CDY1

Summary

CDY1 (chromodomain Y-linked 1, HGNC:1809) is a protein-coding gene on chromosome Yq11.23, encoding Testis-specific chromodomain protein Y 1 (Q9Y6F8). Has histone acetyltransferase activity, with a preference for histone H4.

This gene encodes a protein containing a chromodomain and a histone acetyltransferase catalytic domain. Chromodomain proteins are components of heterochromatin-like complexes and can act as gene repressors. This protein is localized to the nucleus of late spermatids where histone hyperacetylation takes place. Histone hyperacetylation is thought to facilitate the transition in which protamines replace histones as the major DNA-packaging protein. The human chromosome Y has two identical copies of this gene within a palindromic region; this record represents the more telomeric copy. Chromosome Y also contains a pair of closely related genes in another more telomeric palindrome as well as several related pseudogenes. Two protein isoforms are encoded by transcript variants of this gene. Additional transcript variants have been described, but their full-length nature has not been determined.

Source: NCBI Gene 9085 — RefSeq curated summary.

At a glance

• Phenotypes (HPO): 4
• Druggable target: yes
• Dosage sensitivity (ClinGen): haploinsufficiency no evidence, triplosensitivity no evidence
• MANE Select transcript: NM_004680

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1809
Approved symbol	CDY1
Name	chromodomain Y-linked 1
Location	Yq11.23
Locus type	gene with protein product
Status	Approved
Aliases	CDY1A
Ensembl gene	ENSG00000172288
Ensembl biotype	protein_coding
OMIM	400016
Entrez	9085

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000306609, ENST00000361963

RefSeq mRNA: 2 — MANE Select: NM_004680 NM_004680, NM_170723

CCDS: CCDS14801, CCDS14802

Canonical transcript exons

ENST00000306609 — 2 exons

Exon	Start	End
ENSE00001666303	25624455	25624902
ENSE00003978110	25622117	25624034

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 39.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
left testis	UBERON:0004533	39.50	gold quality
testis	UBERON:0000473	38.79	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
right testis	UBERON:0004534	37.10	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
bone marrow cell	CL:0002092	36.16	gold quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
skeletal muscle tissue	UBERON:0001134	33.38	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
muscle tissue	UBERON:0002385	31.06	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	30.68	gold quality
leukocyte	CL:0000738	30.40	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
prefrontal cortex	UBERON:0000451	29.20	gold quality
liver	UBERON:0002107	29.03	gold quality
right uterine tube	UBERON:0001302	28.91	gold quality
duodenum	UBERON:0002114	28.14	gold quality
urinary bladder	UBERON:0001255	27.90	gold quality
lymph node	UBERON:0000029	27.57	gold quality
tonsil	UBERON:0002372	27.05	gold quality
blood	UBERON:0000178	26.66	gold quality
islet of Langerhans	UBERON:0000006	26.55	gold quality
vermiform appendix	UBERON:0001154	26.42	gold quality
gall bladder	UBERON:0002110	25.98	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	25.89	gold quality
placenta	UBERON:0001987	25.81	gold quality
uterine cervix	UBERON:0000002	25.80	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.09

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

27 targeting CDY1, 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-3134	100.00	66.43	777
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-520F-3P	99.82	71.32	1216
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-5584-3P	99.23	68.79	1351
HSA-MIR-4426	99.17	66.74	1949
HSA-MIR-485-5P	99.10	64.78	1889
HSA-MIR-6884-5P	99.10	64.50	1987
HSA-MIR-4720-3P	98.50	68.88	988
HSA-MIR-581	98.39	67.42	835
HSA-MIR-4662B	98.33	66.37	1163
HSA-MIR-4647	98.30	66.41	1139
HSA-MIR-1262	98.17	66.52	757
HSA-MIR-4701-3P	98.17	66.25	788
HSA-MIR-6736-5P	98.17	66.43	760
HSA-MIR-3620-5P	97.42	63.95	792
HSA-MIR-10400-3P	97.29	64.66	597
HSA-MIR-4674	97.29	64.62	597
HSA-MIR-27A-5P	97.01	65.63	528
HSA-MIR-1587	96.95	64.03	932
HSA-MIR-664B-5P	96.74	67.50	509
HSA-MIR-2909	96.36	67.30	562
HSA-MIR-4761-3P	96.27	66.26	524
HSA-MIR-4453	95.61	65.84	436
HSA-MIR-4538	95.61	65.34	449

