ORC4 Gene

HGNC Family	ATPases
Name	origin recognition complex, subunit 4
Description	The origin recognition complex (ORC) is a highly conserved six subunit protein complex essential for the initiation of the DNA replication in eukaryotic cells. Studies in yeast demonstrated that ORC binds specifically to origins of replication and serves as a platform for the assembly of additional initiation factors such as Cdc6 and Mcm proteins. This gene encodes a subunit of the ORC complex. Several alternatively spliced transcript variants, some of which encode the same protein, have been reported for this gene. [provided by RefSeq, Oct 2010]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nORC4 is a highly conserved subunit of the eukaryotic origin recognition complex (ORC) that plays a central role in the initiation of DNA replication. Studies in mammalian cells and model organisms demonstrate that ORC4 is constitutively expressed throughout the cell cycle, interacts with other ORC subunits such as ORC2, and exhibits intrinsic DNA binding properties. In particular, its ability to preferentially target non‐canonical DNA structures—such as triplex or bubble-like regions formed within AT‐rich domains of replication origins—suggests that ORC4 is instrumental in selecting and remodeling replication origins for efficient pre‐replicative complex assembly."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in ORC4 have been directly implicated in human developmental disorders such as Meier-Gorlin syndrome (MGS). In affected individuals, missense mutations in ORC4—as well as in other members of the pre-replication complex—lead to impaired replication initiation. For example, the introduction of a conserved missense mutation (comparable to human alleles) into yeast results in a prolonged S-phase attributed to compromised origin firing at the ribosomal DNA locus, thereby linking defective ORC4 function to critical cellular outcomes including reduced rDNA copy number and perturbed ribosome biogenesis. Genotype-phenotype correlations in MGS emphasize the essential role of ORC4 in cell-cycle progression and organismal growth."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional evidence of ORC4’s biological importance comes from oncology, where a novel A286V mutation within the ORC4L gene has been observed in patients with B-cell lymphoproliferative disorders. Although the mechanistic consequences remain to be fully clarified, the presence of this mutation in advanced disease stages—and its association with favorable clinical outcomes following chemotherapy—suggests that ORC4 mutations may serve as prognostic markers in certain neoplastic conditions, further underscoring the multifaceted role of ORC4 in both normal cell proliferation and disease."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "J Springer, M Kneissl, V Pütter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification and characterization of MmORC4 and MmORC5, two subunits of the mouse origin of replication recognition complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Chromosoma (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s004120050374"}], "href": "https://doi.org/10.1007/s004120050374"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10460412"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10460412"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sahar Sibani, Gerald B Price, Maria Zannis-Hadjopoulos "}, {"type": "b", "children": [{"type": "t", "text": "Ku80 binds to human replication origins prior to the assembly of the ORC complex."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochemistry (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1021/bi047327n"}], "href": "https://doi.org/10.1021/bi047327n"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15910003"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15910003"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "J Kusic, B Tomic, A Divac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human initiation protein Orc4 prefers triple stranded DNA."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Rep (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s11033-009-9735-8"}], "href": "https://doi.org/10.1007/s11033-009-9735-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19690980"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19690980"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Branko Tomic, Jelena Kusic-Tisma "}, {"type": "b", "children": [{"type": "t", "text": "HsOrc4-Dependent Dna Remodeling of the ori-β Dhfr Replicator."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Biol Lett (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1515/cmble-2015-0032"}], "href": "https://doi.org/10.1515/cmble-2015-0032"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26124052"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26124052"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Duane L Guernsey, Makoto Matsuoka, Haiyan Jiang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mutations in origin recognition complex gene ORC4 cause Meier-Gorlin syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.777"}], "href": "https://doi.org/10.1038/ng.777"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21358631"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21358631"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Sonja A de Munnik, Louise S Bicknell, Salim Aftimos, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Meier-Gorlin syndrome genotype-phenotype studies: 35 individuals with pre-replication complex gene mutations and 10 without molecular diagnosis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Hum Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ejhg.2011.269"}], "href": "https://doi.org/10.1038/ejhg.2011.269"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22333897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22333897"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Joseph C Sanchez, Elizabeth X Kwan, Thomas J Pohl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective replication initiation results in locus specific chromosome breakage and a ribosomal RNA deficiency in yeast."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1007041"}], "href": "https://doi.org/10.1371/journal.pgen.1007041"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29036220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29036220"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Milica Radojkovic, Slobodan Ristic, Aleksandra Divac, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Novel ORC4L gene mutation in B-cell lymphoproliferative disorders."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Sci (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MAJ.0b013e3181b7f17c"}], "href": "https://doi.org/10.1097/MAJ.0b013e3181b7f17c"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20010161"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20010161"}]}]}]}
Synonyms	ORC4P, ORC4L
Proteins	ORC4_HUMAN
NCBI Gene ID	5000
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

ORC4 has 5,917 functional associations with biological entities spanning 8 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA) extracted from 119 datasets.

Click the + buttons to view associations for ORC4 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

ORC4 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 ORC4 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 ORC4 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 ORC4 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 ORC4 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 ORC4 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving ORC4 protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of ORC4 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 ORC4 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 ORC4 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 ORC4 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 ORC4 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with ORC4 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with ORC4 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 ORC4 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of ORC4 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 ORC4 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with ORC4 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of ORC4 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing ORC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing ORC4 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing ORC4 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 ORC4 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 ORC4 protein in abstracts of biomedical publications from the COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 dataset.
	CORUM Protein Complexes	protein complexs containing ORC4 protein from the CORUM Protein Complexes dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with ORC4 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with ORC4 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with ORC4 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving ORC4 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with ORC4 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 ORC4 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 ORC4 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 ORC4 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 ORC4 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with ORC4 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 ORC4 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 ORC4 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of ORC4 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 ORC4 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with ORC4 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with ORC4 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.