Table 1.
Neuronal Ceroid Lipofuscinoses (Batten Disease)
| Mutant Gene | NCL Disease | Encoded Protein | Classification and protein size | Posttranslational modification | Subcellular localization | Function | Interactions |
|---|---|---|---|---|---|---|---|
| CLN1 | Infantile NCL (CLN1-disease) | Palmitoyl protein thioesterase 1 (PPT1) | soluble protein, 306 aa | N-gly M6P |
Lysosomal lumen, extralysosomal vesicules, extracellular, presynaptic areas in neurons | Palmitoy-protein lthioesterase | S-acetylated proteins (GAP43, rhodopsin, saposin D) |
| CLN2 | Late infantile NCL | Tripeptidyl peptidase 1 (TPP1) | soluble protein, 563 aa | N-gly M6P |
Lysosomal lumen | Serine protease | CLN3, CLN5 |
| CLN3 | Juvenile NCL, Batten disease | CLN3/Batenin | 6 TM protein, 438 aa | N-gly farnesylated phosphorylated |
Late endosomal/lysosomal membrane, presynaptic vesicles | Unknown / predicted: pH regulation and modulation of vesicular trafficking and fusion | Hook1, kinesin-2, CLN5, Na+, K + ATPase, Rab7, fodrin |
| CLN4 | Kuffs disease | Cysteine-string protein alpha (CSPα), DNAJC5 | soluble protein, 198 aa | Palmitoylated | Cytosolic, vesicular membranes | Hsc70 co-chaperone involved in exocytosis and endocytosis | CSPα, SNAP-25, myosin IIB, calsenilin, DHHC17, dynamin-1, syntaxin, Gαs, Rab3b, synaptotagmin 9, Hsp70, Hsp40, Hsp90, HIP, HOP, SGT |
| CLN5 | CLN5 disease | – | soluble protein, 407 aa | N-gly M6P |
Lysosomal lumen | Unknown / predicted: modulation of vesicular trafficking | PPT1/CLN1, TPP1/CLN2, CLN3, CLN6, CLN8 |
| CLN6 | CLN6 disease | CLN6-protein | 7 TM protein, 311 aa | None | ER-membrane (transmembrane) | Unknown |
CLN5, CLN6 CRMP-2 |
| CLN7 | Turkish variant of late-infantile NCL | MFSD8 | 12 TM protein, 518 aa | N-gly proteolytic cleaved |
Lysosomal membrane | Predicted transmembrane transporter function predicted | AP-1, cathepsin L |
| CLN8 | NCL 8 | CLN8 | 5 TM protein, 286 aa | None | ER-membrane (transmembrane) | Unknown, predicted: to aid in the maturation of lysosomal proteins by transporting them from the ER to the Golgi complex, predicted regulation in lipid metabolism, | CLN5, CLN8, syntaxin 8, VAPA, GATE16, AGA, ARSA, ARSB, ARSG, CTBS, CTSA, CTSB, CTSD, CTSF, CTSZ, DNASE2, GALNS, GGH, GM2A, GNS, GUSB, HPSE, IDS, LIPA, MAN2B1, MAN2B2, MPO, NAGA, NEU1, PCYOX1, PLBD2, PPT1, PPT2, PSAP, RNASET2, SGSH, SIAW, SMPD1, TPP1 |
| CLN9 | – | Currently designated as CLN4 | – | – | – | – | – |
| CLN10 | Congenital NCL | Cathepsin D (CTSD) | soluble protein, 462 aa | N-gly M6P |
Lysosomal lumen | Aspartyl protease | APP, CST3, CTSB, proSAP, and several others |
| CLN11 | Unknown | Progranulin and granulins | soluble protein, 593 aa | None | Extracellular | Unknown/ predicted, roles in inflammation, embryogenesis, cell motility and tumorigenesis | MMPs, ADAMs, TGFα receptors, sortilin, ADAMTS-7/ADAMTS-12/perlecan/HDL/COMP, TGNFα receptors, EPHA2 |
| CLN12 | Unknown | ATPase 13A2, KRPPD, PARK9, HSA9947, RP-37C10.4 | 10 TM protein, 1180 aa | None | Lysosomal membrane | Unknown / predicted regulation of ion homeostasis | ~ 43 vesicular trafficking and synuclein misfolding postulated proteins |
| CLN13 | Unknown | Cathepsin F (CTSF) | soluble protein, 484 aa | N-gly M6P |
Lysosomal lumen | Unknown / predicted: cysteine protease | CD47 antigen |
| CLN14 | Unknown | Potassium channel tetramerization domain-containing protein 7 (KCTD7) | soluble protein, 289 aa | Phosphorylated | Cytosolic, partially associated to membranes | Unknown / predicted modulation of ion channel activity | Cullin-3, KCTD7 |