MUTYH (mutY homolog (E. coli))
2006-06-01 Maurizio Genuardi , Rossella Tricarico AffiliationDepartment of Clinical Pathophysiology, University of Florence, Viale Gaetano Pieraccini 6, 50139 Firenze, Italy
DNA/RNA
Mutyh AUG 1, 2 and 3 are alternative codons for translation initiation; cDNA not drawn to scale (adapted from Parker et al., 2003).
Description
The MUTYH gene contains 16 exons spanning a region of 11147 bp.
Transcription
The transcribed mRNA is 1854 bp long. There are three major classes of human MUTYH mRNAs: a, b and g. Each of these undergoes alternative splicing, suggesting a total of 10 possible mature transcripts. However, their distribution and abundance in different normal tissues have yet to be determined. The reference isoform is MutYa3.
Proteins
Diagram of the MUTYH protein in scale. Filled boxes represent known functional domains (adapted from Sampson et al, 2005).
Description
Expression
Ubiquitous.
Localisation
Nuclear and mithocondrial.
Function
MUTYH is involved in oxidative DNA damage repair. Human MutY is responsible for recognition and removal of inappropriately inserted adenine in Ao8-oxoG mispairs. If unrepaired, the Ao8-oxoG mispairs can result in C:G to A:T transversions. MUTYH functions in a postreplication repair pathway and is targeted to the newly synthesized daughter strand of DNA for removal of the adenine base.
Homology
MUTYH is homologous to the bacterial MutY gene, and MUTYH homologues are also present in eukaryote.
Mutations
Germinal
Biallelic germline mutations of MUTYH are associated with colorectal polyposis. The most common mutations in Caucasians are the missense substitutions Y165C (494A>G) and G382D (1145G>A). Functional analysis of C165 and D382 proteins has shown a severe decrease of catalytic activity. E466X and Y90X are the common mutations reported in Indian and Pakistani cases. Several other missense, nonsense, in-frame, frameshift and splicing mutations have been found in patients with colorectal polyposis.
Somatic
To date, no MUTYH somatic mutation has been described.
Implicated in
Entity name
Disease
Biallelic MUTYH mutations are responsible for the autosomal recessive form of intestinal adenomatous polyposis.
Oncogenesis
Defective BER function associated with MUTYH mutations determines an increase in the somatic mutation rate, namely of G>T transversions at guanine residues that are potential targets of oxidative damage. Tumors from biallelic MUTYH mutation carriers display an excess of somatic G>T mutations in the APC and KRAS genes
Article Bibliography
| Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|
| 11818965 | 2002 | Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors. | Al-Tassan N et al |
| 15673720 | 2005 | Functional characterization of two human MutY homolog (hMYH) missense mutations (R227W and V232F) that lie within the putative hMSH6 binding domain and are associated with hMYH polyposis. | Bai H et al |
| 15523092 | 2004 | Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk. | Croitoru ME et al |
| 14999774 | 2004 | Prevalence of the Y165C, G382D and 1395delGGA germline mutations of the MYH gene in Italian patients with adenomatous polyposis coli and colorectal adenomas. | Gismondi V et al |
| 11801590 | 2002 | Human MutY homolog, a DNA glycosylase involved in base excision repair, physically and functionally interacts with mismatch repair proteins human MutS homolog 2/human MutS homolog 6. | Gu Y et al |
| 12707038 | 2003 | Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers. | Halford SE et al |
| 12393807 | 2002 | Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations. | Jones S et al |
| 15083190 | 2004 | Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas. | Jones S et al |
| 14633673 | 2003 | Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway. | Lipton L et al |
| 15290654 | 2004 | The multiple colorectal adenoma phenotype and MYH, a base excision repair gene. | Lipton L et al |
| 7823963 | 1995 | Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein. | McGoldrick JP et al |
| 10684930 | 2000 | Identification of human MutY homolog (hMYH) as a repair enzyme for 2-hydroxyadenine in DNA and detection of multiple forms of hMYH located in nuclei and mitochondria. | Ohtsubo T et al |
| 14618256 | 2003 | Human MutY: gene structure, protein functions and interactions, and role in carcinogenesis. | Parker AR et al |
| 12966098 | 2003 | Defective human MutY phosphorylation exists in colorectal cancer cell lines with wild-type MutY alleles. | Parker AR et al |
| 15987719 | 2005 | Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair. | Parker AR et al |
| 15661655 | 2005 | Insight into the functional consequences of hMYH variants associated with colorectal cancer: distinct differences in the adenine glycosylase activity and the response to AP endonucleases of Y150C and G365D murine MYH. | Pope MA et al |
| 16042573 | 2005 | MutYH (MYH) and colorectal cancer. | Sampson JR et al |
| 12606733 | 2003 | Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH. | Sieber OM et al |
| 15188161 | 2004 | High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis. | Venesio T et al |
Other Information
Locus ID:
NCBI: 4595
MIM: 604933
HGNC: 7527
Ensembl: ENSG00000132781
Variants:
dbSNP: 4595
ClinVar: 4595
TCGA: ENSG00000132781
COSMIC: MUTYH
RNA/Proteins
Expression (GTEx)
Pathways
Protein levels (Protein atlas)
PharmGKB
| Entity ID | Name | Type | Evidence | Association | PK | PD | PMIDs |
|---|---|---|---|---|---|---|---|
| PA445204 | Ovarian Neoplasms | Disease | ClinicalAnnotation | associated | PD | 24533712 | |
| PA449014 | cisplatin | Chemical | ClinicalAnnotation | associated | PD | 24533712 | |
| PA449165 | cyclophosphamide | Chemical | ClinicalAnnotation | associated | PD | 24533712 |
References
| Pubmed ID | Year | Title | Citations |
|---|---|---|---|
| 37589222 | 2024 | Increased KRAS G12C Prevalence, High Tumor Mutational Burden, and Specific Mutational Signatures Are Associated With MUTYH Mutations: A Pan-Cancer Analysis. | 0 |
| 38062336 | 2024 | Breast cancers in monoallelic MUTYH germline mutation carriers have clinicopathological features overlapping with those in BRCA1 germline mutation carriers. | 1 |
| 38071180 | 2024 | Multiple colorectal adenomas syndrome: The role of MUTYH mutation and the polyps' number in clinical management and colorectal cancer risk. | 0 |
| 38394468 | 2024 | Pan-Cancer Interrogation of MUTYH Variants Reveals Biallelic Inactivation and Defective Base Excision Repair Across a Spectrum of Solid Tumors. | 0 |
| 38790183 | 2024 | Exploring the Role of the MUTYH Gene in Breast, Ovarian and Endometrial Cancer. | 0 |
| 37589222 | 2024 | Increased KRAS G12C Prevalence, High Tumor Mutational Burden, and Specific Mutational Signatures Are Associated With MUTYH Mutations: A Pan-Cancer Analysis. | 0 |
| 38062336 | 2024 | Breast cancers in monoallelic MUTYH germline mutation carriers have clinicopathological features overlapping with those in BRCA1 germline mutation carriers. | 1 |
| 38071180 | 2024 | Multiple colorectal adenomas syndrome: The role of MUTYH mutation and the polyps' number in clinical management and colorectal cancer risk. | 0 |
| 38394468 | 2024 | Pan-Cancer Interrogation of MUTYH Variants Reveals Biallelic Inactivation and Defective Base Excision Repair Across a Spectrum of Solid Tumors. | 0 |
| 38790183 | 2024 | Exploring the Role of the MUTYH Gene in Breast, Ovarian and Endometrial Cancer. | 0 |
| 36245263 | 2023 | Summary of the experiences, knowledge, medical management, and family communication of monoallelic MUTYH carriers. | 0 |
| 36631987 | 2023 | Structural snapshots of base excision by the cancer-associated variant MutY N146S reveal a retaining mechanism. | 3 |
| 36979362 | 2023 | Evolutionary Origin of MUTYH Germline Pathogenic Variations in Modern Humans. | 3 |
| 37749864 | 2023 | A one-stop approach to diagnosing hereditary colorectal cancer in the Chinese population. | 0 |
| 36245263 | 2023 | Summary of the experiences, knowledge, medical management, and family communication of monoallelic MUTYH carriers. | 0 |
Citation
Maurizio Genuardi ; Rossella Tricarico
MUTYH (mutY homolog (E. coli))
Atlas Genet Cytogenet Oncol Haematol. 2006-06-01
Online version: http://atlasgeneticsoncology.org/gene/41464/mutyh
