HNF4G Gene

HGNC Family	Zinc fingers
Name	hepatocyte nuclear factor 4, gamma
Description	Enables DNA-binding transcription activator activity, RNA polymerase II-specific and RNA polymerase II cis-regulatory region sequence-specific DNA binding activity. Involved in positive regulation of transcription by RNA polymerase II. Located in several cellular components, including intercellular bridge; mitotic spindle; and nucleoplasm. [provided by Alliance of Genome Resources, Mar 2025]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The nuclear receptor HNF4G has emerged as a multifaceted regulator at the crossroads of metabolic homeostasis and tumor biology. Genetic studies have implicated HNF4G in the regulation of metabolic traits, with variants in or near this gene associating with serum urate levels and clinical obesity, and a specific single‐nucleotide polymorphism linked to hyperuricemia in men."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": " In the intestine, HNF4G contributes to lipid metabolism – acting redundantly with HNF4A – as its altered expression has been associated with modifications in intestinal lipoprotein gene expression and lipid absorption, with loss of HNF4G activity resulting in increased fecal calorie loss and protection against diet‐induced obesity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the context of cancer, aberrant HNF4G expression has been linked to oncogenic processes in several gastrointestinal malignancies. In pancreatic ductal adenocarcinoma, SMAD4 deficiency drives HNF4G overexpression, which in turn enhances cell invasiveness and metastasis – a process that can be counteracted with Metformin treatment."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " In colorectal cancer, HNF4G is embedded within a core transcriptional network regulating enterocyte differentiation and, when its regulation is disrupted (for instance, under altered KRAS phosphorylation conditions), it is associated with changes in genes that control cell differentiation and invasion."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": " Furthermore, proteomic analyses have uncovered its binding at promoters such as that of MACC1—implicating HNF4G in the modulation of metastatic potential—while elevated HNF4G expression in colorectal tumors correlates with increased proliferation and reduced apoptosis via a caspase‐dependent intrinsic pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, deregulation of HNF4G is also observed in esophageal squamous cell carcinoma as one of several downstream genes affected by the posttranscriptional silencing of oncogenic long noncoding RNA MALAT1."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": " Collectively, these findings highlight HNF4G as a critical molecular integrator of metabolic signals and differentiation cues that, when altered, can drive oncogenesis and metabolic dysregulation – a profile that not only provides novel insights into disease mechanisms but also presents HNF4G as a potential therapeutic target.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Anna Köttgen, Eva Albrecht, Alexander Teumer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide association analyses identify 18 new loci associated with serum urate concentrations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2500"}], "href": "https://doi.org/10.1038/ng.2500"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23263486"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23263486"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sonja I Berndt, Stefan Gustafsson, Reedik Mägi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.2606"}], "href": "https://doi.org/10.1038/ng.2606"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23563607"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23563607"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Bang-Dang Chen, Xiao-Cui Chen, Shuo Pan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TT genotype of rs2941484 in the human HNF4G gene is associated with hyperuricemia in Chinese Han men."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncotarget (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.18632/oncotarget.15851"}], "href": "https://doi.org/10.18632/oncotarget.15851"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28460474"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28460474"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Efstathia Thymiakou, Efsevia Xenikaki, Dimitris Kardassis "}, {"type": "b", "children": [{"type": "t", "text": "Intestine-specific ablation of the Hepatocyte Nuclear Factor 4a (Hnf4a) gene in mice has minimal impact on serum lipids and ileum gene expression profile due to upregulation of its paralog Hnf4g."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochim Biophys Acta Mol Cell Biol Lipids (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbalip.2021.159108"}], "href": "https://doi.org/10.1016/j.bbalip.2021.159108"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34973414"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34973414"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Sami Ayari, Eva Gil-Iturbe, Léa le Gléau, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hnf4g invalidation prevents diet-induced obesity via intestinal lipid malabsorption."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Endocrinol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/JOE-21-0092"}], "href": "https://doi.org/10.1530/JOE-21-0092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34647524"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34647524"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Chengcheng Wang, Taiping Zhang, Quan Liao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Metformin inhibits pancreatic cancer metastasis caused by SMAD4 deficiency and consequent HNF4G upregulation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Protein Cell (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s13238-020-00760-4"}], "href": "https://doi.org/10.1007/s13238-020-00760-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32737864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32737864"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Débora Cabot, Sònia Brun, Noelia Paco, et al. "}, {"type": "b", "children": [{"type": "t", "text": "KRAS phosphorylation regulates cell polarization and tumorigenic properties in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Oncogene (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41388-021-01967-3"}], "href": "https://doi.org/10.1038/s41388-021-01967-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34333552"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34333552"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Soobeom Lee, Chansu Lee, Chae Young Hwang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Network Inference Analysis Identifies SETDB1 as a Key Regulator for Reverting Colorectal Cancer Cells into Differentiated Normal-Like Cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cancer Res (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1158/1541-7786.MCR-19-0450"}], "href": "https://doi.org/10.1158/1541-7786.MCR-19-0450"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31896605"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31896605"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Yahui Huang, Yi Xiang, Zhongpeng Xie, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Mass spectrometry-based proteomic capture of proteins bound to the MACC1 promoter in colon cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Clin Exp Metastasis (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s10585-020-10045-z"}], "href": "https://doi.org/10.1007/s10585-020-10045-z"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32613480"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32613480"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Lu Chen, Huanying Shi, Xinhai Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatocyte nuclear factor 4 gamma (HNF4G) is correlated with poor prognosis and promotes tumor cell growth by inhibiting caspase-dependent intrinsic apoptosis in colorectal cancer."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Pharmacol (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.ejphar.2021.174727"}], "href": "https://doi.org/10.1016/j.ejphar.2021.174727"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34965388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34965388"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Xinyu Wang, Meng Li, Zhiqiong Wang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Silencing of long noncoding RNA MALAT1 by miR-101 and miR-217 inhibits proliferation, migration, and invasion of esophageal squamous cell carcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M114.596866"}], "href": "https://doi.org/10.1074/jbc.M114.596866"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25538231"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25538231"}]}]}]}
Synonyms	NR2A2, NR2A3
Proteins	HNF4G_HUMAN
NCBI Gene ID	3174
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HNF4G has 3,297 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 111 datasets.

Click the + buttons to view associations for HNF4G from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HNF4G 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 HNF4G gene knockdown relative to other cell lines from the Achilles Cell Line Gene Essentiality Profiles dataset.
	Allen Brain Atlas Adult Mouse Brain Tissue Gene Expression Profiles	tissues with high or low expression of HNF4G 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 HNF4G 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 HNF4G gene relative to other tissue samples from the Allen Brain Atlas Developing Human Brain Tissue Gene Expression Profiles by Microarray dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HNF4G 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 HNF4G 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 HNF4G 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 HNF4G gene from the Carcinogenome Chemical Perturbation Carcinogenicity Signatures dataset.
	CCLE Cell Line Gene CNV Profiles	cell lines with high or low copy number of HNF4G 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 HNF4G gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	ChEA Transcription Factor Binding Site Profiles	transcription factor binding site profiles with transcription factor binding evidence at the promoter of HNF4G gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HNF4G 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 HNF4G 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 HNF4G protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HNF4G protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Text-mining Protein Localization Evidence Scores	cellular components co-occuring with HNF4G 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 HNF4G 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 HNF4G gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HNF4G gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HNF4G gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HNF4G gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HNF4G 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 HNF4G gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HNF4G 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 HNF4G 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 HNF4G 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 HNF4G 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 HNF4G gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.
	DisGeNET Gene-Phenotype Associations	phenotypes associated with HNF4G gene in GWAS and other genetic association datasets from the DisGeNET Gene-Phenoptype Associations dataset.
	DrugBank Drug Targets	interacting drugs for HNF4G protein from the curated DrugBank Drug Targets dataset.
	ENCODE Histone Modification Site Profiles	histone modification site profiles with high histone modification abundance at HNF4G 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 HNF4G gene from the ENCODE Transcription Factor Binding Site Profiles dataset.
	ENCODE Transcription Factor Targets	transcription factors binding the promoter of HNF4G 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 HNF4G from the ESCAPE Omics Signatures of Genes and Proteins for Stem Cells dataset.
	GAD Gene-Disease Associations	diseases associated with HNF4G gene in GWAS and other genetic association datasets from the GAD Gene-Disease Associations dataset.
	GAD High Level Gene-Disease Associations	diseases associated with HNF4G 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 HNF4G gene relative to other cell lines from the GDSC Cell Line Gene Expression Profiles dataset.
	GeneRIF Biological Term Annotations	biological terms co-occuring with HNF4G 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 HNF4G from the GeneSigDB Published Gene Signatures dataset.
	GEO Signatures of Differentially Expressed Genes for Diseases	disease perturbations changing expression of HNF4G gene from the GEO Signatures of Differentially Expressed Genes for Diseases dataset.