ETS1

Chr 11

ETS proto-oncogene 1, transcription factor

Also known as: ETS-1, EWSR2, c-ets-1, p54

This transcription factor directly controls expression of cytokine and chemokine genes and regulates lymphoid cell differentiation, survival and proliferation. Mutations cause autosomal dominant thrombocytopenia with elevated serum ETS1, characterized by bleeding tendency and immune dysregulation. The gene is highly constrained against loss-of-function variants (LOEUF 0.389), indicating that haploinsufficiency is likely not tolerated.

Summary from RefSeq, UniProt
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1
Active trials
120
Pubs (1 yr)
77
P/LP submissions
0%
P/LP missense
0.39
LOEUF
LOF
Mechanism· predicted
Clinical SummaryETS1
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Gene-Disease Validity (ClinGen)
congenital heart disease · ADModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.
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ClinVar Variants
77 unique Pathogenic / Likely Pathogenic· 29 VUS of 123 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.39LOEUF
pLI 0.782
Z-score 3.92
OE 0.19 (0.100.39)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.52Z-score
OE missense 0.58 (0.510.66)
165 obs / 284.5 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.19 (0.100.39)
00.351.4
Missense OE0.58 (0.510.66)
00.61.4
Synonymous OE0.99
01.21.6
LoF obs/exp: 5 / 27.0Missense obs/exp: 165 / 284.5Syn Z: 0.06
DN
0.5082th %ile
GOF
0.3590th %ile
LOF
0.65top 25%

The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).

LOFprediction above median · LOEUF 0.39

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

123 submitted variants in ClinVar

Classification Summary

Pathogenic72
Likely Pathogenic5
VUS29
Likely Benign2
Benign5
72
Pathogenic
5
Likely Pathogenic
29
VUS
2
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
0
71
0
72
Likely Pathogenic
0
0
5
0
5
VUS
0
28
1
0
29
Likely Benign
0
1
0
1
2
Benign
0
0
1
4
5
Total129785113

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

ETS1 · protein map & ClinVar variants

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

Clinical Literature
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