CDYL

Summary

CDYL (chromodomain Y like, HGNC:1811) is a protein-coding gene on chromosome 6p25.1, encoding Chromodomain Y-like protein (Q9Y232). Chromatin reader protein that recognizes and binds histone H3 trimethylated at ‘Lys-9’, dimethylated at ‘Lys-27’ and trimethylated at ‘Lys-27’ (H3K9me3, H3K27me2 and H3K27me3, respectively).

Chromodomain Y is a primate-specific Y-chromosomal gene family expressed exclusively in the testis and implicated in infertility. Although the Y-linked genes are testis-specific, this autosomal gene is ubiquitously expressed. The Y-linked genes arose by retrotransposition of an mRNA from this gene, followed by amplification of the retroposed gene. Proteins encoded by this gene superfamily possess a chromodomain, a motif implicated in chromatin binding and gene suppression, and a catalytic domain believed to be involved in histone acetylation. Multiple proteins are encoded by transcript variants of this gene.

Source: NCBI Gene 9425 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 81 total
• Druggable target: yes
• MANE Select transcript: NM_004824

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1811
Approved symbol	CDYL
Name	chromodomain Y like
Location	6p25.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZP586C1622, CDYL1
Ensembl gene	ENSG00000153046
Ensembl biotype	protein_coding
OMIM	603778
Entrez	9425

Gene structure

Transcript identifiers

Ensembl transcripts: 15 — 11 protein_coding, 2 protein_coding_CDS_not_defined, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000328908, ENST00000343762, ENST00000397588, ENST00000440139, ENST00000449732, ENST00000469671, ENST00000472453, ENST00000483019, ENST00000491864, ENST00000891794, ENST00000891795, ENST00000911902, ENST00000942154, ENST00000942155, ENST00000942156

RefSeq mRNA: 6 — MANE Select: NM_004824 NM_001143970, NM_001143971, NM_001368125, NM_001368126, NM_001368127, NM_004824

CCDS: CCDS4491, CCDS47364, CCDS93853

Canonical transcript exons

ENST00000397588 — 7 exons

Exon	Start	End
ENSE00001820854	4953898	4955544
ENSE00001825539	4776404	4776807
ENSE00003531869	4943546	4943756
ENSE00003550207	4952266	4952409
ENSE00003587973	4937565	4937737
ENSE00003631402	4935515	4935771
ENSE00003683066	4891713	4892379

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 96.68.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 18.0370 / max 233.9133, expressed in 1807 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65579	16.8284	1805
65576	0.8271	97
65577	0.2684	75
65578	0.0858	46
65582	0.0200	4
65574	0.0072	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.68	gold quality
amniotic fluid	UBERON:0000173	94.45	gold quality
hair follicle	UBERON:0002073	93.69	gold quality
tibia	UBERON:0000979	92.39	gold quality
tendon	UBERON:0000043	91.91	gold quality
placenta	UBERON:0001987	91.68	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.17	gold quality
esophagus squamous epithelium	UBERON:0006920	90.69	gold quality
sural nerve	UBERON:0015488	90.36	gold quality
bone marrow cell	CL:0002092	90.25	gold quality
squamous epithelium	UBERON:0006914	90.17	gold quality
corpus epididymis	UBERON:0004359	89.96	gold quality
metanephric glomerulus	UBERON:0004736	89.92	gold quality
renal glomerulus	UBERON:0000074	89.79	gold quality
secondary oocyte	CL:0000655	89.56	gold quality
colonic epithelium	UBERON:0000397	89.47	gold quality
cervix squamous epithelium	UBERON:0006922	89.16	gold quality
palpebral conjunctiva	UBERON:0001812	89.14	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.06	gold quality
epithelium of esophagus	UBERON:0001976	89.05	gold quality
epithelium of nasopharynx	UBERON:0001951	89.03	gold quality
decidua	UBERON:0002450	88.99	gold quality
cartilage tissue	UBERON:0002418	88.87	gold quality
visceral pleura	UBERON:0002401	88.74	gold quality
gingival epithelium	UBERON:0001949	88.66	gold quality
middle temporal gyrus	UBERON:0002771	88.30	gold quality
mucosa of sigmoid colon	UBERON:0004993	87.33	gold quality
tongue squamous epithelium	UBERON:0006919	87.31	gold quality
corpus callosum	UBERON:0002336	87.24	gold quality
bone marrow	UBERON:0002371	87.24	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.90

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

122 targeting CDYL, 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-3163	100.00	77.23	8605
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
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-5692A	100.00	74.40	6850
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-4803	99.98	71.99	3117
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548AN	99.97	70.91	2817
HSA-MIR-1229-3P	99.97	66.49	906
HSA-MIR-548AJ-3P	99.96	73.38	5345

Literature-anchored findings (GeneRIF, showing 16)

• Chromodomain on Y-like (CDYL) is identified as a REST corepressor that physically bridges REST and the histone methylase G9a to repress transcription. (PMID:19061646)
• Results imply that multimeric binding to H3K9me3 by CDYL1b homomeric complexes is essential for efficient chromatin targeting. (PMID:19808672)
• CDYL functions as a molecular bridge between PRC2 and the repressive chromatin mark H3K27me3, forming a positive feedback loop to facilitate the establishment and propagation of H3K27me3 modifications along the chromatin (PMID:22009739)
• These findings suggest that h-CDYLb and G9a are cooperatively involved in hepatocellular carcinomas (PMID:23629948)
• The epigenetic regulators CDYL and EZH2 to dendrite morphogenesis and might shed new light on our understanding of the regulation of the neurodevelopment. (PMID:24671995)
• CDYL plays an important role in the maintenance of repressive histone marks during replication, providing a mechanism for understanding of the epigenetic inheritance and memory. (PMID:28402439)
• CDYL negatively regulates histone crotonylation by acting as a crotonyl-CoA hydratase to convert crotonyl-CoA to beta-hydroxybutyryl-CoA and suggest role in spermatogenesis. (PMID:28803779)
• CDYL1 promotes the recruitment of enhancer of zeste homolog 2 (EZH2), stimulates local increase of the repressive methyl mark H3K27me3, and promotes transcription silencing at double-strand break sites. (PMID:29177481)
• This study demonstrated that CDYL is the most likely candidate gene for responsiveness to ketogenic dietary therapies for drug-resistant epilepsy. (PMID:30009487)
• CDYL promotes the chemoresistance of small cell lung cancer by regulating H3K27 trimethylation at the CDKN1C promoter. (PMID:31367252)
• circCDYL overexpression repressed cellular growth and migration via repressing miR-150-5p in colon cancer cells (PMID:31829306)
• circCDYL Acts as a Tumor Suppressor in Triple Negative Breast Cancer by Sponging miR-190a-3p and Upregulating TP53INP1. (PMID:32741666)
• Hypoxia-induced circ-CDYL-EEF1A2 transcriptional complex drives lung metastasis of cancer stem cells from hepatocellular carcinoma. (PMID:37852428)
• Emerging functions and significance of circCDYL in human disorders. (PMID:38085365)
• Interaction between Chromodomain Y-like Protein and Androgen Receptor Signaling in Sertoli Cells Accounts for Spermatogenesis. (PMID:38786072)
• The chromodomain protein CDYL confers forebrain identity to human cortical organoids by inhibiting neuronatin. (PMID:39378153)

Cross-species orthologs

10 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdyl	ENSDARG00000038985
drosophila_melanogaster	CG14787	FBGN0027793
drosophila_melanogaster	CG8778	FBGN0033761
drosophila_melanogaster	Dci	FBGN0035169
drosophila_melanogaster	HIPP1	FBGN0037027
drosophila_melanogaster	Srlp	FBGN0038049
drosophila_melanogaster	CG5611	FBGN0039531
caenorhabditis_elegans		WBGENE00001152
caenorhabditis_elegans		WBGENE00001154
caenorhabditis_elegans		WBGENE00007130

Paralogs (13): ECHDC1 (ENSG00000093144), ECH1 (ENSG00000104823), ECHDC2 (ENSG00000121310), ECHS1 (ENSG00000127884), CDY2B (ENSG00000129873), ECHDC3 (ENSG00000134463), AUH (ENSG00000148090), CDYL2 (ENSG00000166446), ECI1 (ENSG00000167969), CDY1 (ENSG00000172288), CDY1B (ENSG00000172352), CDY2A (ENSG00000182415), HIBCH (ENSG00000198130)

Protein

Protein identifiers

Chromodomain Y-like protein — Q9Y232 (reviewed: Q9Y232)

