CBX1

Summary

CBX1 (chromobox 1, HGNC:1551) is a protein-coding gene on chromosome 17q21.32, encoding Chromobox protein homolog 1 (P83916). Component of heterochromatin, which recognizes and binds histone H3 tails methylated at ‘Lys-9’, leading to epigenetic repression. It is a selective cancer dependency (DepMap: 16.2% of cell lines).

This gene encodes a highly conserved nonhistone protein, which is a member of the heterochromatin protein family . The protein is enriched in the heterochromatin and associated with centromeres. The protein has a single N-terminal chromodomain which can bind to histone proteins via methylated lysine residues, and a C-terminal chromo shadow-domain (CSD) which is responsible for the homodimerization and interaction with a number of chromatin-associated nonhistone proteins. The protein may play an important role in the epigenetic control of chromatin structure and gene expression. Several related pseudogenes are located on chromosomes 1, 3, and X. Multiple alternatively spliced variants, encoding the same protein, have been identified.

Source: NCBI Gene 10951 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Moderate, GenCC)
• GWAS associations: 6
• Clinical variants (ClinVar): 17 total — 1 likely-pathogenic
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 16.2% of screened cell lines
• MANE Select transcript: NM_001127228

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1551
Approved symbol	CBX1
Name	chromobox 1
Location	17q21.32
Locus type	gene with protein product
Status	Approved
Aliases	HP1Hs-beta, M31, MOD1, CBX, HP1-BETA, Hp1beta
Ensembl gene	ENSG00000108468
Ensembl biotype	protein_coding
OMIM	604511
Entrez	10951

Gene structure

Transcript identifiers

Ensembl transcripts: 17 — 17 protein_coding

ENST00000225603, ENST00000393408, ENST00000402583, ENST00000444685, ENST00000495350, ENST00000581003, ENST00000864325, ENST00000864326, ENST00000864327, ENST00000864328, ENST00000864329, ENST00000922219, ENST00000922220, ENST00000922221, ENST00000922222, ENST00000922223, ENST00000922224

RefSeq mRNA: 2 — MANE Select: NM_001127228 NM_001127228, NM_006807

CCDS: CCDS11525

Canonical transcript exons

ENST00000225603 — 5 exons

Exon	Start	End
ENSE00000735651	48075006	48075100
ENSE00001305675	48101268	48101478
ENSE00002771605	48076865	48077041
ENSE00002887933	48076001	48076178
ENSE00003844307	48070059	48071579

Expression profiles

Bgee: expression breadth ubiquitous, 301 present calls, max score 99.31.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 74.1414 / max 943.4404, expressed in 1812 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
166635	69.6543	1812
166634	1.8604	713
166631	0.7872	467
166629	0.5374	248
166632	0.5209	296
166633	0.4132	225
166630	0.3489	183
166628	0.0190	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.31	gold quality
ventricular zone	UBERON:0003053	99.03	gold quality
embryo	UBERON:0000922	98.96	gold quality
cortical plate	UBERON:0005343	98.91	gold quality
secondary oocyte	CL:0000655	98.43	gold quality
tendon of biceps brachii	UBERON:0008188	97.81	gold quality
medial globus pallidus	UBERON:0002477	97.40	gold quality
globus pallidus	UBERON:0001875	97.05	gold quality
endometrium epithelium	UBERON:0004811	96.95	gold quality
oocyte	CL:0000023	96.70	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.59	gold quality
spinal cord	UBERON:0002240	96.57	gold quality
endothelial cell	CL:0000115	96.37	gold quality
endometrium	UBERON:0001295	96.09	gold quality
cranial nerve II	UBERON:0000941	96.08	gold quality
amniotic fluid	UBERON:0000173	96.02	gold quality
amygdala	UBERON:0001876	96.02	gold quality
cerebellar vermis	UBERON:0004720	95.91	gold quality
germinal epithelium of ovary	UBERON:0001304	95.87	gold quality
lateral globus pallidus	UBERON:0002476	95.84	gold quality
Brodmann (1909) area 23	UBERON:0013554	95.78	gold quality
middle temporal gyrus	UBERON:0002771	95.76	gold quality
pons	UBERON:0000988	95.71	gold quality
nucleus accumbens	UBERON:0001882	95.71	gold quality
caudate nucleus	UBERON:0001873	95.70	gold quality
tendon	UBERON:0000043	95.68	gold quality
cingulate cortex	UBERON:0003027	95.61	gold quality
anterior cingulate cortex	UBERON:0009835	95.58	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.52	gold quality
hypothalamus	UBERON:0001898	95.50	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	21.48
E-ANND-3	yes	7.97

