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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

HNF4A Gene

protein-coding GIFtS: 67
GCID: GC20P042984

hepatocyte nuclear factor 4, alpha

(Previous symbols: TCF14, MODY, MODY1)

Explore 76 diseases affiliated with
HNF4A via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Hepatocyte Nuclear Factor 4, Alpha¹ ²		HNF4a7²
TCF14¹ ² ³ ⁵		HNF4a8²
HNF4¹ ² ³		HNF4a9²
NR2A1¹ ² ³		HNF4alpha²
MODY1¹ ² ⁵		HNF4alpha10/11/12²
MODY¹ ²		NR2A21²
Nuclear Receptor Subfamily 2 Group A Member 1² ³		TCF²
Transcription Factor 14² ³		Hepatic Nuclear Factor 4 Alpha²
Transcription Factor HNF-4² ³		Hepatocyte Nuclear Factor 4-Alpha²
TCF-14² ³		HNF-4-Alpha¹

External Ids:	HGNC: 5024¹	Entrez Gene: 3172²	Ensembl: ENSG00000101076⁷	OMIM: 600281⁵	UniProtKB: P41235³

Export aliases for HNF4A gene to outside databases

Previous GC identifers: GC20P042758 GC20P043668 GC20P043715 GC20P042463 GC20P039720

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for HNF4A:

The protein encoded by this gene is a nuclear transcription factor which binds DNA as a homodimer. The encoded protein

controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor which

regulates the expression of several hepatic genes. This gene may play a role in development of the liver, kidney, and

intestines. Mutations in this gene have been associated with monogenic autosomal dominant non-insulin-dependent

diabetes mellitus type I. Alternative splicing of this gene results in multiple transcript variants encoding several

different isoforms. (provided by RefSeq, Apr 2012)

UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235

Function: Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha

1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver,

kidney and intestine

Gene Wiki entry for HNF4A (Hepatocyte nuclear factor 4 alpha)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000020.10 NC_018931.1 NT_011362.10

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the HNF4A gene promoter:
Sp1 NRSF form 1 NRSF form 2
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): HNF4A promoter sequence

Search SABiosciences Chromatin IP Primers for HNF4A

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat HNF4A

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q13.12 Ensembl cytogenetic band: 20q13.12 HGNC cytogenetic band: 20q13.12

HNF4A Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
HNF4A gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P042984: view genomic region (about GC identifiers)

Start:	42,984,340 bp from pter	End:	43,060,030 bp from pter
Size:	75,691 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235 (See protein sequence)

Recommended Name: Hepatocyte nuclear factor 4-alpha

Size: 474 amino acids; 52785 Da

Subunit: Homodimerization is required for HNF4-alpha to bind to its recognition site

Subcellular location: Nucleus

Miscellaneous: Binds fatty acids

Sequence caution: Sequence=CAA54248.1; Type=Erroneous initiation; Sequence=CAA61133.1; Type=Frameshift; Positions=2, 7;

Sequence=CAA61134.1; Type=Frameshift; Positions=2, 7; Sequence=CAA61135.1; Type=Frameshift; Positions=2, 7;

3 PDB 3D structures from and Proteopedia for HNF4A:

1PZL (3D)

3CBB (3D)

3FS1 (3D)

Secondary accessions: A5JW41 B2RPP8 O00659 O00723 Q14540 Q5QPB8 Q6B4V5 Q6B4V6 Q6B4V7 Q92653 Q92654

Q92655 Q99864 Q9NQH0

Alternative promoter usage, Alternative splicing: 7 isoforms: P41235-1 P41235-2 P41235-3 P41235-4 P41235-5 P41235-6 P41235-7 (Produced by alternative splicing of isoform HNF4-Alpha-7)

Explore the universe of human proteins at neXtProt for HNF4A: NX_P41235

Post-translational modifications:

Phosphorylated on tyrosine residue(s); phosphorylation is important for its DNA-binding activity. Phosphorylation may

directly or indirectly play a regulatory role in the subnuclear distribution. Phosphorylation at Ser-313 by AMPK

reduces the ability to form homodimers and bind DNA¹

Acetylation at Lys-458 lowers transcriptional activation by about two-fold¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P41235

