Hepatocyte nuclear factor 4 alpha

Last updated

HNF4A
Protein HNF4A PDB 1m7w.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HNF4A , HNF4, HNF4a7, HNF4a8, HNF4a9, HNF4alpha, MODY, MODY1, NR2A1, NR2A21, TCF, TCF14, FRTS4, Hepatocyte nuclear factor 4 alpha, TCF-14
External IDs OMIM: 600281; MGI: 109128; HomoloGene: 395; GeneCards: HNF4A; OMA:HNF4A - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_008261
NM_001312906
NM_001312907

RefSeq (protein)

NP_001299835
NP_001299836
NP_032287

Location (UCSC) Chr 20: 44.36 – 44.43 Mb Chr 2: 163.35 – 163.41 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Hepatocyte nuclear factor 4 alpha (HNF4A) also known as NR2A1 (nuclear receptor subfamily 2, group A, member 1) is a nuclear receptor that in humans is encoded by the HNF4A gene. [5] [6]

Function

HNF-4α is a nuclear transcription factor that binds DNA as a homodimer. The encoded protein controls the expression of several genes, including hepatocyte nuclear factor 1 alpha, a transcription factor that regulates the expression of several hepatic genes. This gene plays a role in development of the liver, kidney, and intestines. Alternative splicing of this gene results in multiple transcript variants. [7]

HNF4A is required for the PXR and CAR-mediated transcriptional activation of CYP3A4. [8] Genetic mutations in the HNF4A gene can influence the activity of HNF4α's downstream proteins such as CYP2D6, in vitro and in vivo. [9] [10]

The alkaloid berberine upregulates HNF4A expression. [11]

This gene plays a pivotal role in the expression and synthesis of SHBG, an important glycoprotein made primarily in the liver, [12] which in addition to lowering insulin-resistance also reduces levels of free Estrogen as-well as prolonging the half-life of testosterone.[ citation needed ]

Function of HNF4A gene can be effectively examined by siRNA knockdown based on an independent validation. [13]

Clinical significance

Mutations in the HNF4A gene are associated with a form of diabetes called maturity onset diabetes of the young (MODY), [14] specifically MODY 1. At least 56 disease-causing mutations in this gene have been discovered. [15]

Increased amplification of hepatocyte nuclear factor 4 alpha has been observed in colorectal cancer. [16]

It has also associations with the appearance of Fanconi syndrome phenotypes which occurs due to a missense mutation of the gene. [17]

Interactions

Hepatocyte nuclear factor 4 alpha has been shown to interact with:

See also

Related Research Articles

<span class="mw-page-title-main">Glucokinase</span> Enzyme participating to the regulation of carbohydrate metabolism

Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.

Maturity-onset diabetes of the young (MODY) refers to any of several hereditary forms of diabetes mellitus caused by mutations in an autosomal dominant gene disrupting insulin production. Along with neonatal diabetes, MODY is a form of the conditions known as monogenic diabetes. While the more common types of diabetes involve more complex combinations of causes involving multiple genes and environmental factors, each forms of MODY are caused by changes to a single gene (monogenic). GCK-MODY and HNF1A-MODY are the most common forms.

HNF4 is a nuclear receptor protein mostly expressed in the liver, gut, kidney, and pancreatic beta cells that is critical for liver development. In humans, there are two paralogs of HNF4, HNF4α and HNF4γ,encoded by two separate genes HNF4A and HNF4G respectively.

Hepatocyte nuclear factors (HNFs) are a group of phylogenetically unrelated transcription factors that regulate the transcription of a diverse group of genes into proteins. These proteins include blood clotting factors and in addition, enzymes and transporters involved with glucose, cholesterol, and fatty acid transport and metabolism.

<span class="mw-page-title-main">Small heterodimer partner</span> Protein found in humans

The small heterodimer partner (SHP) also known as NR0B2 is a protein that in humans is encoded by the NR0B2 gene. SHP is a member of the nuclear receptor family of intracellular transcription factors. SHP is unusual for a nuclear receptor in that it lacks a DNA binding domain. Therefore, it is technically neither a transcription factor nor nuclear receptor but nevertheless it is still classified as such due to relatively high sequence homology with other nuclear receptor family members.

<span class="mw-page-title-main">HNF1A</span> Protein-coding gene in the species Homo sapiens

HNF1 homeobox A, also known as HNF1A, is a human gene on chromosome 12. It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes. The HNF1A gene also contains a SNP associated with increased risk of coronary artery disease.