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
AFP
FOXP3

Upstream regulators (CollecTRI, top): AR, DNMT1, ZKSCAN7

miRNA regulators (miRDB)

80 targeting CBX1, 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-6867-5P	100.00	82.21	3464
HSA-MIR-4455	100.00	65.48	1587
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-6793-5P	99.97	65.95	758
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-4697-3P	99.89	67.09	1123
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-3941	99.86	70.54	2735
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-5010-3P	99.83	70.60	2357
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-6515-3P	99.82	68.19	1933
HSA-MIR-205-5P	99.81	70.05	1557
HSA-MIR-139-5P	99.80	69.50	1399
HSA-MIR-4713-5P	99.78	67.80	1794
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-548A-3P	99.76	70.58	3524

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 16.2% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 33)

• Isoform-specific interaction of HP1 with human TAFII130. (PMID:11959914)
• Gene regulation by human orthologs of Drosophila heterochromatin protein 1. (PMID:12054505)
• the chromodomain and the chromoshadow domain of HP1 are both required for binding to native chromatin in vivo, but they contribute differentially to binding in euchromatin and heterochromatin (PMID:12560555)
• cells are exquisitely sensitive to the amount of HP1(Hsalpha) or HP1(Hsbeta) present, as their overexpression influences telomere stability, population doubling time, radioresistance, and tumorigenicity (PMID:14585993)
• HP1beta recruits endogenous HP1alpha to the chromatin and this induces heterochromatin formation and enhanced histone lysine methylation. (PMID:15899859)
• analysis of methylation-independent binding to histone H3 and cell cycle-dependent incorporation of HP1beta into heterochromatin (PMID:16547356)
• HP1 binding as analyzed through the crystal structure of the HP1-EMSY complex (PMID:16615912)
• Overexpression of HP1-BETA in eye imaginal discs caused abnormally patterned eyes, with reduced numbers of ommatidia. (PMID:17575412)
• HP1 recruitment-release is a sequential mechanism that is precisely regulated and highly dependent on transcription. (PMID:18239689)
• findings reveal an unrecognized signalling cascade that helps to initiate the DNA damage response, altering chromatin by modifying a histone-code mediator protein, HP1, but not the code itself (PMID:18438399)
• when HP1beta was co-expressed with TIF1beta/S473A, but not TIF1beta/S473E, the colocalization of TIF1beta/S473A and HP1beta to the promoters of Cdc2 and Cdc25A was enhanced. (PMID:18590578)
• a nonconventional interaction between HP1 and a tissue-specific transcription factor, MyoD. In addition, they strongly suggest that HP1 isoforms play important roles during muscle terminal differentiation in an isoform-dependent manner. (PMID:18599480)
• HP1beta is involved in the proliferation of AR-expressing prostate cancer cells and progression to CRPC as an AR coactivator. (PMID:20308360)
• Mislocalized lamins can induce ubiquitin-mediated proteasomal degradation of certain HP1 isoforms by activation of FBXW10, a member of the F-box family of proteins that is involved in E3 ubiquitin ligase activity. (PMID:20498703)
• Abrogating GRP/GRPR signaling specifically down-regulates HP1(Hsbeta) expression and inhibiting GRPR signaling, or ablating HP1(Hsbeta) expression, increases colon cancer cell invasiveness in vitro. (PMID:21281799)
