CLN3

Summary

CLN3 (CLN3 lysosomal/endosomal transmembrane protein, battenin, HGNC:2074) is a protein-coding gene on chromosome 16p12.1, encoding Battenin (Q13286). Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocy….

This gene encodes a protein that is involved in lysosomal function. Mutations in this, as well as other neuronal ceroid-lipofuscinosis (CLN) genes, cause neurodegenerative diseases commonly known as Batten disease or collectively known as neuronal ceroid lipofuscinoses (NCLs). Many alternatively spliced transcript variants have been found for this gene.

Source: NCBI Gene 1201 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neuronal ceroid lipofuscinosis (Definitive, ClinGen) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 1,266 total — 103 pathogenic, 106 likely-pathogenic
• Phenotypes (HPO): 32
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity unscored
• MANE Select transcript: NM_001042432

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2074
Approved symbol	CLN3
Name	CLN3 lysosomal/endosomal transmembrane protein, battenin
Location	16p12.1
Locus type	gene with protein product
Status	Approved
Aliases	BTN1, JNCL, SLC29B1
Ensembl gene	ENSG00000188603
Ensembl biotype	protein_coding
OMIM	607042
Entrez	1201

Gene structure

Transcript identifiers

Ensembl transcripts: 67 — 25 protein_coding, 17 retained_intron, 16 nonsense_mediated_decay, 9 protein_coding_CDS_not_defined

ENST00000333496, ENST00000355477, ENST00000357806, ENST00000357857, ENST00000359984, ENST00000360019, ENST00000395653, ENST00000561505, ENST00000561689, ENST00000563874, ENST00000564091, ENST00000564574, ENST00000565047, ENST00000565140, ENST00000565236, ENST00000565316, ENST00000565354, ENST00000565688, ENST00000565778, ENST00000566040, ENST00000566057, ENST00000566083, ENST00000566472, ENST00000566816, ENST00000566824, ENST00000567160, ENST00000567495, ENST00000567804, ENST00000567963, ENST00000568076, ENST00000568422, ENST00000568443, ENST00000568452, ENST00000568472, ENST00000568497, ENST00000568558, ENST00000569030, ENST00000569430, ENST00000628023, ENST00000635861, ENST00000635958, ENST00000635973, ENST00000636147, ENST00000636172, ENST00000636228, ENST00000636351, ENST00000636355, ENST00000636685, ENST00000636839, ENST00000636853, ENST00000636907, ENST00000636977, ENST00000637050, ENST00000637100, ENST00000637107, ENST00000637110, ENST00000637184, ENST00000637578, ENST00000637686, ENST00000637699, ENST00000637871, ENST00000637985, ENST00000892258, ENST00000892259, ENST00000940182, ENST00000940183, ENST00000940184

RefSeq mRNA: 6 — MANE Select: NM_001042432 NM_000086, NM_001042432, NM_001286104, NM_001286105, NM_001286109, NM_001286110

CCDS: CCDS10632, CCDS73854, CCDS73855

Canonical transcript exons

ENST00000636147 — 16 exons

Exon	Start	End
ENSE00001422783	28477279	28477635
ENSE00002588743	28491714	28491835
ENSE00003472537	28491482	28491560
ENSE00003639562	28488591	28488662
ENSE00003788052	28487662	28487741
ENSE00003790859	28489290	28489386
ENSE00003799201	28492020	28492074
ENSE00003803430	28482626	28482672
ENSE00003804811	28484006	28484118
ENSE00003805432	28482327	28482382
ENSE00003808090	28486347	28486490
ENSE00003809629	28477737	28477877
ENSE00003811192	28487456	28487541
ENSE00003811283	28482105	28482198
ENSE00003811332	28482477	28482545
ENSE00003811346	28486578	28486650

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 97.50.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.9976 / max 128.8878, expressed in 1816 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
156882	12.5023	1799
156881	3.8750	1679
156884	2.6178	369
156879	1.7220	1054
156883	0.1667	79
156880	0.1138	29

Top tissues by expression

134 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
mucosa of transverse colon	UBERON:0004991	97.50	gold quality
placenta	UBERON:0001987	96.13	gold quality
granulocyte	CL:0000094	96.08	gold quality
blood	UBERON:0000178	95.22	gold quality
transverse colon	UBERON:0001157	94.79	gold quality
monocyte	CL:0000576	94.43	gold quality
leukocyte	CL:0000738	94.37	gold quality
colonic epithelium	UBERON:0000397	94.19	gold quality
rectum	UBERON:0001052	93.94	gold quality
right adrenal gland cortex	UBERON:0035827	93.73	gold quality
left adrenal gland	UBERON:0001234	93.57	gold quality
right lobe of thyroid gland	UBERON:0001119	93.56	gold quality
metanephros cortex	UBERON:0010533	93.53	gold quality
left adrenal gland cortex	UBERON:0035825	93.50	gold quality
right adrenal gland	UBERON:0001233	93.43	gold quality
left lobe of thyroid gland	UBERON:0001120	93.30	gold quality
body of stomach	UBERON:0001161	92.89	gold quality
bone marrow cell	CL:0002092	92.88	gold quality
thyroid gland	UBERON:0002046	92.84	gold quality
small intestine Peyer’s patch	UBERON:0003454	92.74	gold quality
right lung	UBERON:0002167	92.72	gold quality
upper lobe of left lung	UBERON:0008952	92.59	gold quality
saliva-secreting gland	UBERON:0001044	92.36	gold quality
minor salivary gland	UBERON:0001830	92.21	gold quality
skin of leg	UBERON:0001511	92.14	gold quality
fundus of stomach	UBERON:0001160	92.08	gold quality
bone marrow	UBERON:0002371	92.08	gold quality
small intestine	UBERON:0002108	92.03	gold quality
spleen	UBERON:0002106	92.01	gold quality
colon	UBERON:0001155	91.96	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	37.42
E-CURD-112	yes	13.64
E-ANND-3	yes	5.81

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ASCL1, ZNF143, ZNF32

miRNA regulators (miRDB)

6 targeting CLN3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-892C-5P	99.16	70.56	2116
HSA-MIR-5006-5P	98.79	66.92	1246
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-125A-3P	97.04	66.92	902
HSA-MIR-6808-3P	94.13	65.24	516

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity Not yet evaluated (unscored). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• cln3 is present during critical periods of neuronal cell differentiation and brain development (PMID:10509355)
• Identification of a transactivation motif in the CLN3 protein (PMID:11699874)
• juvenile and variant late infantile neuronal ceroid lipofuscinoses have mutated CLN genes encoding lysosomal proteins (review) (PMID:12125809)
• Data show that three neuronal ceroid lipofuscinoses disease forms with similar tissue pathology are connected at the molecular level: CLN5 polypeptides directly interact with the CLN2 and CLN3 proteins (PMID:12134079)
• Deletion of glycosylation sites and also mutations within conserved amino acid stretches result in slowed cell growth and apoptosis (PMID:12189165)
• This protein is responsible for Batten Disease. (PMID:12440525)
• Defective transport at the lysosomal membrane caused by an absence of functional CLN3 is the primary biochemical defect that results in Batten disease. (PMID:14660799)
• The presence of CLN3 in endosomes of neurons is functionally important. Endosomal association of the protein was independent of the two lysosomal targeting motifs (PMID:14699076)
• The major mutation is a 1.02 kb deletion, which removes exons 7 and 8. Both homozygotic and heterozygotic deletions at the CLN3 gene site have been associated with the clinical syndromes of juvenile neuronal ceroid-lipofuscinosis. (PMID:15032383)
• These studies identify a novel CLN3 domain that may dictate localization and function of CLN3. (PMID:15240864)
• the second cytoplasmic domain of CLN3 protein has a dileucine motif and a cluster of acidic amino acids which are required for efficient lysosomal targeting (PMID:15469932)
• suggests a link between CLN3 function, microtubule cytoskeleton and endocytic membrane trafficking (PMID:15471887)
• AP-1 and AP-3 facilitate lysosomal targeting of Batten disease protein CLN3 via its dileucine motif (PMID:15598649)
• Batten disease, an inherited neurodegenerative storage disease affecting children, results from the autosomal recessive inheritance of mutations in Cln3. And is resident in the lysosomal/endosomal membrane. (PMID:15657902)
• We report the discovery of a novel mutation identified as a G to T transversion at nucleotide 49 (G49T) in exon 2 of CLN3, introducing a premature stop codon (E17X) near the N-terminus. This mutation represents the most 5’ mutation described to date. (PMID:16087292)
• CLN3 defect in juvenile Batten disease may affect how intracellular levels of arginine are regulated or distributed throughout the cell. (PMID:16251196)
• The CLN3 protein trafficked to the vacuole membrane via early endocytic and pre-vacuolar compartments. (PMID:16291725)
• CLN3P significantly increased the survival rate of the SH-SY5Y neurblastoma cells further evidence that CLN3P has anti-apoptotic properties (PMID:16515873)
• Autophagy is disrupted in juvenile neuronal ceroid lipofuscinosis, likely at the level of autophagic vacuolar maturation in CLN3 knockin mice. (PMID:16714284)
• Co-operative signal structures in different cytoplasmic domains of CLN3 are required for efficient sorting and for transport to the lysosome. (PMID:17286803)
• There is a strong correlation between CLN3 protein expression and synthesis of bis(monoacylglycerol)phosphate. (PMID:17482562)
• Review provides a brief overview and an update of recent research in juvenile neuronal ceroid-lipofuscinosis, specifically that related to the function of CLN3 protein, whose primary function may be that of the enzyme palmitoyl-protein delta-9 desaturase. (PMID:17896996)
• Study concluded that the common mutant CLN3 protein does indeed retain significant function and that juvenile neuronal ceroid lipofuscinoses is a mutation-specific disease phenotype. (PMID:17947292)
• Homozygous Cln3(delta ex7/8) transgenic mice represent the most appropriate disease model for studying the development of the pathogenetic events of juvenile neuronal ceroidlipofuscinoses. (PMID:18265413)
• CLN3p impacts galactosylceramide transport, raft morphology, and lipid content. (PMID:18317235)
• Lysosome-related genes, such as CLN2, CLN3, and HEXB, may be involved in the pathogenesis of adipose tissue hypertrophy in TED. (PMID:18552385)
• a substantial decrease in the transcript level of the truncated CLN3 gene product in cells from 1 kb deletion patients (PMID:18678598)
• CLN3 is essential for trafficking along the route needed for delivery of lysosomal enzymes, and its loss thereby contributes to and may explain the lysosomal dysfunction underlying Batten disease (PMID:18817525)
• CLN3 interacts with Notch and Jun N-terminal kinase signalling pathways. (PMID:19028667)
• S. pombe btn1, the orthologue of the Batten disease gene CLN3, is required for vacuole protein sorting of Cpy1p and Golgi exit of Vps10p. (PMID:19299465)
• A new c.597C>A transversion in exon 8 of CLN3 gene, homozygous in all affected family members and not present in 200 alleles of normal controls, is reported. (PMID:19489875)
• Previous reports of genotype and clinical juvenile neuronal ceroid lipofuscinosis phenotype differences were unsupported in this investigation, which did not find differences between individuals homozygous or heterozygous for the CLN3 deletion. (PMID:20187884)
• The predominant distribution of CLN3 reporter neurons in visual, limbic and subcortical motor structures of transgenic mice correlates well with the clinical symptoms of juvenile neuronal ceroid lipofuscinosis. (PMID:20875858)
• Data suggest that dysfunction of CLN3P may be causative to dysruption of calcium mediated pathways. (PMID:20933060)
• CLN6 and CLN3 mutations trigger distinct processes that converge on a shared pathway, which is responsible for proper subunit c protein turnover and neuronal cell survival. (PMID:21359198)
• Btn1 controls retrograde sorting by regulating SNARE phosphorylation and assembly, a process that may be adversely affected in Batten Disease patients. (PMID:21987636)
• The data presented in this study provide novel insights into the role of CLN3 in late endosomal/lysosomal membrane transport. (PMID:22261744)
• Protein interaction mapping analysis suggests CLN3 is involved in transmembrane transport, lipid homeostasis, neuronal excitability and link it to G-protein signaling and protein folding/sorting in the endoplasmic reticulum. (PMID:23464991)
• CLN3 is involved in the response and adaptation to cellular stress. (PMID:23840424)
• CLN3 was identified as a novel disease gene for non-syndromic retinal diseases as supported by five unrelated patient families in this study. (PMID:24154662)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	cln3	ENSDARG00000037865
mus_musculus	Cln3	ENSMUSG00000030720
rattus_norvegicus	Cln3	ENSRNOG00000019103
drosophila_melanogaster	Cln3	FBGN0036756
caenorhabditis_elegans		WBGENE00000539
caenorhabditis_elegans	cln-3.2	WBGENE00000540
caenorhabditis_elegans		WBGENE00000541

Protein

Protein identifiers

Battenin — Q13286 (reviewed: Q13286)

Alternative names: Batten disease protein, Protein CLN3

All UniProt accessions (23): A0A0D9SF04, A0A1B0GUB1, A0A1B0GUU4, A0A1B0GV41, A0A1B0GV71, A0A1B0GW34, Q13286, A0A1B0GWH8, B4DFF3, F6TI76, H3BMN4, H3BNK7, H3BPL0, H3BQ48, H3BR00, H3BR84, H3BRU8, H3BUF8, O95086, O95090, Q9UBD8, Q9UBH5, Q9UP10

UniProt curated annotations — full annotation on UniProt →

Function. Mediates microtubule-dependent, anterograde transport connecting the Golgi network, endosomes, autophagosomes, lysosomes and plasma membrane, and participates in several cellular processes such as regulation of lysosomal pH, lysosome protein degradation, receptor-mediated endocytosis, autophagy, transport of proteins and lipids from the TGN, apoptosis and synaptic transmission. Facilitates the proteins transport from trans-Golgi network (TGN)-to other membrane compartments such as transport of microdomain-associated proteins to the plasma membrane, IGF2R transport to the lysosome where it regulates the CTSD release leading to regulation of CTSD maturation and thereby APP intracellular processing. Moreover regulates CTSD activity in response to osmotic stress. Also binds galactosylceramide and transports it from the trans Golgi to the rafts, which may have immediate and downstream effects on cell survival by modulating ceramide synthesis. At the plasma membrane, regulates actin-dependent events including filopodia formation, cell migration, and pinocytosis through ARF1-CDC42 pathway and also the cytoskeleton organization through interaction with MYH10 and fodrin leading to the regulation of the plasma membrane association of Na+, K+ ATPase complex. Regulates synaptic transmission in the amygdala, hippocampus, and cerebellum through regulation of synaptic vesicles density and their proximity to active zones leading to modulation of short-term plasticity and age-dependent anxious behavior, learning and memory. Regulates autophagic vacuoles (AVs) maturation by modulating the trafficking between endocytic and autophagolysosomal/lysosomal compartments, which involves vesicle fusion leading to regulation of degradation process. Also participates in cellular homeostasis of compounds such as, water, ions, amino acids, proteins and lipids in several tissue namely in brain and kidney through regulation of their transport and synthesis.

Subunit / interactions. Homooligomer. Interacts with DCTN1, KIF3A, RAB7A and RILP. Interacts with CLN5. May interact with HOOK1. Interacts with KCNIP3; this interaction is disrupted by intracellular increase of calcium level. Interacts with TPP1, CLN6 and CLN8. Interacts with MYH10; this interaction may play a role in regulation of cytoskeleton organization. Interacts with SBDS. Interacts with sodium/potassium-transporting ATPase complex (via ATP1A1) and fodrin heteromer (via SPTAN1); this interaction regulates their localization at the plasma membrane. Interacts with HSPA5. Interacts (via dileucine motif) with AP3D1 and AP1G1; this interaction facilitates lysosomal targeting. Interacts (via dileucine motif) with AP2A2.

Subcellular location. Lysosome membrane. Late endosome. Lysosome. Golgi apparatus. Golgi apparatus membrane. Golgi stack. trans-Golgi network. Cell membrane. Recycling endosome. Membrane raft. Membrane. Caveola. Early endosome membrane. Synapse. Synaptosome. Late endosome membrane. Cytoplasmic vesicle. Autophagosome.

