Human Gene HNF4A (ENST00000316673.9_5) from GENCODE V47lift37
  Description: hepatocyte nuclear factor 4 alpha, transcript variant 5 (from RefSeq NM_175914.5)
Gencode Transcript: ENST00000316673.9_5
Gencode Gene: ENSG00000101076.20_13
Transcript (Including UTRs)
   Position: hg19 chr20:42,984,339-43,061,485 Size: 77,147 Total Exon Count: 10 Strand: +
Coding Region
   Position: hg19 chr20:42,984,445-43,058,305 Size: 73,861 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated at UCSC: 2024-08-22 23:36:26

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr20:42,984,339-43,061,485)mRNA (may differ from genome)Protein (452 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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UniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: HNF4A_HUMAN
DESCRIPTION: RecName: Full=Hepatocyte nuclear factor 4-alpha; Short=HNF-4-alpha; AltName: Full=Nuclear receptor subfamily 2 group A member 1; AltName: Full=Transcription factor 14; Short=TCF-14; AltName: Full=Transcription factor HNF-4;
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.
SUBUNIT: Homodimerization is required for HNF4-alpha to bind to its recognition site.
SUBCELLULAR LOCATION: Nucleus.
PTM: 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 DNA.
PTM: Acetylation at Lys-458 lowers transcriptional activation by about two-fold.
DISEASE: 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.
MISCELLANEOUS: Binds fatty acids.
SIMILARITY: Belongs to the nuclear hormone receptor family. NR2 subfamily.
SIMILARITY: Contains 1 nuclear receptor DNA-binding domain.
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;
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/HNF4A";
WEB RESOURCE: Name=Wikipedia; Note=Hepatocyte nuclear factors entry; URL="http://en.wikipedia.org/wiki/Hepatocyte_nuclear_factors";
WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/hnf4a/";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  MalaCards Disease Associations
  MalaCards Gene Search: HNF4A
Diseases sorted by gene-association score: mody, type i* (1300), fanconi renotubular syndrome 4, with maturity-onset diabetes of the young* (1231), hyperinsulinism due to hnf4a deficiency* (750), hyperinsulinism* (435), hyperinsulinemic hypoglycemia, familial, 2* (283), familial hyperinsulinsism* (283), renal cysts and diabetes syndrome* (247), diabetes mellitus, noninsulin-dependent* (241), maturity-onset diabetes of the young* (206), hnf4a-related hyperinsulinism* (100), fanconi syndrome (32), factor vii deficiency (12), familial adenomatous polyposis (11), monogenic diabetes (11), hepatoid adenocarcinoma (8), hyperinsulinemic hypoglycemia (8), polycystic kidney disease 1 (7), aminoaciduria (6), colorectal cancer (5), glossopharyngeal neuralgia (5), lipid metabolism disorder (3), hepatocellular carcinoma (2), diabetes mellitus, insulin-dependent (2), strabismus (2)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 43.87 RPKM in Liver
Total median expression: 127.91 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -46.80106-0.442 Picture PostScript Text
3' UTR -1162.603180-0.366 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003068 - COUP_TF
IPR008946 - Nucl_hormone_rcpt_ligand-bd
IPR000536 - Nucl_hrmn_rcpt_lig-bd_core
IPR001723 - Str_hrmn_rcpt
IPR001628 - Znf_hrmn_rcpt
IPR013088 - Znf_NHR/GATA

Pfam Domains:
PF00104 - Ligand-binding domain of nuclear hormone receptor
PF00105 - Zinc finger, C4 type (two domains)

SCOP Domains:
48508 - Nuclear receptor ligand-binding domain
57716 - Glucocorticoid receptor-like (DNA-binding domain)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1PZL - X-ray MuPIT 3CBB - X-ray MuPIT 3FS1 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P41235
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0000981 RNA polymerase II transcription factor activity, sequence-specific DNA binding
GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding
GO:0001102 RNA polymerase II activating transcription factor binding
GO:0001228 transcriptional activator activity, RNA polymerase II transcription regulatory region sequence-specific binding
GO:0003677 DNA binding
GO:0003700 transcription factor activity, sequence-specific DNA binding
GO:0003705 transcription factor activity, RNA polymerase II distal enhancer sequence-specific binding
GO:0003707 steroid hormone receptor activity
GO:0004879 RNA polymerase II transcription factor activity, ligand-activated sequence-specific DNA binding
GO:0005102 receptor binding
GO:0005504 fatty acid binding
GO:0005515 protein binding
GO:0008270 zinc ion binding
GO:0042803 protein homodimerization activity
GO:0043565 sequence-specific DNA binding
GO:0044212 transcription regulatory region DNA binding
GO:0046872 metal ion binding

