CDY2A (Chromodomain Y-Linked 2A): A Testis-Specific Chromatin Remodeler Linked to Male Fertility
Explore the genomic context, expression, and clinical significance of the Y-linked CDY2A gene, a key player in spermatogenesis and a potential biomarker for male infertility.
Gene Information Card
| Symbol | CDY2A |
|---|---|
| Full Name | chromodomain Y-linked 2A |
| Gene Type | protein coding |
| Chromosomal Location | Yq11.223 |
| NCBI Gene ID | 9427 ncbi.nlm.nih.gov/gene/9427 |
| Ensembl ID | ENSG00000205916 |
| UniProt ID | Q9BYN7 |
| OMIM ID | 400016 |
| HGNC ID | 1807 |
| Aliases | CDY2, MGC104233 |
Description
CDY2A (chromodomain Y-linked 2A) is a protein-coding gene located on the Y chromosome at Yq11.223. It belongs to the chromodomain family and encodes a protein with chromodomain and histone acetyltransferase (HAT) domains. CDY2A is specifically expressed in the testis, where it plays a crucial role in chromatin remodeling during spermatogenesis. The protein binds to histone H3 methylated at lysine 9 (H3K9me) and acetylates histone H4 at lysine 8 (H4K8ac), facilitating histone-to-protamine transition in elongating spermatids. CDY2A is part of the AZFc (azoospermia factor c) region, and deletions in this region are associated with male infertility. The gene is also implicated in certain cancers, though its role is less defined.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Male infertility (azoospermia/oligospermia) | Deletions in the AZFc region, which includes CDY2A, lead to loss of functional copies, impairing spermatogenesis. | ClinVar and literature reports (e.g., Vogt et al., 1996; Repping et al., 2002) confirm association with spermatogenic failure. |
| Spermatogenic failure | Reduced CDY2A expression due to Yq microdeletions disrupts histone acetylation and chromatin condensation in sperm. | OMIM #400016 and multiple case-control studies. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Testis | High (e.g., 100 nTPM) | Testis-specific expression, highest in spermatids. |
| Other tissues | Not detected | No significant expression in somatic tissues. |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Spermatogenic cells (e.g., GC-1 spg, GC-2 spd) | High | Expressed in spermatogonia and spermatocytes; essential for meiosis. |
| Somatic cell lines (e.g., HeLa, HEK293) | Not detected | No expression in non-germline cells. |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| AZFc deletion (including CDY2A) | Copy number variation (deletion) | ~10-15% of men with azoospermia | Loss of CDY2A copies leads to impaired spermatogenesis. |
| c.1A>G (p.Met1Val) | Missense | Rare (not well characterized) | Potential loss of protein function; not clinically validated. |
Mutation functional classification
Loss of Function (LOF)
Deletions of the AZFc region, which includes CDY2A, result in loss of functional protein, leading to defective histone-to-protamine exchange and male infertility.
Gain of Function (GOF)
No evidence of gain-of-function mutations; CDY2A is not known to be oncogenic.
Dominant Negative (DN)
Not applicable; CDY2A is a Y-linked gene with multiple copies, and no dominant-negative effects have been reported.
View complete mutation data：
Gene Ontology (GO)
| • chromatin binding | • histone acetyltransferase activity |
| • zinc ion binding | • nucleus |
| • spermatogenesis | • chromatin remodeling |
| • male gonad development |
Pathways
• Spermatogenesis
• Chromatin organization
• Histone modification
Protein Summary
The CDY2A protein is a 541-amino acid polypeptide with a chromodomain at the N-terminus and a catalytic HAT domain. It specifically recognizes H3K9me via its chromodomain and acetylates H4K8, a mark associated with active chromatin and histone eviction. This activity is critical for the replacement of histones with protamines during spermatid elongation, ensuring proper DNA compaction in sperm. CDY2A is localized to the nucleus and is expressed predominantly in round and elongating spermatids. Its function is essential for male fertility, and its loss due to Yq deletions is a major genetic cause of spermatogenic failure.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| CDY2A Knockout HEK293 Cell Line | EDJ-KQ50871 | Human | 9426 | Details Get a Quote |
| CDY2A Knockout HeLa Cell Line | EDJ-KQ55162 | Human | 9426 | Details Get a Quote |
| CDY2A Knockout A-549 Cell Line | EDJ-KQ63642 | Human | 9426 | Details Get a Quote |
| CDY2A Knockout HCT 116 Cell Line | EDJ-KQ72103 | Human | 9426 | Details Get a Quote |
