A massive international collaboration involving over 100 research groups spread across Europe and the US, including the BCRM, has today reported on the identification of KIF5A as a new risk gene for ALS. The study, which was published in the journal Neuron, analyzed data derived from 112,000 DNA profiles and involved the use of 2 distinct but complimentary lines of investigation.
In the first analysis, the frequencies of 10 million common genetic variants were compared across 21,000 ALS patients and 60,000 healthy controls using chip-based “DNA snapshots”. In the second analysis DNA sequencing of protein coding genes was used to evaluate the frequencies of rare loss of function variants in 1,100 familial ALS patients and 20,000 controls. The analyses were designed to detect different types of genetic risk factors but both methods independently revealed KIF5A. Validating the project’s findings then required the analysis of DNA sequencing from a further 9,046 patients and 1,955 controls. Project MinE, an international project with BCRM in the lead, contributed to each phase of the analysis, providing data from 47,000 DNA profiles. The analyses of combined datasets were led by researchers at the University of Massachusetts medical school and the US national institute of aging.


KIF5A is one of the several motor protein genes encoded by our DNA. It’s function is to carry biological cargo molecules along cellular railroads called microtubules. In doing so, genes such as KIF5A play a key role in ensuring that essential raw materials are delivered to wherever they are needed most.

Next steps
Gaining further insight into the malfunctioning of KIF5A mutations and using the gene to establish new drug targets are now top priorities for on-going research. Furthermore, similar studies involving larger numbers of DNA donors and extending focused assessments of common and loss function genetic variants to full DNA profiling will likely be required in bringing this about. Such efforts are currently underway.