ZNF274
protein-codingzinc finger protein 274, the group of Zinc fingers C2H2-type|SCAN domain containing
Gene summary
This gene encodes a zinc finger protein containing five C2H2-type zinc finger domains, one or two Kruppel-associated box A (KRAB A) domains, and a leucine-rich domain. The encoded protein has been suggested to be a transcriptional repressor. It localizes predominantly to the nucleolus. Alternatively spliced transcript variants encoding different isoforms exist. These variants utilize alternative polyadenylation signals. [provided by RefSeq, Jul 2008]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~30.5 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 ZNF274 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_133502.3. 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 | 3 | 1 | 4 | |||
| missense | 29 | 29 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 1 | 1 | ||||
| Total | 0 | 0 | 33 | 1 | 0 | 34 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_598009.1 | 7 | MANE Select | |
| Ensembl | ENSP00000484810.1 | 7 | MANE Select | |
| RefSeq | NP_001265663.1 | 6 | Standard | |
| RefSeq | NP_057408.2 | 4 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Neurotrophin signaling pathway - Homo sapiens (human)
- Gene expression (Transcription)
- Generic Transcription Pathway
- RNA Polymerase II Transcription
- p75(NTR)-mediated signaling
Biological Process
- regulation of transcription, DNA-templated
- regulation of transcription by RNA polymerase II
- regulation of histone H3-K9 trimethylation
- negative regulation of nucleic acid-templated transcription
Molecular Function
- DNA-binding transcription factor activity, RNA polymerase II-specific
- chromatin binding
- DNA-binding transcription factor activity
- transcription corepressor activity
- protein binding
Cellular Component
- nucleolus
- cytoplasm
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000326804
- Coding exons
- 8
- Length
- 30533
- Individuals with no LoFs
- 5089
- Homozygous LoFs
- 120537
- Heterozygous LoFs
- 2
- Defined
- 125628
- p
- 0.799
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 1.09 | 292 | 349 | 0.836 | 0.0000194 | 4249 |
| Missense (PolyPhen) | 75 | 108.64 | 0.69036 | 1329 | ||
| Synonymous | 0.923 | 121 | 135 | 0.899 | 0.00000713 | 1253 |
| Loss of Function | 3.65 | 7 | 27.8 | 0.252 | 0.00000146 | 311 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 1.0 | 0.69 | notable |
| Latino/Admixed American | 1.0 | 0.82 | notable |
| Ashkenazi Jewish | 1.0 | 0.85 | notable |
| East Asian | 1.0 | 0.81 | notable |
| Finnish | 1.0 | 0.85 | notable |
| European (Non-Finnish) | 1.0 | 0.79 | notable |
| South Asian | 1.0 | 0.84 | notable |
| Other | 1.0 | 0.81 | notable |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Probable transcription repressor. Specifically binds to the 3'-end of zinc-finger coding genes and recruiting chromatin- modifying proteins such as SETDB1 and TRIM28/KAP1, leading to transcription repression. The SETDB1-TRIM28-ZNF274 complex may play a role in recruiting ATRX to the 3'-exons of zinc-finger coding genes with atypical chromatin signatures to establish or maintain/protect H3K9me3 at these transcriptionally active regions (PubMed:27029610). {ECO:0000269|PubMed:10777669, ECO:0000269|PubMed:27029610}.;
Recessive Scores
- pRec
- 0.106
Essentials
- Essential (CRISPR2)
- N
- Indispensability pred.
- E
- Indispensability score
- 1.00
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |