RGS14 Gene

HGNC Family	Regulators of G-protein signaling (RGS)
Name	regulator of G-protein signaling 14
Description	This gene encodes a member of the regulator of G-protein signaling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco domain. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized. [provided by RefSeq, Jul 2008]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRGS14 is a multifunctional scaffolding protein that integrates diverse signaling pathways through its unique multidomain architecture. It contains an N‐terminal RGS domain that accelerates GTP hydrolysis on Gαi/o proteins, tandem Ras-binding domains that mediate interactions with activated H‐Ras and Raf kinases to influence MAP kinase signaling, and a C‐terminal GoLoco (GPR) motif that binds inactive Gαi1/3. In addition, intramolecular interactions among these domains modulate its GTPase accelerating and guanine nucleotide dissociation inhibitory functions. RGS14 further fine‐tunes receptor signaling by participating in receptor–G protein complexes and by influencing the activity of channel proteins such as TRPC4. Detailed structural studies, including NMR resonance assignments, have provided insights into the domain organization and functional regulation of RGS14."}, {"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": "\nBeyond its role in signaling modulation, RGS14 has been identified as a microtubule‐associated protein that participates in the regulation of cytoskeletal dynamics. It directly binds to polymerized tubulin and associates with components of the mitotic spindle, suggesting a critical function in microtubule polymerization and spindle organization during cell division."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the nervous system, RGS14 exerts important modulatory influences on synaptic function and neuronal excitability. In rodent and primate brains it is prominently expressed—not only in postsynaptic dendritic spines of hippocampal CA2 pyramidal neurons where it suppresses synaptic plasticity and long-term potentiation, but also in pre‑ and postsynaptic compartments of other limbic regions. Moreover, naturally occurring human variants within its nuclear export sequence disrupt its subcellular distribution (leading to altered nucleocytoplasmic shuttling), impair its ability to bind Gαi, and consequently influence its inhibitory actions on synaptic plasticity. RGS14 also has been shown to dampen L‑type Ca²⁺ channel (Cav1) activity, potentially modulating intracellular Ca²⁺ transients that are crucial for learning and memory."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "7", "end_ref": "10"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRGS14 also plays roles in peripheral tissues where its regulatory actions on G protein-coupled receptor signaling can impact metabolic functions. Genetic studies have associated variants in the RGS14 gene with increased susceptibility to nephrolithiasis, and RGS14’s interaction with scaffold proteins (such as NHERF1) is critical for proper hormone-sensitive phosphate transport in renal proximal tubule cells. In addition, by virtue of its inhibitory modulation of GPCR signaling, RGS14 may influence inflammatory responses and liver damage associated with nonalcoholic fatty liver disease."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "11", "end_ref": "14"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Elizabeth F Dowler, Annette Diehl, Peter Schmieder, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Backbone and sidechain 1H, 13C and 15N resonance assignments of the RGS domain from human RGS14."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biomol NMR Assign (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s12104-007-9029-9"}], "href": "https://doi.org/10.1007/s12104-007-9029-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19636837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19636837"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Feng-jue Shu, Suneela Ramineni, John R Hepler "}, {"type": "b", "children": [{"type": "t", "text": "RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Signal (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cellsig.2009.10.005"}], "href": "https://doi.org/10.1016/j.cellsig.2009.10.005"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19878719"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19878719"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Christopher P Vellano, Ellen M Maher, John R Hepler, et al. "}, {"type": "b", "children": [{"type": "t", "text": "G protein-coupled receptors and resistance to inhibitors of cholinesterase-8A (Ric-8A) both regulate the regulator of g protein signaling 14 RGS14·Gαi1 complex in live cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.274928"}], "href": "https://doi.org/10.1074/jbc.M111.274928"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21880739"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21880739"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Peishen Zhao, Caroline Nunn, Suneela Ramineni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The Ras-binding domain region of RGS14 regulates its functional interactions with heterotrimeric G proteins."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.24483"}], "href": "https://doi.org/10.1002/jcb.24483"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23255434"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23255434"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jae-Pyo Jeon, Dhananjay P Thakur, Jin-Bin Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G-protein signalling and GoLoco proteins suppress TRPC4 channel function via acting at Gαi/o."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem J (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BCJ20160214"}], "href": "https://doi.org/10.1042/BCJ20160214"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26987813"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26987813"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Luke Martin-McCaffrey, Francis S Willard, Agnieszka Pajak, et al. "}, {"type": "b", "children": [{"type": "t", "text": "RGS14 is a microtubule-associated protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Cycle (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.4161/cc.4.7.1787"}], "href": "https://doi.org/10.4161/cc.4.7.1787"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "15917656"}], "href": "https://pubmed.ncbi.nlm.nih.gov/15917656"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Elisa Martín-Montañez, Maria José Acevedo, Juan Félix López-Téllez, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G-protein signaling 14 protein modulates Ca²+ influx through Cav1 channels."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuroreport (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/WNR.0b013e32833f7b7b"}], "href": "https://doi.org/10.1097/WNR.0b013e32833f7b7b"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20842066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20842066"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Katherine E Squires, Kyle J Gerber, Jean-Francois Pare, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulator of G protein signaling 14 (RGS14) is expressed pre- and postsynaptically in neurons of hippocampus, basal ganglia, and amygdala of monkey and human brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Brain Struct Funct (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00429-017-1487-y"}], "href": "https://doi.org/10.1007/s00429-017-1487-y"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28776200"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28776200"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Katherine E Squires, Kyle J Gerber, Matthew C Tillman, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Human genetic variants disrupt RGS14 nuclear shuttling and regulation of LTP in hippocampal neurons."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.RA120.016009"}], "href": "https://doi.org/10.1074/jbc.RA120.016009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33410399"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33410399"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Carolina Montanez-Miranda, Sara N Bramlett, John R Hepler "}, {"type": "b", "children": [{"type": "t", "text": "RGS14 expression in CA2 hippocampus, amygdala, and basal ganglia: Implications for human brain physiology and disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hippocampus (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hipo.23492"}], "href": "https://doi.org/10.1002/hipo.23492"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36541898"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36541898"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Wei-Chiao Chen, Wan-Hsuan Chou, Hou-Wei Chu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The rs1256328 (ALPL) and rs12654812 (RGS14) Polymorphisms are Associated with Susceptibility to Calcium Nephrolithiasis in a Taiwanese population."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-019-53261-8"}], "href": "https://doi.org/10.1038/s41598-019-53261-8"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31754202"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31754202"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Fanglin Guan, Wei Han, Tong Ni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genetic Polymorphisms of RGS14 and Renal Stone Disease."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Med Res (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.arcmed.2020.11.011"}], "href": "https://doi.org/10.1016/j.arcmed.2020.11.011"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33309307"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33309307"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Junyong Wang, Yaping Guo, Yunduan He, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic regulator of G protein signaling 14 ameliorates NAFLD through activating cAMP-AMPK signaling by targeting Giα1/3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Metab (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmet.2024.101882"}], "href": "https://doi.org/10.1016/j.molmet.2024.101882"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38237897"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38237897"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "W Bruce Sneddon, Suneela Ramineni, G Emme Van Doorn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct and overlapping RGS14 and RGS12 actions regulate NPT2A-mediated phosphate transport."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2024.150700"}], "href": "https://doi.org/10.1016/j.bbrc.2024.150700"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39293332"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39293332"}]}]}]}
Proteins	RGS14_HUMAN
NCBI Gene ID	10636
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

RGS14 has 5,117 functional associations with biological entities spanning 9 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, sequence feature) extracted from 120 datasets.

Click the + buttons to view associations for RGS14 from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with RGS14 protein from the CCLE Cell Line Proteomics dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of RGS14 gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of RGS14 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 RGS14 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 RGS14 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing RGS14 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing RGS14 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing RGS14 protein in low- or high-throughput protein localization assays from the COMPARTMENTS Experimental Protein Localization Evidence Scores dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with RGS14 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 RGS14 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 RGS14 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with RGS14 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Disease Associations	diseases associated with RGS14 gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with RGS14 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 RGS14 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with RGS14 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 RGS14 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 RGS14 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 RGS14 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 RGS14 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with RGS14 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 RGS14 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 RGS14 gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of RGS14 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 RGS14 from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with RGS14 gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with RGS14 gene in GWAS and other genetic association datasets from the GAD High Level Gene-Disease Associations dataset.
	GDSC Cell Line Gene Expression Profiles	cell lines with high or low expression of RGS14 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with RGS14 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 RGS14 from the GeneSigDB Published Gene Signatures dataset.