EFEMP1 Gene

HGNC Family	Fibulins (FBLN)
Name	EGF containing fibulin-like extracellular matrix protein 1
Description	This gene encodes a member of the fibulin family of extracellular matrix glycoproteins. Like all members of this family, the encoded protein contains tandemly repeated epidermal growth factor-like repeats followed by a C-terminus fibulin-type domain. This gene is upregulated in malignant gliomas and may play a role in the aggressive nature of these tumors. Mutations in this gene are associated with Doyne honeycomb retinal dystrophy. Alternatively spliced transcript variants that encode the same protein have been described.[provided by RefSeq, Nov 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n EFEMP1, also known as fibulin‐3, is a multifunctional extracellular matrix protein whose roles vary markedly with tissue context and disease state. In the retina, wild‐type EFEMP1 is normally secreted where it helps maintain extracellular matrix homeostasis; however, a missense mutation (R345W) causes misfolding and inefficient secretion, leading to its aberrant intracellular and sub‐retinal accumulation. This misprocessing is implicated in the formation of drusen and the development of macular degenerative disorders such as Malattia Leventinese and age‐related macular degeneration (AMD)."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the oncologic setting, EFEMP1 exhibits context‐dependent functions. In pancreatic cancer, up‐regulation of EFEMP1 enhances tumor growth by stimulating vascular endothelial growth factor (VEGF) production, promoting angiogenesis, accelerating cell cycle progression, and inhibiting apoptosis through activation of signaling cascades including the epidermal growth factor receptor (EGFR)/Akt/MAPK pathways."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " By contrast, in breast cancer and lung cancer, promoter hypermethylation and consequent down‐regulation of EFEMP1 have been associated with poorer clinical outcomes, suggesting that in these contexts EFEMP1 may act as a tumor suppressor."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In addition, studies in gliomas reveal a role for secreted fibulin‐3 as a soluble activator of Notch signaling that promotes invasion and cell survival, while separate work in glioblastoma indicates that restoration of EFEMP1 can suppress tumor progression."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond cancer and ocular disease, EFEMP1 contributes to the organization and integrity of connective tissues. Efemp1‐deficient mice display an early onset of aging phenotypes, including elastic fiber abnormalities, generalized tissue atrophy, and an increased prevalence of hernias, underscoring its importance in maintaining fascia and elastin integrity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Moreover, genetic investigations have implicated EFEMP1 in the regulation of human growth, as variants in this extracellular matrix gene are associated with adult height variation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Additional studies in ovarian and prostate cancers, as well as in cervical carcinoma, further support the role of EFEMP1 as a critical modulator of the extracellular matrix that can influence angiogenesis and tumor behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "14", "end_ref": "16"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings illustrate that EFEMP1/fibulin‐3 is a versatile matrix protein with pivotal roles in ocular integrity, tumorigenesis, connective tissue maintenance, and growth regulation, where its dysregulation—whether through mutation, altered expression, or epigenetic modification—can have profound pathobiological consequences"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "17"}]}, {"type": "t", "text": ", \n "}, {"type": "a", "children": [{"type": "t", "text": "5–7"}], "href": "https://pubmed.ncbi.nlm.nih.gov/5–7"}, {"type": "t", "text": ", \n "}, {"type": "a", "children": [{"type": "t", "text": "8–11"}], "href": "https://pubmed.ncbi.nlm.nih.gov/8–11"}, {"type": "t", "text": ", \n "}, {"type": "a", "children": [{"type": "t", "text": "12–16"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12–16"}, {"type": "t", "text": ").\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lihua Y Marmorstein, Francis L Munier, Yvan Arsenijevic, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Aberrant accumulation of EFEMP1 underlies drusen formation in Malattia Leventinese and age-related macular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.202491599"}], "href": "https://doi.org/10.1073/pnas.202491599"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12242346"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12242346"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Philip A Klenotic, Francis L Munier, Lihua Y Marmorstein, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Tissue inhibitor of metalloproteinases-3 (TIMP-3) is a binding partner of epithelial growth factor-containing fibulin-like extracellular matrix protein 1 (EFEMP1). Implications for macular degenerations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M403026200"}], "href": "https://doi.org/10.1074/jbc.M403026200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15123717"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15123717"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Lihua Y Marmorstein, Precious J McLaughlin, Neal S Peachey, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Formation and progression of sub-retinal pigment epithelium deposits in Efemp1 mutation knock-in mice: a model for the early pathogenic course of macular degeneration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddm199"}], "href": "https://doi.org/10.1093/hmg/ddm199"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17664227"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17664227"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Michael K Lin, Jin Yang, Chun Wei Hsu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HTRA1, an age-related macular degeneration protease, processes extracellular matrix proteins EFEMP1 and TSP1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Aging Cell (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/acel.12710"}], "href": "https://doi.org/10.1111/acel.12710"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29730901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29730901"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Hendrik Seeliger, Peter Camaj, Ivan Ischenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EFEMP1 expression promotes in vivo tumor growth in human pancreatic adenocarcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-08-0132"}], "href": "https://doi.org/10.1158/1541-7786.MCR-08-0132"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19208748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19208748"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Peter Camaj, Hendrik Seeliger, Ivan Ischenko, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EFEMP1 binds the EGF receptor and activates MAPK and Akt pathways in pancreatic carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/BC.2009.140"}], "href": "https://doi.org/10.1515/BC.2009.140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19804359"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19804359"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ariane Sadr-Nabavi, Juliane Ramser, Juliane Volkmann, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Cancer (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ijc.24108"}], "href": "https://doi.org/10.1002/ijc.24108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19115204"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19115204"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Wen Yue, Sanja Dacic, Quanhong Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Cancer Res (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1078-0432.CCR-07-0015"}], "href": "https://doi.org/10.1158/1078-0432.CCR-07-0015"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17671114"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17671114"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Bin Hu, Mohan S Nandhu, Hosung Sim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Fibulin-3 promotes glioma growth and resistance through a novel paracrine regulation of Notch signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-12-1060"}], "href": "https://doi.org/10.1158/0008-5472.CAN-12-1060"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22665268"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22665268"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Yuanjie Hu, Peter Dion Pioli, Eric Siegel, et al. 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Synonyms	DRAD, MTLV, FIBL-3, S1-5, DHRD, MLVT, FBLN3, FBNL
Proteins	FBLN3_HUMAN
NCBI Gene ID	2202
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

