HOMER3 Gene

HGNC Family	Homer scaffolding proteins (HOMER)
Name	homer scaffolding protein 3
Description	This gene encodes a member of the HOMER family of postsynaptic density scaffolding proteins that share a similar domain structure consisting of an N-terminal Enabled/vasodilator-stimulated phosphoprotein homology 1 domain which mediates protein-protein interactions, and a carboxy-terminal coiled-coil domain and two leucine zipper motifs that are involved in self-oligomerization. The encoded protein binds numerous other proteins including group I metabotropic glutamate receptors, inositol 1,4,5-trisphosphate receptors and amyloid precursor proteins and has been implicated in diverse biological functions such as neuronal signaling, T-cell activation and trafficking of amyloid beta peptides. Alternative splicing results in multiple transcript variants.[provided by RefSeq, Mar 2009]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n HOMER3 is a multifunctional scaffolding protein whose roles vary markedly with the cellular context. In non‐neuronal cells such as pancreatic acinar cells, for example, Homer3 appears dispensable for proper calcium signaling, suggesting that not all functions of Homer proteins are universally required (see."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In the immune system, Homer3, acting together with Homer2, negatively regulates T‐cell activation by modulating transcriptional programs linked to key factors such as NFAT, thereby influencing cytokine expression and effector T‐cell populations."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, in cellular contexts involved in adhesion and cytoskeletal organization, Homer3 binds to the EVH1 binding site of hFat1, and this competitive interaction with other EVH1 domain proteins suggests a role in coordinating cell morphology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the nervous system, Homer3 has been identified as an interacting partner of the transcriptional regulator PAX6, implying that synaptic activity might be coupled to nuclear events that govern neuronal development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Furthermore, in cancer‐related contexts, Homer3 emerges with distinct roles. In triple-negative breast cancer, Homer3 is selectively overexpressed and facilitates growth factor–induced β‐Catenin activation by acting as a scaffold that brings together c‐Src and β‐Catenin, thereby promoting tumor aggressiveness and metastasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": " Similarly, in aggressive bladder cancers, aberrant cell surface expression of Homer3—with a specific pattern of short-chain O-glycans—is associated with enhanced cellular invasion and worse prognosis, particularly under nutrient-deprived conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings highlight the context-dependent versatility of Homer3. Its involvement in regulating immune responses, linking synaptic activity to transcription, and promoting oncogenic signaling—as well as its apparently minimal role in modulating Ca2+ dynamics in certain peripheral tissues—demonstrates that Homer3 is a pivotal organizer of protein-protein interactions in diverse biological processes.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Dong Min Shin, Marlin Dehoff, Xiang Luo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Homer 2 tunes G protein-coupled receptors stimulus intensity by regulating RGS proteins and PLCbeta GAP activities."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.200210109"}], "href": "https://doi.org/10.1083/jcb.200210109"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12860966"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12860966"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Guo N Huang, David L Huso, Samuel Bouyain, et al. "}, {"type": "b", "children": [{"type": "t", "text": "NFAT binding and regulation of T cell activation by the cytoplasmic scaffolding Homer proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1151227"}], "href": "https://doi.org/10.1126/science.1151227"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18218901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18218901"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Dietmar Schreiner, Kathrin Müller, H Werner Hofer "}, {"type": "b", "children": [{"type": "t", "text": "The intracellular domain of the human protocadherin hFat1 interacts with Homer signalling scaffolding proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.febslet.2006.08.079"}], "href": "https://doi.org/10.1016/j.febslet.2006.08.079"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16979624"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16979624"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Simon T Cooper, Isabel M Hanson "}, {"type": "b", "children": [{"type": "t", "text": "A screen for proteins that interact with PAX6: C-terminal mutations disrupt interaction with HOMER3, DNCL1 and TRIM11."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genet (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2156-6-43"}], "href": "https://doi.org/10.1186/1471-2156-6-43"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16098226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16098226"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Qinghua Liu, Lixin He, Siqi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "HOMER3 facilitates growth factor-mediated β-Catenin tyrosine phosphorylation and activation to promote metastasis in triple negative breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hematol Oncol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13045-020-01021-x"}], "href": "https://doi.org/10.1186/s13045-020-01021-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33407765"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33407765"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Andreia Peixoto, Dylan Ferreira, Rita Azevedo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Glycoproteomics identifies HOMER3 as a potentially targetable biomarker triggered by hypoxia and glucose deprivation in bladder cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Clin Cancer Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13046-021-01988-6"}], "href": "https://doi.org/10.1186/s13046-021-01988-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34108014"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34108014"}]}]}]}
Synonyms	VESL3, HOMER-3
Proteins	HOME3_HUMAN
NCBI Gene ID	9454
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HOMER3 has 7,856 functional associations with biological entities spanning 8 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) extracted from 125 datasets.

Click the + buttons to view associations for HOMER3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HOMER3 Gene

Functional Associations

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

	Dataset	Summary
	Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles	tissues with high or low expression of HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HOMER3 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 HOMER3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HOMER3 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HOMER3 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 HOMER3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HOMER3 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 HOMER3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CM4AI KOLF21J CRISPRi Gene Perturbation Atlas	gene perturbations changing expression of HOMER3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset.
	CM4AI U2OS Cell Map Protein Localization Assemblies	assemblies containing HOMER3 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 HOMER3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HOMER3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HOMER3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HOMER3 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 HOMER3 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 HOMER3 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 HOMER3 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	COSMIC Cell Line Gene CNV Profiles	cell lines with high or low copy number of HOMER3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HOMER3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HOMER3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HOMER3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HOMER3 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 HOMER3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Text-mining Gene-Disease Association Evidence Scores	diseases co-occuring with HOMER3 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 HOMER3 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 HOMER3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HOMER3 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 HOMER3 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 HOMER3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HOMER3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset.
	ESCAPE Omics Signatures of Genes and Proteins for Stem Cells	PubMedIDs of publications reporting gene signatures containing HOMER3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.