• HP1 beta and PCNA, a key player in DNA replication, are closely spaced components of a multiprotein complex involved in replication, both in S phase and during DNA repair, and that the functional complex requires formation of an HP1 dimer. (PMID:22617335)
• a novel mechanism of KAP-1-mediated chromatin restructuring via Chk2-regulated HP1-beta exchange from heterochromatin, promoting DNA repair. (PMID:22715096)
• Methylation of lysine 9 in histone H3 directs alternative modes of highly dynamic interaction of heterochromatin protein hHP1beta with the nucleosome (PMID:22815475)
• study finds that while HP1apha and beta stimulate homologous recombination and single-strand annealing, HP1gamma has an inhibitory role (PMID:23287531)
• HP1beta which is associated with PCNA in regions of DNA repair, is bound and does not exchange with the mobile pool, suggesting that HP1beta in association with PCNA may be a component of a DNA repair complex. (PMID:23337132)
• HP1 isoforms distinctly augment AR signaling and cell growth in prostate cancer. Therefore, silencing of HP1beta and HP1gamma may be a promising therapeutic strategy for treatment of prostate cancer. (PMID:23536649)
• The structural plasticity of HP1beta supports its ability to bind and connect a wide variety of binding partners in epigenetic processes. (PMID:23585859)
• The HP1beta interactome is enriched with Lys methylated proteins.Role of HP1beta in DNA damage response. (PMID:23707759)
• Phosphorylation at Ser89 and Ser175 results in localized conformational changes in HP1beta that do not compromise the ability of the protein to bind chromatin. (PMID:24561199)
• In this review, we summarize the current knowledge about targeting and functional mechanisms of PRCs, emphasizing the recent breakthroughs related to CBX proteins under a number of physiological and pathological conditions. (PMID:24793759)
• Data suggest the reduction of Heterochromatin Protein 1 isoforms HP1beta followed by a decrease in HP1alpha contributes to the pathogenesis of thyroid carcinomas, and their loss is a potential marker of thyroid malignancy and metastatic potential, respectively. (PMID:24840329)
• increased HP1beta expression is associated with the poor prognosis in breast cancer (PMID:25769025)
• Data show that heterochromatin protein 1-beta (HP1beta) is a prototypic HP1 protein exemplifying most basal chromatin binding and effects. (PMID:27090491)
• the prolyl residue of the PXXVXL motif appears to play a role distinct from that of Pro in the known HP1beta CSD-PXVXL complexes. (PMID:28223359)
• The gamma-irradiation-induced hyperphosphorylation of the HP1beta protein; thus, HP1beta-S88ph could be considered as an important marker of DNA damage. (PMID:31533340)
• Beyond the Nucleosome: Nucleosome-Protein Interactions and Higher Order Chromatin Structure. (PMID:33460684)
• HP1 proteins compact DNA into mechanically and positionally stable phase separated domains. (PMID:33661100)
• N[6] -Methyladenosine-Modified CBX1 Regulates Nasopharyngeal Carcinoma Progression Through Heterochromatin Formation and STAT1 Activation. (PMID:36310139)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cbx1a	ENSDARG00000004189
danio_rerio	cbx1b	ENSDARG00000054442
mus_musculus	Cbx1	ENSMUSG00000018666
rattus_norvegicus	Cbx1	ENSRNOG00000008689
drosophila_melanogaster	Su(var)205	FBGN0003607
caenorhabditis_elegans		WBGENE00001995
caenorhabditis_elegans		WBGENE00007615

Paralogs (8): CBX5 (ENSG00000094916), CBX7 (ENSG00000100307), CBX3 (ENSG00000122565), CBX8 (ENSG00000141570), CBX4 (ENSG00000141582), CBX2 (ENSG00000173894), CBX6 (ENSG00000183741), NPTXR (ENSG00000221890)

Protein

Protein identifiers

Chromobox protein homolog 1 — P83916 (reviewed: P83916)

Alternative names: HP1Hsbeta, Heterochromatin protein 1 homolog beta, Heterochromatin protein p25, M31, Modifier 1 protein, p25beta

All UniProt accessions (6): P83916, B5MD17, C9JWS9, J3KS05, K7ELA4, Q6IBN6

UniProt curated annotations — full annotation on UniProt →

Function. Component of heterochromatin, which recognizes and binds histone H3 tails methylated at ‘Lys-9’, leading to epigenetic repression. Also recognizes and binds histone H1.4 methylated at ‘Lys-26’ (H1.4K26me). Excluded from chromatin when histone H1.4 is Simultaneously methylated at Lys-26 (H1.4K26me) and phosphorylated at Ser-27 (H1.4S27Ph). Interaction with lamin B receptor (LBR) can contribute to the association of the heterochromatin with the inner nuclear membrane.

Subunit / interactions. Homodimer. Interacts directly with CHAF1A, EMSY, LBR, TIF1/TIF1A and TRIM28/TIF1B PXVXL motif via the chromoshadow domain. Interacts directly with histone H3 methylated at ‘Lys-9’ via the chromo domain. Interacts with SUV39H1 and SETDB1, KMT5B and KMT5C. Interacts with PRDM6. Interacts with POGZ. Interacts with CHAMP1. Interacts with INCENP. Interacts with SGO1; the CBX1 homodimer binds to one molecule of SGO1. Interacts with LRIF1 (via PxVxL motif). Interacts with HDGFL2. Interacts with CHD3. Interacts with CHD4.

Subcellular location. Nucleus.

Tissue specificity. Expressed in all adult and embryonic tissues.

Post-translational modifications. Not phosphorylated. Ubiquitinated.

RefSeq proteins (2): NP_001120700, NP_006798 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR008251	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
IPR051219	Heterochromatin_chromo-domain	Family

Pfam: PF00385, PF01393

UniProt features (43 total): site 16, strand 7, helix 6, cross-link 4, modified residue 3, domain 2, compositionally biased region 2, chain 1, mutagenesis site 1, region of interest 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
2FMM	X-RAY DIFFRACTION	1.8
3F2U	X-RAY DIFFRACTION	1.8
5T1G	X-RAY DIFFRACTION	1.9
3Q6S	X-RAY DIFFRACTION	1.93
6D07	X-RAY DIFFRACTION	2.1
6D08	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P83916-F1	76.46	0.37

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (16): 42 (histone h3a7 binding); 42 (histone h3k9me2 binding); 45 (histone h3k9me2 binding); 58 (histone h3a7 binding); 60 (histone h3a7 binding); 125 (interacts with the pxvxl motif of trim28/tif1b); 126 (interacts with the pxvxl motif of trim28/tif1b); 135 (interacts with the pxvxl motif of trim28/tif1b); 146 (interacts with the pxvxl motif of trim28/tif1b); 167 (interacts with the pxvxl motif of trim28/tif1b); 168 (interacts with the pxvxl motif of trim28/tif1b); 170 (interacts with the pxvxl motif of trim28/tif1b) …

Post-translational modifications (7): 89, 91, 175, 9, 33, 99, 150

Mutagenesis-validated functional residues (1):

Position	Phenotype
161	abolishes homodimer formation and binding to emsy.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9609690	HCMV Early Events
R-HSA-9940465	ChAHP complex assembly
R-HSA-1643685	Disease
R-HSA-5663205	Infectious disease
R-HSA-9609646	HCMV Infection
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 203 (showing top): MODULE_52, FLECHNER_PBL_KIDNEY_TRANSPLANT_REJECTED_VS_OK_UP, XU_GH1_AUTOCRINE_TARGETS_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, THEILGAARD_NEUTROPHIL_AT_SKIN_WOUND_DN, PATIL_LIVER_CANCER, OUELLET_OVARIAN_CANCER_INVASIVE_VS_LMP_UP, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, MODULE_206, GOBP_DNA_DAMAGE_RESPONSE, GOTZMANN_EPITHELIAL_TO_MESENCHYMAL_TRANSITION_DN, BOYAULT_LIVER_CANCER_SUBCLASS_G123_UP

GO Biological Process (3): DNA damage response (GO:0006974), heterochromatin formation (GO:0031507), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): chromatin binding (GO:0003682), enzyme binding (GO:0019899), identical protein binding (GO:0042802), histone H1K26me1 reader activity (GO:0160267), histone H1K26me2 reader activity (GO:0160268), histone methyltransferase binding (GO:1990226), protein binding (GO:0005515)

GO Cellular Component (13): chromosome, centromeric region (GO:0000775), chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), heterochromatin (GO:0000792), female pronucleus (GO:0001939), male pronucleus (GO:0001940), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), spindle (GO:0005819), chromocenter (GO:0010369), nuclear body (GO:0016604), site of DNA damage (GO:0090734)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
HCMV Infection	1
CHD3, CHD4, CHD5 subfamily	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	3
binding	2
protein binding	2
histone H1 reader activity	2
chromosomal region	2
chromosome	2
pronucleus	2
cellular response to stress	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
enzyme binding	1
chromatin	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
microtubule cytoskeleton	1
nucleoplasm	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

187 interactions, top by confidence:

A	B	Type	Score
CBX1	H3C1	psi-mi:“MI:0915”(physical association)	0.830
CBX1	H3C1	psi-mi:“MI:0407”(direct interaction)	0.830
ADNP2	CBX1	psi-mi:“MI:0915”(physical association)	0.820
CHD4	CBX1	psi-mi:“MI:0914”(association)	0.790
PRR14	PPP2R1A	psi-mi:“MI:0914”(association)	0.790
POGZ	CBX5	psi-mi:“MI:0914”(association)	0.780
CBX1	ADNP	psi-mi:“MI:0915”(physical association)	0.770
CBX1	ZNF280C	psi-mi:“MI:0915”(physical association)	0.740
SUV39H1	CBX1	psi-mi:“MI:0915”(physical association)	0.740
RYBP	E2F6	psi-mi:“MI:0914”(association)	0.740
L3MBTL2	E2F6	psi-mi:“MI:0914”(association)	0.730
LRIF1	SMCHD1	psi-mi:“MI:0914”(association)	0.680
UCHL1	CBX1	psi-mi:“MI:0915”(physical association)	0.670
PCGF6	CBX4	psi-mi:“MI:0914”(association)	0.640
CBX3	E2F6	psi-mi:“MI:0914”(association)	0.640
YAF2	E2F6	psi-mi:“MI:0914”(association)	0.640
CBX1	EMSY	psi-mi:“MI:0407”(direct interaction)	0.620

BioGRID (493): CBX1 (Affinity Capture-Western), CBX1 (Protein-peptide), ZNF280D (Affinity Capture-MS), ADNP (Affinity Capture-MS), AHDC1 (Affinity Capture-MS), CHD4 (Affinity Capture-MS), POGZ (Affinity Capture-MS), CHAMP1 (Affinity Capture-MS), THRAP3 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX1 (Affinity Capture-MS), CBX1 (Two-hybrid)

ESM2 similar proteins: A0A286Y9D1, C8VBH4, F4IV99, G5EDE2, G5EET5, J9VQZ0, J9VW97, O13736, O14026, O94880, O97159, P05205, P0CP02, P0CP03, P23198, P29227, P40381, P45968, P45973, P83916, P83917, Q01491, Q10175, Q10251, Q10267, Q13185, Q19972, Q1DU03, Q1MTR4, Q2H988, Q2UTN6, Q4IB50, Q4P3S3, Q4WTT2, Q5ASA5, Q5R6X7, Q61686, Q6C5G5, Q6C9M9, Q6CND0

Diamond homologs: A0A0P0VUY4, G3V8T1, O60016, O95931, P05205, P23198, P29227, P30658, P45968, P45973, P60889, P83916, P83917, Q10103, Q13185, Q14781, Q3TYA6, Q5F3W5, Q5KQL9, Q5R6X7, Q61686, Q6AYK9, Q8N8U2, Q8VDS3, Q94F87, Q99549, Q9AXT8, Q9D5D8, Q9WTK2, Q9Y232, Q9Y6F7, Q9Y6F8, G5EDE2, G5EET5, O43463, O54864, O95503, Q2NL30, Q339W7, Q5RB81

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
CSNK2A1	down-regulates	CBX1	phosphorylation
EMSY	“up-regulates activity”	CBX1	binding
CBX1	“up-regulates activity”	H3-3A	binding
CBX1	“up-regulates activity”	H3-4	binding
CBX1	“up-regulates activity”	H3C1	binding
CBX1	“up-regulates activity”	“Histone H3”	binding
RNF123	“down-regulates quantity by destabilization”	CBX1	polyubiquitination
CBX1	“form complex”	ChAHP	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 133 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
Transcriptional Regulation by E2F6	9	27.7×	1e-08
RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known	6	19.0×	1e-04
ChAHP complex assembly	6	11.6×	1e-03
SUMO E3 ligases SUMOylate target proteins	6	11.3×	1e-03
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	7	10.8×	4e-04
Amplification of signal from the kinetochores	5	10.4×	5e-03
SUMOylation	6	10.3×	2e-03
PKMTs methylate histone lysines	6	10.2×	2e-03

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	11	22.6×	6e-10
chromatin remodeling	15	8.8×	4e-08
chromatin organization	10	8.0×	1e-04
negative regulation of gene expression	11	6.1×	3e-04
DNA repair	10	5.2×	2e-03

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	1
Uncertain significance	12
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
2506553	GRCh37/hg19 17q21.32(chr17:44949883-46507482)	Likely pathogenic

SpliceAI

1005 predictions. Top by Δscore:

Variant	Effect	Δscore
17:48071575:TTTTC:T	acceptor_gain	1.0000
17:48071576:TTTC:T	acceptor_gain	1.0000
17:48071576:TTTCC:T	acceptor_loss	1.0000
17:48071577:TTC:T	acceptor_gain	1.0000
17:48071578:TC:T	acceptor_gain	1.0000
17:48071579:CC:C	acceptor_gain	1.0000
17:48071580:C:CC	acceptor_gain	1.0000
17:48071580:C:CG	acceptor_loss	1.0000
17:48071581:T:G	acceptor_loss	1.0000
17:48075001:CTCA:C	donor_loss	1.0000
17:48075002:TCACC:T	donor_loss	1.0000
17:48075003:CACCA:C	donor_loss	1.0000
17:48075004:A:T	donor_loss	1.0000
17:48075005:C:CA	donor_loss	1.0000
17:48075097:CTGA:C	acceptor_gain	1.0000
17:48075098:TGA:T	acceptor_gain	1.0000
17:48075098:TGAC:T	acceptor_loss	1.0000
17:48075099:GA:G	acceptor_gain	1.0000
17:48075101:C:CC	acceptor_gain	1.0000
17:48075103:G:C	acceptor_gain	1.0000
17:48075103:G:GC	acceptor_gain	1.0000
17:48075997:TTA:T	donor_loss	1.0000
17:48075999:A:AC	donor_gain	1.0000
17:48076000:C:CC	donor_gain	1.0000
17:48076000:CCT:C	donor_gain	1.0000
17:48076174:CCTCA:C	acceptor_gain	1.0000
17:48076175:CTCA:C	acceptor_gain	1.0000
17:48076175:CTCAC:C	acceptor_gain	1.0000
17:48076176:TCA:T	acceptor_gain	1.0000
17:48076176:TCAC:T	acceptor_gain	1.0000

AlphaMissense

1220 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:48071483:C:A	W170C	1.000
17:48071483:C:G	W170C	1.000
17:48071484:C:A	W170L	1.000
17:48071484:C:G	W170S	1.000
17:48071485:A:G	W170R	1.000
17:48071485:A:T	W170R	1.000
17:48071490:A:C	L168R	1.000
17:48071490:A:G	L168P	1.000
17:48071490:A:T	L168Q	1.000
17:48071492:C:A	R167S	1.000
17:48071492:C:G	R167S	1.000
17:48071493:C:A	R167M	1.000
17:48071493:C:G	R167T	1.000
17:48071494:T:A	R167W	1.000
17:48071494:T:C	R167G	1.000
17:48071496:T:A	E166V	1.000
17:48071498:C:A	E165D	1.000
17:48071498:C:G	E165D	1.000
17:48071499:T:A	E165V	1.000
17:48071500:C:T	E165K	1.000
17:48071502:T:C	Y164C	1.000
17:48071503:A:C	Y164D	1.000
17:48071503:A:G	Y164H	1.000
17:48071503:A:T	Y164N	1.000
17:48071504:G:C	F163L	1.000
17:48071504:G:T	F163L	1.000
17:48071505:A:C	F163C	1.000
17:48071505:A:G	F163S	1.000
17:48071506:A:C	F163V	1.000
17:48071506:A:G	F163L	1.000

dbSNP variants (sampled 300 via entrez): RS1000041252 (17:48102266 G>A), RS1000050851 (17:48084594 G>A), RS1000113924 (17:48085009 T>C), RS1000249796 (17:48101230 C>T), RS1000351057 (17:48071729 C>A), RS1000400724 (17:48084801 T>C), RS1000535905 (17:48102323 C>A,T), RS1000588413 (17:48101994 G>A), RS1000688689 (17:48070575 A>G), RS1000807075 (17:48069685 A>G), RS1000988277 (17:48090487 A>G), RS1001083293 (17:48073138 A>C), RS1001124438 (17:48084494 C>A), RS1001151122 (17:48096609 T>A,C), RS1001158154 (17:48090307 T>C)

Disease associations

OMIM: gene MIM:604511 | disease phenotypes:

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Moderate	Autosomal dominant

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

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST000830_28	Body mass index	4.000000e-07
GCST001662_4	Generalized epilepsy	9.000000e-09
GCST005951_17	Body mass index	3.000000e-09
GCST011125_9	Caffeine consumption from coffee	9.000000e-12
GCST011126_30	Caffeine consumption from coffee or tea	3.000000e-13
GCST90011899_113	Aspartate aminotransferase levels	9.000000e-10

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0006781	coffee consumption measurement
EFO:0010091	tea consumption measurement
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1741193 (SINGLE PROTEIN)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.76	Kd	1750	nM	CHEMBL4647581
5.60	Kd	2500	nM	CHEMBL4646516
5.50	Kd	3200	nM	CHEMBL4635096
5.32	Kd	4750	nM	CHEMBL3780251
5.26	Kd	5500	nM	CHEMBL3780251

PubChem BioAssay actives

5 with measured affinity, of 21 total; 4 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-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	1650074: Binding affinity to CBX1 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	1.7500	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	1650074: Binding affinity to CBX1 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	2.5000	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	1650074: Binding affinity to CBX1 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	3.2000	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	1650074: Binding affinity to CBX1 (unknown origin) assessed as dissociation constant by fluorescence polarization analysis	kd	4.7500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
bisphenol S	affects cotreatment, decreases methylation, decreases expression	2
Fulvestrant	affects cotreatment, decreases methylation, decreases expression	2
Estradiol	increases expression, decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Tretinoin	decreases expression	2
Particulate Matter	decreases expression, decreases reaction, increases abundance	2
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	affects expression	1
afimoxifene	decreases expression	1
aflatoxin B2	decreases methylation	1
beta-methylcholine	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
abrine	decreases expression	1
Grape Seed Proanthocyanidins	increases expression, affects cotreatment	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases expression, decreases reaction	1
dorsomorphin	affects cotreatment, decreases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Troglitazone	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Vehicle Emissions	decreases expression, decreases reaction	1

ChEMBL screening assays

7 unique, capped per target: 5 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1738610	Functional	PUBCHEM_BIOASSAY: qHTS Validation Assay for Inhibitors of HP1-beta Chromodomain Interactions with Methylated Histone Tails. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID488962]	PubChem BioAssay data set
CHEMBL3242419	Binding	Binding affinity to CBX1 (unknown origin) by isothermal titration calorimetry assay	Chromodomain antagonists that target the polycomb-group methyllysine reader protein chromobox homolog 7 (CBX7). — J Med Chem

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2TK	Abcam HEK293T CBX1 KO	Transformed cell line	Female
CVCL_SH06	HAP1 CBX1 (-) 1	Cancer cell line	Male
CVCL_SH07	HAP1 CBX1 (-) 2	Cancer cell line	Male
CVCL_SH08	HAP1 CBX1 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants
NCT02003170	Not specified	COMPLETED	Etiology and Early Diagnosis of Neurodevelopmental Disorders
NCT02118649	Not specified	ACTIVE_NOT_RECRUITING	Enhancing Behavior and Brain Response to Visual Targets Using a Computer Game
NCT02557191	Not specified	TERMINATED	Biomarkers, Neurodevelopment and Preterm Infants
NCT02690675	Not specified	COMPLETED	Iron Supplement Effect on Child Development
NCT02694003	Not specified	COMPLETED	Better Nights, Better Days for Children With Neurodevelopment Disorders
NCT02792894	Not specified	COMPLETED	Family Networks (FaNs) for Children With Developmental Disorders and Delays
NCT02871674	Not specified	UNKNOWN	Good Night Project: Behavioural Sleep Interventions for Children With ADHD: A Randomised Controlled Trial
NCT02887157	Not specified	COMPLETED	Analyzing Retinal Microanatomy in ROP
NCT02898298	Not specified	COMPLETED	Positive Emotion Regulation Training in Children, Adolescents and Young Adults With and Without Developmental Disorder
NCT02912780	Not specified	UNKNOWN	Introduction of Microsystems in a Level 3 Neonatal Intensive Care Unit
NCT03023293	Not specified	COMPLETED	n-3 PUFAs, Irisin and Maternal Glucose Metabolism From Pregnancy to Postpartum
NCT03023644	Not specified	COMPLETED	Improving Neurodevelopmental Outcomes in Children With Congenital Heart Disease: An Intervention Study
NCT03032991	Not specified	UNKNOWN	Early Biomarkers of Neurodevelopment in Offspring of Diabetic Mothers
NCT03088189	Not specified	TERMINATED	Effect of Parental Peri-conceptional Vitamin B12 Supplementation on Infant Neurocognitive Development in Offspring
NCT03096028	Not specified	COMPLETED	Developmental Origins of Mental Health Disorders
NCT03148782	Not specified	COMPLETED	Brain Plasticity Underlying Acquisition of New Organizational Skills in Children-R61 Phase
NCT03172104	Not specified	COMPLETED	Neurobehavioural Development of Infants Born <30 Weeks Gestational Age Between Birth and Five Years of Age
NCT03222375	Not specified	RECRUITING	SQUED™ Series 28.1 Home-use and Treatment of Autowave Reverberator of Autism
NCT03229928	Not specified	COMPLETED	Clinical Testing of a Real-Time Behavior Measurement Tool: Measuring Outcomes for CHAnge
NCT03232489	Not specified	UNKNOWN	Study for the Evaluation of the Feasibility of Applying Advanced MRI Scanning in Pediatric Clinical Practice