Biological Process:
GO:0006351 transcription, DNA-templated
GO:0006355 regulation of transcription, DNA-templated
GO:0006357 regulation of transcription from RNA polymerase II promoter
GO:0006367 transcription initiation from RNA polymerase II promoter
GO:0006591 ornithine metabolic process
GO:0006629 lipid metabolic process
GO:0006805 xenobiotic metabolic process
GO:0007548 sex differentiation
GO:0007596 blood coagulation
GO:0008285 negative regulation of cell proliferation
GO:0009749 response to glucose
GO:0010470 regulation of gastrulation
GO:0019216 regulation of lipid metabolic process
GO:0023019 signal transduction involved in regulation of gene expression
GO:0030308 negative regulation of cell growth
GO:0030522 intracellular receptor signaling pathway
GO:0042593 glucose homeostasis
GO:0042632 cholesterol homeostasis
GO:0043401 steroid hormone mediated signaling pathway
GO:0045893 positive regulation of transcription, DNA-templated
GO:0045944 positive regulation of transcription from RNA polymerase II promoter
GO:0050796 regulation of insulin secretion
GO:0055088 lipid homeostasis
GO:0055091 phospholipid homeostasis
GO:0060395 SMAD protein signal transduction
GO:0060398 regulation of growth hormone receptor signaling pathway
GO:0070328 triglyceride homeostasis

