OMIA:002410-9823 : CMAH enzyme deficiency in Sus scrofa (pig)

In other species: taurine cattle

Categories: Immune system phene

Possibly relevant human trait(s) and/or gene(s) (MIM number): 603209 (gene)

Links to MONDO diseases: No links.

Mendelian trait/disorder: yes

Considered a defect: no

Key variant known: no

Cross-species summary: N-glycolylneuraminic acid (NeuGc), a sialic acid involved in cell-cell recognition and cell-pathogen interactions, is abundantly expressed in most mammals but is not detectable in humans. The synthesis of NeuGc is controlled by cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) activity. The enzyme CMAH is inactivated in humans by a deletion.

Species-specific description: Tu et al. (2022): "red meat cell surface expresses ... N-glycolylneuraminic acid (Neu5Gc; nonhuman glycan) [Jahan et al. 2021], which, once absorbed, is incorporated on the surface of human cells [Tangvoranuntaku et al., 2003] and elicits chronic inflammation, causing a major risk of colorectal cancer and atherosclerosis development [Alisson-Silva et al., 2016]. Transforming Neu5Gc to Neu5Ac (the human form) in pigs through the KO of the responsible CMAH gene has been a goal of xenotransplantation, and in animal production, this would transform red meat into white since poultry and fish also show the Neu5Ac form."

This phene includes references to studies involving genetically modified organisms (GMO).

Genetic engineering: Unknown
Have human generated variants been created, e.g. through genetic engineering and gene editing

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2023). OMIA:002410-9823: 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.

2023 Cooper, D.K.C., Pierson, R.N. :
Milestones on the path to clinical pig organ xenotransplantation. Am J Transplant 23:326-335, 2023. Pubmed reference: 36775767. DOI: 10.1016/j.ajt.2022.12.023.
Morticelli, L., Rossdam, C., Cajic, S., Böthig, D., Magdei, M., Tuladhar, S.R., Petersen, B., Fischer, K., Rapp, E., Korossis, S., Haverich, A., Schnieke, A., Niemann, H., Buettner, F.F.R., Hilfiker, A. :
Genetic knockout of porcine GGTA1 or CMAH/GGTA1 is associated with the emergence of neo-glycans. Xenotransplantation :e12804, 2023. Pubmed reference: 37148126. DOI: 10.1111/xen.12804.
2022 Tu, C.F., Chuang, C.K., Yang, T.S. :
The application of new breeding technology based on gene editing in pig industry - A review. Anim Biosci 35:791-803, 2022. Pubmed reference: 34991204. DOI: 10.5713/ab.21.0390.
2021 Choe, H.M., Luo, Z.B., Kang, J.D., Oh, M.J., An, H.J., Yin, X.J. :
Pathological features in 'humanized' neonatal pig. Anim Biotechnol :1-9, 2021. Pubmed reference: 34392816. DOI: 10.1080/10495398.2021.1962896.
Jahan, M., Thomson, P.C., Wynn, P.C., Wang, B. :
The non-human glycan, N-glycolylneuraminic acid (Neu5Gc), is not expressed in all organs and skeletal muscles of nine animal species. Food Chem 343:128439, 2021. Pubmed reference: 33127222. DOI: 10.1016/j.foodchem.2020.128439.
Yue, Y., Xu, W., Kan, Y., Zhao, H.Y., Zhou, Y., Song, X., Wu, J., Xiong, J., Goswami, D., Yang, M., Lamriben, L., Xu, M., Zhang, Q., Luo, Y., Guo, J., Mao, S., Jiao, D., Nguyen, T.D., Li, Z., Layer, J.V., Li, M., Paragas, V., Youd, M.E., Sun, Z., Ding, Y., Wang, W., Dou, H., Song, L., Wang, X., Le, L., Fang, X., George, H., Anand, R., Wang, S.Y., Westlin, W.F., Güell, M., Markmann, J., Qin, W., Gao, Y., Wei, H.J., Church, G.M., Yang, L. :
Extensive germline genome engineering in pigs. Nat Biomed Eng 5:134-143, 2021. Pubmed reference: 32958897. DOI: 10.1038/s41551-020-00613-9.
2019 Perota, A., Galli, C. :
N-glycolylneuraminic acid (Neu5Gc) null large animals by targeting the CMP-Neu5Gc hydroxylase (CMAH). Front Immunol 10:2396, 2019. Pubmed reference: 31681287. DOI: 10.3389/fimmu.2019.02396.
2017 Gao, H., Zhao, C., Xiang, X., Li, Y., Zhao, Y., Li, Z., Pan, D., Dai, Y., Hara, H., Cooper, D.K., Cai, Z., Mou, L. :
Production of α1,3-galactosyltransferase and cytidine monophosphate-N-acetylneuraminic acid hydroxylase gene double-deficient pigs by CRISPR/Cas9 and handmade cloning. J Reprod Dev 63:17-26, 2017. Pubmed reference: 27725344. DOI: 10.1262/jrd.2016-079.
Salama, A., Mosser, M., Lévêque, X., Perota, A., Judor, J.P., Danna, C., Pogu, S., Mouré, A., Jégou, D., Gaide, N., Abadie, J., Gauthier, O., Concordet, J.P., Le Bas-Bernardet, S., Riochet, D., Le Berre, L., Hervouet, J., Minault, D., Weiss, P., Guicheux, J., Brouard, S., Bosch, S., Lagutina, I., Duchi, R., Lazzari, G., Cozzi, E., Blancho, G., Conchon, S., Galli, C., Soulillou, J.P., Bach, J.M. :
Neu5Gc and α1-3 GAL xenoantigen knockout does not affect glycemia homeostasis and insulin secretion in pigs. Diabetes 66:987-993, 2017. Pubmed reference: 28082457. DOI: 10.2337/db16-1060.
2016 Alisson-Silva, F., Kawanishi, K., Varki, A. :
Human risk of diseases associated with red meat intake: Analysis of current theories and proposed role for metabolic incorporation of a non-human sialic acid. Mol Aspects Med 51:16-30, 2016. Pubmed reference: 27421909. DOI: 10.1016/j.mam.2016.07.002.
2015 Estrada, J.L., Martens, G., Li, P., Adams, A., Newell, K.A., Ford, M.L., Butler, J.R., Sidner, R., Tector, M., Tector, J. :
Evaluation of human and non-human primate antibody binding to pig cells lacking GGTA1/CMAH/β4GalNT2 genes. Xenotransplantation 22:194-202, 2015. Pubmed reference: 25728481. DOI: 10.1111/xen.12161.
2014 Li, P., Estrada, J.L., Burlak, C., Montgomery, J., Butler, J.R., Santos, R.M., Wang, Z.Y., Paris, L.L., Blankenship, R.L., Downey, S.M., Tector, M., Tector, A.J. :
Efficient generation of genetically distinct pigs in a single pregnancy using multiplexed single-guide RNA and carbohydrate selection. Xenotransplantation 22:20-31, 2014. Pubmed reference: 25178170. DOI: 10.1111/xen.12131.
Moon, J., Lee, C., Kim, S.J., Choi, J.Y., Lee, B.C., Kim, J.S., Jang, G. :
Production of CMAH knockout preimplantation embryos derived from immortalized porcine cells via TALE nucleases. Mol Ther Nucleic Acids 3:e166, 2014. Pubmed reference: 24866481. DOI: 10.1038/mtna.2014.15.
2013 Kwon, D.N., Lee, K., Kang, M.J., Choi, Y.J., Park, C., Whyte, J.J., Brown, A.N., Kim, J.H., Samuel, M., Mao, J., Park, K.W., Murphy, C.N., Prather, R.S., Kim, J.H. :
Production of biallelic CMP-Neu5Ac hydroxylase knock-out pigs. Sci Rep 3:1981, 2013. Pubmed reference: 23760311. DOI: 10.1038/srep01981.
Lutz, A.J., Li, P., Estrada, J.L., Sidner, R.A., Chihara, R.K., Downey, S.M., Burlak, C., Wang, Z.Y., Reyes, L.M., Ivary, B., Yin, F., Blankenship, R.L., Paris, L.L., Tector, A.J. :
Double knockout pigs deficient in N-glycolylneuraminic acid and galactose α-1,3-galactose reduce the humoral barrier to xenotransplantation. Xenotransplantation 20:27-35, 2013. Pubmed reference: 23384142. DOI: 10.1111/xen.12019.
2003 Tangvoranuntakul, P., Gagneux, P., Diaz, S., Bardor, M., Varki, N., Varki, A., Muchmore, E. :
Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci U S A 100:12045-50, 2003. Pubmed reference: 14523234. DOI: 10.1073/pnas.2131556100.

Edit History

  • Created by Imke Tammen2 on 28 Aug 2021
  • Changed by Imke Tammen2 on 28 Aug 2021
  • Changed by Imke Tammen2 on 17 Sep 2021
  • Changed by Imke Tammen2 on 11 Jan 2022
  • Changed by Imke Tammen2 on 19 Jan 2023