Functional genomics

ClinGen dosage: haploinsufficiency 0 (no evidence), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 5)

• different functional roles for CDY isoforms during spermatogenesis (PMID:14569460)
• Partial AZFc deletions including CDY1-DAZ gene is associated with impaired spermatogenesis. (PMID:18807255)
• Assessing the expression of both CDY1 and BOULE by qualitative RT-PCR is a sensitive and feasible test for predicting the presence of sperm cells in testicular tissue biopsies. (PMID:21474125)
• Findings showed that deletion of CDY1b copy gene is a significant risk factor for male infertility independent of sperm concentration, whereas deletion of CDY1a gene seems to have no effect on fertility in the Tunisian population. (PMID:25042452)
• Y-chromosome haplogroups and Azoospermia Factor (AZF) analysis in Tunisian infertile male. (PMID:36591797)

Cross-species orthologs

12 orthologs

Organism	Symbol	Gene ID
danio_rerio	cdyl	ENSDARG00000038985
mus_musculus	Cdyl	ENSMUSG00000059288
rattus_norvegicus	AABR07039112.1	ENSRNOG00000022855
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), CDYL (ENSG00000153046), CDYL2 (ENSG00000166446), ECI1 (ENSG00000167969), CDY1B (ENSG00000172352), CDY2A (ENSG00000182415), HIBCH (ENSG00000198130)

Protein

Protein identifiers

Testis-specific chromodomain protein Y 1 — Q9Y6F8 (reviewed: Q9Y6F8)

All UniProt accessions (1): Q9Y6F8

UniProt curated annotations — full annotation on UniProt →

Function. Has histone acetyltransferase activity, with a preference for histone H4.

Subunit / interactions. Interacts (via chromo domain) with histone H3K9me3.

Subcellular location. Nucleus.

Tissue specificity. Testis-specific. Detected in spermatids (at protein level).

Isoforms (2)

UniProt ID	Names	Canonical?
Q9Y6F8-1	1	yes
Q9Y6F8-2	2

RefSeq proteins (2): NP_004671, NP_733841 (=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
IPR017984	Chromo_dom_subgr	Domain
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

Catalyzed reactions (Rhea), 1 shown:

• L-lysyl-[protein] + acetyl-CoA = N(6)-acetyl-L-lysyl-[protein] + CoA + H(+) (RHEA:45948)

UniProt features (28 total): helix 13, strand 9, chain 1, domain 1, region of interest 1, turn 1, compositionally biased region 1, splice variant 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
6V41	X-RAY DIFFRACTION	1.6
2FBM	X-RAY DIFFRACTION	2.28

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6F8-F1	70.79	0.49

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 66 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GOBP_MALE_GAMETE_GENERATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_PROTEIN_ACYLATION, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_MODIFICATION_PROCESS, GOBP_REGULATION_OF_PROTEIN_MODIFICATION_PROCESS, GOMF_ACETYLTRANSFERASE_ACTIVITY, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_N_ACYLTRANSFERASE_ACTIVITY, GOMF_TRANSCRIPTION_COREPRESSOR_ACTIVITY, GOMF_N_ACETYLTRANSFERASE_ACTIVITY, GOBP_REGULATION_OF_PROTEIN_METABOLIC_PROCESS, chrYq11, GOBP_NEGATIVE_REGULATION_OF_NUCLEOBASE_CONTAINING_COMPOUND_METABOLIC_PROCESS

GO Biological Process (4): spermatogenesis (GO:0007283), chromatin organization (GO:0006325), chromatin remodeling (GO:0006338), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (7): transcription corepressor activity (GO:0003714), histone H3K27me3 reader activity (GO:0061628), protein-lysine-acetyltransferase activity (GO:0061733), histone H3K9me2/3 reader activity (GO:0062072), histone acetyltransferase activity (GO:0004402), transferase activity (GO:0016740), acyltransferase activity (GO:0016746)

GO Cellular Component (1): nucleus (GO:0005634)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H3 reader activity	2
developmental process involved in reproduction	1
male gamete generation	1
cellular component organization	1
chromatin organization	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
protein N-acetyltransferase activity	1
protein-lysine-acetyltransferase activity	1
histone modifying activity	1
catalytic activity	1
transferase activity	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

2288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDY1	BPY2	O14599	964
CDY1	DAZ1	Q9NQZ3	956
CDY1	DAZ2	Q13117	943
CDY1	VCY	O14598	918
CDY1	PRY	O14603	916
CDY1	E7ERQ6	E7ERQ6	916
CDY1	RBMY1A1	P0DJD3	852
CDY1	USP9Y	O00507	789
CDY1	DDX3Y	O15523	765
CDY1	UTY	O14607	764
CDY1	TSPY1	P09002	720
CDY1	RBMY1D	P0C7P1	717
CDY1	HSFY1	Q96LI6	714
CDY1	KDM5D	Q9BY66	546
CDY1	RPS4Y2	Q8TD47	529

IntAct

0 interactions, top by confidence:

BioGRID (7): CDY1 (Synthetic Growth Defect), CDY1 (Proximity Label-MS), CDY1 (Affinity Capture-MS), LIG1 (Protein-peptide), CDY1 (Affinity Capture-MS), VWA3A (Cross-Linking-MS (XL-MS)), CDY1B (Reconstituted Complex)

ESM2 similar proteins: A0A0B7P3V8, A4FUB7, A4H7G5, A4HVU6, A6NKG5, B4NSS9, B6EU02, F4I1N8, H2KZW3, O10318, O13329, P04586, P0C2J7, P18475, P34601, P47024, Q01577, Q05101, Q09178, Q09293, Q1L6Q1, Q3S4A7, Q4DCH3, Q4QFY1, Q4R6I1, Q52QI2, Q57X81, Q5RBK0, Q5RDX4, Q62120, Q66H30, Q6R2W3, Q7KLI1, Q7LHG5, Q8CDM1, Q8K259, Q8N157, Q90179, Q91829, Q99315

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.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (0)

SpliceAI

15 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:25623862:G:C	acceptor_gain	0.3800
Y:25622465:TTG:T	donor_gain	0.2800
Y:25622961:G:GA	donor_gain	0.2700
Y:25622242:GGCA:G	donor_gain	0.2500
Y:25622243:GCAG:G	donor_gain	0.2500
Y:25622960:T:TA	donor_gain	0.2500
Y:25622246:G:GG	donor_gain	0.2400
Y:25623941:A:AG	donor_gain	0.2400
Y:25623083:T:G	donor_gain	0.2200
Y:25623860:A:AC	acceptor_gain	0.2200
Y:25622408:GGCAC:G	donor_gain	0.2000
Y:25622902:AGTGG:A	acceptor_gain	0.2000
Y:25622962:G:GG	donor_gain	0.2000
Y:25623383:T:G	donor_gain	0.2000
Y:25623559:G:GG	donor_gain	0.2000

AlphaMissense

3669 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:25622556:G:C	W38C	0.997
Y:25622556:G:T	W38C	0.997
Y:25622526:G:C	W28C	0.996
Y:25622526:G:T	W28C	0.996
Y:25622554:T:A	W38R	0.996
Y:25622554:T:C	W38R	0.996
Y:25623593:T:A	V384D	0.996
Y:25623602:T:A	V387D	0.996
Y:25622512:T:G	Y24D	0.995
Y:25622519:T:A	V26D	0.995
Y:25622522:G:C	R27P	0.995
Y:25623463:T:C	F341L	0.995
Y:25623465:T:A	F341L	0.995
Y:25623465:T:G	F341L	0.995
Y:25624000:T:A	W520R	0.995
Y:25624000:T:C	W520R	0.995
Y:25622513:A:C	Y24S	0.994
Y:25622524:T:A	W28R	0.994
Y:25622524:T:C	W28R	0.994
Y:25623608:G:A	G389D	0.994
Y:25623661:G:C	A407P	0.994
Y:25623680:T:C	F413S	0.994
Y:25622525:G:C	W28S	0.993
Y:25623404:T:C	L321P	0.993
Y:25623400:G:C	A320P	0.992
Y:25623607:G:C	G389R	0.992
Y:25623662:C:A	A407D	0.992
Y:25623808:G:C	A456P	0.992
Y:25622602:T:C	F54L	0.991
Y:25622604:T:A	F54L	0.991