Cellular Component:
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm


-  Descriptions from all associated GenBank mRNAs
  AY680698 - Homo sapiens hepatocyte nuclear factor 4 alpha, transcript variant 9 (HNF4A) mRNA, complete cds, alternatively spliced.
AY680696 - Homo sapiens hepatocyte nuclear factor 4 alpha, transcript variant 7 (HNF4A) mRNA, complete cds, alternatively spliced.
AY680697 - Homo sapiens hepatocyte nuclear factor 4 alpha, transcript variant 8 (HNF4A) mRNA, complete cds, alternatively spliced.
FJ608822 - Homo sapiens HNF4alpha10/11/12 (HNF4alpha) mRNA, partial cds, alternatively spliced.
HQ692868 - Homo sapiens hepatocyte nuclear factor 4 4 alpha variant 4 (NR2A1) mRNA, complete cds.
AK096973 - Homo sapiens cDNA FLJ39654 fis, clone SMINT2005621.
Z49825 - H.sapiens mRNA for hepatocyte nuclear factor 4 alpha.
X87872 - H.sapiens mRNA for hepatocyte nuclear factor 4c.
X87870 - H.sapiens mRNA for hepatocyte nuclear factor 4a.
X87871 - H.sapiens mRNA for hepatocyte nuclear factor 4b.
BC137539 - Homo sapiens hepatocyte nuclear factor 4, alpha, mRNA (cDNA clone MGC:169162 IMAGE:9021539), complete cds.
BC137540 - Homo sapiens hepatocyte nuclear factor 4, alpha, mRNA (cDNA clone MGC:169163 IMAGE:9021540), complete cds.
KJ891369 - Synthetic construct Homo sapiens clone ccsbBroadEn_00763 HNF4A gene, encodes complete protein.
KR712014 - Synthetic construct Homo sapiens clone CCSBHm_00034706 HNF4A (HNF4A) mRNA, encodes complete protein.
KR712015 - Synthetic construct Homo sapiens clone CCSBHm_00034733 HNF4A (HNF4A) mRNA, encodes complete protein.
AB463726 - Synthetic construct DNA, clone: pF1KB9731, Homo sapiens HNF4A gene for hepatocyte nuclear factor 4, alpha, without stop codon, in Flexi system.
HQ692860 - Homo sapiens hepatocyte nuclear factor 4 4 alpha variant 1 (NR2A1) mRNA, complete cds.
HQ692869 - Homo sapiens hepatocyte nuclear factor 4 4 alpha variant 2 (NR2A1) mRNA, complete cds.
X76930 - H.sapiens HNF4 mRNA for hepatocyte nuclear factor 4.
AB307703 - Homo sapiens NR2A1 mRNA for hepatocyte nuclear factor 4, alpha, complete cds.
JD510473 - Sequence 491497 from Patent EP1572962.
JD267909 - Sequence 248933 from Patent EP1572962.
JD341244 - Sequence 322268 from Patent EP1572962.
JD095849 - Sequence 76873 from Patent EP1572962.
JD298299 - Sequence 279323 from Patent EP1572962.
JD557653 - Sequence 538677 from Patent EP1572962.
JD195277 - Sequence 176301 from Patent EP1572962.
JD095126 - Sequence 76150 from Patent EP1572962.
JD249090 - Sequence 230114 from Patent EP1572962.
JD360995 - Sequence 342019 from Patent EP1572962.
JD150583 - Sequence 131607 from Patent EP1572962.
JD278968 - Sequence 259992 from Patent EP1572962.
JD402784 - Sequence 383808 from Patent EP1572962.
JD157294 - Sequence 138318 from Patent EP1572962.
JD272557 - Sequence 253581 from Patent EP1572962.
JD422625 - Sequence 403649 from Patent EP1572962.
JD403154 - Sequence 384178 from Patent EP1572962.
JD493086 - Sequence 474110 from Patent EP1572962.
JD074509 - Sequence 55533 from Patent EP1572962.
JD045219 - Sequence 26243 from Patent EP1572962.
JD221607 - Sequence 202631 from Patent EP1572962.
JD496082 - Sequence 477106 from Patent EP1572962.
JD043275 - Sequence 24299 from Patent EP1572962.
JD204288 - Sequence 185312 from Patent EP1572962.
JD185035 - Sequence 166059 from Patent EP1572962.
JD042929 - Sequence 23953 from Patent EP1572962.
JD219796 - Sequence 200820 from Patent EP1572962.
JD528942 - Sequence 509966 from Patent EP1572962.
JD290696 - Sequence 271720 from Patent EP1572962.
JD203641 - Sequence 184665 from Patent EP1572962.
JD468927 - Sequence 449951 from Patent EP1572962.
JD437190 - Sequence 418214 from Patent EP1572962.
JD415625 - Sequence 396649 from Patent EP1572962.
JD389144 - Sequence 370168 from Patent EP1572962.
JD284740 - Sequence 265764 from Patent EP1572962.
JD454574 - Sequence 435598 from Patent EP1572962.
JD085014 - Sequence 66038 from Patent EP1572962.
JD249257 - Sequence 230281 from Patent EP1572962.
JD284981 - Sequence 266005 from Patent EP1572962.
JD299689 - Sequence 280713 from Patent EP1572962.
JD128721 - Sequence 109745 from Patent EP1572962.
JD260023 - Sequence 241047 from Patent EP1572962.
JD411324 - Sequence 392348 from Patent EP1572962.
JD520042 - Sequence 501066 from Patent EP1572962.
MP113339 - Sequence 10 from Patent WO2019053272.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P41235 (Reactome details) participates in the following event(s):

R-HSA-210745 Regulation of gene expression in beta cells
R-HSA-186712 Regulation of beta-cell development
R-HSA-1266738 Developmental Biology
R-HSA-210745 Regulation of gene expression in beta cells
R-HSA-186712 Regulation of beta-cell development
R-HSA-1266738 Developmental Biology
R-HSA-210745 Regulation of gene expression in beta cells
R-HSA-186712 Regulation of beta-cell development
R-HSA-1266738 Developmental Biology
R-HSA-376419 Formation of NR-MED1 Coactivator Complex
R-HSA-383280 Nuclear Receptor transcription pathway
R-HSA-212436 Generic Transcription Pathway
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: A5JW41, B2RPP8, ENST00000316673.1, ENST00000316673.2, ENST00000316673.3, ENST00000316673.4, ENST00000316673.5, ENST00000316673.6, ENST00000316673.7, ENST00000316673.8, HNF4, HNF4A_HUMAN, NM_175914, NR2A1, O00659, O00723, P41235, Q14540, Q5QPB8, Q6B4V5, Q6B4V6, Q6B4V7, Q92653, Q92654, Q92655, Q99864, Q9NQH0, TCF14, uc317qbp.1, uc317qbp.2
UCSC ID: ENST00000316673.9_5
RefSeq Accession: NM_175914.5
Protein: P41235 (aka HNF4A_HUMAN or HN4A_HUMAN)

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene HNF4A:
hi (Nonsyndromic Genetic Hyperinsulinism Overview)
mody-ov (Maturity-Onset Diabetes of the Young Overview)

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.