I382S	1.000
22:38866303:A:G	I382T	1.000
22:38866303:A:T	I382N	1.000
22:38866309:A:T	V380D	1.000
22:38866318:A:G	L377P	1.000
22:38866330:A:T	V373D	1.000
22:38866333:T:A	D372V	1.000
22:38866333:T:C	D372G	1.000
22:38866336:G:A	T371I	1.000
22:38866339:A:T	V370D	1.000
22:38866915:A:G	L178P	1.000
22:38866972:A:C	I159S	1.000
22:38866972:A:G	I159T	1.000
22:38871508:C:T	G73E	1.000
22:38871510:C:A	R72S	1.000
22:38871510:C:G	R72S	1.000
22:38871511:C:A	R72M	1.000
22:38871700:G:C	F57L	1.000
22:38871700:G:T	F57L	1.000
22:38871701:A:C	F57C	1.000
22:38871701:A:G	F57S	1.000
22:38871702:A:G	F57L	1.000
22:38871702:A:T	F57I	1.000
22:38871713:A:G	L53P	1.000
22:38871713:A:T	L53H	1.000
22:38871722:T:A	D50V	1.000
22:38871723:C:A	D50Y	1.000
22:38871723:C:G	D50H	1.000

dbSNP variants (sampled 300 via entrez): RS1000397628 (22:38864701 C>A), RS1000728666 (22:38865584 G>A), RS1000740137 (22:38865444 G>A), RS1001046923 (22:38871236 C>A,T), RS1001059501 (22:38870908 T>C), RS1001179047 (22:38870412 C>A,G,T), RS1001293376 (22:38864781 G>A,T), RS1001470964 (22:38864065 C>T), RS1001486255 (22:38873761 T>C), RS1001716878 (22:38868551 C>A,T), RS1001752401 (22:38863814 A>T), RS1001824078 (22:38865110 C>T), RS1002477237 (22:38862929 A>G), RS1002852763 (22:38871874 C>T), RS1002959510 (22:38865896 G>A,T)

Disease associations

OMIM: gene MIM:617438 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST000842_7	Bladder cancer	8.000000e-12
GCST002240_10	Bladder cancer	1.000000e-11
GCST90002400_508	Plateletcrit	2.000000e-10

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0007985	platelet crit

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3779762 (SINGLE PROTEIN)

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

ChEMBL bioactivities

18 potent at pChembl≥5 of 20 total, top 17 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.33	Kd	47	nM	CHEMBL3780251
7.11	Kd	78	nM	CHEMBL4647581
6.96	Kd	110	nM	CHEMBL3780663
6.52	Kd	300	nM	CHEMBL3780251
6.46	Kd	350	nM	CHEMBL4635096
6.40	Kd	400	nM	CHEMBL4643012
6.26	Kd	543	nM	CHEMBL5715919
6.21	Kd	610	nM	CHEMBL3939958
6.10	Kd	800	nM	CHEMBL3780712
6.10	Kd	800	nM	CHEMBL4640223
6.05	Kd	900	nM	CHEMBL3780489
6.05	Kd	900	nM	CHEMBL4646516
6.04	Kd	910	nM	CHEMBL3781600
6.00	Kd	1000	nM	CHEMBL4640186
5.96	Kd	1100	nM	CHEMBL4637043
5.55	IC50	2800	nM	CHEMBL4646032
5.22	IC50	6000	nM	CHEMBL4642464

PubChem BioAssay actives

16 with measured affinity, of 20 total; 15 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]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.0470	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.0780	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-1-amino-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	1288275: Binding affinity to N-terminal His6-tagged human CBX6 (8 to 65 residues) expressed in Escherichia coli BL21 by surface plasmon resonance assay	kd	0.1100	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]-2-cyclopentylacetyl]amino]-6-oxohexyl]-trimethylazanium	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.3500	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.4000	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	1319529: Binding affinity to human N-terminal his-tagged CBX6 chromodomain (8 to 65 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS by ITC method	kd	0.6100	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	1288273: Binding affinity to N-terminal His6-tagged human CBX6 (8 to 65 residues) expressed in Escherichia coli BL21 using FITC-peptide-3 as competitive binding probe by fluorescence polarization assay	kd	0.8000	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.8000	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	1288273: Binding affinity to N-terminal His6-tagged human CBX6 (8 to 65 residues) expressed in Escherichia coli BL21 using FITC-peptide-3 as competitive binding probe by fluorescence polarization assay	kd	0.9000	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	0.9000	uM
[(5S)-6-[[(2S)-1-[[(2S)-1-[[(2S)-6-[5-[(3aS,4S,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-1-amino-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	1288275: Binding affinity to N-terminal His6-tagged human CBX6 (8 to 65 residues) expressed in Escherichia coli BL21 by surface plasmon resonance assay	kd	0.9100	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	1.0000	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	1650077: Binding affinity to CBX6 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	1.1000	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	1650080: Inhibition of CBX6 (unknown origin) assessed as inhibition of CBX4 disruption by competitive FP assay	ic50	2.8000	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]propanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-6-oxohexyl]-trimethylazanium	1650080: Inhibition of CBX6 (unknown origin) assessed as inhibition of CBX4 disruption by competitive FP assay	ic50	6.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	3
Tunicamycin	decreases expression	2
Genistein	decreases expression, increases expression	2
FR900359	decreases phosphorylation	1
dicrotophos	increases expression	1
methylmercuric chloride	decreases expression	1
alpha-pinene	affects cotreatment, decreases expression, increases abundance	1
lead acetate	increases expression	1
trichostatin A	affects expression	1
sulforaphane	increases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
nickel chloride	decreases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ferrous chloride	decreases expression	1
cupric chloride	increases expression	1
methacrylaldehyde	increases abundance, affects cotreatment, decreases expression	1
K 7174	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Norethindrone Acetate	affects cotreatment, decreases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, decreases expression, increases abundance	1
Air Pollutants	decreases expression, increases abundance, affects cotreatment	1
Arbutin	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	decreases expression	1
Dieldrin	decreases expression	1

ChEMBL screening assays

9 unique, capped per target: 9 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3782544	Binding	Binding affinity to N-terminal His6-tagged human CBX6 (8 to 65 residues) expressed in Escherichia coli BL21 using FITC-peptide-3 as competitive binding probe by fluorescence polarization assay	Selective Inhibition of CBX6: A Methyllysine Reader Protein in the Polycomb Family. — ACS Med Chem Lett

Clinical trials (associated diseases)

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