ETV4
protein-codingETS variant transcription factor 4, the group of ETS transcription factor family
Gene summary
Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of keratinocyte differentiation and positive regulation of transcription by RNA polymerase II. Located in nucleolus. [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 ~51.8 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 ETV4 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001079675.5. 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 | 2 | 5 | |||
| missense | 1 | 85 | 3 | 3 | 92 | |
| nonsense | 1 | 1 | 2 | |||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 1 | 92 | 6 | 3 | 102 |
Highest pathogenic variant AF is 0.00012019514
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001073143.1 | 12 | MANE Select | |
| Ensembl | ENSP00000321835.4 | 12 | MANE Select | |
| RefSeq | NP_001248366.1 | 11 | Standard | |
| RefSeq | NP_001248367.1 | 11 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| etv4 | Danio rerio | Structure: pronephros Quality: has fewer parts of type abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Transcriptional misregulation in cancer - Homo sapiens (human)
- Androgen Receptor Network in Prostate Cancer
- Signal Transduction
- MAPK6/MAPK4 signaling
- MAPK family signaling cascades
Biological Process
- regulation of transcription by RNA polymerase II
- cell differentiation
- positive regulation of transcription by RNA polymerase II
Molecular Function
- RNA polymerase II proximal promoter sequence-specific DNA binding
- DNA-binding transcription factor activity, RNA polymerase II-specific
- DNA-binding transcription activator activity, RNA polymerase II-specific
- protein binding
Cellular Component
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000319349
- Coding exons
- 12
- Length
- 51777
- Individuals with no LoFs
- 125704
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 44
- Defined
- 125748
- p
- 0.000175
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.558 | 263 | 290 | 0.908 | 0.0000169 | 3135 |
| Missense (PolyPhen) | 101 | 125 | 0.80799 | 1387 | ||
| Synonymous | -0.132 | 126 | 124 | 1.01 | 0.00000768 | 950 |
| Loss of Function | 2.22 | 17 | 30.1 | 0.564 | 0.00000161 | 306 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00025 | 0.00025 | rare |
| Latino/Admixed American | 0.00017 | 0.00017 | rare |
| Ashkenazi Jewish | 0.00011 | 0.000099 | rare |
| East Asian | 0.00087 | 0.00082 | rare |
| Finnish | 0.00014 | 0.00014 | rare |
| European (Non-Finnish) | 0.000080 | 0.000079 | rare |
| South Asian | 0.00013 | 0.00013 | rare |
| Other | 0.00033 | 0.00033 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional activator that binds to the enhancer of the adenovirus E1A gene; the core-binding sequence is 5'[AC]GGA[AT]GT-3'. {ECO:0000269|PubMed:19307308}.;
Recessive Scores
- pRec
- 0.460
Intolerance Scores
- LoFtool
- 0.868
- RVIS EVS
- 0.29
- RVIS percentile EVS
- 71.5
Essentials
- Essential (CRISPR)
- N
- Essential (CRISPR2)
- N
- Essential (gene trap)
- N
- Indispensability pred.
- E
- Indispensability score
- 0.996
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |