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MUTYH (mutY homolog (E. coli))

Written2006-06Maurizio Genuardi, Rossella Tricarico
Department of Clinical Pathophysiology, University of Florence, Viale Gaetano Pieraccini 6, 50139 Firenze, Italy

(Note : for Links provided by Atlas : click)


Other aliasMYH
MutY homolog (hMYH)
mutY (E. coli) homolog
mutY homolog
LocusID (NCBI) 4595
Atlas_Id 41464
Location 1p34.1  [Link to chromosome band 1p34]
Location_base_pair Starts at and ends at bp from pter
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
CBFB (16q22.1) / MUTYH (1p34.1)GTF2B (1p22.2) / MUTYH (1p34.1)THRAP3 (1p34.3) / MUTYH (1p34.1)


  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.


  Diagram of the MUTYH protein in scale. Filled boxes represent known functional domains (adapted from Sampson et al, 2005).
Description Aminoacids: 535. Molecular Weight: 52 kDa. MUTYH is a protein involved in base excision repair (BER). It contains a DNA binding domain, an adenine binding motif and several interaction domains for APE1, PCNA, RPA and MSH6, located in different regions of the gene.
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.


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 MAP (MUTYH-associated polyposis).
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


Inherited variants of MYH associated with somatic G:C-->T:A mutations in colorectal tumors.
Al-Tassan N, Chmiel NH, Maynard J, Fleming N, Livingston AL, Williams GT, Hodges AK, Davies DR, David SS, Sampson JR, Cheadle JP
Nature genetics. 2002 ; 30 (2) : 227-232.
PMID 11818965
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, Jones S, Guan X, Wilson TM, Sampson JR, Cheadle JP, Lu AL
Nucleic acids research. 2005 ; 33 (2) : 597-604.
PMID 15673720
Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk.
Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S
Journal of the National Cancer Institute. 2004 ; 96 (21) : 1631-1634.
PMID 15523092
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, Meta M, Bonelli L, Radice P, Sala P, Bertario L, Viel A, Fornasarig M, Arrigoni A, Gentile M, Ponz de Leon M, Anselmi L, Mareni C, Bruzzi P, Varesco L
International journal of cancer. Journal international du cancer. 2004 ; 109 (5) : 680-684.
PMID 14999774
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, Parker A, Wilson TM, Bai H, Chang DY, Lu AL
The Journal of biological chemistry. 2002 ; 277 (13) : 11135-11142.
PMID 11801590
Germline mutations but not somatic changes at the MYH locus contribute to the pathogenesis of unselected colorectal cancers.
Halford SE, Rowan AJ, Lipton L, Sieber OM, Pack K, Thomas HJ, Hodgson SV, Bodmer WF, Tomlinson IP
The American journal of pathology. 2003 ; 162 (5) : 1545-1548.
PMID 12707038
Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations.
Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP
Human molecular genetics. 2002 ; 11 (23) : 2961-2967.
PMID 12393807
Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas.
Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP
British journal of cancer. 2004 ; 90 (8) : 1591-1593.
PMID 15083190
Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway.
Lipton L, Halford SE, Johnson V, Novelli MR, Jones A, Cummings C, Barclay E, Sieber O, Sadat A, Bisgaard ML, Hodgson SV, Aaltonen LA, Thomas HJ, Tomlinson IP
Cancer research. 2003 ; 63 (22) : 7595-7599.
PMID 14633673
The multiple colorectal adenoma phenotype and MYH, a base excision repair gene.
Lipton L, Tomlinson I
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2004 ; 2 (8) : 633-638.
PMID 15290654
Characterization of a mammalian homolog of the Escherichia coli MutY mismatch repair protein.
McGoldrick JP, Yeh YC, Solomon M, Essigmann JM, Lu AL
Molecular and cellular biology. 1995 ; 15 (2) : 989-996.
PMID 7823963
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, Nishioka K, Imaiso Y, Iwai S, Shimokawa H, Oda H, Fujiwara T, Nakabeppu Y
Nucleic acids research. 2000 ; 28 (6) : 1355-1364.
PMID 10684930
Human MutY: gene structure, protein functions and interactions, and role in carcinogenesis.
Parker AR, Eshleman JR
Cellular and molecular life sciences : CMLS. 2003 ; 60 (10) : 2064-2083.
PMID 14618256
Defective human MutY phosphorylation exists in colorectal cancer cell lines with wild-type MutY alleles.
Parker AR, O'Meally RN, Sahin F, Su GH, Racke FK, Nelson WG, DeWeese TL, Eshleman JR
The Journal of biological chemistry. 2003 ; 278 (48) : 47937-47945.
PMID 12966098
Cells with pathogenic biallelic mutations in the human MUTYH gene are defective in DNA damage binding and repair.
Parker AR, Sieber OM, Shi C, Hua L, Takao M, Tomlinson IP, Eshleman JR
Carcinogenesis. 2005 ; 26 (11) : 2010-2018.
PMID 15987719
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, Chmiel NH, David SS
DNA repair. 2005 ; 4 (3) : 315-325.
PMID 15661655
MutYH (MYH) and colorectal cancer.
Sampson JR, Jones S, Dolwani S, Cheadle JP
Biochemical Society transactions. 2005 ; 33 (Pt 4) : 679-683.
PMID 16042573
Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH.
Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP
The New England journal of medicine. 2003 ; 348 (9) : 791-799.
PMID 12606733
High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis.
Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN
Gastroenterology. 2004 ; 126 (7) : 1681-1685.
PMID 15188161


This paper should be referenced as such :
Genuardi, M ; Tricarico, R. MUTYH (mutY homolog (E
Atlas Genet Cytogenet Oncol Haematol. 2006;10(4):236-238.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ]
  Colon: Colorectal adenocarcinoma

Other Cancer prone implicated (Data extracted from papers in the Atlas) [ 2 ]
  MUTYH-Associated Polyposis (MAP) MUTYH associated polyposis

External links

Genomic and cartography
Gene and transcription
RefSeq transcript (Entrez)
RefSeq genomic (Entrez)
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
BioGPS (Tissue expression)4595
Protein : pattern, domain, 3D structure
Domain families : Pfam (Sanger)
Domain families : Pfam (NCBI)
Protein Interaction databases
Ontologies - Pathways
Clinical trials, drugs, therapy
canSAR (ICR) (select the gene name)
REVIEW articlesautomatic search in PubMed
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