Alternative names: Crotonyl-CoA hydratase

All UniProt accessions (3): Q9Y232, A0A669KAZ7, C9JQG7

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader protein that recognizes and binds histone H3 trimethylated at ‘Lys-9’, dimethylated at ‘Lys-27’ and trimethylated at ‘Lys-27’ (H3K9me3, H3K27me2 and H3K27me3, respectively). Part of multimeric repressive chromatin complexes, where it is required for transmission and restoration of repressive histone marks, thereby preserving the epigenetic landscape. Required for chromatin targeting and maximal enzymatic activity of Polycomb repressive complex 2 (PRC2); acts as a positive regulator of PRC2 activity by bridging the pre-existing histone H3K27me3 and newly recruited PRC2 on neighboring nucleosomes. Acts as a corepressor for REST by facilitating histone-lysine N-methyltransferase EHMT2 recruitment and H3K9 dimethylation at REST target genes for repression. Involved in X chromosome inactivation in females: recruited to Xist RNA-coated X chromosome and facilitates propagation of H3K9me2 by anchoring EHMT2. Promotes EZH2 accumulation and H3K27me3 methylation at DNA double strand breaks (DSBs), thereby facilitating transcriptional repression at sites of DNA damage and homology-directed repair of DSBs. Required for neuronal migration during brain development by repressing expression of RHOA. By repressing the expression of SCN8A, contributes to the inhibition of intrinsic neuronal excitability and epileptogenesis. In addition to acting as a chromatin reader, acts as a hydro-lyase. Shows crotonyl-coA hydratase activity by mediating the conversion of crotonyl-CoA ((2E)-butenoyl-CoA) to beta-hydroxybutyryl-CoA (3-hydroxybutanoyl-CoA), thereby acting as a negative regulator of histone crotonylation. Histone crotonylation is required during spermatogenesis; down-regulation of histone crotonylation by CDYL regulates the reactivation of sex chromosome-linked genes in round spermatids and histone replacement in elongating spermatids. By regulating histone crotonylation and trimethylation of H3K27, may be involved in stress-induced depression-like behaviors, possibly by regulating VGF expression. Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the presence of a N-terminal extension that inactivates the chromo domain. Not able to recognize and bind histone H3K9me3, histone H3K27me2 and histone H3K27me3, due to the absence of the chromo domain. Acts as a negative regulator of isoform 2 by displacing isoform 2 from chromatin.

Subunit / interactions. Forms multimers and multimerization is required for stable binding to chromatin. Interacts with HDAC1 and HDAC2 via its C-terminal acetyl-CoA-binding domain. Interacts with EZH2, EED, SUZ12, REST, EHMT1 and EHMT2. Part of a complex containing at least CDYL, REST, WIZ, SETB1, EHMT1 and EHMT2. Part of a complex containing at least CDYL, MIER1, MIER2, HDAC1 and HDAC2. Interacts with CHAF1A and CHAF1B; bridging the CAF-1 complex to the MCM2-7 (MCM) complex. Interacts with MCM3 and MCM5; bridging the CAF-1 complex to the MCM2-7 (MCM) complex. Recruited to Xist RNA-coated X chromosome. Interacts with EHMT2 and PRDM9; interaction only takes place when PRDM9 is bound to hotspot DNA.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in the hippocampus with reduced expression in epileptic tissue compared to normal adjacent tissue (at protein level). Ubiquitous. Expressed at moderate levels in all tissues examined. Isoform 2: Most abundantly expressed isoform.

Domain organisation. The chromo domain recognizes and binds histone H3K9me3, histone H3K27me2 and histone H3K27me3. The acetyl-CoA-binding domain mediates crotonyl-coA hydratase activity. The acetyl-CoA-binding domain is required for recruitment to sites of DNA double strand breaks and for binding to poly (ADP ribose) moieties.

