RHBDF1 Gene

HGNC Family	Rhomboid family (RHB)
Name	rhomboid 5 homolog 1 (Drosophila)
Description	Predicted to enable growth factor binding activity and serine-type endopeptidase activity. Involved in several processes, including negative regulation of protein secretion; regulation of epidermal growth factor receptor signaling pathway; and regulation of proteasomal protein catabolic process. Located in Golgi membrane and endoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRHBDF1 is an atypical multi‐transmembrane protein that localizes primarily to the endoplasmic reticulum and Golgi, and although it lacks the critical residues of an active serine protease, it plays pivotal regulatory roles in cancer cell biology. Initial studies revealed that RHBDF1 is highly upregulated in epithelial cancers such as invasive ductal carcinoma and head and neck cancers, where its silencing leads to apoptosis or autophagy through marked attenuation of key growth signals like activated AKT and ERK."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " Moreover, RHBDF1 participates in G protein–coupled receptor (GPCR)-stimulated transactivation of the epidermal growth factor receptor (EGFR) by promoting the secretion of latent EGFR ligands such as transforming growth factor–α (TGFα), while its activity remains dispensable for direct EGFR stimulation by exogenous ligands."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " In addition, RHBDF1 interacts with proteins involved in hypoxic signaling; for instance, by binding to RACK1 it prevents oxygen-independent degradation of HIF1α, thereby enhancing survival signals in cancer cells under low oxygen conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in sustaining mitogenic and survival signals, RHBDF1 also promotes oncogenesis by driving cell proliferation and epithelial-to-mesenchymal transition (EMT) in colorectal cancers through the upregulation of effectors such as APC, c-myc, CyclinD1, MMP-14, and Twist."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " A further layer of regulation is provided by alternative splicing; a variant transcript (RHBDF1 X6) that predominates in normal tissues acts as a natural inhibitor of RHBDF1 activities by blocking the maturation of TACE and the intracellular trafficking of pro-TGFα."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " In melanoma, high levels of RHBDF1 maintain elevated glycolytic enzyme expression – notably protecting glucose-6-phosphate isomerase from lysosomal degradation via interference with TRIM32 binding – which supports tumor metabolism, dampens immune infiltration, and ultimately contributes to resistance to immunotherapy."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Takatoshi Nakagawa, Annabel Guichard, Carolina Perez Castro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Characterization of a human rhomboid homolog, p100hRho/RHBDF1, which interacts with TGF-alpha family ligands."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Dyn (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/dvdy.20450"}], "href": "https://doi.org/10.1002/dvdy.20450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15965977"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15965977"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Zhenwen Yan, Huafei Zou, Fang Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rhomboid family-1 gene silencing causes apoptosis or autophagy to epithelial cancer cells and inhibits xenograft tumor growth."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Ther (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1535-7163.MCT-08-0104"}], "href": "https://doi.org/10.1158/1535-7163.MCT-08-0104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18524845"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18524845"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Huafei Zou, Sufi M Thomas, Zhen-Wen Yan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rhomboid family-1 gene RHBDF1 participates in GPCR-mediated transactivation of EGFR growth signals in head and neck squamous cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.08-112771"}], "href": "https://doi.org/10.1096/fj.08-112771"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18832597"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18832597"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Jie Li, Tai-Ran Bai, Shan Gao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rhomboid family-1 modulates clathrin coated vesicle-dependent pro-transforming growth factor α membrane trafficking to promote breast cancer progression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "EBioMedicine (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ebiom.2018.09.038"}], "href": "https://doi.org/10.1016/j.ebiom.2018.09.038"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30279141"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30279141"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Zhuan Zhou, Fangfang Liu, Zhi-Song Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human rhomboid family-1 suppresses oxygen-independent degradation of hypoxia-inducible factor-1α in breast cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/0008-5472.CAN-13-1027"}], "href": "https://doi.org/10.1158/0008-5472.CAN-13-1027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24648344"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24648344"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Huiping Yuan, Ran Wei, Yuhong Xiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RHBDF1 regulates APC-mediated stimulation of the epithelial-to-mesenchymal transition and proliferation of colorectal cancer cells in part via the Wnt/β-catenin signalling pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Exp Cell Res (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.yexcr.2018.04.009"}], "href": "https://doi.org/10.1016/j.yexcr.2018.04.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29654741"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29654741"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Renpeng Ji, Qianqian Shi, Yixin Cao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Alternative splicing of the human rhomboid family-1 gene RHBDF1 inhibits epidermal growth factor receptor activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jbc.2022.102033"}], "href": "https://doi.org/10.1016/j.jbc.2022.102033"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "35595096"}], "href": "https://pubmed.ncbi.nlm.nih.gov/35595096"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Lei Wang, Yuan-Yuan Song, Yan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RHBDF1 deficiency suppresses melanoma glycolysis and enhances efficacy of immunotherapy by facilitating glucose-6-phosphate isomerase degradation via TRIM32."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pharmacol Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.phrs.2023.106995"}], "href": "https://doi.org/10.1016/j.phrs.2023.106995"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37979663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37979663"}]}]}]}
Synonyms	GENE-89, EGFR-RS, GENE-90, HDIST1, C16ORF8, DIST1
Proteins	RHDF1_HUMAN
NCBI Gene ID	64285
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RHBDF1 has 5,367 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 106 datasets.

Click the + buttons to view associations for RHBDF1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RHBDF1 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 RHBDF1 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 RHBDF1 gene relative to other tissues from the Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles dataset.
	Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray	tissue samples with high or low expression of RHBDF1 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 RHBDF1 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 RHBDF1 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 RHBDF1 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 RHBDF1 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 RHBDF1 gene relative to other cell types and tissues from the BioGPS Mouse Cell Type and Tissue Gene Expression Profiles dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RHBDF1 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 RHBDF1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RHBDF1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RHBDF1 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 RHBDF1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RHBDF1 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 RHBDF1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RHBDF1 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RHBDF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RHBDF1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RHBDF1 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 RHBDF1 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 RHBDF1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RHBDF1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RHBDF1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RHBDF1 protein relative to other small molecule perturbations from the DeepCoverMOA Drug Mechanisms of Action dataset.
	DepMap CRISPR Gene Dependency	cell lines with fitness changed by RHBDF1 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores 2025	diseases associated with RHBDF1 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 RHBDF1 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 RHBDF1 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 RHBDF1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RHBDF1 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 RHBDF1 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 RHBDF1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RHBDF1 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 RHBDF1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RHBDF1 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with RHBDF1 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RHBDF1 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RHBDF1 gene in literature-supported statements describing functions of genes from the GeneRIF Biological Term Annotations dataset.
	GeneSigDB Published Gene Signatures	PubMedIDs of publications reporting gene signatures containing RHBDF1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RHBDF1 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.