GPSM1 Gene

HGNC Family	Tetratricopeptide repeat domain containing (TTC)
Name	G-protein signaling modulator 1
Description	G-protein signaling modulators (GPSMs) play diverse functional roles through their interaction with G-protein subunits. This gene encodes a receptor-independent activator of G protein signaling, which is one of several factors that influence the basal activity of G-protein signaling systems. The protein contains seven tetratricopeptide repeats in its N-terminal half and four G-protein regulatory (GPR) motifs in its C-terminal half. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Activator of G‐protein signaling 3 (AGS3), also known as G‐protein signaling modulator 1 (GPSM1), has emerged as a key regulator of heterotrimeric G‐protein signaling through its ability to bind the GDP‐bound form of Gαi via its multiple G‐protein regulatory (GPR) motifs, thereby functioning as a guanine nucleotide dissociation inhibitor. In doing so, AGS3/GPSM1 modulates the balance between receptor‐dependent and receptor‐independent signaling, influencing processes such as receptor coupling, desensitization, and downstream effector activation including cAMP–PKA–CREB, MAPK, and JNK pathways."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Genetic association studies have implicated variants in GPSM1 in metabolic disorders such as type 2 diabetes, where risk alleles have been linked to increased disease susceptibility and altered insulin signaling in skeletal muscle."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": " Similarly, a GPSM1 variant has been identified as a susceptibility allele for premature ovarian insufficiency, with experimental evidence demonstrating that reduced GPSM1 expression in ovarian granulosa cells attenuates cAMP signaling, increases apoptotic markers, and diminishes cell proliferation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its roles in metabolic regulation, AGS3/GPSM1 has been shown to influence cellular proliferation, survival, and differentiation in diverse contexts. In polycystic kidney disease models, loss of GPSM1 exacerbates cyst progression by impairing polycystin ion‐channel activity mediated via Gβγ subunits, while in various cancer models—including B‐cell acute lymphoblastic leukemia and esophageal squamous cell carcinoma—GPSM1 modulates tumor growth, apoptosis, and cell adhesion through its impact on downstream signaling cascades."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Moreover, studies in animal models have revealed that ablation of AGS3 disrupts normal cardiovascular and metabolic homeostasis, as well as renal tubular regeneration following injury, highlighting its broader physiological significance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In immune cells, modulation of AGS3 levels alters chemokine‐stimulated calcium mobilization, ERK/Akt activation, and overall chemotactic responses, suggesting that GPSM1 plays important roles in the coordination of innate and adaptive immune functions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies position AGS3/GPSM1 as a pivotal scaffold that integrates multiple signaling inputs—ranging from receptor activation to intracellular trafficking—thereby influencing cell growth, survival, metabolism, differentiation, and tissue regeneration. Such multifunctionality not only helps explain its involvement in diverse disease states but also identifies AGS3/GPSM1 as a potential therapeutic target for disorders including type 2 diabetes, polycystic kidney disease, certain cancers, and immune dysfunction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}, {"type": "fg_f", "ref": "11"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_f", "ref": "6"}, {"type": "fg_fs", "start_ref": "3", "end_ref": "5"}, {"type": "fg_f", "ref": "7"}, {"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Kazuo Hara, Hayato Fujita, Todd A Johnson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association study identifies three novel loci for type 2 diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/ddt399"}], "href": "https://doi.org/10.1093/hmg/ddt399"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23945395"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23945395"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sukru Sadik Oner, Ningfei An, Ali Vural, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of the AGS3·G{alpha}i signaling complex by a seven-transmembrane span receptor."}]}, {"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.M110.138073"}], "href": "https://doi.org/10.1074/jbc.M110.138073"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20716524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20716524"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "L De Vries, T Fischer, H Tronchère, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2000)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.97.26.14364"}], "href": "https://doi.org/10.1073/pnas.97.26.14364"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11121039"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11121039"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Qiuju Ding, Amelia Li Min Tan, E J Parra, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide meta-analysis associates GPSM1 with type 2 diabetes, a plausible gene involved in skeletal muscle function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hum Genet (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s10038-019-0720-3"}], "href": "https://doi.org/10.1038/s10038-019-0720-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31959871"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31959871"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Xuzi Cai, Huijiao Fu, Yan Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Depletion of GPSM1 enhances ovarian granulosa cell apoptosis via cAMP-PKA-CREB pathway in vitro."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Ovarian Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13048-020-00740-6"}], "href": "https://doi.org/10.1186/s13048-020-00740-6"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33220708"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33220708"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Michelle Kwon, Tengis S Pavlov, Kandai Nozu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G-protein signaling modulator 1 deficiency accelerates cystic disease in an orthologous mouse model of autosomal dominant polycystic kidney disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.1216830110"}], "href": "https://doi.org/10.1073/pnas.1216830110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23236168"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23236168"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Ye Zhang, Bo Zhou, Jingjing Sun, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockdown of GPSM1 Inhibits the Proliferation and Promotes the Apoptosis of B-Cell Acute Lymphoblastic Leukemia Cells by Suppressing the ADCY6-RAPGEF3-JNK Signaling Pathway."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Oncol Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3389/pore.2021.643376"}], "href": "https://doi.org/10.3389/pore.2021.643376"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34257610"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34257610"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Hui Shi, Hanru Ren, Xiaojing Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Overexpression of activator of G-protein signaling 3 decreases the proliferation of esophageal squamous cell carcinoma."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pathol Res Pract (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prp.2014.12.016"}], "href": "https://doi.org/10.1016/j.prp.2014.12.016"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25812748"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25812748"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Joe B Blumer, Kevin Lord, Thomas L Saunders, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascular function."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocrinology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1210/en.2008-0050"}], "href": "https://doi.org/10.1210/en.2008-0050"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18450958"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18450958"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Melissa Branham-O'Connor, William G Robichaux, Xian-Kui Zhang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Defective chemokine signal integration in leukocytes lacking activator of G protein signaling 3 (AGS3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.515031"}], "href": "https://doi.org/10.1074/jbc.M113.515031"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24573680"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24573680"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Joe B Blumer, Michael L Bernard, Yuri K Peterson, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a serine/threonine kinase involved in cell polarity and cell cycle progression: phosphorylation of the G-protein regulatory (GPR) motif as a regulatory mechanism for the interaction of GPR motifs with Gi alpha."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.C200686200"}], "href": "https://doi.org/10.1074/jbc.C200686200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12719437"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12719437"}]}]}]}
Synonyms	AGS3
Proteins	GPSM1_HUMAN
NCBI Gene ID	26086
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

GPSM1 has 4,833 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, chemical, disease, phenotype or trait, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 112 datasets.

Click the + buttons to view associations for GPSM1 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	BioGPS Human Cell Type and Tissue Gene Expression Profiles	cell types and tissues with high or low expression of GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with GPSM1 protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with GPSM1 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 GPSM1 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of GPSM1 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 GPSM1 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing GPSM1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing GPSM1 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores 2025	cellular components containing GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with GPSM1 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with GPSM1 gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with GPSM1 gene/protein from the curated CTD Gene-Disease Associations dataset.
	DeepCoverMOA Drug Mechanisms of Action	small molecule perturbations with high or low expression of GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 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 GPSM1 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with GPSM1 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 GPSM1 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 GPSM1 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of GPSM1 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 GPSM1 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with GPSM1 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 GPSM1 from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of GPSM1 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 GPSM1 gene from the GEO Signatures of Differentially Expressed Genes for Gene Perturbations dataset.