| HGNC Family | G protein-coupled receptors |
| Name | hydroxycarboxylic acid receptor 3 |
| Description | Predicted to enable GTP binding activity; nicotinic acid receptor activity; and purinergic nucleotide receptor activity. Predicted to be involved in G protein-coupled receptor signaling pathway. Located in cell junction. [provided by Alliance of Genome Resources, Mar 2025] |
| Summary |
{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hydroxycarboxylic acid receptor 3 (HCAR3) is a metabolite‐sensing G protein–coupled receptor that plays a key role in linking cellular energy status to lipid metabolism. Studies have shown that when activated—most likely by endogenous metabolites produced during fatty acid β–oxidation—HCAR3 couples selectively to G<sub>i</sub> proteins (specifically Gα<sub>i1</sub> and Gα<sub>i3</sub>), leading to a reduction in intracellular cyclic adenosine monophosphate (cAMP) levels. This signaling is important for mediating anti–lipolytic effects and regulating fatty acid and lipid homeostasis."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of breast cancer, for example, increased HCAR3 mRNA expression has been observed in patient samples, and experimental knockdown of HCAR3 was found to induce significant cancer cell death that could be rescued by inhibitors of fatty acid β–oxidation. This indicates that HCAR3 is involved in controlling intracellular lipid/fatty acid metabolism, thereby supporting cancer cell survival. Moreover, when viewed as part of a cluster of paralogous hydroxycarboxylic acid receptors (along with HCAR1 and HCAR2), HCAR3 emerges as a potential oncogene, in contrast to HCAR2 which has been described to function as a tumor suppressor.\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Together, these findings suggest that HCAR3 is an important metabolic sensor whose activation orchestrates cellular adaptations in lipid handling. Its selective Gi–protein coupling, impact on cAMP, and regulation of fatty acid metabolism in adipocytes and cancer cells make it a promising candidate for therapeutic intervention in metabolic disorders and oncologic contexts."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Claudia Stäubert, Oliver Jay Broom, Anders Nordström "}, {"type": "b", "children": [{"type": "t", "text": "Hydroxycarboxylic acid receptors are essential for breast cancer cells to control their lipid/fatty acid metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.3565"}], "href": "https://doi.org/10.18632/oncotarget.3565"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25839160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25839160"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Rongfang Liu, Jacobus P D van Veldhoven, Adriaan P IJzerman "}, {"type": "b", "children": [{"type": "t", "text": "The role of the C-terminus of the human hydroxycarboxylic acid receptors 2 and 3 in G protein activation using Gα-engineered yeast cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2015.11.052"}], "href": "https://doi.org/10.1016/j.ejphar.2015.11.052"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "26656756"}], "href": "https://pubmed.ncbi.nlm.nih.gov/26656756"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Cierla McGuire Sams, Kasey Shepp, Jada Pugh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Rare and potentially pathogenic variants in hydroxycarboxylic acid receptor genes identified in breast cancer cases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Med Genomics (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s12920-021-01126-3"}], "href": "https://doi.org/10.1186/s12920-021-01126-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34852802"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34852802"}]}]}]}
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| Synonyms | GPR109B, HM74, Puma-g, PUMAG |
| Proteins | HCAR3_HUMAN |
| NCBI Gene ID | 8843 |
| API | |
| Download Associations | |
| Predicted Functions |
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| Co-expressed Genes |
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| Expression in Tissues and Cell Lines |
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HCAR3 has 3,039 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 86 datasets.
Click the + buttons to view associations for HCAR3 from the datasets below.