dbSNP variants (sampled 8 via entrez): RS112604390 (Y:25621799 A>G), RS1556284587 (Y:25622359 C>T), RS1556284596 (Y:25622823 C>T), RS1556284601 (Y:25624283 A>G), RS2520733287 (Y:25621802 T>TCAAAA), RS2520733336 (Y:25623355 GA>G), RS2520733364 (Y:25624489 C>A), RS2520733377 (Y:25625574 CTTT>C,CT,CTT)

Disease associations

OMIM: gene MIM:400016 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

4 total (4 of 4 shown, HPO-id order):

HPO	Term
HP:0000027	Azoospermia
HP:0001450	Y-linked inheritance
HP:0003251	Male infertility
HP:0011462	Young adult onset

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3879864 (SINGLE PROTEIN)

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

ChEMBL bioactivities

13 potent at pChembl≥5 of 43 total, top 12 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
6.10	Kd	800	nM	CHEMBL4442553
6.00	Kd	1000	nM	CHEMBL1524534
5.82	Kd	1500	nM	CHEMBL4444535
5.77	Kd	1700	nM	CHEMBL4553597
5.57	Kd	2700	nM	CHEMBL4569763
5.40	Kd	4000	nM	CHEMBL4455971
5.36	Kd	4400	nM	CHEMBL4541008
5.35	Kd	4500	nM	CHEMBL4469115
5.34	Kd	4600	nM	CHEMBL4513804
5.24	Kd	5800	nM	CHEMBL4461125
5.20	Kd	6300	nM	CHEMBL3939958
5.19	Kd	6500	nM	CHEMBL4529457

PubChem BioAssay actives

26 with measured affinity, of 112 total; 12 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-naphthalen-1-yl-2-(2-oxo-1,3-benzoxazol-3-yl)acetamide	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	0.8000	uM
N-(3-methoxyphenyl)-2-(2-oxo-1,3-benzoxazol-3-yl)acetamide	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.0000	uM
5-methoxy-3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.5000	uM
6-bromo-3-(2-naphthalen-2-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	1.7000	uM
3-[2-[4-(dimethylamino)phenyl]-2-oxoethyl]-5-methoxy-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	2.7000	uM
2-(benzimidazol-1-yl)-1-(3-methoxyphenyl)ethanone	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.0000	uM
3-[2-(3,4-dimethoxyphenyl)-2-oxoethyl]-5-fluoro-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.4000	uM
3-[2-[4-(diethylamino)piperidin-1-yl]-2-oxoethyl]-5-fluoro-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.5000	uM
3-[2-(1H-indol-3-yl)-2-oxoethyl]-2-oxo-1,3-benzoxazole-5-carbonitrile	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	4.6000	uM
3-[2-(3-methoxyphenyl)-2-oxoethyl]-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	5.8000	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	1319527: Binding affinity to human N-terminal GST-tagged CDY1 chromodomain (1 to 101 residues) expressed in Escherichia coli Rosetta BL21(DE3)pLysS by ITC method	kd	6.3000	uM
3-(2-naphthalen-1-yl-2-oxoethyl)-1,3-benzoxazol-2-one	1565816: Binding affinity to recombinant human N-terminal GST-tagged CDY1 (1 to 65 residues) expressed in Escherichia coli BL2 by SPR analysis	kd	6.5000	uM

CTD chemical–gene interactions

3 total (human), top 3 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
CGP 52608	affects binding, increases reaction	1
Doxorubicin	decreases response to substance	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

4 unique, capped per target: 4 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3858702	Binding	Binding affinity to human N-terminal GST-tagged CDY1 chromodomain (1 to 101 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

Clinical trials (associated diseases)

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