HNF4A Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (7 alternative transcripts):

NP_000448.3 NP_001025174.1 NP_001025175.1 NP_001245284.1 NP_787110.2 NP_849180.1 NP_849181.1

ENSEMBL proteins:

ENSP00000315180 ENSP00000362011 ENSP00000312987 ENSP00000410911 ENSP00000396216

ENSP00000412111

Reactome Protein details: P41235
Human Recombinant Protein Products:

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	Novus Biologicals HNF4A Proteins Novus Biologicals HNF4A Lysates
	Browse Sino Biological Recombinant Proteins
	Browse ProSpec Recombinant Proteins
	Browse Proteins at Uscn

Gene Ontology (GO): 4 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005634	nucleus	IDA	14563941
GO:0005654	nucleoplasm	TAS	--
GO:0005667	transcription factor complex	--	--
GO:0005737	cytoplasm	IDA	14563941

HNF4A for ontologies About GeneDecksing

HNF4A Antibody Products:

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	Novus Biologicals HNF4A Antibodies
	Abcam antibodies for HNF4A
	Browse Antibodies at Uscn
	ThermoFisher Antibody for HNF4A

Assay Products for HNF4A:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for HNF4A
	Browse Enzo Life Sciences for kits & assays
	Browse ELISAs and CLIAs at Uscn

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

HNF4A for domains About GeneDecksing

5/6 InterPro domains/families (see all 6):

IPR008946 Nucl_hormone_rcpt_ligand-bd

IPR003068 COUP_TF

IPR001723 Str_hrmn_rcpt

IPR013088 Znf_NHR/GATA

IPR000536 Nucl_hrmn_rcpt_lig-bd_core

Graphical View of Domain Structure for InterPro Entry P41235

ProtoNet protein and cluster: P41235

2 Blocks protein families:

IPB000003 Retinoic acid receptor signature

IPB001723 Steroid hormone receptor signature

UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235

Similarity: Belongs to the nuclear hormone receptor family. NR2 subfamily

Similarity: Contains 1 nuclear receptor DNA-binding domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235

Function: Transcriptionally controlled transcription factor. Binds to DNA sites required for the transcription of alpha

1-antitrypsin, apolipoprotein CIII, transthyretin genes and HNF1-alpha. May be essential for development of the liver,

kidney and intestine

Genatlas biochemistry entry for HNF4A:

transcription factor 4,hepatocyte nuclear factor 4 alpha,steroid/thyroid hormone receptor superfamily,coexpressed with

TCF1 and binding TCF1 promoter (see also RGHE),including the alternatively spliced isoforms

HNF4A1,HNF4A2,HNF4A4,expressed in pancreatic beta cells,regulating expression of genes required for glucose transport

and metabolism,and of sex hormones-binding globulin,interacting with TCF1 for regulation of gene activity and

chromatin structure of serpin cluster (PI)

miRNA Products:		miRTarBase miRNAs that target HNF4A: hsa-mir-197 (MIRT003822), hsa-mir-24 (MIRT003355), hsa-mir-34a (MIRT003356)

		OriGene 3'-UTR Clone (see all 3): HNF4A Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat HNF4A
		4 QIAGEN miScript miRNA Assays for microRNAs that regulate HNF4A:
		hsa-miR-374a* hsa-miR-185* hsa-miR-26b* hsa-miR-378*
		SwitchGear 3'UTR luciferase reporter plasmids (see all 2): HNF4A 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
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Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for HNF4A

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
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		GenScript: all cDNA clones in your preferred vector (see all 6): HNF4A (NM_175914)
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Cell Line Products:		GenScript Custom overexpressing Cell Line Services for HNF4A
		Search LifeMap BioReagents cell lines for HNF4A

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for HNF4A

Gene Ontology (GO): 5/18 molecular function terms (GO ID links to tree view) (see all 18): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000062	fatty-acyl-CoA binding	--	--
GO:0001077	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription	ISS	--
GO:0003677	DNA binding	IDA	10551874
GO:0003700	sequence-specific DNA binding transcription factor activity	IDA	16488887
GO:0003705	RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity	IEA	--

