OMIA:002145-9544 : Colorectal cancer, MLH1-related in Macaca mulatta (Rhesus monkey)

Categories: Neoplasm

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 609310 (trait) , 120436 (gene)

Links to relevant human diseases in MONDO:

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Cross-species summary: Lynch syndrome; HNPCC2

Species-specific symbol: MLH1-rheMac

Molecular basis: Brammer et al. (2018) reported that "current results provide supportive evidence for the existence of HNPCC (MLH1-rheMac syndrome) in rhesus macaques resulting from the loss of MLH1 protein expression, which represents a simian ortholog of Lynch syndrome in humans. The loss of MLH1 expression is potentially due to several reasons, including a deletion mutation in the MLH1 promoter region, which results in decreased transcriptional activity." These authors identified the likely causal variant as a "deletion in the putative promoter region of the MLH1 gene (rheMac2: 2:99,561,829–99,561,830; hg19: ∼3:37,034,780; c.−258_259)". Dray et al. (2018) reported a likely causal variant as "a de novo stop codon in the coding region of MLH1. This de novo stop codon occurs in exon 11 out of 19 in the MLH1 gene, and thus would produce a dramatically truncated and possibly non-functional protein". These authors did not provide any details on this variant. Ozirmak Lermi et al. (2022) report that a "cohort of rhesus macaques from our institution developed spontaneous mismatch repair deficient (MMRd) CRC with a notable fraction harboring a pathogenic germline mutation in MLH1 (c.1029C

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
MLH1 mutL homolog 1 Macaca mulatta 2 NC_041755.1 (92414222..92469110) MLH1 Homologene, Ensembl , NCBI gene


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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
1014 Colorectal cancer, MLH1-related MLH1 nonsense (stop-gain) Naturally occurring variant 2 c.1029C<G p.(Y343*) Dray et al. (2018): "a de novo stop codon in the coding region of MLH1. This de novo stop codon occurs in exon 11 out of 19 in the MLH1 gene, and thus would produce a dramatically truncated and possibly non-functional protein". Ozirmak Lermi et al. (2022) reported the c. and p. coordinates of this variant. 2018 30108684
1013 Colorectal cancer, hereditary nonpolyposis, MLH1-related MLH1 deletion, small (<=20) Naturally occurring variant 2 g.99561829_99561830del Brammer et al. (2018): "a heterozygous deletion in the putative promoter region of the MLH1 gene (rheMac2: 2:99,561,829– 99,561,830; hg19: ∼3:37,034,780; c.−258_259)" 2018 29490919

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:002145-9544: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2024 Deycmar, S., Johnson, B.J., Ray, K., Schaaf, G.W., Ryan, D.P., Cullin, C., Dozier, B.L., Ferguson, B., Bimber, B.N., Olson, J.D., Caudell, D.L., Whitlow, C.T., Solingapuram Sai, K.K., Romero, E.C., Villinger, F.J., Burgos, A.G., Ainsworth, H.C., Miller, L.D., Hawkins, G.A., Chou, J.W., Gomes, B., Hettich, M., Ceppi, M., Charo, J., Cline, J.M. :
Epigenetic MLH1 silencing concurs with mismatch repair deficiency in sporadic, naturally occurring colorectal cancer in rhesus macaques. J Transl Med 22:292, 2024. Pubmed reference: 38504345. DOI: 10.1186/s12967-024-04869-6.
2022 Ozirmak Lermi, N., Gray, S.B., Bowen, C.M., Reyes-Uribe, L., Dray, B.K., Deng, N., Harris, R.A., Raveendran, M., Benavides, F., Hodo, C.L., Taggart, M.W., Colbert Maresso, K., Sinha, K.M., Rogers, J., Vilar, E. :
Comparative molecular genomic analyses of a spontaneous rhesus macaque model of mismatch repair-deficient colorectal cancer. PLoS Genet 18:e1010163, 2022. Pubmed reference: 35446842. DOI: 10.1371/journal.pgen.1010163.
2018 Brammer, D.W., Gillespie, P.J., Tian, M., Young, D., Raveendran, M., Williams, L.E., Gagea, M., Benavides, F.J., Perez, C.J., Broaddus, R.R., Bernacky, B.J., Barnhart, K.F., Alauddin, M.M., Bhutani, M.S., Gibbs, R.A., Sidman, R.L., Pasqualini, R., Arap, W., Rogers, J., Abee, C.R., Gelovani, J.G. :
MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques. Proc Natl Acad Sci U S A 115:2806-2811, 2018. Pubmed reference: 29490919. DOI: 10.1073/pnas.1722106115.
Dray, B.K., Raveendran, M., Harris, R.A., Benavides, F., Gray, S.B., Perez, C.J., McArthur, M.J., Williams, L.E., Baze, W.B., Doddapaneni, H., Muzny, D.M., Abee, C.R., Rogers, J. :
Mismatch repair gene mutations lead to lynch syndrome colorectal cancer in rhesus macaques. Genes Cancer 9:142-152, 2018. Pubmed reference: 30108684. DOI: 10.18632/genesandcancer.170.

Edit History

  • Created by Frank Nicholas on 26 Mar 2018
  • Changed by Frank Nicholas on 26 Mar 2018
  • Changed by Frank Nicholas on 21 Sep 2018
  • Changed by Imke Tammen2 on 15 Nov 2022