IRF6
Encyclopedia
Interferon regulatory factor 6 also known as IRF6 is a protein
that in humans is encoded by the IRF6 gene
.
(IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix
DNA-binding domain and a less conserved C-terminal protein-binding domain.
The function of IRF6 is related to the formation of connective tissue
, for example that of the palate
. This gene encodes a member of the interferon
regulatory transcription factor (IRF) family.
of the IRF6 gene
can lead to van der Woude syndrome
or the related popliteal pterygium syndrome
. These disorders are caused by mutations in the IRF6 gene and some of the phenotypic heterogeneity is due to different types of IRF6 mutations.
One explanation for this phenotypic variation between syndromes is based on a differential impact on the structure of the dimerized mutant proteins. VWS mutations appear to result in haploinsufficiency
while PPS mutations may be dominant negative in nature. The spectrum of mutations in VWS and PPS has been recently summarized. IRF6 has been shown to play a critical role in keratinocyte development. A role for IRF6 in the common forms of cleft lip and palate has also been demonstrated and may explain ~20% of cases of cleft lip only.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
that in humans is encoded by the IRF6 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
.
Function
This gene encodes a member of the interferon regulatory transcription factorInterferon regulatory factors
Interferon regulatory factors are proteins which regulate transcription of interferons .They are used in the JAK-STAT signaling pathway....
(IRF) family. Family members share a highly-conserved N-terminal helix-turn-helix
Helix-turn-helix
In proteins, the helix-turn-helix is a major structural motif capable of binding DNA. It is composed of two α helices joined by a short strand of amino acids and is found in many proteins that regulate gene expression...
DNA-binding domain and a less conserved C-terminal protein-binding domain.
The function of IRF6 is related to the formation of connective tissue
Connective tissue
"Connective tissue" is a fibrous tissue. It is one of the four traditional classes of tissues . Connective Tissue is found throughout the body.In fact the whole framework of the skeleton and the different specialized connective tissues from the crown of the head to the toes determine the form of...
, for example that of the palate
Palate
The palate is the roof of the mouth in humans and other mammals. It separates the oral cavity from the nasal cavity. A similar structure is found in crocodilians, but, in most other tetrapods, the oral and nasal cavities are not truly separate. The palate is divided into two parts, the anterior...
. This gene encodes a member of the interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
regulatory transcription factor (IRF) family.
Pathology
A mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
of the IRF6 gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
can lead to van der Woude syndrome
Van der Woude syndrome
Van Der Woude syndrome is a genetic disorder and congenital malformation. People with VDWS have cleft lip with or without cleft palate, pits or mucous cysts on the lower lip, hypodontia, a hypernasal voice, cleft or bifid uvula, syngnathia, narrow high arched palate, and ankyloglossia...
or the related popliteal pterygium syndrome
Popliteal pterygium syndrome
Popliteal pterygium syndrome is an inherited condition affecting the face, limbs, and genitalia. The syndrome goes by a number of names including the popliteal web syndrome and, more inclusively, the facio-genito-popliteal syndrome...
. These disorders are caused by mutations in the IRF6 gene and some of the phenotypic heterogeneity is due to different types of IRF6 mutations.
One explanation for this phenotypic variation between syndromes is based on a differential impact on the structure of the dimerized mutant proteins. VWS mutations appear to result in haploinsufficiency
Haploinsufficiency
Haploinsufficiency occurs when a diploid organism only has a single functional copy of a gene and the single functional copy of the gene does not produce enough of a gene product to bring about a wild-type condition, leading to an abnormal or diseased state...
while PPS mutations may be dominant negative in nature. The spectrum of mutations in VWS and PPS has been recently summarized. IRF6 has been shown to play a critical role in keratinocyte development. A role for IRF6 in the common forms of cleft lip and palate has also been demonstrated and may explain ~20% of cases of cleft lip only.