ERG
protein-codingETS transcription factor ERG, the group of ETS transcription factor family
Gene summary
This gene encodes a member of the erythroblast transformation-specific (ETS) family of transcriptions factors. All members of this family are key regulators of embryonic development, cell proliferation, differentiation, angiogenesis, inflammation, and apoptosis. The protein encoded by this gene is mainly expressed in the nucleus. It contains an ETS DNA-binding domain and a PNT (pointed) domain which is implicated in the self-association of chimeric oncoproteins. This protein is required for platelet adhesion to the subendothelium, inducing vascular cell remodeling. It also regulates hematopoesis, and the differentiation and maturation of megakaryocytic cells. This gene is involved in chromosomal translocations, resulting in different fusion gene products, such as TMPSSR2-ERG and NDRG1-ERG in prostate cancer, EWS-ERG in Ewing's sarcoma and FUS-ERG in acute myeloid leukemia. More than two dozens of transcript variants generated from combinatorial usage of three alternative promoters and multiple alternative splicing events have been reported, but the full-length nature of many of these variants has not been determined. [provided by RefSeq, Apr 2014]
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~281.8 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
Inheritance Pattern: AD
Disease ID:MONDO:0957954
Submitter: Ambry Genetics
Inheritance Pattern: AD
Disease ID:MONDO:0018881
Submitter: PanelApp Australia
Clinical Genomic Database (CGD)
Manifestation: Cardiovascular
Intervention: General
Rationale: Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing
Comments: Reported clinical information has been limited
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to ERG variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_182918.4. 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 | 2 | ||||
| missense | 45 | 45 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 3 | 1 | 4 | |||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 3 | 0 | 49 | 2 | 0 | 54 |
Highest pathogenic variant AF is 0.000006571857
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_891548.1 | 10 | MANE Select | |
| Ensembl | ENSP00000288319.7 | 10 | MANE Select | |
| RefSeq | NP_001129626.1 | 10 | Standard | |
| RefSeq | NP_001129627.1 | 8 | Standard |
Model Organisms & Knockout Phenotypes
Observed phenotypic effects in mouse and zebrafish models
| Gene / Model | Organism | Observed Phenotype |
|---|---|---|
| erg | Danio rerio | Structure: intersegmental vessel Quality: irregular spatial pattern abnormal |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Prostate cancer - Homo sapiens (human)
- Transcriptional misregulation in cancer - Homo sapiens (human)
- TarBasePathway
- miR-targeted genes in muscle cell - TarBase
- Androgen Receptor Network in Prostate Cancer
Biological Process
- regulation of transcription by RNA polymerase II
- protein phosphorylation
- signal transduction
- multicellular organism development
- cell population proliferation
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
- DNA binding
- protein binding
Cellular Component
- nucleus
- cytoplasm
- ribonucleoprotein complex
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000417133
- Coding exons
- 10
- Length
- 281756
- Individuals with no LoFs
- 125670
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 8
- Defined
- 125678
- p
- 0.0000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 2.53 | 174 | 297 | 0.587 | 0.0000183 | 3190 |
| Missense (PolyPhen) | 33 | 94.471 | 0.34931 | 1033 | ||
| Synonymous | 0.228 | 118 | 121 | 0.974 | 0.00000862 | 925 |
| Loss of Function | 3.93 | 3 | 23.6 | 0.127 | 0.00000101 | 287 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.00012 | 0.00012 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000055 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.0000088 | 0.0000088 | rare |
| South Asian | 0.000066 | 0.000065 | rare |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Transcriptional regulator. May participate in transcriptional regulation through the recruitment of SETDB1 histone methyltransferase and subsequent modification of local chromatin structure.;
- Disease
- DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. {ECO:0000269|PubMed:8076344}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ERG has been found in patients with Erwing sarcoma. Translocation t(21;22)(q22;q12) with EWSR1. {ECO:0000269|PubMed:8076344}.; DISEASE: Note=Chromosomal aberrations involving ERG have been found in acute myeloid leukemia (AML). Translocation t(16;21)(p11;q22) with FUS (PubMed:8187069). Translocation t(X;21)(q25-26;q22) with ELF4 (PubMed:16303180). {ECO:0000269|PubMed:16303180, ECO:0000269|PubMed:8187069}.;
Recessive Scores
- pRec
- 0.303
Intolerance Scores
- LoFtool
- 0.0739
- RVIS EVS
- -0.6
- RVIS percentile EVS
- 17.91
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- N
- Essential (gene trap)
- K
- Indispensability pred.
- E
- Indispensability score
- 0.873
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |