ETV6

Chr 12AD

ETS variant transcription factor 6

Also known as: TEL, TEL/ABL, THC5

This gene encodes an ETS family transcription factor. The product of this gene contains two functional domains: a N-terminal pointed (PNT) domain that is involved in protein-protein interactions with itself and other proteins, and a C-terminal DNA-binding domain. Gene knockout studies in mice suggest that it is required for hematopoiesis and maintenance of the developing vascular network. This gene is known to be involved in a large number of chromosomal rearrangements associated with leukemia and congenital fibrosarcoma. [provided by RefSeq, Sep 2008]

Primary Disease Associations & Inheritance

Leukemia, acute myeloid, somaticMIM #601626
Thrombocytopenia 5MIM #616216
AD
UniProtMyeloproliferative disorder chronic with eosinophilia
3
Active trials
200
Pubs (1 yr)
0
P/LP submissions
P/LP missense
0.32
LOEUF· LoF intol.
Multiple*
Mechanism· predicted
Clinical SummaryETV6
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Gene-Disease Validity (ClinGen)
thrombocytopenia 5 · ADDefinitive

Definitive — sufficient evidence for diagnostic panels

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.97). One damaged copy is likely sufficient to cause disease.
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Clinical Trials
3 active or recruiting trials — potential therapeutic options may be available
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GeneReview available — ETV6
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.32LOEUF
pLI 0.974
Z-score 4.02
OE 0.12 (0.060.32)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
1.78Z-score
OE missense 0.70 (0.620.79)
196 obs / 279.9 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.12 (0.060.32)
00.351.4
Missense OE0.70 (0.620.79)
00.61.4
Synonymous OE1.16
01.21.6
LoF obs/exp: 3 / 24.4Missense obs/exp: 196 / 279.9Syn Z: -1.32
DN
0.2798th %ile
GOF
0.1999th %ile
LOF
0.78top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · 1 literature citation · LOEUF 0.32
DN1 literature citation

Literature Evidence

DNMissense variants retained dimerization with wild-type ETV6 with potentially dominant-negative effects.PMID:32693409
LOFHaploinsufficiency of ETV6 and CDKN1B in patients with acute myeloid leukemia and complex karyotype.PMID:25213837

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

ETV6 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