Miscellaneous. Major isoform.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y232-1	1, a, CDYL1a	yes
Q9Y232-2	2, b, CDYL1b
Q9Y232-3	3, c, CDYL1c
Q9Y232-4	4

RefSeq proteins (6): NP_001137442, NP_001137443, NP_001355054, NP_001355055, NP_001355056, NP_004815* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000953	Chromo/chromo_shadow_dom	Domain
IPR001753	Enoyl-CoA_hydra/iso	Domain
IPR014748	Enoyl-CoA_hydra_C	Homologous_superfamily
IPR016197	Chromo-like_dom_sf	Homologous_superfamily
IPR023779	Chromodomain_CS	Conserved_site
IPR023780	Chromo_domain	Domain
IPR029045	ClpP/crotonase-like_dom_sf	Homologous_superfamily
IPR051053	ECH/Chromodomain_protein	Family

Pfam: PF00378, PF00385

Enzyme classification (BRENDA):

• EC 4.2.1.150 — short-chain-enoyl-CoA hydratase (BRENDA: 8 organisms, 14 substrates, 4 inhibitors, 14 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

3 substrates with measured Km, best-characterized 3. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
CROTONYL-COA	0.03–0.45	8
(S)-3-HYDROXYBUTYRYL-COA	0.034–1.31	3
HEXENOYL-COA	0.13	2

Catalyzed reactions (Rhea), 1 shown:

• 3-hydroxybutanoyl-CoA = (2E)-butenoyl-CoA + H2O (RHEA:45584)

UniProt features (64 total): helix 15, strand 11, modified residue 7, sequence conflict 6, region of interest 5, compositionally biased region 4, splice variant 4, sequence variant 4, turn 4, mutagenesis site 2, chain 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
7N27	X-RAY DIFFRACTION	1.85
2GTR	X-RAY DIFFRACTION	1.9
2DNT	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y232-F1	68.33	0.42

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 (7): 88, 135, 135, 135, 170, 201, 216

Mutagenesis-validated functional residues (2):

Position	Phenotype
205	no impact on recruitment to dna double strand breaks.
521	abolishes coa-binding and ability to inhibit histone crotonylation.

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 264 (showing top): BEGUM_TARGETS_OF_PAX3_FOXO1_FUSION_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, ACTACCT_MIR196A_MIR196B, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GOBP_MALE_GAMETE_GENERATION, chr6p25, IRF7_01, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, DOANE_RESPONSE_TO_ANDROGEN_DN, AML_Q6, DACOSTA_UV_RESPONSE_VIA_ERCC3_COMMON_DN, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS

GO Biological Process (6): spermatogenesis (GO:0007283), spermatid development (GO:0007286), random inactivation of X chromosome (GO:0060816), negative regulation of peptidyl-lysine crotonylation (GO:0120094), cell differentiation (GO:0030154), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), (2E)-butenoyl-CoA hydratase activity (GO:0120092), protein binding (GO:0005515), lyase activity (GO:0016829)

GO Cellular Component (5): nucleus (GO:0005634), chromosome (GO:0005694), cytoplasm (GO:0005737), nuclear speck (GO:0016607), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	2
protein binding	2
cellular anatomical structure	2
developmental process involved in reproduction	1
male gamete generation	1
germ cell development	1
spermatid differentiation	1
dosage compensation by inactivation of X chromosome	1
negative regulation of protein modification process	1
regulation of peptidyl-lysine crotonylation	1
peptidyl-lysine crotonylation	1
cellular developmental process	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
transcription coregulator activity	1
negative regulation of DNA-templated transcription	1
molecular adaptor activity	1
3-hydroxyacyl-CoA dehydratase activity	1
catalytic activity	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1

Protein interactions and networks

STRING

3286 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDYL	EHMT2	Q96KQ7	979
CDYL	EHMT1	Q9H9B1	894
CDYL	EZH2	Q15910	847
CDYL	SETDB1	Q15047	783
CDYL	WIZ	O95785	773
CDYL	RCOR1	Q9UKL0	761
CDYL	VCY	O14598	698
CDYL	HIF1AN	Q9NWT6	695
CDYL	MIER1	Q8N108	660
CDYL	PRDM9	Q9NQV7	642
CDYL	HDGF	P51858	634
CDYL	HDAC1	Q13547	617
CDYL	KDM1A	O60341	598
CDYL	DAZ1	Q9NQZ3	565
CDYL	NTRK3	Q16288	553

IntAct

80 interactions, top by confidence:

A	B	Type	Score
HDAC2	KDM1A	psi-mi:“MI:0914”(association)	0.890
HDAC1	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
H2AZ1	ZNHIT1	psi-mi:“MI:0914”(association)	0.770
EHMT2	WIZ	psi-mi:“MI:0914”(association)	0.730
HDAC1	ZNF609	psi-mi:“MI:0914”(association)	0.730
MAD2L1	INSR	psi-mi:“MI:0914”(association)	0.700
H2AC4	PPM1G	psi-mi:“MI:0914”(association)	0.670
EFNB3	DENND11	psi-mi:“MI:0914”(association)	0.640
FAM136A	RBFOX3	psi-mi:“MI:0914”(association)	0.640
H2BC1	PPM1G	psi-mi:“MI:0914”(association)	0.640
CDYL	H3C1	psi-mi:“MI:0407”(direct interaction)	0.620
SLC15A1	METTL15	psi-mi:“MI:0914”(association)	0.530
CD79A	METTL15	psi-mi:“MI:0914”(association)	0.530
H2BC26	PPM1G	psi-mi:“MI:0914”(association)	0.530
H2AC20	PPM1G	psi-mi:“MI:0914”(association)	0.530
CYBRD1	MIER1	psi-mi:“MI:0914”(association)	0.530
APLNR	SLC33A1	psi-mi:“MI:0914”(association)	0.530
MIER2	WIZ	psi-mi:“MI:0914”(association)	0.530
FAM136A	PIK3C2A	psi-mi:“MI:0914”(association)	0.530

BioGRID (146): CDYL (Protein-peptide), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Proximity Label-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS), CDYL (Affinity Capture-MS)

ESM2 similar proteins: A0A068FIK2, A8MQG7, B7PXE3, F4I7L1, F4JVB8, O14470, O23463, O80931, P34442, P34550, Q1A173, Q1G3C4, Q38851, Q39162, Q3B8D5, Q4FE47, Q58FS3, Q5RDX4, Q61T02, Q6AYK9, Q6H638, Q6NNN0, Q6NRL1, Q719N1, Q75F26, Q7XHR2, Q84XV2, Q8BXK8, Q8GS71, Q8GW75, Q8LF97, Q8S905, Q8S950, Q8S9H7, Q8WYB5, Q94166, Q94LW7, Q9AWM8, Q9C6G0, Q9ESK4

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

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 94 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
ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression	11	23.3×	2e-10
NuRD complex assembly	11	21.5×	4e-10
ChAHP complex assembly	8	20.5×	2e-07
HDACs deacetylate histones	12	20.0×	2e-10
Interaction of NuRD complexes with transcription factors	11	19.4×	9e-10
FXIIa activates plasma kallikrein-kinin system	8	19.2×	2e-07
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	8	18.7×	3e-07
Negative Regulation of CDH1 Gene Transcription	11	18.4×	1e-09

GO biological processes:

GO term	Partners	Fold	FDR
heterochromatin formation	7	20.5×	3e-05
nucleosome assembly	6	9.7×	5e-03
chromatin remodeling	10	8.4×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	2
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

3187 predictions. Top by Δscore:

Variant	Effect	Δscore
6:4937734:TCAGG:T	donor_loss	1.0000
6:4937735:CAGG:C	donor_loss	1.0000
6:4937736:AGG:A	donor_loss	1.0000
6:4937737:GGT:G	donor_loss	1.0000
6:4937738:G:GG	donor_gain	1.0000
6:4937738:GT:G	donor_loss	1.0000
6:4937739:T:A	donor_loss	1.0000
6:4952261:TGCA:T	acceptor_loss	1.0000
6:4952263:CA:C	acceptor_loss	1.0000
6:4952265:GGCA:G	acceptor_gain	1.0000
6:4952352:G:T	donor_gain	1.0000
6:4952365:G:GT	donor_gain	1.0000
6:4952365:G:T	donor_gain	1.0000
6:4952386:G:GT	donor_gain	1.0000
6:4952407:GTT:G	donor_gain	1.0000
6:4952410:G:GG	donor_gain	1.0000
6:4953890:C:CA	acceptor_gain	1.0000
6:4953893:TGCA:T	acceptor_loss	1.0000
6:4953896:A:AG	acceptor_gain	1.0000
6:4953896:AGG:A	acceptor_loss	1.0000
6:4953896:AGGT:A	acceptor_gain	1.0000
6:4953897:G:A	acceptor_loss	1.0000
6:4953897:G:GG	acceptor_gain	1.0000
6:4953897:GGT:G	acceptor_gain	1.0000
6:4953897:GGTG:G	acceptor_gain	1.0000
6:4776798:GCT:G	donor_gain	0.9900
6:4867437:G:GG	donor_gain	0.9900
6:4891473:A:G	donor_gain	0.9900
6:4891706:T:G	acceptor_gain	0.9900
6:4891711:A:AG	acceptor_gain	0.9900

