RIN2 Gene

HGNC Family	VPS9 domain containing
Name	Ras and Rab interactor 2
Description	The RAB5 protein is a small GTPase involved in membrane trafficking in the early endocytic pathway. The protein encoded by this gene binds the GTP-bound form of the RAB5 protein preferentially over the GDP-bound form, and functions as a guanine nucleotide exchange factor for RAB5. The encoded protein is found primarily as a tetramer in the cytoplasm and does not bind other members of the RAB family. Mutations in this gene cause macrocephaly alopecia cutis laxa and scoliosis (MACS) syndrome, an elastic tissue disorder, as well as the related connective tissue disorder, RIN2 syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRIN2 is a ubiquitously expressed protein that plays a critical role in endocytic trafficking by interacting with Rab5 and regulating early endocytosis. Disruption of RIN2 function, most notably through frameshift mutations, is causally linked to a recessively inherited connective tissue disorder originally described as MACS syndrome (macrocephaly, alopecia, cutis laxa, and scoliosis) and later termed RIN2 syndrome. Loss-of-function mutations in RIN2 lead to abnormal cellular trafficking, which manifests as defective extracellular matrix organization (including a paucity of dermal microfibrils and reduced fibulin-5), dysmorphic facial features, and other developmental abnormalities that overlap with features found in Ehlers–Danlos syndrome."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn endothelial cells, RIN2 collaborates with the early endosomal GTPase Rab5C to prevent the lysosomal degradation of internalized, ligand-bound VEGF receptor 2 (VEGFR2). This action stabilizes endosomal VEGFR2 levels, thereby maintaining VEGF-mediated signaling through downstream effectors such as ERK and PI3K. Such receptor retention is essential for the expression of immediate VEGF target genes and for regulating both angiogenic cell fate decisions and the sprouting of new blood vessels."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditionally, RIN2 can serve as a fusion partner in oncogenic rearrangements. A reported fusion between RIN2 and BRAF yields a chimeric protein that retains critical domains of BRAF, including a dimerization region and an intact kinase domain, thereby contributing to aberrant activation of BRAF signaling pathways. This fusion event exemplifies the diverse roles of RIN2, extending its impact from developmental and connective tissue disorders to certain oncogenic contexts."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Lina Basel-Vanagaite, Ofer Sarig, Dov Hershkovitz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIN2 deficiency results in macrocephaly, alopecia, cutis laxa, and scoliosis: MACS syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Hum Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ajhg.2009.07.001"}], "href": "https://doi.org/10.1016/j.ajhg.2009.07.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19631308"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19631308"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Delfien Syx, Fransiska Malfait, Lut Van Laer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The RIN2 syndrome: a new autosomal recessive connective tissue disorder caused by deficiency of Ras and Rab interactor 2 (RIN2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Genet (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00439-010-0829-0"}], "href": "https://doi.org/10.1007/s00439-010-0829-0"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20424861"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20424861"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Ayca D Aslanger, Umut Altunoglu, Emre Aslanger, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Newly described clinical features in two siblings with MACS syndrome and a novel mutation in RIN2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.36277"}], "href": "https://doi.org/10.1002/ajmg.a.36277"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24449201"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24449201"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Simonetta Rosato, Delfien Syx, Ivan Ivanovski, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RIN2 syndrome: Expanding the clinical phenotype."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Med Genet A (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/ajmg.a.37789"}], "href": "https://doi.org/10.1002/ajmg.a.37789"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27277385"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27277385"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Reyhaneh Kameli, Mahmoud Reza Ashrafi, Farveh Ehya, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Leukoencephalopathy in RIN2 syndrome: Novel mutation and expansion of clinical spectrum."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Med Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejmg.2019.02.002"}], "href": "https://doi.org/10.1016/j.ejmg.2019.02.002"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30769224"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30769224"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Lanette Kempers, Yuki Wakayama, Ivo van der Bijl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The endosomal RIN2/Rab5C machinery prevents VEGFR2 degradation to control gene expression and tip cell identity during angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Angiogenesis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10456-021-09788-4"}], "href": "https://doi.org/10.1007/s10456-021-09788-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33983539"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33983539"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Xinglei Liu, Xiaoxiao Dai, Chungang Dai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare adult pilocytic astrocytoma of the septum pellucidum with novel RIN2::BRAF fusion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Virchows Arch (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00428-022-03477-3"}], "href": "https://doi.org/10.1007/s00428-022-03477-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36520196"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36520196"}]}]}]}
Synonyms	MACS, RASSF4
Proteins	RIN2_HUMAN
NCBI Gene ID	54453
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RIN2 has 9,074 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 126 datasets.

Click the + buttons to view associations for RIN2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of RIN2 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 RIN2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RIN2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RIN2 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 RIN2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RIN2 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 RIN2 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 RIN2 gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with RIN2 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 RIN2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RIN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RIN2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RIN2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RIN2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RIN2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 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 RIN2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RIN2 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 RIN2 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 RIN2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.