ETV6

ETS variant transcription factor 6, the group of ETS transcription factor family

Basic information

Region (hg38): 12:11649673-11895377

Links

ENSG00000139083 ∙ NCBI:2120 ∙ OMIM:600618 ∙ HGNC:3495 ∙ Uniprot:P41212 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• 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: CGD

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 ClinVar and linked to the ETV6 gene.

• not provided (205 variants)
• not specified (41 variants)
• Thrombocytopenia 5 (21 variants)
• Inborn genetic diseases (11 variants)
• ETV6-related condition (10 variants)
• Thrombocytopenia (6 variants)
• Hematologic neoplasm;Thrombocytopenia (3 variants)
• Abnormal bleeding;Thrombocytopenia (2 variants)
• See cases (2 variants)
• Acute lymphoid leukemia;Thrombocytopenia (1 variants)
• Acute myeloid leukemia (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.

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.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			2	35	4	41
missense	1	5	89	3		98
nonsense	2	3	1			6
start loss						0
frameshift	2	2	1			5
inframe indel			3			3
splice donor/acceptor (+/-2bp)	2	3	4			9
splice region			6	4	1	11
non coding			2	31	37	70
Total	7	13	102	69	41

Variants in ETV6

This is a list of pathogenic ClinVar variants found in the ETV6 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
12-11649797-C-CG			Likely benign (Nov 08, 2020)
12-11650099-G-A		not specified	Uncertain significance (Aug 02, 2023)
12-11650121-G-A		ETV6-related disorder	Likely benign (Oct 13, 2022)
12-11650133-T-C			Likely benign (Oct 27, 2023)
12-11650144-C-A			Uncertain significance (Nov 28, 2022)
12-11650150-G-T		Inborn genetic diseases	Uncertain significance (Nov 21, 2022)
12-11650161-G-A		Malignant lymphoma, large B-cell, diffuse	Likely pathogenic (Jul 25, 2023)
12-11650167-A-G		not specified	Likely benign (Jan 02, 2024)
12-11650170-T-A		ETV6-related disorder	Likely benign (Dec 28, 2023)
12-11650170-T-C			Likely benign (Nov 07, 2023)
12-11650172-C-T			Likely benign (Jan 19, 2024)
12-11650174-C-T			Likely benign (Sep 08, 2023)
12-11650175-C-T			Likely benign (Oct 13, 2022)
12-11650179-CCTT-C			Likely benign (Jun 13, 2022)
12-11650180-C-T			Likely benign (Mar 26, 2023)
12-11650286-A-C			Benign (Apr 09, 2019)
12-11650294-A-G			Benign (Apr 09, 2019)
12-11650344-T-TC			Benign (Nov 27, 2018)
12-11650345-C-G			Likely benign (Jun 06, 2019)
12-11650349-C-CG			Benign (Mar 24, 2019)
12-11650369-G-C			Benign (Dec 21, 2018)
12-11650397-T-C			Likely benign (Jan 28, 2019)
12-11650420-A-G			Benign (Apr 03, 2019)
12-11650453-C-T			Likely benign (Jan 06, 2019)
12-11650466-C-T			Likely benign (Aug 15, 2019)

GnomAD

Source: gnomAD

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: dbNSFP

• 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