CDY2A

Summary

CDY2A (chromodomain Y-linked 2A, HGNC:1810) is a protein-coding gene on chromosome Yq11.222, encoding Testis-specific chromodomain protein Y 2 (Q9Y6F7). May have histone acetyltransferase activity.

This intronless 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. Two nearly identical copies of this gene are found in a palindromic region on chromosome Y; this record represents the telomeric copy. Chromosome Y also contains a pair of closely related genes in another more telomeric palindrome as well as several related pseudogenes.

Source: NCBI Gene 9426 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 12 total — 1 pathogenic
• Phenotypes (HPO): 4
• MANE Select transcript: NM_004825

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1810
Approved symbol	CDY2A
Name	chromodomain Y-linked 2A
Location	Yq11.222
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000182415
Ensembl biotype	protein_coding
OMIM	400018
Entrez	9426

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000250838

RefSeq mRNA: 1 — MANE Select: NM_004825 NM_004825

CCDS: CCDS14789

Canonical transcript exons

ENST00000250838 — 1 exons

Exon	Start	End
ENSE00002310447	18025787	18027746

Expression profiles

Bgee: expression breadth tissue_specific, 4 present calls, max score 42.50.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	42.50	gold quality
testis	UBERON:0000473	42.34	gold quality
left testis	UBERON:0004533	42.01	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
skeletal muscle tissue	UBERON:0001134	36.56	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
muscle tissue	UBERON:0002385	33.40	gold quality
hindlimb stylopod muscle	UBERON:0004252	32.15	gold quality
bone marrow	UBERON:0002371	31.74	gold quality
sural nerve	UBERON:0015488	30.93	gold quality
monocyte	CL:0000576	29.91	gold quality
stromal cell of endometrium	CL:0002255	29.87	gold quality
leukocyte	CL:0000738	29.70	gold quality
prefrontal cortex	UBERON:0000451	29.04	gold quality
liver	UBERON:0002107	29.01	gold quality
duodenum	UBERON:0002114	28.14	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
right coronary artery	UBERON:0001625	26.36	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
muscle of leg	UBERON:0001383	25.26	gold quality
uterine cervix	UBERON:0000002	24.73	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.17

Regulation

Is transcription factor: no

Literature-anchored findings (GeneRIF, showing 1)

• data indicate that CDY2 and HSFY are located within a segment of the Y chromosome that is important for sperm maturation, and are underexpressed in testicular tissue derived from men with maturation arrest (PMID:22820855)

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), CDY1 (ENSG00000172288), CDY1B (ENSG00000172352), HIBCH (ENSG00000198130)

Protein

Protein identifiers

Testis-specific chromodomain protein Y 2 — Q9Y6F7 (reviewed: Q9Y6F7)

All UniProt accessions (1): Q9Y6F7

UniProt curated annotations — full annotation on UniProt →

Function. May have histone acetyltransferase activity.

Subcellular location. Nucleus.

Tissue specificity. Testis specific.

RefSeq proteins (1): NP_004816* (*=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 (25 total): helix 12, strand 9, chain 1, domain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2FW2	X-RAY DIFFRACTION	2.2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y6F7-F1	71.50	0.50

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 44 (showing top): 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, GOMF_TRANSCRIPTION_COREGULATOR_ACTIVITY

GO Biological Process (3): spermatogenesis (GO:0007283), chromatin remodeling (GO:0006338), negative regulation of DNA-templated transcription (GO:0045892)

GO Molecular Function (5): transcription corepressor activity (GO:0003714), protein-lysine-acetyltransferase activity (GO:0061733), 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
developmental process involved in reproduction	1
male gamete generation	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

672 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CDY2A	BPY2	O14599	948
CDY2A	DAZ1	Q9NQZ3	943
CDY2A	VCY	O14598	933
CDY2A	DAZ2	Q13117	894
CDY2A	PRY	O14603	883
CDY2A	E7ERQ6	E7ERQ6	849
CDY2A	RBMY1A1	P0DJD3	769
CDY2A	HSFY1	Q96LI6	761
CDY2A	TSPY1	P09002	720
CDY2A	USP9Y	O00507	663
CDY2A	DDX3Y	O15523	655
CDY2A	EIF1AY	O14602	601
CDY2A	UTY	O14607	593
CDY2A	ZFY	P08048	591
CDY2A	KDM5D	Q9BY66	590

IntAct

2 interactions, top by confidence:

A	B	Type	Score
CDY2A	SMPD2	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350