HNF4A for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for HNF4A:

Increased G1 DNA content

Animal Models:
Mouse knock-outs for HNF4A: Hnf4a^tm1.2Gonz Hnf4a^tm1Dnl
8 MGI mutant phenotypes (inferred from 10 alleles) (MGI details for Hnf4a):

cellular	embryogenesis	growth/size	homeostasis/metabolism	liver/biliary system
mortality/aging	nervous system	normal

HNF4A for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/22 super-pathways (see all 22) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Regulation of beta-cell development

	Regulation of beta-cell development	1.00			Regulation of gene expression in beta cells	0.56
	Maturity onset diabetes of the young	0.56

Dichloroethylene metabolism

	Dichloroethylene metabolism	1.00			HNF1A-dependent synthesis of HNF4A	0.12
	Dichloroethylene metabolism	1.00

Nuclear Receptor transcription pathway

Nuclear Receptor transcription pathway

1.00

Nuclear Receptors

0.68

Generic Transcription Pathway

Generic Transcription Pathway

1.00

Gene Expression

0.46

Integrated Pancreatic Cancer Pathway

Integrated Pancreatic Cancer Pathway

1.00

Integrated Pancreatic Cancer Pathway

0.99

Pathway sources
See GeneCards unified pathways
Show all pathways

1 EMD Millipore Pathway for HNF4A

Dichloroethylene metabolism

1 R&D Systems Pathway for HNF4A

TGF-beta Signaling Pathways

5/10 Downloadable PowerPoint Slides of QIAGEN Pathway Central Maps for HNF4A (see all 10)

	MAPK Signaling
	Factors Promoting Cardiogenesis in Vertebrates
	HIF1Alpha Pathway
	JNK Pathway
	Epithelial Adherens Junctions

1 Cell Signaling Technology (CST) Pathway for HNF4A

Glucose / Energy Metabolism

1 GeneGo (Thomson Reuters) Pathway for HNF4A

Dichloroethylene metabolism

5/8 BioSystems Pathways for HNF4A (see all 8)

	Nuclear Receptors
	AMPK signaling
	Integrated Pancreatic Cancer Pathway
	Integrated Pancreatic Cancer Pathway
	TGF-beta Receptor Signaling Pathway

5/7 Reactome Pathways for HNF4A (see all 7)

	Regulation of gene expression in beta cells
	Developmental Biology
	Generic Transcription Pathway
	Nuclear Receptor transcription pathway
	Regulation of beta-cell development

1 PharmGKB Pathway for HNF4A

Anti-diabetic Drug Potassium Channel Inhibitors Pathway, Pharmacodynamics

1 Kegg Pathway (Kegg details for HNF4A):

Maturity onset diabetes of the young

HNF4A for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for HNF4A

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/104 Interacting proteins for HNF4A (P41235^{2, 3} ENSP00000312987⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 104)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
CITED2	Q99967²^,³, ENSP00000356623⁴	MINT-6175330 MINT-6175313 MINT-6175350 I2D: score=1 STRING: ENSP00000356623
SREBF2	Q12772²^,³, ENSP00000354476⁴	MINT-16696 MINT-16697 I2D: score=3 STRING: ENSP00000354476
FOXO1	Q12778³, ENSP00000368880⁴	I2D: score=3 STRING: ENSP00000368880
PPARGC1A	Q9UBK2³, ENSP00000264867⁴	I2D: score=3 STRING: ENSP00000264867
CREBBP	Q92793³, ENSP00000262367⁴	I2D: score=2 STRING: ENSP00000262367

About this table

Gene Ontology (GO): 5/41 biological process terms (GO ID links to tree view) (see all 41): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006351	transcription, DNA-dependent	--	--
GO:0006355	regulation of transcription, DNA-dependent	--	--
GO:0006357	regulation of transcription from RNA polymerase II promoter	IMP	18163890
GO:0006367	transcription initiation from RNA polymerase II promoter	TAS	--
GO:0006591	ornithine metabolic process	IMP	17827783

