Donate Now

CureMAPK8IP3

MAPK8IP3-Related Neurodevelopmental Disorder

MAPK8IP3– Related Neurodevelopmental Disorder, also known as Neurodevelopmental Disorder with or without Variable Brain Anomalies (NEDBA), is a rare disease (OMIM, 2019). It has been a recognized disorder since 2019 when the first two scientific papers on MAPK8IP3 gene variants in the human population were published:

MAPK8IP3 Gene

MAPK8IP3, or Mitogen-Activated Protein Kinase 8 Interacting Protein 3, is a gene on Chromosome 16 (16p13) that encodes a protein called JIP3 that is a connector protein to motors that transport lysosomes and endosomes along microtubules along the axon of neurons (nerve cells) of the brain (Chung, 2020; Iwasawa, 2019). With a MAPK8IP3 variant diagnosis, one copy of the MAPK8IP3 gene is normal and the second copy has a change (variant). Most cases are “de novo,” meaning they were not passed down from parent to child.

Diagnosis

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). We currently have approximately 90+ families known to our foundation.

Symptoms

There is a range of symptoms and severity of symptoms, meaning some individuals are more affected in certain areas than others (Chung, 2020). The location of each individual’s specific MAPK8IP3 variant within the gene may also affect symptoms that are seen. Variants can be loss of function (shortened protein or no protein) or gain of function (abnormal protein made that could have a toxic effect). Researchers are currently conducting a natural history study to better understand symptoms. A MAPK8IP3 variant can affect many areas. Based on the ongoing natural history study and parent report in our family group, current symptoms that can be seen in individuals include:

  • Speech delays
  • Fine and gross motor delays
  • Cognitive delays
  • Muscle tone abnormalities–some individuals have hypotonia (low tone), others have hypertonia or dystonia
  • Autism or autistic like behaviors
  • Problems with attention and impulse control
  • Problems with vision
  • Short stature
  • Early puberty
  • Abnormal EEGs/seizures
  • Abnormal brain imaging (MRIs)
  • Difficulties around sleep
  • Facial dysmorphism
  • Feeding/Gastrointestinal issues

Recent research into MAPK8IP3

Additional resources:

MAPK8IP3-Poster-Session-1-2-1Download
MAPK8IP3 brochureDownload

Additional information can also be found on the National Organization for Rare Disorders’ description of MAPK8IP3-related neurodevelopmental disorder here.

Additional Publications Relevant to JIP3 and MAPK8IP3

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/

Celestino, Ricardo et al. “JIP3 interacts with dynein and kinesin-1 to regulate bidirectional organelle transport.” The Journal of cell biology vol. 221,8 (2022): e202110057. doi:10.1083/jcb.202110057. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35829703/

Rafiq, N M et al. “JIP3 links lysosome transport to regulation of multiple components of the axonal cytoskeleton.” Communications biology vol. 5,1 5. 10 Jan. 2022, doi:10.1038/s42003-021-02945-x.

Drozd, Cody J et al. “UNC-16 interacts with LRK-1 and WDFY-3 to regulate the termination of axon growth.” Genetics vol. 227,2 (2024): iyae053. doi:10.1093/genetics/iyae053. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/35013510/

https://pmc.ncbi.nlm.nih.gov/articles/PMC11151918

References:

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 Neurology, 85(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.

Disclaimer:

Any information on our site should not constitute or replace personal medical advice. Families should always consult with a qualified medical professional for all information and treatment regarding MAPK8IP3 and MAPK8IP3-Related Neurodevelopmental Disorder. While the foundation does its best to keep information on our website accurate, information may come out that changes our understanding of MAPK8IP3 and MAPK8IP3-Related Neurodevelopmental Disorder. Therefore, is important to check with a qualified medical professional to ensure the most accurate and up-to-date information regarding this disorder and treatment.

Translate »