ETV6
ETS variant transcription factor 6, the group of ETS transcription factor family
Basic information
Region (hg38): 12:11649674-11895377
Links
Phenotypes
GenCC
Source:
- acute myeloid leukemia (Strong), mode of inheritance: AD
- thrombocytopenia 5 (Strong), mode of inheritance: AD
- acute myeloid leukemia (Limited), mode of inheritance: Unknown
- thrombocytopenia 5 (Definitive), mode of inheritance: AD
- hereditary thrombocytopenia and hematologic cancer predisposition syndrome (Supportive), mode of inheritance: AD
- thrombocytopenia 5 (Definitive), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Thrombocytopenia 5 | AD | Hematologic; Oncologic | Individuals have bleeding tendency, and awareness may allow preventive measures and early management of bleeding episodes; Individuals are at risk of hematologic malignancy (other other cancer types have also been reported), and awareness may allow early diagnosis and management; HSCT has been described | Hematologic; Oncologic | 25581430; 25807284 |
ClinVar
This is a list of variants' phenotypes submitted to
- Inborn_genetic_diseases (523 variants)
- not_provided (330 variants)
- not_specified (42 variants)
- Thrombocytopenia_5 (37 variants)
- ETV6-related_disorder (33 variants)
- Thrombocytopenia (13 variants)
- Acute_myeloid_leukemia (4 variants)
- Hematologic_neoplasm (3 variants)
- Abnormal_bleeding (2 variants)
- Acute_lymphoid_leukemia (2 variants)
- See_cases (2 variants)
- Hereditary_cancer-predisposing_syndrome (1 variants)
- EBV-positive_nodal_T-_and_NK-cell_lymphoma (1 variants)
- Hermansky-Pudlak_syndrome_1 (1 variants)
- Malignant_lymphoma,_large_B-cell,_diffuse (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the ETV6 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000001987.5. Only rare variants are included in the table.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 207 | 209 | ||||
| missense | 11 | 300 | 59 | 373 | ||
| nonsense | 14 | |||||
| start loss | 0 | |||||
| frameshift | 16 | 23 | ||||
| splice donor/acceptor (+/-2bp) | 10 | 16 | ||||
| Total | 27 | 29 | 312 | 266 | 1 |
Highest pathogenic variant AF is 0.00000656892
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| ETV6 | protein_coding | protein_coding | ENST00000396373 | 8 | 245549 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.974 | 0.0265 | 125739 | 0 | 7 | 125746 | 0.0000278 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 1.78 | 196 | 280 | 0.700 | 0.0000176 | 2973 |
| Missense in Polyphen | 25 | 80.763 | 0.30955 | 897 | ||
| Synonymous | -1.32 | 128 | 110 | 1.16 | 0.00000698 | 882 |
| Loss of Function | 4.02 | 3 | 24.4 | 0.123 | 0.00000162 | 226 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000615 | 0.0000615 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.0000462 | 0.0000462 |
| European (Non-Finnish) | 0.0000353 | 0.0000352 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000328 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Transcriptional repressor; binds to the DNA sequence 5'- CCGGAAGT-3'. Plays a role in hematopoiesis and malignant transformation. {ECO:0000269|PubMed:25581430}.;
- Disease
- DISEASE: Note=A chromosomal aberration involving ETV6 is found in a form of chronic myelomonocytic leukemia (CMML). Translocation t(5;12)(q33;p13) with PDGFRB. It is characterized by abnormal clonal myeloid proliferation and by progression to acute myelogenous leukemia (AML). {ECO:0000269|PubMed:8168137}.; DISEASE: Note=Chromosomal aberrations involving ETV6 are found in acute myeloid leukemia (AML). Translocation t(12;22)(p13;q11) with MN1 (PubMed:7731705). Translocation t(4;12)(q12;p13) with CHIC2 (PubMed:10477709). {ECO:0000269|PubMed:10477709, ECO:0000269|PubMed:7731705}.; DISEASE: Note=Chromosomal aberrations involving ETV6 are found in childhood acute lymphoblastic leukemia (ALL). Translocations t(12;21)(p12;q22) and t(12;21)(p13;q22) with RUNX1/AML1. {ECO:0000269|PubMed:7761424}.; DISEASE: Note=A chromosomal aberration involving ETV6 is found in a form of pre-B acute lymphoid leukemia. Translocation t(9;12)(p24;p13) with JAK2. {ECO:0000269|PubMed:9326218}.; DISEASE: Note=A chromosomal aberration involving ETV6 and JAK2 is found in an atypical chronic myelogenous leukemia. Translocation t(9;15;12)(p24;q15;p13). {ECO:0000269|PubMed:9326218}.; DISEASE: Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS) with basophilia. Translocation t(5;12)(q31;p13) with ACSL6. {ECO:0000269|PubMed:10502316}.; DISEASE: Note=A chromosomal aberration involving ETV6 is found in acute eosinophilic leukemia (AEL). Translocation t(5;12)(q31;p13) with ACSL6. {ECO:0000269|PubMed:10502316}.; DISEASE: Note=A chromosomal aberration involving ETV6 is found in myelodysplastic syndrome (MDS). Translocation t(1;12)(p36.1;p13) with MDS2. {ECO:0000269|PubMed:12203785}.; DISEASE: Note=A chromosomal aberration involving ETV6 is found in acute lymphoblastic leukemia. Translocation t(9;12)(p13;p13) with PAX5. {ECO:0000269|PubMed:17344859}.; DISEASE: Myeloproliferative disorder chronic with eosinophilia (MPE) [MIM:131440]: A hematologic disorder characterized by malignant eosinophils proliferation. {ECO:0000269|PubMed:12181402}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving ETV6 is found in many instances of myeloproliferative disorder chronic with eosinophilia. Translocation t(5;12) with PDGFRB on chromosome 5 creating an ETV6-PDGFRB fusion protein. {ECO:0000269|PubMed:12181402}.; DISEASE: Leukemia, acute myelogenous (AML) [MIM:601626]: A subtype of acute leukemia, a cancer of the white blood cells. AML is a malignant disease of bone marrow characterized by maturational arrest of hematopoietic precursors at an early stage of development. Clonal expansion of myeloid blasts occurs in bone marrow, blood, and other tissue. Myelogenous leukemias develop from changes in cells that normally produce neutrophils, basophils, eosinophils and monocytes. {ECO:0000269|PubMed:15806161}. Note=The gene represented in this entry is involved in disease pathogenesis.; DISEASE: Thrombocytopenia 5 (THC5) [MIM:616216]: Thrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting. THC5 is an autosomal dominant disorder, associated with an increased susceptibility to the development of hematologic and solid malignancies. {ECO:0000269|PubMed:25581430}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Transcriptional misregulation in cancer - Homo sapiens (human);Hematopoietic Stem Cell Gene Regulation by GABP alpha-beta Complex;Exercise-induced Circadian Regulation;FGF
(Consensus)
Recessive Scores
- pRec
- 0.514
Intolerance Scores
- loftool
- 0.177
- rvis_EVS
- -0.62
- rvis_percentile_EVS
- 17.16
Haploinsufficiency Scores
- pHI
- 0.914
- hipred
- Y
- hipred_score
- 0.825
- ghis
- 0.565
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- K
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.803
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Etv6
- Phenotype
- endocrine/exocrine gland phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype; cellular phenotype; homeostasis/metabolism phenotype; digestive/alimentary phenotype; neoplasm; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; embryo phenotype; immune system phenotype;
Zebrafish Information Network
- Gene name
- etv6
- Affected structure
- whole organism
- Phenotype tag
- abnormal
- Phenotype quality
- has extra parts of type
Gene ontology
- Biological process
- negative regulation of transcription by RNA polymerase II;regulation of transcription by RNA polymerase II;vitellogenesis;neurogenesis;cell differentiation;positive regulation of transcription by RNA polymerase II;hematopoietic stem cell proliferation;mesenchymal cell apoptotic process
- Cellular component
- nucleus;nucleolus;cytosol
- Molecular function
- RNA polymerase II regulatory region sequence-specific DNA binding;RNA polymerase II proximal promoter sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription repressor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA-binding transcription factor activity;protein binding;protein domain specific binding