FLI1
Chr 11ADARFli-1 proto-oncogene, ETS transcription factor
Also known as: BDPLT21, EWSR2, FLI-1, SIC-1
FLI1 encodes a transcription factor with an ETS DNA-binding domain that functions as a sequence-specific transcriptional activator. Mutations cause bleeding disorder, platelet-type, 21, inherited in both autosomal dominant and autosomal recessive patterns. The gene is highly constrained against loss-of-function variants (pLI 0.99, LOEUF 0.28), indicating intolerance to functional disruption.
Primary Disease Associations & Inheritance
Moderate evidence — consider for supplementary testing
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly LoF-intolerant (top ~10% of genes)
Moderately missense-constrained (top ~2.5%)
The highest-scoring mechanism for this gene is loss-of-function (haploinsufficiency).
Literature Evidence
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
200 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 0 | 12 | 0 | 13 |
Likely Pathogenic | 1 | 1 | 3 | 0 | 5 |
VUS | 3 | 69 | 8 | 0 | 80 |
Likely Benign | 0 | 0 | 14 | 23 | 37 |
Benign | 0 | 0 | 39 | 4 | 43 |
Conflicting | — | 1 | |||
| Total | 5 | 70 | 76 | 27 | 179 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
FLI1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
Lurbinectedin in FET-Fused Tumors
RECRUITINGFertility Preservation in Children With Solid Tumors: Detection of Residual Disease by a Sensitive Method
RECRUITINGExternal Resources
Links to major genomics databases and tools