FLI1

Chr 11ADAR

Fli-1 proto-oncogene, ETS transcription factor

Also known as: BDPLT21, EWSR2, FLI-1, SIC-1

NCBI Gene: 2313ENSG00000151702UniProt: Q01543OMIM: 193067

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.

OMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismAD/ARLOEUF 0.281 OMIM phenotype
Clinical Summary— FLI1
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Gene-Disease Validity (ClinGen)
bleeding disorder, platelet-type, 21 · ADModerate

Moderate evidence — consider for supplementary testing

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Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.99). One damaged copy is likely sufficient to cause disease.
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ClinVar Variants
89 unique Pathogenic / Likely Pathogenic· 127 VUS of 395 total submissions
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Clinical Trials
2 active or recruiting trials — potential therapeutic options may be available
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint
0.28LOEUF
pLI 0.989
Z-score 4.00
OE 0.09 (0.04–0.28)
Highly constrained

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

Missense Constraint
2.40Z-score
OE missense 0.59 (0.52–0.68)
164 obs / 276.4 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.09 (0.04–0.28)
0≤0.351.4
Missense OE0.59 (0.52–0.68)
0≤0.61.4
Synonymous OE1.09
0≤1.21.6
LoF obs/exp: 2 / 22.5Missense obs/exp: 164 / 276.4Syn Z: -0.79
DN
0.3892th %ile
GOF
0.3094th %ile
LOF
0.82top 5%

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

LOFprediction above median · 1 literature citation · LOEUF 0.28

Literature Evidence

LOFFli1 haploinsufficiency underlies Paris-Trousseau thrombopeniaPMID:15525489

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

395 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic79
Likely Pathogenic10
VUS127
Likely Benign108
Benign44
Conflicting6
79
Pathogenic
10
Likely Pathogenic
127
VUS
108
Likely Benign
44
Benign
6
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
2
75
0
79
Likely Pathogenic
3
2
5
0
10
VUS
6
108
13
0
127
Likely Benign
0
1
30
77
108
Benign
0
0
39
5
44
Conflicting
—6
Total1111316282374

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.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Integrated analysis reveals FLI1 regulates the tumor immune microenvironment via its cell-type-specific expression and transcriptional regulation of distinct target genes of immune cells in breast cancer
Pei J et al.·BMC Genomics
2024
The importance of fusion protein activity in Ewing sarcoma and the cell intrinsic and extrinsic factors that regulate it: A review
Apfelbaum AA et al.·Front Oncol
2022Review
RUNX2 Represses the EWS-FLI1-mediated Transcription in Ewing's Sarcoma Cells
Kitagawa T et al.·Cancer Genomics Proteomics
2026
Ewing sarcoma from molecular biology to the clinic
Dupuy M et al.·Front Cell Dev Biol
2023
Fli1 deficiency suppresses RALDH1 activity of dermal dendritic cells and related induction of regulatory T cells: a possible role in scleroderma
Miura S et al.·Arthritis Res Ther
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
The Molecular Taxonomy of Primary Prostate Cancer.
Cancer Genome Atlas Research Network·Cell
2015
Emerging therapies in Ewing sarcoma.
Strauss SJ et al.·Curr Opin Oncol
2024Review
Pseudomyogenic Hemangioendothelioma.
Al-Qaderi A et al.·Arch Pathol Lab Med
2019Review
The Epigenetic Regulation of Scleroderma and Its Clinical Application.
Luo Y et al.·Adv Exp Med Biol
2020Review
STAG2 loss rewires oncogenic and developmental programs to promote metastasis in Ewing sarcoma.
Adane B et al.·Cancer Cell
2021
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Trabectedin and low-dose irinotecan to target EWS::FLI1 in Ewing sarcoma: a phase 1/2 trial.
Grohar PJ et al.·Nat Med
2026
Acute Myeloid Leukemia, Myelodysplasia-Related (AML-MR), With del(5q) and Double Minutes Containing Chromosomal Segment 11q24 Leading to Amplification and Expression of FLI1.
Hiya S et al.·Case Rep Hematol
2026Open Access
STAG2 loss amplifies EWS-FLI1-driven microsatellite enhancer activity promoting Ewing sarcoma aggressiveness.
Eyunni S et al.·Proc Natl Acad Sci U S A
2026Open Access
Tissue-Specific Expression of the EWSR1::FLI1 Fusion Protein Identifies col2a1a-Positive Cells as a Source of Ewing Sarcoma-like Tumors in Zebrafish.
Anderson RA et al.·Int J Mol Sci
2026Open AccessFunctional
A positive SPTBN2-FLI1 feedback axis promotes bladder cancer via PI3K/AKT activation.
Guo X et al.·Cell Signal
2026
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients