RUSC2 Gene

Name	RUN and SH3 domain containing 2
Description	This gene encodes a RUN and SH3 domain containing protein that interacts with Rab1b and Rab1-binding protein GM130. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Jun 2012]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRUSC2 plays a critical role in intracellular vesicle trafficking by acting as an adaptor protein. In neurons and other cell types, RUSC2 associates with the AP‐4 complex to facilitate the exit of ATG9A‐positive vesicles from the trans‐Golgi network and their directed transport toward the cell periphery—an essential process for autophagosome biogenesis and proper autophagy regulation. Structural studies further reveal that RUSC2 couples ATG9A‐containing vesicles to kinesin‐1 by engaging its light chain, thereby promoting microtubule plus‐end directed movement."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to its role in vesicular transport, RUSC2 functions in regulating cell polarity, migration, and receptor trafficking. In lung cancer cells, RUSC2 interacts with the SHD of GIT2 to stabilize GIT2 by decreasing its degradation and enhancing its phosphorylation, which is vital for the proper reorientation of the Golgi toward the leading edge and for directional cell migration. High‐resolution structural analysis of the Rab35–RUSC2 complex shows that RUSC2 utilizes a “pseudo‐arginine finger” to stabilize GTP‐bound Rab35, underscoring its broader contribution to membrane trafficking. Moreover, RUSC2 is implicated in the basal transport of unstimulated EGFR from the Golgi to the cell surface, a process that is essential for normal cellular responses and proliferation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its protein functions, a circular RNA derived from the RUSC2 locus (circ_RUSC2) has been identified to play a role in vascular smooth muscle cells where it modulates proliferation, migration, and apoptosis via a miR‐661/SYK signaling axis. In a parallel strand of investigation, inherited mutations in RUSC2 have been associated with central hypotonia, microcephaly, intellectual disability, and epilepsy, reinforcing the importance of RUSC2 in neuronal development and function."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Alexandra K Davies, Daniel N Itzhak, James R Edgar, et al. "}, {"type": "b", "children": [{"type": "t", "text": "AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-06172-7"}], "href": "https://doi.org/10.1038/s41467-018-06172-7"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30262884"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30262884"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Carlos M Guardia, Akansha Jain, Rafael Mattera, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RUSC2 and WDR47 oppositely regulate kinesin-1-dependent distribution of ATG9A to the cell periphery."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Biol Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1091/mbc.E21-06-0295"}], "href": "https://doi.org/10.1091/mbc.E21-06-0295"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34432492"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34432492"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Biao Duan, Jie Cui, Shixiu Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGF-stimulated activation of Rab35 regulates RUSC2-GIT2 complex formation to stabilize GIT2 during directional lung cancer cell migration."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2016.05.027"}], "href": "https://doi.org/10.1016/j.canlet.2016.05.027"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27238570"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27238570"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Lin Lin, Yingdong Shi, Mengli Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rab35/ACAP2 and Rab35/RUSC2 Complex Structures Reveal Molecular Basis for Effector Recognition by Rab35 GTPase."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Structure (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.str.2019.02.008"}], "href": "https://doi.org/10.1016/j.str.2019.02.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30905672"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30905672"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Eric C Tom, Insha Mushtaq, Bhopal C Mohapatra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EHD1 and RUSC2 Control Basal Epidermal Growth Factor Receptor Cell Surface Expression and Recycling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00434-19"}], "href": "https://doi.org/10.1128/MCB.00434-19"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31932478"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31932478"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Jingang Sun, Zhigang Zhang, Shuguo Yang "}, {"type": "b", "children": [{"type": "t", "text": "Circ_RUSC2 upregulates the expression of miR-661 target gene "}, {"type": "a", "children": [{"type": "t", "text": "i"}], "href": "i"}, {"type": "t", "text": "SYK"}, {"type": "a", "children": [{"type": "t", "text": "/i"}], "href": "/i"}, {"type": "t", "text": " and regulates the function of vascular smooth muscle cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1139/bcb-2019-0031"}], "href": "https://doi.org/10.1139/bcb-2019-0031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31199889"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31199889"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ali H Alwadei, Ruba Benini, Adel Mahmoud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss-of-function mutation in RUSC2 causes intellectual disability and secondary microcephaly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Dev Med Child Neurol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/dmcn.13250"}], "href": "https://doi.org/10.1111/dmcn.13250"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27612186"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27612186"}]}]}]}
Synonyms	MRT61, IPORIN
Proteins	RUSC2_HUMAN
NCBI Gene ID	9853
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RUSC2 has 6,490 functional associations with biological entities spanning 8 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) extracted from 105 datasets.

Click the + buttons to view associations for RUSC2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RUSC2 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 RUSC2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RUSC2 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 RUSC2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RUSC2 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 RUSC2 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 RUSC2 gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of RUSC2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RUSC2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RUSC2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RUSC2 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 RUSC2 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 RUSC2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RUSC2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RUSC2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RUSC2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 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 RUSC2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RUSC2 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 RUSC2 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 RUSC2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RUSC2 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 RUSC2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RUSC2 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RUSC2 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 RUSC2 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of RUSC2 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.
	GEO Signatures of Differentially Expressed Genes for Gene Perturbations	gene perturbations changing expression of RUSC2 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.