ZNF451
protein-codingzinc finger protein 451, the group of Zinc fingers C2H2-type
Gene summary
Enables SUMO ligase activity; transcription corepressor activity; and transcription regulator inhibitor activity. Involved in negative regulation of transcription initiation by RNA polymerase II; negative regulation of transforming growth factor beta receptor signaling pathway; and protein sumoylation. Located in PML body. [provided by Alliance of Genome Resources, Jul 2025]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~83.5 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 ZNF451 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001031623.3. 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 | 1 | 1 | 2 | |||
| missense | 101 | 7 | 108 | |||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 4 | 4 | ||||
| Total | 0 | 0 | 106 | 8 | 0 | 114 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001026794.1 | 15 | MANE Select | |
| Ensembl | ENSP00000359740.4 | 15 | MANE Select | |
| RefSeq | NP_001244202.1 | 4 | Standard | |
| RefSeq | NP_056370.2 | 14 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Biological Process
- regulation of gene expression
- protein sumoylation
- negative regulation of transforming growth factor beta receptor signaling pathway
- negative regulation of transcription initiation from RNA polymerase II promoter
- negative regulation of histone H3-K9 acetylation
Molecular Function
- RNA polymerase II core promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- nucleic acid binding
- transcription corepressor activity
- protein binding
Cellular Component
- nucleus
- PML body
- histone methyltransferase complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000370706
- Coding exons
- 15
- Length
- 83464
- Individuals with no LoFs
- 125636
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 111
- Defined
- 125747
- p
- 0.000441
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.10 | 467 | 539 | 0.866 | 0.0000264 | 7124 |
| Missense (PolyPhen) | 187 | 253.21 | 0.73853 | 3312 | ||
| Synonymous | 0.0161 | 184 | 184 | 0.998 | 0.00000888 | 1856 |
| Loss of Function | 2.79 | 27 | 47.8 | 0.564 | 0.00000261 | 644 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00012 | 0.00012 | rare |
| Latino/Admixed American | 0.00036 | 0.00035 | rare |
| Ashkenazi Jewish | 0.00030 | 0.00030 | rare |
| East Asian | 0.00017 | 0.00016 | rare |
| Finnish | 0.0019 | 0.0018 | notable |
| European (Non-Finnish) | 0.00038 | 0.00038 | rare |
| South Asian | 0.00020 | 0.00020 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: E3 SUMO-protein ligase; has a preference for SUMO2 and SUMO3 and facilitates UBE2I/UBC9-mediated sumoylation of target proteins (PubMed:26524493, PubMed:26524494). Plays a role in protein SUMO2 modification in response to stress caused by DNA damage and by proteasome inhibitors (in vitro). Required for MCM4 sumoylation (By similarity). Has no activity with SUMO1 (PubMed:26524493). Preferentially transfers an additional SUMO2 chain onto the SUMO2 consensus site 'Lys-11' (PubMed:26524493). Negatively regulates transcriptional activation mediated by the SMAD4 complex in response to TGF-beta signaling. Inhibits EP300- mediated acetylation of histone H3 at 'Lys-9' (PubMed:24324267). Plays a role in regulating the transcription of AR targets (PubMed:18656483). {ECO:0000250|UniProtKB:Q8C0P7, ECO:0000269|PubMed:18656483, ECO:0000269|PubMed:24324267, ECO:0000269|PubMed:26524493, ECO:0000269|PubMed:26524494}.;
Recessive Scores
- pRec
- 0.0975
Intolerance Scores
- LoFtool
- 0.860
- RVIS EVS
- -0.78
- RVIS percentile EVS
- 13.05
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.802
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |