About MAPK8IP3

MAPK8IP3– related neurodevelopmental disorder, also known as neurodevelopmental disorder with or without variable brain anomalies (NEDBA), has been a recognized neurodevelopmental disorder for less than two years (OMIM, 2019). We will continue to update this page as we families learn more.


MAPK8IP3, or Mitogen-Activated Protein Kinase 8 Interacting Protein 3, is a gene on Chromosome 16 (16p13) that encodes a protein that works like a motor in the nerve cells of the brain (Chung, 2020). This motor moves items along the axon of the nerve cells of the brain (Iwasawa, 2019). With a MAPK8IP3 variant diagnosis, one copy of the MAPK8IP3 gene is normal and the second copy has a change (variant) . This change can affect how the motor works by producing a shortened protein or a protein that does not work correctly, thus affecting nerves (Chung, 2020).


Based on published studies, we know there is range of symptom severity, meaning some individuals are more affected in certain areas than others (Chung, 2020). A MAPK8IP3 variant can affect growth, puberty, cognition, speech, motor control, tone, sleep, feeding, vision, and behavior. Abnormalities have been reported on patient brain imaging (MRIs) and electrical activity (EEGs). Several individuals have autism and/or difficulties with attention.

Researchers are currently conducting a natural history study to better understand symptoms. Additional information can be found on the National Organization for Rare Disorders’ description of MAPK8IP3-related neurodevelopmental disorder here and the Wolverine Foundation’s general discussion of MAPK8IP3 here. Researchers presented on MAPK8IP3 during the 2019 AsiaPacific Forum on Population Genomics Presentation.


A diagnosis of a MAPK8IP3 gene variant is based on genetic testing. Because the MAPK8IP3 variant was recognized so recently, the exact number of cases within the population is not known at this time (Chung, 2020). It is estimated that the incidence of having a MAPK8IP3 variant is approximately 1 in 100,000 individuals throughout the world (Chung, 2020).


Several papers documenting the MAPK8IP3* gene variant in humans were recently published in 2019 which led to it classified as a pathogenic variant. In addition, researchers have studied the corresponding MAPK8IP3 gene/protein in various animal models. While this is not an exhaustive list, we have tried to include as many applicable papers as possible.

*MAPK8IP3 gene page on OMIM (catalog of human genes and genetics disorders): https://www.omim.org/entry/605431. Please note that MAPK8IP3 is also known as NEDBA (Neurodevelopmental disorder with or without variable brain abnormalities), JSAP1, JIP3, JIP-3, SYD2, syd, among other names.

Relevant Articles

Platzer, K., Sticht, H., Edwards, S., Allen, W., Angione, K., Bonati, M., … Jamra, R. (2019). De novo variants in MAPK8IP3 cause intellectual disability with variable brain anomalies. American Journal of Human Genetics, 104(2), 203-212. https://www.sciencedirect.com/science/article/pii/S0002929718304592

Iwasawa, S., Yanagi, K., Kikuchi, A., Kobayashi, Y., Haginoya, K., Matsumoto, H., … Kure, S. (2019). Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. Annals of Neurology, 85(6), 927-933. https://doi.org/10.1002/ana.25481

Gowrishankar, Swetha et al. “Overlapping roles of JIP3 and JIP4 in promoting axonal transport of lysosomes in human iPSC-derived neurons.” Molecular biology of the cell vol. 32,11 (2021): 1094-1103. https://www.molbiolcell.org/doi/10.1091/mbc.E20-06-0382?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub%20%200pubmed

Gowrishankar, S., Yumei, W., & Ferguson, S. Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology. (2017). The Journal of Cell Biology, 216(10), 3291–3305. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5626538/

Miller, K. (2016). Keeping neuronal cargoes on the right track: new insights into regulators of axonal transport. (2017). The Neuroscientist 23(3), 232–250. https://journals.sagepub.com/doi/full/10.1177/1073858416648307

Snead AM, Gowrishankar S. Loss of MAPK8IP3 Affects Endocytosis in Neurons. Front Cell Neurosci. 2022 May 27;16:828071. doi: 10.3389/fncel.2022.828071. PMID: 35711470; PMCID: PMC9196590. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9196590/


Chung, W. K. (2020). MAPK8ip3 research presentation to families [PowerPoint slides]

Iwasawa, S., Yanagi, K., Kikuchi, A., Kobayashi, Y., Haginoya, K., Matsumoto, H., … Kure, S. (2019). Recurrent de novo MAPK8IP3 variants cause neurological phenotypes. Annals of Neurology85(6), 927-933. https://doi.org/10.1002/ana.25481

OMIM. (2019, May 22). #618443- Nuerodevelopmental disorder with or without brain anomalies. Retrieved from https://www.omim.org/entry/618443.