HNF4A for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

HNF4A for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for HNF4A

1 DrugBank Compound for HNF4A About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
MYRISTIC ACID	--	--	target	--	10592235

10/63 Novoseek chemical compound relationships for HNF4A gene (see all 63) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
hmtp	74.3	40	15547294 (2), 16226723 (2)
androstane	73.8	20	17576804 (2), 19058292 (1), 19690166 (1), 17595319 (1) (see all 13)
glycogen	57.6	15	11915024 (2), 12808453 (1), 16352701 (1), 7508874 (1) (see all 11)
chenodeoxycholic acid	57.1	14	15337761 (2), 16436500 (2), 11402042 (2), 15692145 (2) (see all 5)
gw 4064	55.7	1	15692145 (1)
sterol	51.9	10	12957378 (1), 16368706 (1), 14685799 (1), 17403900 (1) (see all 8)
phosphoenolpyruvate	49.9	12	19252740 (1), 7508874 (1), 15468681 (1), 16488887 (1) (see all 9)
retinoic acid	46.7	30	10799735 (4), 8288643 (3), 9792724 (3), 9886825 (2) (see all 12)
glucose	41.2	80	9812974 (3), 11916906 (3), 20382893 (2), 9371825 (2) (see all 47)
cholesterol	36.4	28	18080173 (2), 14748721 (2), 11535594 (1), 15123688 (1) (see all 20)

Search CenterWatch for drugs/clinical trials and news about HNF4A

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for HNF4A gene (7 alternative transcripts):

NM_000457.4 NM_001030003.2 NM_001030004.2 NM_001258355.1 NM_175914.4 NM_178849.2 NM_178850.2

Unigene Cluster for HNF4A:

Hepatocyte nuclear factor 4, alpha

Hs.116462 [show with all ESTs]

Unigene Representative Sequence: NM_001258355

6 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000316673 ENST00000372920(uc010ggq.3) ENST00000316099(uc002xlv.3 uc002xma.3)

ENST00000443598(uc002xlt.3 uc002xly.3) ENST00000457232(uc010zwo.1)

ENST00000415691(uc002xlu.3 uc002xlz.3)

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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat HNF4A

Additional cDNA sequence:

AB307703.1 AY680696.1 AY680697.1 AY680698.1 BC137539.1 BC137540.1 FJ608822.1 HQ692860.1

HQ692868.1 HQ692869.1 X76930.1 X87870.1 X87871.1 X87872.1 Z49825.1

12 DOTS entries:

DT.100756991 DT.107774 DT.452485 DT.87046459 DT.120822103 DT.100756993 DT.95363008 DT.120822062

DT.120822074 DT.75128134 DT.435193 DT.92414368

24/33 AceView cDNA sequences (see all 33):

AI033279 AY680697 NM_000457 AV658197 AI301528 CB161598 AI052807 AI631717

AY680698 AY680696 NM_178849 BE221792 BF062005 NM_178850 AI056785 X87872

X76930 Z49825 BX112336 X87871 BF766102 AW082799 BI764073 X87870

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

HNF4A expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: --

About this image

HNF4A expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

10/27 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 27)

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Gut Tube

Ventral Foregut Endoderm

Hepatic Endoderm Cells

Selective marker (cell-identifying gene)

Liver

Epiblast

Intraembryonic Epiblast Cells

Early Embryo

Liver

Intrahepatic Biliary Tree

Immature Biliary Epithelial Cells

Liver

Gut Tube

Primitive Gut Endoderm Cells

Endoderm

Hypoblast

Extraembryonic Endoderm

Extraembryonic Endoderm Cells

Extraembryonic Tissues, Yolk Sac

Hypoblast

Extraembryonic Visceral Endoderm

Extraembryonic Visceral Endoderm Cells

Extraembryonic Tissues, Yolk Sac

Hypoblast

Hypoblast Cells

Extraembryonic Tissues

Liver

Hepatic Diverticulum

Hepatic Diverticulum Cells

Liver

Liver

Liver

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 10/18 LifeMap Cells (see all 18)

Name

Category

Extra-embryonic endoderm cells (Fetal Stem / Progenitor Cell)

Extraembryonic Tissues

Endoderm progenitor-like cells (Generation and expan...)

Hepatoblasts (Generation of hepato...)

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See HNF4A Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for HNF4A

SOURCE GeneReport for Unigene cluster: Hs.116462

SABiosciences Expression via Pathway-Focused PCR Arrays including HNF4A (see all 6):

Cell Lineage Identification in human mouse rat

Transcription Factors in human mouse rat

Nuclear Receptors & Coregulators in human mouse rat

Hypoxia Signaling Pathway in human mouse rat

Fatty Liver in human mouse rat

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for HNF4A gene from 6/19 species (see all 19) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	HNF4A¹	hepatocyte nuclear factor 4, alpha	82.16(n) 87.89(a)		419198 NM_001030855.1 NP_001026026.1
lizard (Anolis carolinensis)	Reptilia	HNF4A⁶	--	85(a)	1 ↔ 1	4(144117386-144141394)
African clawed frog (Xenopus laevis)	Amphibia	hnf4-prov²	hepatic nuclear factor 4	76.87(n)		Z37526.1
zebrafish (Danio rerio)	Actinopterygii	hnf4a²	hepatocyte nuclear factor 4, alpha	75.61(n)		322358 BC056550.1
fruit fly (Drosophila melanogaster)	Insecta	Hnf4⁶	Hepatocyte nuclear factor 4	33(a)	1 → many	2L(8687281-8709038)
worm (Caenorhabditis elegans)	Secernentea	nhr-69¹	Protein NHR-69	47.14(n) 42.02(a)		172840 NM_060214.3 NP_492615.2

ENSEMBL Gene Tree for HNF4A (if available)
TreeFam Gene Tree for HNF4A (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for HNF4A gene

ESRRA² RXRG² PGR² ESR2² ESRRB² HNF4G² NR2F6² NR2E1²

ESRRG² NR3C2² RXRA² NR2F1² NR3C1² NR2F2² AR² ESR1²

NR2C1² NR2C2² RXRB²

18/19 SIMAP similar genes for HNF4A using alignment to 3 protein entries: HNF4A_HUMAN (see all proteins) (see all similar genes):

HNF4alpha NR2A1 HNF4G NR2A2 NR2A3 RXRB

NR2B2 NR2B1 NR2B3 RXRG RXRA NR2F2

NR2F1 NR2F6 ESRRG NR3B3 NR2E1 NR2E3

HNF4A for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs61737145^1,2	C,F,	non-pathogenic	39798367(+)	`ACCAAC/TGTCAT`	10	N	syn¹		3		NS NA EU	5919
rs41282026^1,2	C,F	probable-non-pathogenic	39776049(+)	`AACGCG/ACCCAA`	14	/A	syn¹		2		NA EU	5637
rs193922473^1,2	C	probable-non-pathogenic	39783713(+)	`AGCCTA/GCCCTC`	14	L	syn¹		0	--	--	--	--
rs113308087^1,2	C,F,	probable-non-pathogenic	39783725(+)	`ATCAAT/CGCGCT`	14	/N	syn¹		2		CSA NA	4548
rs150078978^1,2	C,F,	probable-non-pathogenic	39789705(+)	`CGGCAC/TTGCCC`	14	H	syn¹		1		NA	4552
rs6031592^1,2	C,F,H,	probable-non-pathogenic	39789753(+)	`CTTGAC/TGAGCT`	14	D	syn¹ ese³		7		NS EA CSA NA	4974
rs181559088^1,2	C,	probable-non-pathogenic	39793990(+)	`GGGCTA/GAGCGA`	14	L	syn¹		0	--	--	--	--
rs140146223^1,2	C	probable-non-pathogenic	39794074(+)	`GACTCA/G/TCGTGG`	21	S	syn¹		1		NA	4512
rs142204928^1,2	C,	probable-pathogenic	39784477(+)	`CCCCCG/ATCTCC`	14	/I /V	mis¹		1		NA	4552
rs182980547^1,2	C,F,	unknown	39783764(+)	`GTACCG/AGGGTG`	7	--	int¹		1		EU	803

HapMap Linkage Disequilibrium report for HNF4A (42984340 - 43060030 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 2 variations for HNF4A
2 Indels: 59644 102978
Human Gene Mutation Database (HGMD): HNF4A

Locus Specific Mutation Databases (LSDB): HNF4A

SABiosciences Cancer Mutation PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

HNF4A for disorders           About GeneDecksing

OMIM gene information: 600281
OMIM disorders: 125850  125853
UniProtKB/Swiss-Prot: HNF4A_HUMAN, P41235

Defects in HNF4A are the cause of maturity-onset diabetes of the young type 1 (MODY1) [MIM:125850]; also

symbolized MODY-1. MODY is a form of diabetes that is characterized by an autosomal dominant mode of inheritance,

onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and

frequent insulin-independence at the beginning of the disease

20/76 diseases for HNF4A (see all 76): About MalaCards

diabetes mellitus hepatitis diabetes mellitus, noninsulin-dependent maturity-onset diabetes of the young

factor vii deficiency maturity-onset diabetes of the young, type 3 maturity-onset diabetes of the young, type 1 familial adenomatous polyposis

retinol binding protein adenomatous polyposis coli developmental disabilities hyperinsulinemic hypoglycemia

type 2 diabetes mellitus herpes simplex ureteral obstruction hypoglycemia

insulin resistance strabismus metabolic disorders diabetic ketoacidosis

4 diseases from the University of Copenhagen DISEASES database for HNF4A:

maturity-onset diabetes of the young Diabetes mellitus Colorectal cancer Familial adenomatous polyposis

10/70 Novoseek disease relationships for HNF4A gene (see all 70) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
niddm	79.9	191	9267996 (5), 9029679 (4), 10983627 (3), 9133559 (3) (see all 99)
familial adenomatous polyposis	68.5	12	11774242 (1), 17005722 (1), 9065401 (1), 10987283 (1) (see all 11)
colon cancer	54.3	17	16151476 (3), 14566053 (2), 15930030 (1), 17005722 (1) (see all 14)
hepatoblastoma	53	4	19200579 (2), 17047077 (1), 19336534 (1)
hyperglycemia	47.7	7	16444761 (1), 11984998 (1), 10905494 (1), 9356021 (1) (see all 6)
colon carcinoma	46.8	5	11774242 (1), 12901858 (1), 9065401 (1), 8288643 (1) (see all 5)
cholestasis	43.8	2	19239393 (1)
embryonal tumor	41.2	1	11956596 (1)
neonatal hypoglycemia	40.1	6	17407387 (2), 20164212 (1), 17891372 (1)
diabetes mellitus	38.8	22	7951673 (2), 17563455 (2), 11590126 (1), 14654354 (1) (see all 15)

Genetic Association Database (GAD): HNF4A
Human Genome Epidemiology (HuGE) Navigator: HNF4A (76 documents)

Export disorders for HNF4A gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for HNF4A gene, integrated from 9 sources (see all 912):
(articles sorted by number of sources associating them with HNF4A)