<span class="mw-page-title-main">PDX1</span> A protein involved in the pancreas and duodenum differentiation

PDX1, also known as insulin promoter factor 1, is a transcription factor in the ParaHox gene cluster. In vertebrates, Pdx1 is necessary for pancreatic development, including β-cell maturation, and duodenal differentiation. In humans this protein is encoded by the PDX1 gene, which was formerly known as IPF1. The gene was originally identified in the clawed frog Xenopus laevis and is present widely across the evolutionary diversity of bilaterian animals, although it has been lost in evolution in arthropods and nematodes. Despite the gene name being Pdx1, there is no Pdx2 gene in most animals; single-copy Pdx1 orthologs have been identified in all mammals. Coelacanth and cartilaginous fish are, so far, the only vertebrates shown to have two Pdx genes, Pdx1 and Pdx2.

<span class="mw-page-title-main">HNF1B</span> Mammalian protein found in Homo sapiens

HNF1 homeobox B, also known as HNF1B or transcription factor 2 (TCF2), is a human gene.

<span class="mw-page-title-main">NEUROD1</span> Protein-coding gene in the species Homo sapiens

Neurogenic differentiation 1 (Neurod1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1.

<span class="mw-page-title-main">COUP-TFI</span> Protein found in humans

COUP-TF1 also known as NR2F1 is a protein that in humans is encoded by the NR2F1 gene. This protein is a member of nuclear hormone receptor family of steroid hormone receptors.

<span class="mw-page-title-main">Hepatocyte nuclear factor 4 gamma</span> Protein-coding gene in the species Homo sapiens

Hepatocyte nuclear factor 4 gamma (HNF4G) also known as NR2A2 is a nuclear receptor that in humans is encoded by the HNF4Ggene.

<span class="mw-page-title-main">MED1</span> Protein-coding gene in the species Homo sapiens

Mediator of RNA polymerase II transcription subunit 1 also known as DRIP205 or Trap220 is a subunit of the Mediator complex and is a protein that in humans is encoded by the MED1 gene. MED1 functions as a nuclear receptor coactivator.

<span class="mw-page-title-main">MED14</span> Protein-coding gene in humans

Mediator of RNA polymerase II transcription subunit 14 is an enzyme that in humans is encoded by the MED14 gene.

<span class="mw-page-title-main">PCBD1</span> Protein-coding gene in the species Homo sapiens

Pterin-4-alpha-carbinolamine dehydratase is an enzyme that in humans is encoded by the PCBD1 gene.

<span class="mw-page-title-main">AKR1C4</span> Protein-coding gene in the species Homo sapiens

Aldo-keto reductase family 1 member C4, also known as 3α-Hydroxysteroid dehydrogenase type 1 (3α-HSD1), is an enzyme that in humans is encoded by the AKR1C4 gene. It is known to be necessary for the synthesis of the endogenous neurosteroids allopregnanolone, tetrahydrodeoxycorticosterone, and 3α-androstanediol. It is also known to catalyze the reversible conversion of 3α-androstanediol (5α-androstane-3α,17β-diol) to dihydrotestosterone and vice versa.

<span class="mw-page-title-main">MODY 1</span> Medical condition

MODY 1 or HNF4A-MODY is a form of maturity onset diabetes of the young.

MODY 3 or HNF1A-MODY is a form of maturity-onset diabetes of the young. It is caused by mutations of the HNF1-alpha gene, a homeobox gene on human chromosome 12. This is the most common type of MODY in populations with European ancestry, accounting for about 70% of all cases in Europe. HNF1α is a transcription factor that is thought to control a regulatory network important for differentiation of beta cells. Mutations of this gene lead to reduced beta cell mass or impaired function. MODY 1 and MODY 3 diabetes are clinically similar. About 70% of people develop this type of diabetes by age 25 years, but it occurs at much later ages in a few. This type of diabetes can often be treated with sulfonylureas with excellent results for decades. However, the loss of insulin secretory capacity is slowly progressive and most eventually need insulin.

<span class="mw-page-title-main">FOXA1</span> Protein-coding gene in the species Homo sapiens

Forkhead box protein A1 (FOXA1), also known as hepatocyte nuclear factor 3-alpha (HNF-3A), is a protein that in humans is encoded by the FOXA1 gene.

<span class="mw-page-title-main">FOXA2</span> Mammalian protein found in Homo sapiens

Forkhead box protein A2 (FOXA2), also known as hepatocyte nuclear factor 3-beta (HNF-3B), is a transcription factor that plays an important role during development, in mature tissues and, when dysregulated or mutated, also in cancer.

<span class="mw-page-title-main">FOXA3</span> Protein-coding gene in the species Homo sapiens

Hepatocyte nuclear factor 3-gamma (HNF-3G), also known as forkhead box protein A3 (FOXA3) or transcription factor 3G (TCF-3G) is a protein that in humans is encoded by the FOXA3 gene.

References

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Further reading

This article incorporates text from the United States National Library of Medicine, which is in the public domain.