ETS1

Chr 11

ETS proto-oncogene 1, transcription factor

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

NCBI Gene: 2113 ENSG00000134954 UniProt: P14921 OMIM: 164720

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.

OMIM ResearchSummary from RefSeq, UniProt

This gene encodes a member of the ETS family of transcription factors, which are defined by the presence of a conserved ETS DNA-binding domain that recognizes the core consensus DNA sequence GGAA/T in target genes. These proteins function either as transcriptional activators or repressors of numerous genes, and are involved in stem cell development, cell senescence and death, and tumorigenesis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Jul 2011]

OMIM ResearchGenerating clinical summary…

LOFmechanismLOEUF 0.39

Clinical Summary— ETS1

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Gene-Disease Validity (ClinGen)

congenital heart disease · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)

Moderately constrained gene (pLI 0.78) — some intolerance to loss-of-function variants.

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Clinical Trials

1 active or recruiting trial — potential therapeutic options may be available

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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Moderate LoF intolerance

LoF Constraint?

0.39LOEUF

pLI 0.782

Z-score 3.92

OE 0.19 (0.10–0.39)

Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?

2.52Z-score

OE missense 0.58 (0.51–0.66)

165 obs / 284.5 exp

Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?

LoF OE?0.19 (0.10–0.39)

0≤0.351.4

Missense OE?0.58 (0.51–0.66)

0≤0.61.4

Synonymous OE?0.99

0≤1.21.6

LoF obs/exp: 5 / 27.0Missense obs/exp: 165 / 284.5Syn Z: 0.06

This gene — mechanism propensity

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.