Utopia: connect your pdf to the dynamic
world of online information

Mutations in the hepatocyte nuclear factor-4alpha gene in maturity- onset diabetes of the young (MODY1). (PubMed id 8945471)^{1, 2, 4, 9} Yamagata K.... Bell G.I. (1996)
Cloning and sequencing of cDNAs encoding the human hepatocyte nuclear factor 4 indicate the presence of two isoforms in human liver. (PubMed id 7926813)^{1, 2, 3} Chartier F.L.... Laine B. (1994)
Molecular genetics and phenotypic characteristics of MODY caused by hepatocyte nuclear factor 4alpha mutations in a large European collection. (PubMed id 15830177)^{1, 4, 9} Pearson E.R....Hattersley A.T. (2005)
Variants in hepatocyte nuclear factor 4alpha are modestly associated with type 2 diabetes in Pima Indians. (PubMed id 16186411)^{1, 4, 9} Muller Y.L....Baier L.J. (2005)
Studies of the genetic variability of the coding region of the hepatocyte nuclear factor-4alpha in Caucasians with maturity onset NIDDM. (PubMed id 9267996)^{1, 2, 9} Moeller A.M.... Pedersen O. (1997)
Polymorphisms in both promoters of hepatocyte nuclear factor 4-alpha are associated with type 2 diabetes in the Amish. (PubMed id 15561969)^{1, 4, 9} Damcott C.M....Shuldiner A.R. (2004)
T130I mutation in HNF-4alpha gene is a loss-of-function mutation in hepatocytes and is associated with late-onset Type 2 diabetes mellitus in Japanese subjects. (PubMed id 12669197)^{1, 4, 9} Zhu Q....Matsuzawa Y. (2003)
A missense mutation in hepatocyte nuclear factor-4-alpha, resulting in a reduced transactivation activity, in human late-onset non- insulin-dependent diabetes mellitus. (PubMed id 9449683)^{1, 2, 9} Hani E.H....Froguel P. (1998)
Recruitment of hepatocyte nuclear factor 4 into specific intranuclear compartments depends on tyrosine phosphorylation that affects its DNA- binding and transactivation potential. (PubMed id 7568236)^{1, 2, 9} Ktistaki E.... Talianidis I. (1995)
Genetic analysis of HNF4A polymorphisms in Caucasian-American type 2 diabetes. (PubMed id 15793260)^{1, 4, 9} Bagwell A.M....Bowden D.W. (2005)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 3172	HGNC: 5024	AceView: HNF4A	Ensembl:ENSG00000101076	euGenes: HUgn3172
ECgene: HNF4A	Kegg: 3172	H-InvDB: HNF4A

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for HNF4A	Pharmacogenomics, SNPs, Pathways
GeneReviews	http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HNF4A
Wikipedia	http://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors
SeattleSNPs	http://pga.gs.washington.edu/data/hnf4a/

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HNF4A Gene

hepatocyte nuclear factor 4, alpha

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HNF4A (Gene Symbol)
Hepatocyte Nuclear Factor 4, Alpha
TCF14
HNF4
NR2A1
MODY1
MODY
Nuclear Receptor Subfamily 2 Group A Member 1
Transcription Factor 14
Transcription Factor HNF-4
TCF-14
HNF4a7
HNF4a8
HNF4a9
HNF4alpha
HNF4alpha10/11/12
NR2A21
TCF
Hepatic Nuclear Factor 4 Alpha
Hepatocyte Nuclear Factor 4-Alpha
HNF-4-Alpha

Fatty Liver
familial adenomatous polyposis
Hyperinsulinemia
Genetic Susceptibility
Herpes Simplex
coagulopathy
Polyps
COLON CARCINOMA
insulin sensitivity
Factor VII Deficiency
Atherosclerosis
Liver diseases
Breast Cancer
Metaplasia
Cholestasis
Hypoglycemia
Adenocarcinoma
Cancer
Diabetes Mellitus Insulin-Dependent
Colorectal Carcinoma
ADENOCARCINOMA GASTRIC
Dyslipidemia
Shock
RENAL DISEASE
polyposis
Colorectal Cancer
Inflammation
Neonatal hypoglycemia
TUMOR LIVER
Insulinoma
Hepatitis
Hyperglycemia
Hepatitis B
ENDOMETRIAL CARCINOMA
embryonal tumor
prostate cancer
Tumors
Cardiovascular Diseases
Metastasis
metabolic disorder
Necrosis
Autoimmunity
Hepatoblastoma
neoplastic transformation
COLON TUMOR
Developmental Disabilities
Gastric Cancer
Cirrhosis
Colon Cancer
Carcinoma
Diabetes Gestational
Diabetes Mellitus
HEPATOCELLULAR CARCINOMA
Carcinoma Renal Cell
Pancreatic Cancer
early disease onset
Cancer Lung
Response Acute Phase
Insulin Resistance
impaired glucose tolerance
Adenoma
OVARIAN CARCINOMA
OBESITY
Carcinoma Squamous Cell
Colorectal Tumors
Strabismus
NIDDM
Diabetes Autoimmune
Growth retardation
Choriocarcinoma

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HNF4A Gene

hepatocyte nuclear factor 4, alpha

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