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Current Research Findings



The following will show you more about this unique problem, which can have serious consequences if it attacks.

The exact function of Cln3 is still unknown, but we would like to inform you about some facts here.


CLN3 Profile | Current Knowledge | Remaining questions


CLN3 Profile




CLN3 or Battenin in high eukaryotes or Btn1 in low eukaryotes



1995 in a JNCL patient


Position in the genome

Chromosome 16 (16p 12.1)



Gene 1314 bp(basic pairs), 15 exons

Protein 438 AA (amino acids)

Structure of CLN3 genes (exon/intron structure), most common mutation: deletion                        

between intron 6 and 8



Most patients (74%) are homozygous for a 1,02 kb deletion of exons 7 and 8 and the surrounding intron areas of the CLN3 gene, about 22% possess a version of this mutation, together with another rare mutation and only about 2% possess two rare mutations. All known mutations can be found in the NCL Mutation Database.



CLN3, with its 6 transmembrane domains, is suspected to be grounded in the target 




The domain structure is comparable to members of the, “major facilitator superfamily”, one of the biggest two families of membrane transporters. These so-called permease transport agents, basic sugars, nucleosides, organophosphates, metabolites of the citric acid cycle as well as different inorganic anions and cations. Older algorithms show a lower homology of the N-terminus from Cln3 to fatty acid desaturase



N-Glycosylation at aspartic acid 75 and aspartic acid 81, prenylation (most likely farnesylation) at cysteine 435.

Source: Illustration courtesy of Future Medicine Ltd. Taken from The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking by SL Cotman  and  J F Staropol  published in Clinical Lipidology (2012)  vol. 7 (1) p. 79-91







Structure of the CLN3 proteins: 6 membrane domains: modifications, N-Glycosylation, (blue forks), prenylation(zig-zag lines), point mutations: missense (red circles), nonsense (yellow circles), polymorphism (navy circle)


Targeted Sequences

Two which are lysosomal, EEEX8LIandMX8G (E=Glutamic acid, G=Glycine, L=Leucine, I = Isoleucine, M=Methionine, X=any AA)




In the brain in small amounts in granule neurons of the Gyrustentatus of the Hippocampus and endothelium cells of the micro-vasculature and other tissues outside of the central nervous system such as the skin, lungs, intestines and above all the inner medulla of the kidneys 




Most of CLN3 can be found in the lysosome membrane. CLN3 can also be found, however,  inendoplasmatic reticulum (ER), in Golgi apparatus, in endosomes, as well as at or in the plasma membrane


Protein transport

CLN3 is synthesised in the ER, modified in the Golgi apparatus, and transported afterwards to different subcellular membranes.

Source: Illustration courtesy of Future Medicine Ltd. Taken from The juvenile Batten disease protein, CLN3, and its role in regulating anterograde and retrograde post-Golgi trafficking by SL Cotman  and  J F Staropol  published in Clinical Lipidology (2012)  vol. 7 (1) p. 79-91.






Transport of the CLN3 protein in the cell: anterograde and retrograde transport between Golgi-Network, endosomes, lysosomes,autophagosomes and cell membrane.



The exact function is unknown. Cln3 influences different cell functions such as endocytosis, vesicular transport, pH balance of vacuoles and lysosomes, arginine-import, galactosylceramide-transport, Bis-(monoacylglycero)phosphate synthesis, palmitoyl protein desaturation, apopthosis resistance and autophagy.


Current Knowledge

  • Ceroidlipofuscin, the storage material of the lysosomes, is very heterogeneous and contains dolichol, dolichol phosphates, and iron, as well as important proteins such as non-alcohol soluble lipids. Mostly the c Subunit of the mitochondrial ATP-Synthase F0 accumulated in CLN3 patients
  • CLN3 is not only expressed in the brain, but also in the inner medulla of the kidney. In an examination of the water and potassium balance of the kidneys, it was suspected that it plays an osmoregulative role (Stein et al.2013).


Remaining Questions

With the further development of innovative methods, such as the use of induced pluripotent stem cells, researchers are learning more and more. However new answers lead to new questions. For example:

  • What is the main function of Cln3?

  • What influence does a lack of Cln3 have on the trans-Golgi network?

  • Which mechanism regulates Cln3 lipids and lipid modified protein?

  • Are deposits in the cells really dangerous?

  • What role does Cln3 have to play, apart from that in the central nervous system?

  • What link is there between Cln3 and autophagy?

  • Can new results from the yeast models be transferred over to humans?

  • Which proteins does Cln3 interact with?

  • Can some patients be helped by stabilising mutated proteins?

  • Why do patients first symptoms appear at school going age?

  • Which compensatory methods are available to the body?



Contact Person

Dr. Herman van der Putten

Mobile: +49 (0) 163-7383083


This German - English translation was done by the translators Tizzy Mann, Andrea Murphy, Kate Humby and Marcia Neff for the PerMondo initiative that involves providing free translations for NGOs. PerMondo is sponsored and run by the translation agency Mondo Agit.