MUTYH
Encyclopedia
MUTYH is a human
gene
encoding a DNA glycosylase, MUTYH glycosylase, involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene.
The MUTYH gene is located on the short (p) arm of chromosome 1
between positions 34.3 and 32.1, from base pair 45,464,007 to base pair 45,475,152.
(also called MUTYH-associated polyposis). Polyps caused by mutated MYH do not appear until adulthood and are less numerous than those found in patients with APC gene
mutations.
Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication
. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian
Europeans are exchanges of amino acid
s (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine
with cysteine
at position 165 (also written as Tyr165Cys or Y165C). The other common mutation switches the amino acid glycine
with aspartic acid
at position 382 (also written as Gly382Asp or G382D).
with Replication protein A1, PCNA
and APEX1
.
Human
Humans are the only living species in the Homo genus...
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...
encoding a DNA glycosylase, MUTYH glycosylase, involved in oxidative DNA damage repair. The enzyme excises adenine bases from the DNA backbone at sites where adenine is inappropriately paired with guanine, cytosine, or 8-oxo-7,8-dihydroguanine, a major oxidatively damaged DNA lesion. The protein is localized to the nucleus and mitochondria. Mutations in this gene result in heritable predisposition to colon and stomach cancer. Multiple transcript variants encoding different isoforms have been found for this gene.
The MUTYH gene is located on the short (p) arm of chromosome 1
Chromosome 1 (human)
Chromosome 1 is the designation for the largest human chromosome. Humans have two copies of chromosome 1, as they do with all of the autosomes, which are the non-sex chromosomes. Chromosome 1 spans about 247 million nucleotide base pairs, which are the basic units of information for DNA...
between positions 34.3 and 32.1, from base pair 45,464,007 to base pair 45,475,152.
Related conditions
Mutations in the MUTYH gene cause an autosomal recessive form of familial adenomatous polyposisFamilial adenomatous polyposis
Familial adenomatous polyposis is an inherited condition in which numerous polyps form mainly in the epithelium of the large intestine. While these polyps start out benign, malignant transformation into colon cancer occurs when not treated....
(also called MUTYH-associated polyposis). Polyps caused by mutated MYH do not appear until adulthood and are less numerous than those found in patients with APC gene
APC (gene)
Adenomatous polyposis coli also known as deleted in polyposis 2.5 is a protein that in humans is encoded by the APC gene. Mutations in the APC gene may result in colorectal cancer....
mutations.
Mutations in this gene affect the ability of cells to correct mistakes made during DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...
. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis. Most reported mutations in this gene cause production of a nonfunctional or low functioning glycosylase enzyme. When base excision repair in the cell is compromised, mutations in other genes build up, leading to cell overgrowth and possibly tumor formation. The two most common mutations in Caucasian
Caucasian race
The term Caucasian race has been used to denote the general physical type of some or all of the populations of Europe, North Africa, the Horn of Africa, Western Asia , Central Asia and South Asia...
Europeans are exchanges of amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
s (the building blocks of proteins) in the enzyme. One mutation replaces the amino acid tyrosine
Tyrosine
Tyrosine or 4-hydroxyphenylalanine, is one of the 22 amino acids that are used by cells to synthesize proteins. Its codons are UAC and UAU. It is a non-essential amino acid with a polar side group...
with cysteine
Cysteine
Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
at position 165 (also written as Tyr165Cys or Y165C). The other common mutation switches the amino acid glycine
Glycine
Glycine is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its 'side chain', glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG cf. the genetic code.Glycine is a colourless, sweet-tasting crystalline solid...
with aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...
at position 382 (also written as Gly382Asp or G382D).
Interactions
MUTYH has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with Replication protein A1, PCNA
PCNA
Proliferating Cell Nuclear Antigen, commonly known as PCNA, is a protein that acts as a processivity factor for DNA polymerase δ in eukaryotic cells. It achieves this processivity by encircling the DNA, thus creating a topological link to the genome...
and APEX1
APEX1
DNA- lyase is an enzyme that in humans is encoded by the APEX1 gene.-Interactions:APEX1 has been shown to interact with MUTYH, Flap structure-specific endonuclease 1 and XRCC1.-Further reading:...
.