GPSM3 Gene

Name	G-protein signaling modulator 3
Description	Predicted to enable GTPase regulator activity. Predicted to be involved in positive regulation of inflammatory response. Predicted to act upstream of or within positive regulation of cytokine production involved in inflammatory response and positive regulation of leukocyte chemotaxis. Predicted to be located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n GPSM3 is a leukocyte‐specific regulator of G protein–coupled receptor signaling that plays a critical role in modulating immune cell function. It is predominantly expressed in myeloid cells, where its conserved GoLoco motifs bind inactive Gα<sub>i</sub>·GDP subunits, thereby preventing their reassociation with Gβγ dimers. This mechanism influences downstream signaling events that control monocyte and neutrophil chemotaxis as well as cell survival, contributing to pro‐inflammatory responses. In fact, genetic polymorphisms that decrease GPSM3 transcript abundance have been associated with protection from autoimmune arthritis, and experimental models demonstrate that reduced GPSM3 expression leads to impaired migration toward chemokines (e.g. CCL2, CX3CL1, LTB4, IL-8) and increased apoptosis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its classic role as a guanine nucleotide dissociation inhibitor (GDI) via its GoLoco domains, GPSM3 also interacts directly with Gβ subunits to stabilize them during heterotrimeric G protein assembly, thereby affecting pathways such as phospholipase Cβ activation and Akt signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Phosphorylation of GPSM3 creates a binding site for 14-3-3 proteins, which further regulates its stability and subcellular localization."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Intriguingly, studies of the protein also known as G18 or AGS4 reveal that distinct domains within GPSM3 can modulate its regulatory effects on Gα<sub>i/o</sub> subunits. Whereas the GoLoco region exhibits conventional inhibitory activity with respect to nucleotide dissociation, the N-terminal domain has been implicated in promoting guanine nucleotide exchange under certain conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore the multifaceted role of GPSM3 as a modulator of G protein signaling in immune cells, influencing key processes such as cellular differentiation, migration, and survival, which in turn impact inflammatory responses and the pathogenesis of autoimmune diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Patrick M Giguère, Matthew J Billard, Geneviève Laroche, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G-protein signaling modulator-3, a gene linked to autoimmune diseases, regulates monocyte function and its deficiency protects from inflammatory arthritis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Immunol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molimm.2012.12.001"}], "href": "https://doi.org/10.1016/j.molimm.2012.12.001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23280397"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23280397"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "B J Gall, A Wilson, A B Schroer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic variations in GPSM3 associated with protection from rheumatoid arthritis affect its transcript abundance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2016.3"}], "href": "https://doi.org/10.1038/gene.2016.3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26821282"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26821282"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "B J Gall, A B Schroer, J D Gross, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reduction of GPSM3 expression akin to the arthritis-protective SNP rs204989 differentially affects migration in a neutrophil model."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Immun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/gene.2016.26"}], "href": "https://doi.org/10.1038/gene.2016.26"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27307211"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27307211"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Patrick M Giguère, Geneviève Laroche, Emily A Oestreich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G-protein signaling modulator-3 regulates heterotrimeric G-protein dynamics through dual association with Gβ and Gαi protein subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.311712"}], "href": "https://doi.org/10.1074/jbc.M111.311712"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22167191"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22167191"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Patrick M Giguère, Geneviève Laroche, Emily A Oestreich, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the subcellular localization of the G-protein subunit regulator GPSM3 through direct association with 14-3-3 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.394379"}], "href": "https://doi.org/10.1074/jbc.M112.394379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22843681"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22843681"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Peishen Zhao, Chau H Nguyen, Peter Chidiac "}, {"type": "b", "children": [{"type": "t", "text": "The proline-rich N-terminal domain of G18 exhibits a novel G protein regulatory function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.057174"}], "href": "https://doi.org/10.1074/jbc.M109.057174"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20097748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20097748"}]}]}]}
Synonyms	C6ORF9, G18.1B, G18.1A, G18.2, NG1
Proteins	GPSM3_HUMAN
NCBI Gene ID	63940
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GPSM3 has 4,729 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 GPSM3 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of GPSM3 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 GPSM3 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GPSM3 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 GPSM3 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GPSM3 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 GPSM3 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 GPSM3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GPSM3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with GPSM3 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 GPSM3 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 GPSM3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GPSM3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GPSM3 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GPSM3 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 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 GPSM3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GPSM3 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 GPSM3 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 GPSM3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GPSM3 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 GPSM3 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with GPSM3 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of GPSM3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GPSM3 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 GPSM3 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of GPSM3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.