AlphaMissense

3618 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:4891736:G:C	R70S	1.000
6:4891736:G:T	R70S	1.000
6:4891761:T:C	Y79H	1.000
6:4891761:T:G	Y79D	1.000
6:4891768:T:A	V81D	1.000
6:4891771:G:C	R82P	1.000
6:4891773:T:A	W83R	1.000
6:4891773:T:C	W83R	1.000
6:4891774:G:C	W83S	1.000
6:4891775:G:C	W83C	1.000
6:4891775:G:T	W83C	1.000
6:4891803:T:A	W93R	1.000
6:4891803:T:C	W93R	1.000
6:4891804:G:C	W93S	1.000
6:4891805:G:C	W93C	1.000
6:4891805:G:T	W93C	1.000
6:4891822:T:C	L99P	1.000
6:4891851:T:C	F109L	1.000
6:4891852:T:C	F109S	1.000
6:4891853:C:A	F109L	1.000
6:4891853:C:G	F109L	1.000
6:4935659:G:C	R333T	1.000
6:4935659:G:T	R333M	1.000
6:4935660:G:C	R333S	1.000
6:4935660:G:T	R333S	1.000
6:4935698:T:A	V346D	1.000
6:4937587:C:A	A378D	1.000
6:4937620:T:C	L389P	1.000
6:4937626:T:C	L391P	1.000
6:4943596:T:A	V445D	1.000

dbSNP variants (sampled 300 via entrez): RS1000021407 (6:4744300 C>G), RS1000035173 (6:4786024 G>A,C), RS1000048589 (6:4885390 T>C), RS1000053210 (6:4735084 C>T), RS1000054192 (6:4944921 G>T), RS1000057246 (6:4847630 T>C), RS1000058893 (6:4953252 T>C), RS1000077495 (6:4880368 C>T), RS1000080544 (6:4885580 C>G), RS1000109561 (6:4712320 C>G), RS1000118061 (6:4889457 T>G), RS1000118158 (6:4842165 TTA>T), RS1000123811 (6:4871906 T>C), RS1000141608 (6:4909078 G>A), RS1000145097 (6:4805139 C>G)

Disease associations

OMIM: gene MIM:603778 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST001113_2	Age at smoking initiation in chronic obstructive pulmonary disease	3.000000e-07
GCST006567_1	Response to ketogenic dietary therapies in epilepsy	4.000000e-08
GCST007538_3	Cellular nuclear factor (erythroid-derived 2)-like 2 levels	7.000000e-07
GCST008152_38	Weight	4.000000e-07
GCST008158_63	Body mass index	5.000000e-08
GCST90002404_238	Red cell distribution width	6.000000e-14

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005670	smoking initiation
EFO:0009372	response to ketogenic diet
EFO:0009794	NRF2 measurement
EFO:0004338	body weight
EFO:0004340	body mass index
EFO:0009188	Red cell distribution width

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879827 (SINGLE PROTEIN)

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

ChEMBL bioactivities

27 potent at pChembl≥5 of 62 total, top 24 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.31	Kd	490	nM	CHEMBL4168117
6.30	Kd	500	nM	CHEMBL4551565
6.04	Kd	910	nM	CHEMBL3939958
5.92	Kd	1200	nM	CHEMBL4435408
5.82	Kd	1500	nM	CHEMBL4444535
5.72	Kd	1900	nM	CHEMBL4460103
5.58	Kd	2600	nM	CHEMBL4464033
5.55	Kd	2800	nM	CHEMBL4469115
5.52	Kd	3000	nM	CHEMBL4529457
5.46	Kd	3500	nM	CHEMBL4593169
5.31	Kd	4900	nM	CHEMBL1411763
5.31	Kd	4900	nM	CHEMBL4461125
5.31	Kd	4900	nM	CHEMBL4514325
5.29	Kd	5100	nM	CHEMBL4448020
5.26	Kd	5500	nM	CHEMBL4542090
5.25	Kd	5600	nM	CHEMBL3939958
5.24	Kd	5800	nM	CHEMBL4590713
5.24	Kd	5800	nM	CHEMBL4531061
5.21	Kd	6200	nM	CHEMBL4473110
5.14	Kd	7200	nM	CHEMBL4592689
5.14	Kd	7300	nM	CHEMBL1524534
5.11	Kd	7700	nM	CHEMBL4435053
5.02	Kd	9500	nM	CHEMBL4473633
5.00	Kd	1.01e+04	nM	CHEMBL4455971

