# Hepatocyte nuclear factors

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.

## Function

As the name suggests, hepatocyte nuclear factors are expressed predominantly in the liver. However HNFs are also expressed and play important roles in a number of other tissues so that the name hepatocyte nuclear factor is somewhat misleading. Nevertheless, the liver is the only tissue in which a significant number of different HNFs are expressed at the same time. In addition, there are a number of genes which contain multiple promoter and enhancer regions each regulated by a different HNF. Furthermore, efficient expression of these genes require synergistic activation by multiple HNFs. Hence hepatocyte nuclear factors function to ensure liver specific expression of certain genes.
As is the case with many transcription factors, HNFs regulate the expression of a wide variety of target genes and therefore functions. These functions (and especially functions involving the liver) include development and metabolic homeostasis of the organism. For example, HNFs influence expression of the insulin gene as well as genes involved in glucose transport and metabolism. In embryo development, HNF4α is thought to have an important role in the development of the liver, kidney, and intestines.

## Disease implication

Variants of the genes can cause several relatively rare forms of MODY, an inherited, early onset form of diabetes. Mutations in the HNF4α, HNF1α, or HNF1β genes are linked to MODY 1, MODY 3, and MODY 5 respectively. Mutations in HNF genes are also associated with a number of others diseases including hepatic adenomas and renal cysts.

## Members

The following is a list of human hepatocyte nuclear factors (see also boxes to the right for additional information about these proteins):

### HNF1

Members of the HNF1 subfamily contain a POU-homeodomain and bind to DNA as homodimers.
* HNF1α/TCF1/MODY3 (related disease: MODY 3)
* HNF1β/TCF2/MODY5 (related disease: MODY 5)
| hepatocyte nuclear factor 1, alphaStructure of the hepatocyte nuclear factor 1A (green cartoon) bound to DNA (magenta) based on the crystallographic coordinates PDB: 1IC8​.IdentifiersSymbolHNF1AAlt. symbolsMODY3, HNF1, LFB1, TCF1NCBI gene6927HGNC11621OMIM142410PDB1JB6RefSeqNM_000545UniProtP20823Other dataLocusChr. 12 q24.3-12q24.3Search forStructuresSwiss-modelDomainsInterPro | hepatocyte nuclear factor 1, betaIdentifiersSymbolHNF1BAlt. symbolsTCF2, HNF1beta, LFB3 MODY5, VHNF1NCBI gene6928HGNC11630OMIM189907PDB2H8RRefSeqNM_000458UniProtP35680Other dataLocusChr. 17 q12-17q12Search forStructuresSwiss-modelDomainsInterPro |

### HNF3

The HNF3 subfamily members contain a winged helix DNA-binding domain and bind to DNA as monomers.
* HNF3α/FOXA1 (forkhead box A1)
* HNF3β/FOXA2 (forkhead box A2)
* HNF3γ/FOXA3 (forkhead box A3)
| hepatocyte nuclear factor 3, alphaIdentifiersSymbolFOXA1Alt. symbolsHNF3ANCBI gene3169HGNC5021OMIM602294RefSeqNM_004496UniProtP55317Other dataLocusChr. 14 q12-q13Search forStructuresSwiss-modelDomainsInterPro | hepatocyte nuclear factor 3, betaIdentifiersSymbolFOXA2Alt. symbolsHNF3BNCBI gene3170HGNC5022OMIM600288RefSeqNM_021784UniProtQ9Y261Other dataLocusChr. 20 p1120p11Search forStructuresSwiss-modelDomainsInterPro | hepatocyte nuclear factor 3, gammaIdentifiersSymbolFOXA3Alt. symbolsHNF3GNCBI gene3171HGNC5023OMIM602295RefSeqNM_004497UniProtP55318Other dataLocusChr. 19 q13.2-q13.4Search forStructuresSwiss-modelDomainsInterPro |

### HNF4

Members of the HNF4 subfamily are nuclear receptors and bind to DNA either as homodimers or RXR heterodimers.
* HNF4α/TCF14/MODY1
* HNF4γ
| hepatocyte nuclear factor 4 alphaIdentifiersSymbolHNF4AAlt. symbolsMODY, MODY1, NR2A1, TCF14NCBI gene3172HGNC5024OMIM600281PDB1M7WRefSeqNM_001030004UniProtP41235Other dataLocusChr. 20 q12-20q13.1Search forStructuresSwiss-modelDomainsInterPro | hepatocyte nuclear factor 4 gammaIdentifiersSymbolHNF4GAlt. symbolsNR2A2NCBI gene3174HGNC5026OMIM605966PDB1LV2RefSeqNM_004133UniProtQ14541Other dataLocusChr. 8 q21-q22Search forStructuresSwiss-modelDomainsInterPro |

### HNF6

The HNF6 subfamily members contain a cut-homeodomain (ONECUT) bind to DNA as monomers.
* HNF6α/OC-1/ONECUT1 (ONECUT1)
* HNF6β/OC-2/ONECUT2 (ONECUT2)
| hepatocyte nuclear factor 6, alphaIdentifiersSymbolONECUT1Alt. symbolsHNF6, HNF6ANCBI gene3175HGNC8138OMIM604164RefSeqNM_004498UniProtQ9UBC0Other dataLocusChr. 15 q21-q21.2Search forStructuresSwiss-modelDomainsInterPro | hepatocyte nuclear factor 6, betaIdentifiersSymbolONECUT2Alt. symbolsHNF6B, OC-2NCBI gene9480HGNC8139OMIM604894RefSeqNM_004852UniProtO95948Other dataLocusChr. 18 q21.1-21.2Search forStructuresSwiss-modelDomainsInterPro |