BioGRID (25): MYCBP (Affinity Capture-MS), SMPD2 (Affinity Capture-MS), PRSS1 (Affinity Capture-MS), CDY2A (Affinity Capture-MS), SPIN1 (Affinity Capture-MS), CHCHD2 (Affinity Capture-MS), CDY2A (Affinity Capture-MS), HIST1H2AE (Affinity Capture-MS), WIZ (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), ATF7IP (Affinity Capture-MS), ZNF644 (Affinity Capture-MS), SPIN3 (Affinity Capture-MS), CLTCL1 (Affinity Capture-MS), CDYL (Affinity Capture-MS)

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

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	5
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
147317	GRCh38/hg38 Yq11.221-11.223(chrY:13908860-22358529)x1	Pathogenic

SpliceAI

26 predictions. Top by Δscore:

Variant	Effect	Δscore
Y:18026636:G:GA	donor_gain	0.3100
Y:18027537:G:T	acceptor_gain	0.3000
Y:18025918:G:GG	donor_gain	0.2900
Y:18025914:GGCA:G	donor_gain	0.2800
Y:18025915:GCAG:G	donor_gain	0.2800
Y:18026635:T:TA	donor_gain	0.2800
Y:18026657:G:T	donor_gain	0.2700
Y:18027423:A:G	donor_gain	0.2700
Y:18025917:A:AG	donor_gain	0.2600
Y:18026758:T:G	donor_gain	0.2500
Y:18026514:A:G	donor_gain	0.2400
Y:18027430:A:AG	donor_gain	0.2400
Y:18026574:G:GG	donor_gain	0.2300
Y:18026080:GGCAC:G	donor_gain	0.2200
Y:18026637:G:GG	donor_gain	0.2200
Y:18026137:TTG:T	donor_gain	0.2100
Y:18026575:TGAG:T	acceptor_gain	0.2100
Y:18026638:TCTTC:T	donor_gain	0.2100
Y:18026991:G:GT	donor_gain	0.2100
Y:18027057:A:AG	donor_gain	0.2100
Y:18027182:G:GT	donor_gain	0.2100
Y:18025798:G:GT	donor_gain	0.2000
Y:18026430:TCCA:T	donor_gain	0.2000
Y:18027164:CTTT:C	donor_gain	0.2000
Y:18027428:TA:T	donor_gain	0.2000
Y:18027429:AA:A	donor_gain	0.2000

AlphaMissense

3592 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
Y:18027277:T:A	V388D	0.995
Y:18026194:G:C	R27P	0.994
Y:18026198:G:C	W28C	0.994
Y:18026198:G:T	W28C	0.994
Y:18026228:G:C	W38C	0.994
Y:18026228:G:T	W38C	0.994
Y:18027138:T:C	F342L	0.994
Y:18027140:T:A	F342L	0.994
Y:18027140:T:G	F342L	0.994
Y:18027355:T:C	F414S	0.994
Y:18027483:G:C	A457P	0.994
Y:18027502:T:A	V463D	0.994
Y:18026184:T:G	Y24D	0.993
Y:18027268:T:A	V385D	0.993
Y:18026185:A:C	Y24S	0.992
Y:18026226:T:A	W38R	0.992
Y:18026226:T:C	W38R	0.992
Y:18027141:T:C	C343R	0.992
Y:18027675:T:A	W521R	0.992
Y:18027675:T:C	W521R	0.992
Y:18026191:T:A	V26D	0.991
Y:18026196:T:A	W28R	0.991
Y:18026196:T:C	W28R	0.991
Y:18027283:G:A	G390D	0.991
Y:18027325:A:T	D404V	0.991
Y:18027336:G:C	A408P	0.991
Y:18027289:C:A	A392D	0.990
Y:18026197:G:C	W28S	0.989
Y:18027398:T:G	C428W	0.989
Y:18027139:T:C	F342S	0.988

dbSNP variants (sampled 41 via entrez): RS1181659057 (Y:18025785 G>A), RS1194997792 (Y:18026668 G>A), RS1211238886 (Y:18026495 C>T), RS1214417066 (Y:18025505 C>T), RS1233869725 (Y:18026012 CA>C), RS1256282807 (Y:18026510 G>A), RS1270338249 (Y:18026407 C>T), RS1275062232 (Y:18025729 T>A), RS1287991566 (Y:18025151 T>C), RS1334339924 (Y:18025281 G>C), RS1339259884 (Y:18026106 T>A), RS1349404329 (Y:18026449 T>C), RS1471358022 (Y:18026063 G>A), RS1484573172 (Y:18026556 T>C), RS1603534008 (Y:18024928 T>C)

Disease associations

OMIM: gene MIM:400018 | 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: no

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

CTD chemical–gene interactions

4 total (human), top 4 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
cyclic 3’,5’-uridine monophosphate	affects binding	1
CGP 52608	affects binding, increases reaction	1
Tobacco Smoke Pollution	affects expression	1
Aflatoxin B1	increases methylation	1

Clinical trials (associated diseases)

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