FIP1L1 Gene

Name	factor interacting with PAPOLA and CPSF1
Description	This gene encodes a subunit of the CPSF (cleavage and polyadenylation specificity factor) complex that polyadenylates the 3' end of mRNA precursors. This gene, the homolog of yeast Fip1 (factor interacting with PAP), binds to U-rich sequences of pre-mRNA and stimulates poly(A) polymerase activity. Its N-terminus contains a PAP-binding site and its C-terminus an RNA-binding domain. An interstitial chromosomal deletion on 4q12 creates an in-frame fusion of human genes FIP1L1 and PDGFRA (platelet-derived growth factor receptor, alpha). The FIP1L1-PDGFRA fusion gene encodes a constitutively activated tyrosine kinase that joins the first 233 amino acids of FIP1L1 to the last 523 amino acids of PDGFRA. This gene fusion and chromosomal deletion is the cause of some forms of idiopathic hypereosinophilic syndrome (HES). This syndrome, recently reclassified as chronic eosinophilic leukemia (CEL), is responsive to treatment with tyrosine kinase inhibitors. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Oct 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n FIP1L1 is a multifunctional protein whose normal role is associated with mRNA 3′‐end processing as a component of the cleavage and polyadenylation specificity factor (CPSF) complex. In a subset of myeloproliferative neoplasms and eosinophilic disorders, an interstitial deletion on chromosome 4q12 leads to the formation of an aberrant fusion gene in which FIP1L1 is joined to the platelet‐derived growth factor receptor α (PDGFRA) gene. This fusion results in a constitutively activated tyrosine kinase that drives uncontrolled proliferation and survival of eosinophils and related hematopoietic cells, underpinning conditions such as the hypereosinophilic syndrome and chronic eosinophilic leukemia (see."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " Although the FIP1L1 moiety itself does not intrinsically activate PDGFRA’s kinase activity, its fusion serves to eliminate a critical autoinhibitory juxtamembrane domain of PDGFRA, thereby permitting ligand‐independent dimerization and continuous downstream signaling that promotes cellular transformation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " The resulting FIP1L1–PDGFRA fusion protein exhibits exquisite sensitivity to tyrosine kinase inhibitors such as imatinib, which has revolutionized the treatment of these otherwise aggressive disorders. However, resistance mutations (for example, T674I) have been documented, underlining the need for alternative targeted strategies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Moreover, systematic screening for FIP1L1–PDGFRA serves both as a diagnostic tool and a guide for rational targeted therapies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jan Cools, Daniel J DeAngelo, Jason Gotlib, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A tyrosine kinase created by fusion of the PDGFRA and FIP1L1 genes as a therapeutic target of imatinib in idiopathic hypereosinophilic syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "N Engl J Med (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1056/NEJMoa025217"}], "href": "https://doi.org/10.1056/NEJMoa025217"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12660384"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12660384"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Animesh Pardanani, Rhett P Ketterling, Stephanie R Brockman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHIC2 deletion, a surrogate for FIP1L1-PDGFRA fusion, occurs in systemic mastocytosis associated with eosinophilia and predicts response to imatinib mesylate therapy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-05-1627"}], "href": "https://doi.org/10.1182/blood-2003-05-1627"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12842979"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12842979"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Animesh Pardanani, Stephanie R Brockman, Sarah F Paternoster, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FIP1L1-PDGFRA fusion: prevalence and clinicopathologic correlates in 89 consecutive patients with moderate to severe eosinophilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2004-03-0787"}], "href": "https://doi.org/10.1182/blood-2004-03-0787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15284118"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15284118"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Elizabeth H Stover, Jing Chen, Cedric Folens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activation of FIP1L1-PDGFRalpha requires disruption of the juxtamembrane domain of PDGFRalpha and is FIP1L1-independent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0601192103"}], "href": "https://doi.org/10.1073/pnas.0601192103"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16690743"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16690743"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "E Lierman, L Michaux, E Beullens, et al. "}, {"type": "b", "children": [{"type": "t", "text": "FIP1L1-PDGFRalpha D842V, a novel panresistant mutant, emerging after treatment of FIP1L1-PDGFRalpha T674I eosinophilic leukemia with single agent sorafenib."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/leu.2009.2"}], "href": "https://doi.org/10.1038/leu.2009.2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19212337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19212337"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "J Pan, A Quintás-Cardama, T Manshouri, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The novel tyrosine kinase inhibitor EXEL-0862 induces apoptosis in human FIP1L1-PDGFR-alpha-expressing cells through caspase-3-mediated cleavage of Mcl-1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.leu.2404714"}], "href": "https://doi.org/10.1038/sj.leu.2404714"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17495975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17495975"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "J Score, C Curtis, K Waghorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a novel imatinib responsive KIF5B-PDGFRA fusion gene following screening for PDGFRA overexpression in patients with hypereosinophilia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Leukemia (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/sj.leu.2404154"}], "href": "https://doi.org/10.1038/sj.leu.2404154"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16498388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16498388"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Jan Cools, Hilmar Quentmeier, Brian J P Huntly, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The EOL-1 cell line as an in vitro model for the study of FIP1L1-PDGFRA-positive chronic eosinophilic leukemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2003-07-2479"}], "href": "https://doi.org/10.1182/blood-2003-07-2479"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14630792"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14630792"}]}]}]}
Synonyms	HFIP1
Proteins	FIP1_HUMAN
NCBI Gene ID	81608
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

FIP1L1 has 7,581 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, functional term, phrase or reference, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 124 datasets.

Click the + buttons to view associations for FIP1L1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

FIP1L1 Gene

Functional Associations

Please acknowledge the Harmonizome in your publications by citing the following reference(s):

	Dataset	Summary
	Achilles Cell Line Gene Essentiality Profiles	cell lines with fitness changed by FIP1L1 gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FIP1L1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles	tissue samples with high or low expression of FIP1L1 gene relative to other tissue samples from the Allen Brain Atlas Aging Dementia and Traumatic Brain Injury Tissue Sample Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of FIP1L1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq dataset.
	Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of FIP1L1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of FIP1L1 gene relative to other cell lines from the BioGPS Cell Line Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FIP1L1 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset.
	BioGPS Mouse Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of FIP1L1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	Carcinogenome Chemical Perturbation Carcinogenicity Signatures	small molecule perturbations changing expression of FIP1L1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of FIP1L1 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset.
	CCLE Cell Line Gene Expression Profiles	cell lines with high or low expression of FIP1L1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with FIP1L1 gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with FIP1L1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with FIP1L1 gene from the CellMarker Gene-Cell Type Associations dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FIP1L1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of FIP1L1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets dataset.
	ChEA Transcription Factor Targets 2022	transcription factors binding the promoter of FIP1L1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing FIP1L1 protein from integrated AP-MS and IF data from the CM4AI U2OS Cell Map Protein Localization Assemblies dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of FIP1L1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing FIP1L1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing FIP1L1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing FIP1L1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing FIP1L1 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with FIP1L1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025	cellular components co-occuring with FIP1L1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing FIP1L1 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of FIP1L1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with FIP1L1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with FIP1L1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with FIP1L1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with FIP1L1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving FIP1L1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with FIP1L1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with FIP1L1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores 2025	diseases co-occuring with FIP1L1 gene in abstracts of biomedical publications from the DISEASES Text-mining Gene-Disease Assocation Evidence Scores 2025 dataset.
	DisGeNET Gene-Disease Associations	diseases associated with FIP1L1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with FIP1L1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at FIP1L1 gene from the ENCODE Histone Modification Site Profiles dataset.
	ENCODE Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of FIP1L1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of FIP1L1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.