RASA2 Gene

HGNC Family	C2 domain containing, Pleckstrin homology domain containing (PLEKH)
Name	RAS p21 protein activator 2
Description	The protein encoded by this gene is member of the GAP1 family of GTPase-activating proteins. The gene product stimulates the GTPase activity of normal RAS p21 but not its oncogenic counterpart. Acting as a suppressor of RAS function, the protein enhances the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, thereby allowing control of cellular proliferation and differentiation. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2014]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRASA2 is a Ras GTPase‐activating protein that plays a pivotal role in regulating Ras signalling across diverse cellular contexts. In immune cells, RASA2 acts as an intrinsic signalling checkpoint: it is acutely downregulated following T cell receptor activation yet increases during chronic antigen exposure, thereby limiting MAPK signalling and T cell cytotoxicity. Its loss in adoptive T cell and CAR T cell therapies potentiates activation, cytokine production, metabolism and sustained cancer cell killing. In parallel, loss‐of‐function mutations in RASA2 in melanoma lead to increased Ras activation, enhanced cell growth and migration, supporting its role as a tumor suppressor. Moreover, studies of related RasGAPs highlight common mechanisms by which these proteins are recruited to the plasma membrane following PI3‐kinase stimulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond cancer immunology and melanoma, genetic variations in or near RASA2 have been implicated in other disease phenotypes. Polymorphisms at the ZBTB38‐RASA2 locus correlate with specific clinical manifestations in neurodegenerative disorders such as sporadic Creutzfeldt–Jakob disease, suggesting that RASA2-dependent modulation of Ras signalling may impact neuronal function and symptom expression. In medullary thyroid carcinoma, RASA2 is found to be overexpressed and is negatively regulated by miR‑31‑3p; knockdown of RASA2 inhibited tumour cell proliferation, underscoring its functional involvement in aberrant Ras pathway activation in thyroid cancers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nEmerging genetic studies further extend the functional relevance of RASA2 to developmental and inflammatory processes. Genome‑wide association analyses have identified variants in RASA2 that are significantly associated with adult human height, implying a role in developmental growth regulation. Additionally, recent investigations are probing the function of a circular RNA derived from the RASA2 locus (circRASA2) in the pathogenesis of periodontitis, hinting at novel layers of post‑transcriptional regulation linked to RASA2."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Julia Carnevale, Eric Shifrut, Nupura Kale, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RASA2 ablation in T cells boosts antigen sensitivity and long-term function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nature (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41586-022-05126-w"}], "href": "https://doi.org/10.1038/s41586-022-05126-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36002574"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36002574"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rand Arafeh, Nouar Qutob, Rafi Emmanuel, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Recurrent inactivating RASA2 mutations in melanoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3427"}], "href": "https://doi.org/10.1038/ng.3427"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26502337"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26502337"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "P J Lockyer, S Wennström, S Kupzig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of the ras GTPase-activating protein GAP1(m) as a phosphatidylinositol-3,4,5-trisphosphate-binding protein in vivo."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Biol (1999)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0960-9822(99)80116-x"}], "href": "https://doi.org/10.1016/s0960-9822(99"}, {"type": "t", "text": "80116-x) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "10074452"}], "href": "https://pubmed.ncbi.nlm.nih.gov/10074452"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Chen Gao, Qiang Shi, Jing Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The associations of two SNPs in miRNA-146a and one SNP in ZBTB38-RASA2 with the disease susceptibility and the clinical features of the Chinese patients of sCJD and FFI."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prion (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/19336896.2017.1405885"}], "href": "https://doi.org/10.1080/19336896.2017.1405885"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29216791"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29216791"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Mei Jiang, Xin Shi, Hua Zhu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Two GEO MicroRNA Expression Profile Based High-Throughput Screen to Identify MicroRNA-31-3p Regulating Growth of Medullary Thyroid Carcinoma Cell by Targeting RASA2."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/MSM.916815"}], "href": "https://doi.org/10.12659/MSM.916815"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31298226"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31298226"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Eugene Lin, Shih-Jen Tsai, Po-Hsiu Kuo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study in the Taiwan Biobank identifies four novel genes for human height: NABP2, RASA2, RNF41 and SLC39A5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddab202"}], "href": "https://doi.org/10.1093/hmg/ddab202"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34270706"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34270706"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Bing Xie, Zhen-Yu Yang, Xu-Na Tang "}, {"type": "b", "children": [{"type": "t", "text": "[Effect of circRASA2 targeting miR-543/TRAF6 axis on LPS-induced periodontal ligament cell proliferation and osteogenic differentiation]."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Shanghai Kou Qiang Yi Xue (2023)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "37153995"}], "href": "https://pubmed.ncbi.nlm.nih.gov/37153995"}]}]}]}
Synonyms	GAP1M
Proteins	RASA2_HUMAN
NCBI Gene ID	5922
API
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Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RASA2 has 5,055 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 108 datasets.

Click the + buttons to view associations for RASA2 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RASA2 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with RASA2 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 RASA2 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RASA2 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 RASA2 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 RASA2 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RASA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RASA2 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RASA2 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with RASA2 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with RASA2 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of RASA2 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 RASA2 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving RASA2 gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with RASA2 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 RASA2 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 RASA2 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 RASA2 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 RASA2 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RASA2 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 RASA2 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 RASA2 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RASA2 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 RASA2 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.