HNF1A Gene

HGNC Family	Homeoboxes
Name	HNF1 homeobox A
Description	The protein encoded by this gene is a transcription factor required for the expression of several liver-specific genes. The encoded protein functions as a homodimer and binds to the inverted palindrome 5'-GTTAATNATTAAC-3'. Defects in this gene are a cause of maturity onset diabetes of the young type 3 (MODY3) and also can result in the appearance of hepatic adenomas. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Summary	{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Hepatocyte nuclear factor‐1α (HNF1A) is a liver‐enriched transcription factor that plays a central role in orchestrating tissue‐specific gene expression programs in the liver, pancreatic islets, and intestinal epithelium. In hepatocytes and pancreatic islet cells, HNF1A participates in regulatory networks with other transcription factors (for example, HNF4α and HNF6) to establish and maintain differentiated functions and to control key metabolic pathways. In the liver, HNF1A regulates the expression of genes involved in lipid and cholesterol homeostasis—for example, by modulating proprotein convertase subtilisin/kexin type 9 (PCSK9) expression—which in turn impacts low‐density lipoprotein clearance and cardiovascular risk. Genome‐wide association studies have linked common HNF1A variants to dyslipidemia and coronary artery disease risk. At the same time, studies in hepatic tissues indicate that loss or defective signaling through HNF1A (also historically referred to as TCF1) is associated with benign liver adenomas and may contribute to tumorigenesis through altered microRNA profiles (such as correlations with decreased miR‐107 expression)."}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the intestine, HNF1A is one of the key activators of differentiation‐specific genes, such as the sucrase–isomaltase gene, functioning in concert with factors like GATA‐4 and Cdx proteins. In the pancreatic β‐cell compartment, heterozygous mutations in HNF1A cause a form of maturity‐onset diabetes of the young (MODY3) by impairing insulin secretion; importantly, patients with such mutations tend to be particularly sensitive to sulphonylurea therapy. In addition, HNF1A has been implicated in the regulation of the glycosylation machinery, as it directly controls the expression of key fucosyltransferase and fucose biosynthesis genes, thereby influencing plasma protein glycosylation. \n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings underscore that HNF1A is a master regulator in metabolic homeostasis, tissue differentiation, and tumor suppression. Its multifaceted functions make it a critical determinant of not only normal physiology but also disease processes including dyslipidemia, diabetes, and liver tumorigenesis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Sekar Kathiresan, Cristen J Willer, Gina M Peloso, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Common variants at 30 loci contribute to polygenic dyslipidemia."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.291"}], "href": "https://doi.org/10.1038/ng.291"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19060906"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19060906"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Duncan T Odom, Nora Zizlsperger, D Benjamin Gordon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Control of pancreas and liver gene expression by HNF transcription factors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Science (2004)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1126/science.1089769"}], "href": "https://doi.org/10.1126/science.1089769"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "14988562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/14988562"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Yannick Ladeiro, Gabrielle Couchy, Charles Balabaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hepatology (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/hep.22256"}], "href": "https://doi.org/10.1002/hep.22256"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18433021"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18433021"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Ewan R Pearson, Sylvia F Boj, Anna M Steele, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Macrosomia and hyperinsulinaemic hypoglycaemia in patients with heterozygous mutations in the HNF4A gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Med (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pmed.0040118"}], "href": "https://doi.org/10.1371/journal.pmed.0040118"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17407387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17407387"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Jeanette Erdmann, Anika Grosshennig, Peter S Braund, et al. "}, {"type": "b", "children": [{"type": "t", "text": "New susceptibility locus for coronary artery disease on chromosome 3q22.3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.307"}], "href": "https://doi.org/10.1038/ng.307"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19198612"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19198612"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Isabelle Schmutz, Jürgen A Ripperger, Stéphanie Baeriswyl-Aebischer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Genes Dev (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1101/gad.564110"}], "href": "https://doi.org/10.1101/gad.564110"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20159955"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20159955"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Olivier Bluteau, Emmanuelle Jeannot, Paulette Bioulac-Sage, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Bi-allelic inactivation of TCF1 in hepatic adenomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng1001"}], "href": "https://doi.org/10.1038/ng1001"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12355088"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12355088"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "François Boudreau, Edmond H H M Rings, Herbert M van Wering, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatocyte nuclear factor-1 alpha, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription. Implication for the developmental regulation of the sucrase-isomaltase gene."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2002)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M204622200"}], "href": "https://doi.org/10.1074/jbc.M204622200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12060663"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12060663"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Camilla Pilati, Mohamed Amessou, Michel P Bihl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Somatic mutations activating STAT3 in human inflammatory hepatocellular adenomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Exp Med (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1084/jem.20110283"}], "href": "https://doi.org/10.1084/jem.20110283"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21690253"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21690253"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Ming Zhuang, Wen Gao, Jing Xu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The long non-coding RNA H19-derived miR-675 modulates human gastric cancer cell proliferation by targeting tumor suppressor RUNX1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2013.12.126"}], "href": "https://doi.org/10.1016/j.bbrc.2013.12.126"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24388988"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24388988"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Aaron D Tward, Kirk D Jones, Stephen Yant, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Distinct pathways of genomic progression to benign and malignant tumors of the liver."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.0706578104"}], "href": "https://doi.org/10.1073/pnas.0706578104"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17785413"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17785413"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "M Shepherd, B Shields, S Ellard, et al. "}, {"type": "b", "children": [{"type": "t", "text": "A genetic diagnosis of HNF1A diabetes alters treatment and improves glycaemic control in the majority of insulin-treated patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabet Med (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1111/j.1464-5491.2009.02690.x"}], "href": "https://doi.org/10.1111/j.1464-5491.2009.02690.x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19388975"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19388975"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Thomas A Lagace "}, {"type": "b", "children": [{"type": "t", "text": "PCSK9 and LDLR degradation: regulatory mechanisms in circulation and in cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Curr Opin Lipidol (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1097/MOL.0000000000000114"}], "href": "https://doi.org/10.1097/MOL.0000000000000114"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25110901"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25110901"}]}]}]}
Synonyms	HNF4A, LFB1, TCF1, HNF-1A, HNF1, MODY3, IDDM20
Proteins	HNF1A_HUMAN
NCBI Gene ID	6927
API
Download Associations
Predicted Functions
Co-expressed Genes
Expression in Tissues and Cell Lines

Functional Associations

HNF1A has 9,460 functional associations with biological entities spanning 9 categories (molecular profile, organism, functional term, phrase or reference, disease, phenotype or trait, chemical, structural feature, cell line, cell type or tissue, gene, protein or microRNA, sequence feature) extracted from 128 datasets.

Click the + buttons to view associations for HNF1A from the datasets below.

If available, associations are ranked by standardized value

Harmonizome 3.0

HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A gene relative to other tissues from the Allen Brain Atlas Prenatal Human Brain Tissue Gene Expression Profiles dataset.
	Biocarta Pathways	pathways involving HNF1A protein from the Biocarta Pathways dataset.
	BioGPS Cell Line Gene Expression Profiles	cell lines with high or low expression of HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A gene relative to other cell lines from the CCLE Cell Line Gene Expression Profiles dataset.
	CCLE Cell Line Gene Mutation Profiles	cell lines with HNF1A gene mutations from the CCLE Cell Line Gene Mutation Profiles dataset.
	CCLE Cell Line Proteomics	Cell lines associated with HNF1A protein from the CCLE Cell Line Proteomics dataset.
	CellMarker Gene-Cell Type Associations	cell types associated with HNF1A 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 HNF1A gene from the CHEA Transcription Factor Binding Site Profiles dataset.
	ChEA Transcription Factor Targets	transcription factors binding the promoter of HNF1A 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 HNF1A gene in low- or high-throughput transcription factor functional studies from the CHEA Transcription Factor Targets 2022 dataset.
	ClinVar Gene-Phenotype Associations	phenotypes associated with HNF1A gene from the curated ClinVar Gene-Phenotype Associations dataset.
	ClinVar Gene-Phenotype Associations 2025	phenotypes associated with HNF1A gene from the curated ClinVar Gene-Phenotype Associations 2025 dataset.
	CMAP Signatures of Differentially Expressed Genes for Small Molecules	small molecule perturbations changing expression of HNF1A gene from the CMAP Signatures of Differentially Expressed Genes for Small Molecules dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores	cellular components containing HNF1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores dataset.
	COMPARTMENTS Curated Protein Localization Evidence Scores 2025	cellular components containing HNF1A protein from the COMPARTMENTS Curated Protein Localization Evidence Scores 2025 dataset.
	COMPARTMENTS Experimental Protein Localization Evidence Scores	cellular components containing HNF1A 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 HNF1A 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 HNF1A 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 HNF1A gene relative to other cell lines from the COSMIC Cell Line Gene CNV Profiles dataset.
	COSMIC Cell Line Gene Mutation Profiles	cell lines with HNF1A gene mutations from the COSMIC Cell Line Gene Mutation Profiles dataset.
	CTD Gene-Chemical Interactions	chemicals interacting with HNF1A gene/protein from the curated CTD Gene-Chemical Interactions dataset.
	CTD Gene-Disease Associations	diseases associated with HNF1A gene/protein from the curated CTD Gene-Disease Associations dataset.
	dbGAP Gene-Trait Associations	traits associated with HNF1A 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 HNF1A gene knockdown relative to other cell lines from the DepMap CRISPR Gene Dependency dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores	diseases involving HNF1A gene from the DISEASES Curated Gene-Disease Assocation Evidence Scores dataset.
	DISEASES Curated Gene-Disease Association Evidence Scores 2025	diseases involving HNF1A gene from the DISEASES Curated Gene-Disease Association Evidence Scores 2025 dataset.
	DISEASES Experimental Gene-Disease Association Evidence Scores	diseases associated with HNF1A 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 HNF1A 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 HNF1A 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 HNF1A 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 HNF1A gene in GWAS and other genetic association datasets from the DisGeNET Gene-Disease Associations dataset.