If available, associations are ranked by standardized value
| Dataset | Summary | |
|---|---|---|
| Allen Brain Atlas Adult Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of HCAR3 gene relative to other tissues from the Allen Brain Atlas Adult Human 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 HCAR3 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 HCAR3 gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset. | |
| Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles | tissues with high or low expression of HCAR3 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 HCAR3 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 HCAR3 gene relative to other cell types and tissues from the BioGPS Human Cell Type and Tissue Gene Expression Profiles dataset. | |
| Carcinogenome Chemical Perturbation Carcinogenicity Signatures | small molecule perturbations changing expression of HCAR3 gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset. | |
| CCLE Cell Line Gene CNV Profiles | cell lines with high or low copy number of HCAR3 gene relative to other cell lines from the CCLE Cell Line Gene CNV Profiles dataset. | |
| CellMarker Gene-Cell Type Associations | cell types associated with HCAR3 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 HCAR3 gene from the CHEA Transcription Factor Binding Site Profiles dataset. | |
| ChEA Transcription Factor Targets | transcription factors binding the promoter of HCAR3 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 HCAR3 gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset. | |
| CM4AI KOLF21J CRISPRi Gene Perturbation Atlas | gene perturbations changing expression of HCAR3 gene from the CM4AI KOLF21J CRISPRi Gene Perturbation Atlas dataset. | |
| CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of HCAR3 gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| COMPARTMENTS Curated Protein Localization Evidence Scores 2025 | cellular components containing HCAR3 protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset. | |
| COMPARTMENTS Text-mining Protein Localization Evidence Scores 2025 | cellular components co-occuring with HCAR3 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 HCAR3 gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset. | |
| COSMIC Cell Line Gene Mutation Profiles | cell lines with HCAR3 gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset. | |
| CTD Gene-Chemical Interactions | chemicals interacting with HCAR3 gene/protein from the curated CTD Gene-Chemical Interactions dataset. | |
| CTD Gene-Disease Associations | diseases associated with HCAR3 gene/protein from the curated CTD Gene-Disease Associations dataset. | |
| DepMap CRISPR Gene Dependency | cell lines with fitness changed by HCAR3 gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset. | |
| DGIdb Drug Targets 2026 | interacting drugs for HCAR3 protein from the DGIdb Drug Targets 2026 dataset. | |
| DISEASES Experimental Gene-Disease Association Evidence Scores 2025 | diseases associated with HCAR3 gene in GWAS datasets from the DISEASES Experimental Gene-Disease Assocation Evidence Scores 2025 dataset. | |
| DISEASES Text-mining Gene-Disease Association Evidence Scores 2025 | diseases co-occuring with HCAR3 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 HCAR3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset. | |
| DisGeNET Gene-Phenotype Associations | phenotypes associated with HCAR3 gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset. | |
| DrugBank Drug Targets | interacting drugs for HCAR3 protein from the curated DrugBank Drug Targets dataset. | |
| ENCODE Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at HCAR3 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 HCAR3 gene from the ENCODE Transcription Factor Binding Site Profiles dataset. | |
| ENCODE Transcription Factor Targets | transcription factors binding the promoter of HCAR3 gene in ChIP-seq datasets from the ENCODE Transcription Factor Targets dataset. | |
| GDSC Cell Line Gene Expression Profiles | cell lines with high or low expression of HCAR3 gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset. | |
| GeneRIF Biological Term Annotations | biological terms co-occuring with HCAR3 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 HCAR3 from the GeneSigDB Published Gene Signatures dataset. | |
| GEO Signatures of Differentially Expressed Genes for Diseases | disease perturbations changing expression of HCAR3 gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset. | |
| GEO Signatures of Differentially Expressed Genes for Kinase Perturbations | kinase perturbations changing expression of HCAR3 gene from the GEO Signatures of Differentially Expressed Genes for Kinase Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of HCAR3 gene from the GEO Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations | transcription factor perturbations changing expression of HCAR3 gene from the GEO Signatures of Differentially Expressed Genes for Transcription Factor Perturbations dataset. | |
| GEO Signatures of Differentially Expressed Genes for Viral Infections | virus perturbations changing expression of HCAR3 gene from the GEO Signatures of Differentially Expressed Genes for Viral Infections dataset. | |
| GO Biological Process Annotations 2015 | biological processes involving HCAR3 gene from the curated GO Biological Process Annotations 2015 dataset. | |
| GO Cellular Component Annotations 2015 | cellular components containing HCAR3 protein from the curated GO Cellular Component Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2015 | molecular functions performed by HCAR3 gene from the curated GO Molecular Function Annotations 2015 dataset. | |
| GO Molecular Function Annotations 2023 | molecular functions performed by HCAR3 gene from the curated GO Molecular Function Annotations 2023 dataset. | |
| GO Molecular Function Annotations 2025 | molecular functions performed by HCAR3 gene from the curated GO Molecular Function Annotations 2025 dataset. | |
| GTEx eQTL 2025 | SNPs regulating expression of HCAR3 gene from the GTEx eQTL 2025 dataset. | |
| GTEx Tissue Gene Expression Profiles 2023 | tissues with high or low expression of HCAR3 gene relative to other tissues from the GTEx Tissue Gene Expression Profiles 2023 dataset. | |
| GTEx Tissue-Specific Aging Signatures | tissue samples with high or low expression of HCAR3 gene relative to other tissue samples from the GTEx Tissue-Specific Aging Signatures dataset. | |
| Guide to Pharmacology Chemical Ligands of Receptors | ligands (chemical) binding HCAR3 receptor from the curated Guide to Pharmacology Chemical Ligands of Receptors dataset. | |
| GWAS Catalog SNP-Phenotype Associations 2025 | phenotypes associated with HCAR3 gene in GWAS datasets from the GWAS Catalog SNP-Phenotype Associations 2025 dataset. | |
| HMDB Metabolites of Enzymes | interacting metabolites for HCAR3 protein from the curated HMDB Metabolites of Enzymes dataset. | |
| HPA Cell Line Gene Expression Profiles | cell lines with high or low expression of HCAR3 gene relative to other cell lines from the HPA Cell Line Gene Expression Profiles dataset. | |
| HPA Tissue Gene Expression Profiles | tissues with high or low expression of HCAR3 gene relative to other tissues from the HPA Tissue Gene Expression Profiles dataset. | |
| HPA Tissue Protein Expression Profiles | tissues with high or low expression of HCAR3 protein relative to other tissues from the HPA Tissue Protein Expression Profiles dataset. | |
| HPA Tissue Sample Gene Expression Profiles | tissue samples with high or low expression of HCAR3 gene relative to other tissue samples from the HPA Tissue Sample Gene Expression Profiles dataset. | |
| HuGE Navigator Gene-Phenotype Associations | phenotypes associated with HCAR3 gene by text-mining GWAS publications from the HuGE Navigator Gene-Phenotype Associations dataset. | |
| IMPC Knockout Mouse Phenotypes | phenotypes of mice caused by HCAR3 gene knockout from the IMPC Knockout Mouse Phenotypes dataset. | |
| InterPro Predicted Protein Domain Annotations | protein domains predicted for HCAR3 protein from the InterPro Predicted Protein Domain Annotations dataset. | |
| JASPAR Predicted Human Transcription Factor Targets 2025 | transcription factors regulating expression of HCAR3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Human Transcription Factor Targets dataset. | |
| JASPAR Predicted Mouse Transcription Factor Targets 2025 | transcription factors regulating expression of HCAR3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Mouse Transcription Factor Targets 2025 dataset. | |
| JASPAR Predicted Transcription Factor Targets | transcription factors regulating expression of HCAR3 gene predicted using known transcription factor binding site motifs from the JASPAR Predicted Transcription Factor Targets dataset. | |
| KEGG Pathways 2026 | pathways involving HCAR3 protein from the KEGG Pathways 2026 dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles | cell lines with high or low copy number of HCAR3 gene relative to other cell lines from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene CNV Profiles dataset. | |
| Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles | cell lines with HCAR3 gene mutations from the Klijn et al., Nat. Biotechnol., 2015 Cell Line Gene Mutation Profiles dataset. | |
| LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules | small molecule perturbations changing expression of HCAR3 gene from the LINCS L1000 CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset. | |
| LOCATE Curated Protein Localization Annotations | cellular components containing HCAR3 protein in low- or high-throughput protein localization assays from the LOCATE Curated Protein Localization Annotations dataset. | |
| LOCATE Predicted Protein Localization Annotations | cellular components predicted to contain HCAR3 protein from the LOCATE Predicted Protein Localization Annotations dataset. | |
| MGI Mouse Phenotype Associations 2023 | phenotypes of transgenic mice caused by HCAR3 gene mutations from the MGI Mouse Phenotype Associations 2023 dataset. | |
| MotifMap Predicted Transcription Factor Targets | transcription factors regulating expression of HCAR3 gene predicted using known transcription factor binding site motifs from the MotifMap Predicted Transcription Factor Targets dataset. | |
| MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations | gene perturbations changing expression of HCAR3 gene from the MSigDB Signatures of Differentially Expressed Genes for Cancer Gene Perturbations dataset. | |
| PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations | gene perturbations changing expression of HCAR3 gene from the PerturbAtlas Signatures of Differentially Expressed Genes for Gene Perturbations dataset. | |
| PFOCR Pathway Figure Associations 2023 | pathways involving HCAR3 protein from the PFOCR Pathway Figure Associations 2023 dataset. | |
| PFOCR Pathway Figure Associations 2024 | pathways involving HCAR3 protein from the Wikipathways PFOCR 2024 dataset. | |
| Reactome Pathways 2014 | pathways involving HCAR3 protein from the Reactome Pathways dataset. | |
| Reactome Pathways 2024 | pathways involving HCAR3 protein from the Reactome Pathways 2024 dataset. | |
| Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles | cell types and tissues with high or low DNA methylation of HCAR3 gene relative to other cell types and tissues from the Roadmap Epigenomics Cell and Tissue DNA Methylation Profiles dataset. | |
| Roadmap Epigenomics Histone Modification Site Profiles | histone modification site profiles with high histone modification abundance at HCAR3 gene from the Roadmap Epigenomics Histone Modification Site Profiles dataset. | |
| Rummagene Transcription Factor Associations 2026 | transcription factors regulating expression of HCAR3 gene from the Rummagene Transcription Factor Associations 2026 dataset. | |
| RummaGEO Drug Perturbation Signatures | drug perturbations changing expression of HCAR3 gene from the RummaGEO Drug Perturbation Signatures dataset. | |
| RummaGEO Gene Perturbation Signatures | gene perturbations changing expression of HCAR3 gene from the RummaGEO Gene Perturbation Signatures dataset. | |
| Tabula Sapiens Gene-Cell Associations | cell types with high or low expression of HCAR3 gene relative to other cell types from the Tabula Sapiens Gene-Cell Associations dataset. | |
| TargetScan Predicted Conserved microRNA Targets | microRNAs regulating expression of HCAR3 gene predicted using conserved miRNA seed sequences from the TargetScan Predicted Conserved microRNA Targets dataset. | |
| TargetScan Predicted Nonconserved microRNA Targets | microRNAs regulating expression of HCAR3 gene predicted using nonconserved miRNA seed sequences from the TargetScan Predicted Nonconserved microRNA Targets dataset. | |
| TCGA Signatures of Differentially Expressed Genes for Tumors | tissue samples with high or low expression of HCAR3 gene relative to other tissue samples from the TCGA Signatures of Differentially Expressed Genes for Tumors dataset. | |
| TISSUES Curated Tissue Protein Expression Evidence Scores 2025 | tissues with high expression of HCAR3 protein from the TISSUES Curated Tissue Protein Expression Evidence Scores 2025 dataset. | |
| TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 | tissues co-occuring with HCAR3 protein in abstracts of biomedical publications from the TISSUES Text-mining Tissue Protein Expression Evidence Scores 2025 dataset. | |
| WikiPathways Pathways 2014 | pathways involving HCAR3 protein from the Wikipathways Pathways 2014 dataset. | |
| WikiPathways Pathways 2024 | pathways involving HCAR3 protein from the WikiPathways Pathways 2024 dataset. | |
