How variations in the MERTK gene modify the risk of MS

Professor Trevor Kilpatrick

Professor Trevor Kilpatrick

The Florey Institute of Neuroscience and Mental Health, VIC

| Causes and Prevention | Epidemiology | Genetics | Project | 2014 | Investigator Led Research |


Genetic studies in MS have uncovered over 110 genes that lead to increased susceptibility of MS. These large multinational studies have involved thousands of patients and compared their genetic sequence to healthy individuals to determine differences. While the discovery of 110 genes associated with susceptibility to MS is important, how and why they cause MS is still unknown. Determining this will require individual mapping and functional studies of each gene such as the study proposed for the MERTK gene.

Professor Kilpatrick has already identified a rare change within the MERTK gene that is strongly associated with MS susceptibility. However, this change is not predicted to produce structural variations within the MERTK protein, nor is it within an obvious regulatory region of the gene that would be predicted to change the gene activity of MERTK, which means it is unlikely to produce functional differences. In order to understand whether changes to the MERTK gene contribute to MS susceptibility, it is essential that the causal variation within the MERTK gene is clearly identified.

Once identified, this will direct future work on the potential of MERTK as a therapeutic target in MS. Further, identification of the mode of inheritance of the risk associated with the MERTK gene will help to determine whether undertaking MERTK genetic testing for family members of MS patients is practical.

Project Outcomes

Professor Kilpatrick and his team have previously identified three genes –TYRO3, AXL and MERTK, as potentially important genes in myelination repair. In this study, the team analysed the DNA of 3004 people, half with MS and the other half without MS. They found 73 different genetic variations in the MERTK gene. And because each individual genetic change can have different effects on a gene, the team investigated the impact of 54 of those variants on the functions of the MERTK gene.

The team discovered a number of interesting and unexpected findings. First, they discovered that MERTK variants which resulted in more MERTK protein can either lead to an increased risk of developing MS or lead to a decreased risk of MS, depending on the presence of the major MS susceptibility gene HLA-DRB1*1501. Not only where these genetic variants in the MERTK gene associated with an altered risk but they also correlated with the clinical course of the disease. Secondly the researchers discovered new rare variants of the MERTK gene which could independently influence the risk of MS.

This study revealed a number of interesting findings, including specific interactions between susceptibility genes coming together to influence the overall risk of MS in an individual, they also showed that there are rare variants in the MERTK gene that play a role in MS susceptibility. Understanding the complex genetics of MS is vital to the understanding how MS develops, since changes to genes that influence MS can provide scientists with clues about what is going wrong in MS and how the disease develops.


  • Binder, M.D., Fox, A.D., Merlo, D., Johnson, L.J., Giuffrida, L., Calvert, S.E., Akkermann, R., Ma, G.Z.M., ANZgene, Perera, A.A., Gresle, M.M., Laverick, L., Foo, G., Fabis-Pedrini, M., Spelman, T., Jordan, M.A., Baxter, A.G., Foote, S., Butzkueven, H., Kilpatrick, T.J., Field, J. Common and low frequency variants IN MERTK are independently associated with Multiple Sclerosis susceptibility with discordant association dependent upon HLA-DRB1*15:01 status. PLoS Genet (2016) 12(3): e1005853

Updated: 17 August 2016

Updated: 06 January, 2014



  • Dr Judith Field, The Florey Institute of Neuroscience and Mental Health, VIC
  • Michele Binder, The Florey Institute of Neuroscience and Mental Health, VIC

Grant Awarded

  • Project Grant

Total Funding

  • $92,000


  • 2 years over 2014 - 2015

Funding Partner

  • Trish MS Research Foundation
Read More

Newsletter subscription

  • Enter your details

How variations in the MERTK gene modify the risk of MS