EFEMP1 has 11,882 functional associations with biological entities spanning 9 categories (molecular profile, organism, chemical, disease, phenotype or trait, functional term, phrase or reference, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 126 datasets.

Click the + buttons to view associations for EFEMP1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

EFEMP1 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 EFEMP1 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 EFEMP1 gene relative to other tissues from the Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of EFEMP1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse 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 EFEMP1 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 Microarray	tissue samples with high or low expression of EFEMP1 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by RNA-seq	tissue samples with high or low expression of EFEMP1 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 EFEMP1 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 EFEMP1 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 EFEMP1 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 EFEMP1 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 EFEMP1 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of EFEMP1 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 EFEMP1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with EFEMP1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with EFEMP1 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 EFEMP1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of EFEMP1 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 EFEMP1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with EFEMP1 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing EFEMP1 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 EFEMP1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing EFEMP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing EFEMP1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with EFEMP1 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 EFEMP1 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with EFEMP1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with EFEMP1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with EFEMP1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with EFEMP1 gene in GWAS and other genetic association datasets from the dbGAP Gene-Trait Associations dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by EFEMP1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving EFEMP1 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with EFEMP1 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with EFEMP1 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 EFEMP1 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 EFEMP1 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 EFEMP1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with EFEMP1 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 EFEMP1 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 EFEMP1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of EFEMP1 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.