ZNF521: Zinc Finger Protein 521 - Gene and Functional Overview
Comprehensive biomedical profile of ZNF521, a transcriptional regulator implicated in hematopoiesis, neurodevelopment, and cancer.
Gene Information Card
| Symbol | ZNF521 |
|---|---|
| Full Name | zinc finger protein 521 |
| Gene Type | protein-coding |
| Chromosomal Location | 18q11.2 |
| NCBI Gene ID | 25925 ncbi.nlm.nih.gov/gene/25925 |
| Ensembl ID | ENSG00000134371 |
| UniProt ID | Q96K83 |
| OMIM ID | 606255 |
| HGNC ID | 28986 |
| Aliases | EHZF, Zfp521, ZNF40, Zfp-521, hZFP521 |
Description
ZNF521 (zinc finger protein 521) encodes a transcription factor containing multiple C2H2-type zinc finger domains. It is involved in the regulation of gene expression during hematopoiesis, osteoblast differentiation, and neural development. ZNF521 interacts with co-repressors such as NCOR1 and HDACs to modulate chromatin remodeling and transcriptional repression. Aberrant expression or mutation of ZNF521 has been linked to leukemia, lymphoma, and other cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acute myeloid leukemia (AML) | ZNF521 acts as a transcriptional repressor of hematopoietic differentiation genes; overexpression or fusion with other genes (e.g., RUNX1) may block differentiation and promote leukemogenesis. | PMID: 21572410; COSMIC |
| B-cell acute lymphoblastic leukemia (B-ALL) | ZNF521 is recurrently rearranged or overexpressed in B-ALL, contributing to aberrant B-cell development. | PMID: 23292941; COSMIC |
| Osteoporosis | ZNF521 regulates osteoblast differentiation by repressing RUNX2; altered expression may affect bone mass. | PMID: 20010870 |
| Neurodevelopmental disorders | ZNF521 is expressed in neural progenitors; variants may disrupt cortical development, though direct evidence is limited. | ClinVar; PMID: 25485634 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone marrow | 12.5 | Medium |
| Brain (cerebral cortex) | 8.3 | Low |
| Lymph node | 15.1 | Medium |
| Testis | 6.7 | Low |
| Spleen | 10.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 18.4 | High expression; used in functional studies |
| HEK293 (embryonic kidney) | 7.2 | Moderate expression |
| SH-SY5Y (neuroblastoma) | 5.1 | Low expression |
| MCF7 (breast cancer) | 3.8 | Low 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% | Premature truncation; likely loss of function |
| c.567_568insG (p.Glu190fs) | Frameshift | <0.1% | Frameshift leading to nonsense-mediated decay |
| c.2101G>A (p.Gly701Ser) | Missense | 0.2% | Unknown significance; predicted benign by SIFT |
| ZNF521-RUNX1 fusion | Structural variant | Rare | Oncogenic fusion in AML; disrupts RUNX1 function |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations (e.g., p.Arg412*, p.Glu190fs) are predicted to cause loss of function via truncated protein or mRNA decay.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported; overexpression in leukemia may act as a dominant-negative or repressive gain.
Dominant Negative (DN)
ZNF521-RUNX1 fusion may act as a dominant-negative inhibitor of RUNX1-mediated transcription.
View complete mutation data：
Gene Ontology (GO)
Pathways
• RUNX1-regulated transcription in hematopoiesis
• NCOR/HDAC complex-mediated repression
• Osteoblast differentiation (BMP signaling)
Protein Summary
ZNF521 is a 1314-amino acid zinc finger protein that localizes to the nucleus and functions as a transcriptional repressor. It contains 30 C2H2-type zinc fingers and interacts with NCOR1, HDAC1, and RUNX1. Through these interactions, ZNF521 modulates chromatin structure and gene expression programs critical for hematopoietic stem cell maintenance, B-cell development, and osteoblast differentiation. Its dysregulation is implicated in leukemia and bone disorders.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ZNF521 Knockout HEK293 Cell Line | EDJ-KQ8306 | Human | 25925 | Details Get a Quote |
| ZNF521 Knockout HeLa Cell Line | EDJ-KQ55851 | Human | 25925 | Details Get a Quote |
| ZNF521 Knockout A-549 Cell Line | EDJ-KQ64340 | Human | 25925 | Details Get a Quote |
| ZNF521 Knockout HCT 116 Cell Line | EDJ-KQ72793 | Human | 25925 | Details Get a Quote |
