FLI1

Fli-1 proto-oncogene, ETS transcription factor, the group of ETS transcription factor family

Basic information

Region (hg38): 11:128686535-128813267

Links

ENSG00000151702 ∙ NCBI:2313 ∙ OMIM:193067 ∙ HGNC:3749 ∙ Uniprot:Q01543 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• bleeding disorder, platelet-type, 21 (Moderate), mode of inheritance: AD
• bleeding disorder, platelet-type, 21 (Limited), mode of inheritance: AR
• bleeding disorder, platelet-type, 21 (Strong), mode of inheritance: AD
• bleeding disorder, platelet-type, 21 (Moderate), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Thrombocytopenia, Paris-Trousseau type; Bleeding disorder, platelet type 21	AD/AR	Hematologic	Individuals may have bleeding tendency, and precautions (eg, in surgical situations) may be beneficial	Hematologic	14597985; 22887642; 24100448; 26316623; 28255014

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the FLI1 gene.

• Bleeding disorder, platelet-type, 21 (2 variants)
• Bleeding disorder platelet type macrothrombocytopenia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the FLI1 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				50	4	54
missense	1	2	52	1		56
nonsense	1		1			2
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region				7		7
non coding			3	16	40	59
Total	2	2	56	67	44

Highest pathogenic variant AF is 0.00000657

Variants in FLI1

This is a list of pathogenic ClinVar variants found in the FLI1 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-128693881-TG-T			Benign (Jun 18, 2021)
11-128693941-CGAGA-C			Benign (Jun 20, 2021)
11-128693941-CGAGAGA-C			Benign (Jun 19, 2021)
11-128693941-CGAGAGAGA-C			Benign (Jun 19, 2021)
11-128693941-CGAGAGAGAGA-C			Benign (Jun 18, 2021)
11-128693941-CGAGAGAGAGAGAGAGAGA-C			Benign (Jun 19, 2021)
11-128694265-G-T			Uncertain significance (Aug 05, 2022)
11-128694270-T-C			Likely benign (Aug 30, 2017)
11-128694274-AAG-T			Uncertain significance (Mar 07, 2019)
11-128694284-G-A			Likely benign (May 10, 2023)
11-128694286-G-A			Likely benign (Apr 30, 2023)
11-128694294-G-A			Likely benign (Nov 26, 2022)
11-128694294-G-T			Likely benign (Dec 25, 2023)
11-128694478-AC-A			Benign (Jun 18, 2021)
11-128694497-GC-G			Benign (Jun 18, 2021)
11-128694511-GC-G			Benign (Jun 19, 2021)
11-128694517-GC-G			Benign (Jun 18, 2021)
11-128694542-CG-C			Benign (Jun 18, 2021)
11-128694581-CA-C			Benign (Jun 18, 2021)
11-128694587-A-G			Benign (Jun 18, 2021)
11-128694592-A-C			Benign (Jun 18, 2021)
11-128757831-T-A			Benign (Nov 12, 2018)
11-128758111-G-T			Likely benign (Oct 24, 2023)
11-128758126-G-A			Likely benign (Jul 25, 2023)
11-128758132-G-A		FLI1-related disorder	Likely benign (Jul 06, 2021)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
FLI1	protein_coding	protein_coding	ENST00000527786	9	126733

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.989	0.0106	124926	0	4	124930	0.0000160

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	2.40	164	276	0.593	0.0000169	2978
Missense in Polyphen		51	111.98	0.45542		1167
Synonymous	-0.785	131	120	1.09	0.00000878	836
Loss of Function	4.00	2	22.5	0.0889	0.00000106	262

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00	0.00
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.00	0.00
European (Non-Finnish)	0.0000358	0.0000353
Middle Eastern	0.00	0.00
South Asian	0.00	0.00
Other	0.00	0.00

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Sequence-specific transcriptional activator (PubMed:24100448, PubMed:26316623, PubMed:28255014). Recognizes the DNA sequence 5'-C[CA]GGAAGT-3'. {ECO:0000269|PubMed:24100448, ECO:0000269|PubMed:26316623, ECO:0000269|PubMed:28255014}.
• Disease: DISEASE: Ewing sarcoma (ES) [MIM:612219]: A highly malignant, metastatic, primitive small round cell tumor of bone and soft tissue that affects children and adolescents. It belongs to the Ewing sarcoma family of tumors, a group of morphologically heterogeneous neoplasms that share the same cytogenetic features. They are considered neural tumors derived from cells of the neural crest. Ewing sarcoma represents the less differentiated form of the tumors. {ECO:0000269|PubMed:1522903, ECO:0000269|PubMed:1765382}. Note=The gene represented in this entry is involved in disease pathogenesis. A chromosomal aberration involving FLI1 is found in patients with Erwing sarcoma. Translocation t(11;22)(q24;q12) with EWSR1. {ECO:0000269|PubMed:1522903, ECO:0000269|PubMed:1765382}.; DISEASE: Bleeding disorder, platelet-type 21 (BDPLT21) [MIM:617443]: A disorder characterized by increased bleeding tendency due to platelet dysfunction. Clinical features include epistaxis, hematomas, bleeding after tooth extraction, and menorrhagia. BDPLT21 patients may have mild to moderate thrombocytopenia. {ECO:0000269|PubMed:24100448, ECO:0000269|PubMed:26316623, ECO:0000269|PubMed:28255014}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Transcriptional misregulation in cancer - Homo sapiens (human);Hematopoietic Stem Cell Differentiation;FGF (Consensus)

Intolerance Scores

• loftool: 0.368
• rvis_EVS: -0.89
• rvis_percentile_EVS: 10.3

Haploinsufficiency Scores

• pHI: 0.615
• hipred: Y
• hipred_score: 0.792
• ghis: 0.603

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: K
• gene_indispensability_pred: E
• gene_indispensability_score: 0.953

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Fli1
• Phenotype: endocrine/exocrine gland phenotype; growth/size/body region phenotype; muscle phenotype; immune system phenotype; cellular phenotype; liver/biliary system phenotype; embryo phenotype; neoplasm; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: fli1a
• Affected structure: head
• Phenotype tag: abnormal
• Phenotype quality: hemorrhagic

Gene ontology

• Biological process: regulation of transcription by RNA polymerase II;hemostasis;blood circulation;animal organ morphogenesis;cell differentiation;megakaryocyte development;positive regulation of transcription, DNA-templated;positive regulation of transcription by RNA polymerase II
• Cellular component: nucleus;cytosol;nuclear body
• Molecular function: RNA polymerase II proximal promoter sequence-specific DNA binding;RNA polymerase II distal enhancer sequence-specific DNA binding;DNA-binding transcription factor activity, RNA polymerase II-specific;DNA-binding transcription activator activity, RNA polymerase II-specific;DNA binding;chromatin binding;DNA-binding transcription factor activity;protein binding