ZNF521
protein-codingzinc finger protein 521, the group of Zinc fingers C2H2-type
Gene summary
Enables protein domain specific binding activity. Predicted to be involved in regulation of transcription by RNA polymerase II. Located in nucleoplasm. [provided by Alliance of Genome Resources, Jun 2026]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~290.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ZNF521 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_015461.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | 3 | 1 | 6 | ||
| missense | 135 | 1 | 136 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | 1 | ||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 139 | 4 | 1 | 144 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_056276.1 | 7 | MANE Select | |
| Ensembl | ENSP00000354794.3 | 7 | MANE Select | |
| RefSeq | NP_001295154.1 | 5 | Standard | |
| Ensembl | ENSP00000382352.2 | 5 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RUNX2 regulates osteoblast differentiation
- RUNX2 regulates bone development
- Transcriptional regulation by RUNX2
- Gene expression (Transcription)
- Generic Transcription Pathway
Biological Process
- regulation of transcription by RNA polymerase II
- neuron fate commitment
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA binding
- protein domain specific binding
- metal ion binding
Cellular Component
- nucleus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000361524
- Coding exons
- 7
- Length
- 290265
- Individuals with no LoFs
- 125729
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 3
- Defined
- 125732
- p
- 0.0000119
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.45 | 539 | 725 | 0.744 | 0.0000406 | 8842 |
| Missense (PolyPhen) | 184 | 301.29 | 0.61071 | 3881 | ||
| Synonymous | -1.23 | 313 | 287 | 1.09 | 0.0000181 | 2373 |
| Loss of Function | 6.32 | 1 | 48.5 | 0.0206 | 0.00000283 | 583 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0 | 0.0 | absent |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0 | 0.0 | absent |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000026 | 0.000026 | rare |
| South Asian | 0 | 0.0 | absent |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcription factor that can both act as an activator or a repressor depending on the context. Involved in BMP signaling and in the regulation of the immature compartment of the hematopoietic system. Associates with SMADs in response to BMP2 leading to activate transcription of BMP target genes. Acts as a transcriptional repressor via its interaction with EBF1, a transcription factor involved specification of B-cell lineage; this interaction preventing EBF1 to bind DNA and activate target genes. {ECO:0000269|PubMed:14630787}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving ZNF521 is found in acute lymphoblastic leukemia. Translocation t(9;18)(p13;q11.2) with PAX5. The translocation generates the PAX5-ZNF521 oncogene consisting of the N-terminus part of PAX5 and the C-terminus part of ZNF521. {ECO:0000269|PubMed:17344859}.;
Recessive Scores
- pRec
- 0.108
Intolerance Scores
- LoFtool
- 0.00496
- RVIS EVS
- -1.77
- RVIS percentile EVS
- 2.32
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.927
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |