View source for MUTYH

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''''MUTYH''''' ('''mutY DNA glycosylase''') is a human [[gene]] that encodes a [[DNA glycosylase]], MUTYH glycosylase. It is involved in oxidative DNA damage repair and is part of the [[base excision repair]] pathway. 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 common form of oxidative DNA damage.
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.<ref name="entrez">{{cite web | title = Entrez Gene: MUTYH mutY homolog (E. coli)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4595}}</ref>
==Location and structure==
MUTYH has its locus on the short (p) arm of chromosome 1 (1p34.1), from base pair 45,464,007 to base pair 45,475,152 (45,794,835–45,806,142). The gene is composed of 16 exons and has a size of 546 amino acids<ref name = "GeneCard">{{GeneCard|MUTYH}}</ref> and is approximately 7.1kb.<ref name="pmid8682794">{{cite journal | vauthors = Slupska MM, Baikalov C, Luther WM, Chiang JH, Wei YF, Miller JH | title = Cloning and sequencing a human homolog (hMYH) of the Escherichia coli mutY gene whose function is required for the repair of oxidative DNA damage | journal = Journal of Bacteriology | volume = 178 | issue = 13 | pages = 3885–92 | date = July 1996 | pmid = 8682794 | pmc = 232650 | doi =  10.1128/jb.178.13.3885-3892.1996}}</ref> The presence of disulfide crosslinking gives rise to a complex crystal structure of the MUTY-DNA.<ref>{{OMIM|604933|MUTYH}}</ref> The protein structure of the MUTYH gene has its N-terminal on the 5' and the C-terminal on the 3'.  Within the N-terminal, there is a helix-hairpin-helix and pseudo helix-hairpin-helix in addition to an iron cluster motif.
==Mechanism==
Repair of oxidative DNA damage is the result of a collaborative effort of MUTYH, [[Oxoguanine glycosylase|OGG1]], and [[2-hydroxy-dATP diphosphatase|MTH1]]. MUTYH acts on the adenine base that is mispaired to 8-oxoG, while OGG1 detects and acts on [[8-Oxoguanine|8-oxoG]], removing it.<ref name="pmid11554447">{{cite journal | vauthors = Shinmura K, Yokota J | title = The OGG1 gene encodes a repair enzyme for oxidatively damaged DNA and is involved in human carcinogenesis | journal = Antioxidants & Redox Signaling | volume = 3 | issue = 4 | pages = 597–609 | date = August 2001 | pmid = 11554447 | doi = 10.1089/15230860152542952 }}</ref><ref name="pmid21441539">{{cite journal | vauthors = Kitsera N, Stathis D, Lühnsdorf B, Müller H, Carell T, Epe B, Khobta A | title = 8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1 | journal = Nucleic Acids Research | volume = 39 | issue = 14 | pages = 5926–34 | date = August 2011 | pmid = 21441539 | pmc = 3152326 | doi = 10.1093/nar/gkr163 }}</ref>
[[TP53]] transcriptionally regulates MUTYH and may potentially act as a regulator for p53.<ref name="pmid25706342">{{cite journal | vauthors = Oka S, Leon J, Tsuchimoto D, Sakumi K, Nakabeppu Y | title = MUTYH, an adenine DNA glycosylase, mediates p53 tumor suppression via PARP-dependent cell death | journal = Oncogenesis | volume = 4 | issue =  2| pages = e142 | date = February 2015 | pmid = 25706342 | pmc = 4338427 | doi = 10.1038/oncsis.2015.4 }}</ref>
==Expression==
MUTYH is overexpressed in CD4-T cells, the [[prostate]], the colon, where cells frequently divide, and the rectum.  There is evidence of MUTYH expression in kidney, intestinal, nervous system and muscle tissues.<ref name = "GeneCard" />
== Protein interactions ==
MUTYH has been shown to [[Protein-protein interaction|interact]] with [[Replication protein A1]],<ref name=pmid11092888>{{cite journal | vauthors = Parker A, Gu Y, Mahoney W, Lee SH, Singh KK, Lu AL | title = Human homolog of the MutY repair protein (hMYH) physically interacts with proteins involved in long patch DNA base excision repair | journal = The Journal of Biological Chemistry | volume = 276 | issue = 8 | pages = 5547–55 | date = February 2001 | pmid = 11092888 | doi = 10.1074/jbc.M008463200 | doi-access = free }}</ref> [[PCNA]]<ref name=pmid11092888/> and [[APEX1]].<ref name=pmid11092888/>
MUTYH and OGG1 excision of bases causes the formation of apurinic/ apyrimidinic sites ([[AP site]]s). These sites are mutagenic in nature and require constant and immediate repair which is achieved by the active involvement of protein complexes that repair the AP site via short and long patch repair pathways.
The short patch repair pathway employs POLB ([[DNA polymerase beta]]), APE1, [[XRCC1]], [[PARP1]] with the addition of either the [[LIG1]] or [[LIG3]] genes. When an insertion of one nucleotide occurs, the enzyme [[AP endonuclease]] (APEX/APE1) cuts out the mismatched base pairs at the AP site and this causes the evolvement of 5'dRP (5' deoxyribose phosphate), a terminal blocking group, and 3'-OH ( 3' hydroxyl end). POLB is required to remove the 5'dRP, and it does this by enzymatic activity, namely polymerase and dRP lyase. DNA ligase is used to seal the fragments after dRP excision causes the formation of 5'PO4 that is necessary to form the [[phosphodiester bond]]s of DNA. The purpose of PARP1 and XRCC1 in the single strand break repair pathway, is to stabilize the strands of DNA while they undergo repair, synthesis, gap-filling and ligation. PARP1 acts as a recruit agent for XRCC1. The nick sealing of the strands is accomplished by the formation of LIG1 (DNA ligase 1) and/or LIG3/ XRCCI complex that attach to processed end of the corrected strands and reinstate the original conformation of the strand.
Long patch repair comes into play when more nucleotides are involved, ranging from 2 to 12. It is hypothesized that Polymerase 𝜹 (POLD) and Polymerase 𝛆 (POLE), assisted by the PCNA ([[proliferating cell nuclear antigen]]) in conjunction with [[replication factor C]] (RFC) that acts as a stabilizer and places newly synthesized nucleotides on the DNA strand. Both the polymerases repair the DNA by employing the strand displacement synthesis mechanism. This mechanism occurs downstream a DNA strand and the 5' is transformed into a "flap intermediate" causing it to be "displaced". FEN1 ([[flap structure-specific endonuclease 1]]), a nuclease, removes the displaced strand and this results in a ligatable strand of DNA.Long patch repair, like short patch repair, includes the use of APE1 and PARP1 and LIG1.
The repair pathway is partially determined by the amount of ATP present after the removal of the deoxyribose phosphate end. The long patch repair pathway is preferred under conditions of low ATP concentration while the short repair pathway is preferred under high concentrations of ATP.<ref name="pmid22122461">{{cite journal | vauthors = Kim YJ, Wilson DM | title = Overview of base excision repair biochemistry | journal = Current Molecular Pharmacology | volume = 5 | issue = 1 | pages = 3–13 | date = January 2012 | pmid = 22122461 | pmc = 3459583 | doi =  10.2174/1874467211205010003}}</ref>
Other notable interactions include MUTYH and [[Replication protein A]] is a single strand binding protein that prevents the annealing of DNA during replication, it also plays a role as an activator for damage repair on DNA. There is a hypothetical relation between the interaction of Mismatch Repair proteins (MMR) such as MSH 2,3 and 6, MLH1, PMS1 and 2, and MUTYH in which the proposed result of their partnering is to increase susceptibility to cancer.<ref name="pmid16408224">{{cite journal | vauthors = Niessen RC, Sijmons RH, Ou J, Olthof SG, Osinga J, Ligtenberg MJ, Hogervorst FB, Weiss MM, Tops CM, Hes FJ, de Bock GH, Buys CH, Kleibeuker JH, Hofstra RM | title = MUTYH and the mismatch repair system: partners in crime? | journal = Human Genetics | volume = 119 | issue = 1–2 | pages = 206–11 | date = March 2006 | pmid = 16408224 | doi = 10.1007/s00439-005-0118-5 | s2cid = 22651739 | url = https://pure.rug.nl/ws/files/6693534/Niessen_2006_Hum_Genet.pdf }}</ref>
== Chemical interactions ==
The gene interacts with the following chemicals:
a) [[Carbon tetrachloride]]: decreased expression of MUTYH mRNA
b) [[Ethanol]]: When treated together with dronabinol) increased expression of MUTYH mRNA. When used alone, it has conflicting results of decreased and increased the MUTYH mRNA.
c) [[Ethinylestradiol]]: When used alone it results in the increased expression of MUTYH mRNA.When treated together with tetrachlorodibenzo p dioxin, there is increased expression of MUTYH mRNA.
d) [[Tamoxifen]]: affects MUTYH<ref>{{cite web | url = https://cgwb.nci.nih.gov/cgi-bin/hgGene?showAllRef=Y&hgsid=4466793&db=hg18&hgg_gene=uc001cnm.1&hgg_chrom=chr1&hgg_start=45567500&hgg_end=45578729 | title = MUTYH | work = Entrez Gene }}{{Dead link|date=October 2022 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
== Related conditions ==
The table of the Gene-phenotype associations summarizes the diseases/conditions that arise from mutations in MUTYH
{| class="wikitable"
|-
! Phenotype/Condition !! Mode of Inheritance
|-
| [[Familial adenomatous polyposis]] || Autosomal recessive<ref>{{OMIM|608456|Familial adenomatous polyposis 2; FAP2}}</ref>
|-
| [[Pilomatricoma]] || Somatic mutation<ref>{{OMIM|132600|Pilomatricoma}}</ref>
|-
| [[Gastric cancer]] || Somatic mutation<ref>{{OMIM|613659|Gastric Cancer}}</ref>
|-
|[[Endometrial cancer]]
|Biallelic germline mutation<ref>{{cite journal | vauthors = Tricarico R, Bet P, Ciambotti B, Di Gregorio C, Gatteschi B, Gismondi V, Toschi B, Tonelli F, Varesco L, Genuardi M | title = Endometrial cancer and somatic G>T KRAS transversion in patients with constitutional MUTYH biallelic mutations | journal = Cancer Letters | volume = 274 | issue = 2 | pages = 266–70 | date = February 2009 | pmid = 18980800 | doi = 10.1016/j.canlet.2008.09.022 }}</ref>
|}
Mutations in the MUTYH gene cause an [[autosomal recessive]] disorder similar to [[familial adenomatous polyposis]] (also called [[MUTYH-associated polyposis]]). Polyps caused by mutated MUTYH do not appear until adulthood and are less numerous than those found in patients with [[APC (gene)|APC gene]] mutations. Both copies of the MUTYH gene are mutated in individuals who have autosomal recessive familial adenomatous polyposis i.e., the mutations for the MUTYH gene is biallelic. Mutations in this gene affect the ability of cells to correct mistakes made during [[DNA replication]]. 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 race|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 179 (also written as p.Tyr179Cys (p.Y179C)) or, when describing the nucleotide change, written as c.536A>G). The other common mutation switches the amino acid [[glycine]] with [[aspartic acid]] at position 396 (also written as p.Gly396Asp (G396D) or c.1187G>A)).<ref>{{cite journal|vauthors=Aretz S, Tricarico R, Papi L, Spier I, Pin E, Horpaopan S, Cordisco EL, Pedroni M, Stienen D, Gentile A, Panza A, Piepoli A, de Leon MP, Friedl W, Viel A, Genuardi M|date=July 2014|title=MUTYH-associated polyposis (MAP): evidence for the origin of the common European mutations p.Tyr179Cys and p.Gly396Asp by founder events|journal=European Journal of Human Genetics|volume=22|issue=7|pages=923–9|doi=10.1038/ejhg.2012.309|pmc=4060104|pmid=23361220}}</ref>
The association of the gene with gastric cancer is somewhat indirect and multifactorial. When a subject is infected with [[Helicobacter pylori]] (''H. pylori''), the bacteria cause the formation of free oxygen radicals that are present in the gastric mucosa and this increases the propensity of the genes to incur oxidative damage . A study of 95 cases of patients who had sporadic cancers, initiated by the presence of H. pylori, and two of the 95 patients had biallelic mutation of the MUTYH gene. The somatic missense mutations for the first identified cancer occurred at codon 391, in which there was a change in the nucleotide bases from CCG (codon for amino acid proline) to TCG (codon for amino acid serine), while the second cancer had a nucleotide base change at codon 400 from CAG (codon for amino acid glutamine) to GGG (codon for amino acid arginine). The mutations were found to be highly conserved in the [[Nudix hydrolase]] domain of MUTYH. These amino acid mutations provide the basis for the somatic mutations in the gastric system.<ref name="pmid15273732">{{cite journal | vauthors = Kim CJ, Cho YG, Park CH, Kim SY, Nam SW, Lee SH, Yoo NJ, Lee JY, Park WS | title = Genetic alterations of the MYH gene in gastric cancer | journal = Oncogene | volume = 23 | issue = 40 | pages = 6820–2 | date = September 2004 | pmid = 15273732 | doi = 10.1038/sj.onc.1207574 | doi-access = free }}</ref>
[[Pilomatricoma]] has been noted in a case that concerned two siblings who were the offspring of consanguineous parents. The siblings had a 2 base pair homozygous insertion on the MUTYH gene ( exon 13). Consequently, a frameshift occurred due to the insertion and a premature stop codon was read at 438 on the gene. Pilomatricoma was the phenotypic manifestation of this mutation. One of the siblings was also found to have rectal adenocarcinoma. It is worthy to note that CTNNB1, a gene associated with pilomatricoma, was also investigated. However, no mutations in this gene were found, thereby dismissing it as a possible cause for this case.<ref name="pmid15690400">{{cite journal | vauthors = Baglioni S, Melean G, Gensini F, Santucci M, Scatizzi M, Papi L, Genuardi M | title = A kindred with MYH-associated polyposis and pilomatricomas | journal = American Journal of Medical Genetics. Part A | volume = 134A | issue = 2 | pages = 212–4 | date = April 2005 | pmid = 15690400 | doi = 10.1002/ajmg.a.30585 | s2cid = 21866377 }}</ref>
There is an established correlation between aging and the elevation 8-oxoG concentrations, particularly in organs that exhibit reduced cell proliferation such as the kidneys, liver, brain and lungs.<ref name="pmid20149865">{{cite journal | vauthors = Møller P, Løhr M, Folkmann JK, Mikkelsen L, Loft S | title = Aging and oxidatively damaged nuclear DNA in animal organs | journal = Free Radical Biology & Medicine | volume = 48 | issue = 10 | pages = 1275–85 | date = May 2010 | pmid = 20149865 | doi = 10.1016/j.freeradbiomed.2010.02.003 }}</ref> Presence of 8-oxoG also occurs in large concentrations in patients with neurological conditions such as Alzheimer's, Parkinson's and Huntington's disease.<ref name="pmid26711335">{{cite journal | vauthors = Bjørge MD, Hildrestrand GA, Scheffler K, Suganthan R, Rolseth V, Kuśnierczyk A, Rowe AD, Vågbø CB, Vetlesen S, Eide L, Slupphaug G, Nakabeppu Y, Bredy TW, Klungland A, Bjørås M | title = Synergistic Actions of Ogg1 and Mutyh DNA Glycosylases Modulate Anxiety-like Behavior in Mice | journal = Cell Reports | volume = 13 | issue = 12 | pages = 2671–8 | date = December 2015 | pmid = 26711335 | doi = 10.1016/j.celrep.2015.12.001 | url = https://www.duo.uio.no/bitstream/10852/55259/2/mmc2.pdf | doi-access = free }}</ref> MUTYH causes immoderate formation of single stranded breaks via base excision repair, under acute oxidative stress conditions.<ref name="Oka_2008">{{cite journal | vauthors = Oka S, Ohno M, Tsuchimoto D, Sakumi K, Furuichi M, Nakabeppu Y | title = Two distinct pathways of cell death triggered by oxidative damage to nuclear and mitochondrial DNAs | journal = The EMBO Journal | volume = 27 | issue = 2 | pages = 421–32 | year = 2008 | pmid = 18188152 | pmc = 2234344 | doi = 10.1038/sj.emboj.7601975 }}</ref><ref name="Oka_2011">{{cite journal | vauthors = Oka S, Nakabeppu Y | title = DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis | journal = Cancer Science | volume = 102 | issue = 4 | pages = 677–82 | year = 2011 | pmid = 21235684 | doi = 10.1111/j.1349-7006.2011.01869.x | doi-access = free }}</ref> When the 8-oxoguanine species accumulate and increase in concentration in the neurons, MUTYH responds by triggering their degeneration.<ref name="Sheng_2012">{{cite journal | vauthors = Sheng Z, Oka S, Tsuchimoto D, Abolhassani N, Nomaru H, Sakumi K, Yamada H, Nakabeppu Y | title = 8-Oxoguanine causes neurodegeneration during MUTYH-mediated DNA base excision repair | journal = The Journal of Clinical Investigation | volume = 122 | issue = 12 | pages = 4344–61 | year = 2012 | pmid = 23143307 | pmc = 3533558 | doi = 10.1172/JCI65053 }}</ref>
== See also ==
* [[NTHL1]]
* [[NEIL1]]
== References ==
{{reflist|32em}}
== Further reading ==
{{refbegin|32em}}
* {{cite journal | vauthors = Cheadle JP, Sampson JR | title = Exposing the MYtH about base excision repair and human inherited disease | journal = Human Molecular Genetics | volume = 12 Spec No 2 | issue = 90002 | pages = R159–65 | date = October 2003 | pmid = 12915454 | doi = 10.1093/hmg/ddg259 | doi-access = free }}
* {{cite journal | vauthors = Croitoru ME, Cleary SP, Di Nicola N, Manno M, Selander T, Aronson M, Redston M, Cotterchio M, Knight J, Gryfe R, Gallinger S | title = Association between biallelic and monoallelic germline MYH gene mutations and colorectal cancer risk | journal = Journal of the National Cancer Institute | volume = 96 | issue = 21 | pages = 1631–4 | date = November 2004 | pmid = 15523092 | doi = 10.1093/jnci/djh288 | doi-access = free }}
* {{cite journal | vauthors = Fleischmann C, Peto J, Cheadle J, Shah B, Sampson J, Houlston RS | title = Comprehensive analysis of the contribution of germline MYH variation to early-onset colorectal cancer | journal = International Journal of Cancer | volume = 109 | issue = 4 | pages = 554–8 | date = April 2004 | pmid = 14991577 | doi = 10.1002/ijc.20020 | doi-access = free }}
* {{cite journal | vauthors = Jones S, Emmerson P, Maynard J, Best JM, Jordan S, Williams GT, Sampson JR, Cheadle JP | title = Biallelic germline mutations in MYH predispose to multiple colorectal adenoma and somatic G:C-->T:A mutations | journal = Human Molecular Genetics | volume = 11 | issue = 23 | pages = 2961–7 | date = November 2002 | pmid = 12393807 | doi = 10.1093/hmg/11.23.2961 | doi-access = free }}
* {{cite journal | vauthors = Jones S, Lambert S, Williams GT, Best JM, Sampson JR, Cheadle JP | title = Increased frequency of the k-ras G12C mutation in MYH polyposis colorectal adenomas | journal = British Journal of Cancer | volume = 90 | issue = 8 | pages = 1591–3 | date = April 2004 | pmid = 15083190 | pmc = 2410274 | doi = 10.1038/sj.bjc.6601747 }}
* {{cite journal | vauthors = Kambara T, Whitehall VL, Spring KJ, Barker MA, Arnold S, Wynter CV, Matsubara N, Tanaka N, Young JP, Leggett BA, Jass JR | title = Role of inherited defects of MYH in the development of sporadic colorectal cancer | journal = Genes, Chromosomes & Cancer | volume = 40 | issue = 1 | pages = 1–9 | date = May 2004 | pmid = 15034862 | doi = 10.1002/gcc.20011 | s2cid = 10087815 }}
* {{cite journal | vauthors = 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 | title = Carcinogenesis in MYH-associated polyposis follows a distinct genetic pathway | journal = Cancer Research | volume = 63 | issue = 22 | pages = 7595–9 | date = November 2003 | pmid = 14633673 }}
* {{cite journal | vauthors = Sampson JR, Dolwani S, Jones S, Eccles D, Ellis A, Evans DG, Frayling I, Jordan S, Maher ER, Mak T, Maynard J, Pigatto F, Shaw J, Cheadle JP | title = Autosomal recessive colorectal adenomatous polyposis due to inherited mutations of MYH | journal = Lancet | volume = 362 | issue = 9377 | pages = 39–41 | date = July 2003 | pmid = 12853198 | doi = 10.1016/S0140-6736(03)13805-6 | s2cid = 35336308 }}
* {{cite journal | vauthors = Sieber OM, Lipton L, Crabtree M, Heinimann K, Fidalgo P, Phillips RK, Bisgaard ML, Orntoft TF, Aaltonen LA, Hodgson SV, Thomas HJ, Tomlinson IP | title = Multiple colorectal adenomas, classic adenomatous polyposis, and germ-line mutations in MYH | journal = The New England Journal of Medicine | volume = 348 | issue = 9 | pages = 791–9 | date = February 2003 | pmid = 12606733 | doi = 10.1056/NEJMoa025283 | doi-access = free }}
* {{cite journal | vauthors = Venesio T, Molatore S, Cattaneo F, Arrigoni A, Risio M, Ranzani GN | title = High frequency of MYH gene mutations in a subset of patients with familial adenomatous polyposis | journal = Gastroenterology | volume = 126 | issue = 7 | pages = 1681–5 | date = June 2004 | pmid = 15188161 | doi = 10.1053/j.gastro.2004.02.022 | doi-access = free }}
* {{cite journal | vauthors = Wang L, Baudhuin LM, Boardman LA, Steenblock KJ, Petersen GM, Halling KC, French AJ, Johnson RA, Burgart LJ, Rabe K, Lindor NM, Thibodeau SN | title = MYH mutations in patients with attenuated and classic polyposis and with young-onset colorectal cancer without polyps | journal = Gastroenterology | volume = 127 | issue = 1 | pages = 9–16 | date = July 2004 | pmid = 15236166 | doi = 10.1053/j.gastro.2004.03.070 | doi-access = free }}
* {{cite journal | title = MUTYH-Associated Polyposis. | journal = GeneReviews | year = 2012 | pmid = 23035301 | last1 = Nielsen | first1 = M. | last2 = Lynch | first2 = H. | last3 = Infante | first3 = E. | last4 = Brand | first4 = R. | last5 = Adam | first5 = M. P. | last6 = Ardinger | first6 = H. H. | last7 = Pagon | first7 = R. A. | last8 = Wallace | first8 = S. E. | author9 = Bean LJH | last10 = Stephens | first10 = K. | last11 = Amemiya | first11 = A. }}
* {{cite journal | vauthors = Nielsen M, Morreau H, Vasen HF, Hes FJ | title = MUTYH-associated polyposis (MAP) | journal = Critical Reviews in Oncology/Hematology | volume = 79 | issue = 1 | pages = 1–16 | date = July 2011 | pmid = 20663686 | doi = 10.1016/j.critrevonc.2010.05.011 }}
{{refend}}
== External links ==
* {{OMIM|604933}}
* {{EntrezGene|4595}}
* [https://www.genecards.org/cgi-bin/carddisp.pl?gene=MUTYH GeneCard]
* [http://familyhistorybowelcancer.wordpress.com/2012/08/28/hereditary-colorectal-cancer-syndromes/ Hereditary Colorectal Cancer Syndromes] {{Webarchive|url=https://web.archive.org/web/20170525182412/https://familyhistorybowelcancer.wordpress.com/2012/08/28/hereditary-colorectal-cancer-syndromes/ |date=2017-05-25 }}
* [http://chromium.lovd.nl/LOVD2/colon_cancer/home.php?select_db=MUTYH LOVD database] {{Webarchive|url=https://web.archive.org/web/20160304031950/http://chromium.lovd.nl/LOVD2/colon_cancer/home.php?select_db=MUTYH |date=2016-03-04 }}