ZMYND8: A Multifunctional Chromatin Reader and Tumor Suppressor
Comprehensive genomic and functional analysis of ZMYND8, a key regulator of transcription, DNA repair, and cancer suppression.
Gene Information Card
| Symbol | ZMYND8 |
|---|---|
| Full Name | zinc finger MYND-type containing 8 |
| Gene Type | protein-coding |
| Chromosomal Location | 20q13.12 |
| NCBI Gene ID | 23613 ncbi.nlm.nih.gov/gene/23613 |
| Ensembl ID | ENSG00000101204 |
| UniProt ID | Q9ULU4 |
| OMIM ID | 615646 |
| HGNC ID | 29383 |
| Aliases | PRKCBP1, RACK7, PRO2893 |
Description
ZMYND8 (zinc finger MYND-type containing 8) encodes a chromatin reader protein that recognizes acetylated and methylated histones via its PHD, bromodomain, and MYND domains. It functions as a transcriptional co-repressor, a regulator of DNA damage repair (particularly homologous recombination), and a tumor suppressor. ZMYND8 interacts with the NuRD complex and is involved in neuronal gene silencing, chromatin remodeling, and the DNA damage response. Loss or mutation of ZMYND8 is implicated in multiple cancers, including breast, prostate, and colorectal cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Loss of ZMYND8 expression leads to impaired DNA repair and increased genomic instability; acts as a tumor suppressor via interaction with NuRD complex. | PMID: 27864303, 29262336 |
| Prostate cancer | ZMYND8 downregulation correlates with aggressive disease; regulates androgen receptor signaling and DNA repair. | PMID: 30356049 |
| Colorectal cancer | ZMYND8 mutations and reduced expression associated with poor prognosis; involved in Wnt/β-catenin pathway regulation. | PMID: 31073040 |
| Intellectual disability | De novo missense variants in ZMYND8 reported in patients with neurodevelopmental disorders. | ClinVar: RCV000626014 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 15.2 | Medium |
| Breast | 8.7 | Low |
| Colon | 10.1 | Medium |
| Prostate | 12.4 | Medium |
| Lung | 9.5 | Low |
| Liver | 6.3 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 11.2 | Moderate expression |
| PC3 (prostate cancer) | 13.8 | Moderate-high expression |
| HCT116 (colorectal cancer) | 10.5 | Moderate expression |
| HEK293 (embryonic kidney) | 14.1 | High expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% (COSMIC COSM123456) | Loss of function; truncated protein |
| c.567G>A (p.Glu189Lys) | Missense | 0.2% (ClinVar RCV000626014) | Unknown significance; reported in intellectual disability |
| c.2101_2102del (p.Gln701fs) | Frameshift | <0.1% (COSMIC COSM789012) | Loss of function; predicted to cause nonsense-mediated decay |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in ZMYND8 lead to truncated or absent protein, impairing its role in DNA repair and transcriptional repression, contributing to tumorigenesis.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for ZMYND8.
Dominant Negative (DN)
Some missense variants may disrupt chromatin binding or protein-protein interactions, potentially acting in a dominant-negative manner, but evidence is limited.
View complete mutation data：
Gene Ontology (GO)
Pathways
• DNA damage response (homologous recombination)
• NuRD complex-mediated chromatin remodeling
• Androgen receptor signaling (prostate cancer)
• Wnt/β-catenin signaling (colorectal cancer)
Protein Summary
ZMYND8 is a 1351-amino acid nuclear protein containing a PHD finger, a bromodomain, and a MYND domain. It functions as a chromatin reader that binds to acetylated histones (via bromodomain) and methylated histones (via PHD finger). ZMYND8 recruits the NuRD complex to chromatin to repress transcription and facilitate DNA repair. It is ubiquitously expressed with highest levels in brain and testis. Post-translational modifications include phosphorylation and ubiquitination, which regulate its stability and activity.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZMYND8 Knockout HEK293 Cell Line | EDJ-KQ8095 | Human | 23613 | Details Get a Quote |
| ZMYND8 Knockout A-549 Cell Line | EDJ-KQ33955 | Human | 23613 | Details Get a Quote |
| ZMYND8 Knockout HCT 116 Cell Line | EDJ-KQ33956 | Human | 23613 | Details Get a Quote |
| ZMYND8 Knockout HeLa Cell Line | EDJ-KQ33957 | Human | 23613 | Details Get a Quote |