PubChem BioAssay actives

25 with measured affinity, of 97 total; 22 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
N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-amino-3-hydroxy-1-oxobutan-2-yl]amino]-6-[ethyl(propan-2-yl)amino]-1-oxohexan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]cyclohexanecarboxamide	1506818: Binding affinity to N-terminal GST-tagged CDYL (1 to 78 residues) (unknown origin) expressed in Rosetta2 BL21(DE3)pLysS cells after 30 mins by fluorescence polarization assay	kd	0.4900	uM
3-[2-oxo-2-(4-pyrrolidin-1-ylpiperidin-1-yl)ethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	0.5000	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	1319526: Binding affinity to human N-terminal GST-tagged CDYL1b chromodomain (1 to 78 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS by ITC method	kd	0.9100	uM
5-chloro-3-[2-(3-methoxyphenyl)-2-oxoethyl]-1,3-dihydroindol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.2000	uM
5-methoxy-3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.5000	uM
3-[2-(1H-indol-3-yl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.9000	uM
3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	2.6000	uM
3-[2-[4-(diethylamino)piperidin-1-yl]-2-oxoethyl]-5-fluoro-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	2.8000	uM
3-(2-naphthalen-1-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	3.0000	uM
6-amino-3-[2-(1H-indol-3-yl)-2-oxoethyl]-1,3-benzothiazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	3.5000	uM
6-amino-3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzothiazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.9000	uM
5-chloro-3-hydroxy-3-[2-(3-methoxyphenyl)-2-oxoethyl]-1H-indol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.9000	uM
3-[2-(3-methoxyphenyl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.9000	uM
5-fluoro-3-[2-(1H-indol-3-yl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	5.1000	uM
3-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-5-methoxy-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	5.5000	uM
3-[2-[4-(diethylamino)piperidin-1-yl]-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	5.8000	uM
5-bromo-3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	5.8000	uM
5-fluoro-3-[2-(3-methoxyphenyl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	6.2000	uM
3-[2-(1H-indol-3-yl)-2-oxoethyl]-5-methoxy-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	7.2000	uM
N-(3-methoxyphenyl)-2-(2-oxo-1,3-benzoxazol-3-yl)acetamide	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	7.3000	uM
5-methoxy-3-[2-(3-methoxyphenyl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	7.7000	uM
3-[2-[4-(dimethylamino)piperidin-1-yl]-2-oxoethyl]-1,3-benzoxazol-2-one	1565811: Binding affinity to recombinant human N-terminal GST-tagged CDYL (1 to 60 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases mutagenesis	3
sodium arsenite	increases abundance, decreases expression	2
entinostat	increases expression, affects cotreatment	2
Arsenic	affects methylation, decreases expression, increases abundance	2
Valproic Acid	affects expression, increases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	increases phosphorylation	1
2,4,6-tribromophenol	decreases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
decabromobiphenyl ether	increases expression	1
tetrabromobisphenol A	decreases expression	1
coumarin	increases phosphorylation	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	increases expression	1
Caffeine	affects phosphorylation	1
Calcitriol	increases expression	1
Cannabidiol	increases expression	1
Coumestrol	decreases expression	1
Formaldehyde	decreases expression	1

ChEMBL screening assays

28 unique, capped per target: 28 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3858701	Binding	Binding affinity to human N-terminal GST-tagged CDYL1b chromodomain (1 to 78 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS by ITC method	Structure-Activity Relationships and Kinetic Studies of Peptidic Antagonists of CBX Chromodomains. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A0N4	SEES3-1V human CDYL, clone1	Embryonic stem cell	Male
CVCL_A0N5	SEES3-1V human CDYL, clone2	Embryonic stem cell	Male
CVCL_A0N6	SEES3-1V human CDYL, clone3	Embryonic stem cell	Male
CVCL_D8GA	Ubigene H9 CDYL KO	Embryonic stem cell	Female

Clinical trials (associated diseases)

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