Tissue specificity. Expressed in the cortical brain, pancreas, spleen, and testis with weaker expression in the peripheral nerve (at protein level). Highly expressed in gray matter (at protein level).

Post-translational modifications. Highly glycosylated. Farnesylation is important for trafficking to lysosomes. Phosphorylated on both serine and threonine residues by PKA, PKG and CK2.

Disease relevance. Ceroid lipofuscinosis, neuronal, 3 (CLN3) [MIM:204200] A form of neuronal ceroid lipofuscinosis. Neuronal ceroid lipofuscinoses are progressive neurodegenerative, lysosomal storage diseases characterized by intracellular accumulation of autofluorescent liposomal material, and clinically by seizures, dementia, visual loss, and/or cerebral atrophy. The hallmark of CLN3 is the ultrastructural pattern of lipopigment with a fingerprint profile, which can have 3 different appearances: pure within a lysosomal residual body; in conjunction with curvilinear or rectilinear profiles; and as a small component within large membrane-bound lysosomal vacuoles. The combination of fingerprint profiles within lysosomal vacuoles is a regular feature of blood lymphocytes from patients with neuronal ceroid lipofuscinosis type 3. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The C-terminal (153-438) mediates KCNIP3 interaction and the cytoprotective activity. the dileucine motif mediates AP1G1 and AP3D1 interaction.

Induction. Increased by osmotic stress.

Miscellaneous. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Similarity. Belongs to the battenin family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q13286-1	1	yes
Q13286-2	2
Q13286-3	3
Q13286-4	4
Q13286-5	5
Q13286-6	6
Q13286-7	7

RefSeq proteins (6): NP_000077, NP_001035897, NP_001273033, NP_001273034, NP_001273038, NP_001273039 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003492	Battenin_disease_Cln3	Family
IPR018460	Battenin_disease_Cln3_subgr	Family
IPR036259	MFS_trans_sf	Homologous_superfamily

Pfam: PF02487

UniProt features (54 total): sequence variant 10, splice variant 8, mutagenesis site 8, topological domain 7, transmembrane region 6, short sequence motif 3, modified residue 3, glycosylation site 3, region of interest 2, chain 1, propeptide 1, lipid moiety-binding region 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13286-F1	81.81	0.55

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (4): 12, 14, 435, 435

Glycosylation sites (3): 71, 85, 310

Mutagenesis-validated functional residues (8):

Position	Phenotype
242–244	loss of lysosomal targeting; when associated with a-409 and a-419. loss of lysosomal localization; when associated with
246	loss of lysosomal localization; when associated with 242-a–a-244.
253–254	does not affect lysosomal localization in ap3d1 or ap2a2 or ap1g1 deficient cells. abolishes the interaction of ap3d1, a
253	loss of lysosomal targeting; when associated with a-254. does not affect interaction with cln5; when associated with a-2
254	loss of lysosomal targeting. does not affect interaction with cln5; when associated with a-253. does not affect interact
310	does not affect glycosylation.
409	does not affect lysosomal targeting; when associated with a-419. loss of lysosomal targeting; when associated with a-253
419	does not affect lysosomal targeting; when associated with a-409. loss of lysosomal targeting; when associated with a-253

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9845576	Glycosphingolipid transport

MSigDB gene sets: 519 (showing top): GOBP_EXCRETION, GOBP_NEGATIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_AUTOPHAGY, GOBP_PHOSPHOLIPID_METABOLIC_PROCESS, GOBP_GLUTAMINE_FAMILY_AMINO_ACID_BIOSYNTHETIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_PROTEOLYSIS, GOBP_PINOCYTOSIS, GOBP_COGNITION, GOBP_POSITIVE_REGULATION_OF_ENDOCYTOSIS, GOBP_LYSOSOMAL_TRANSPORT, GOBP_BEHAVIOR, GOBP_VACUOLE_ORGANIZATION, MORF_RAB5A, GOBP_VESICLE_LOCALIZATION, GOCC_VACUOLAR_MEMBRANE

GO Biological Process (59): action potential (GO:0001508), receptor-mediated endocytosis (GO:0006898), lysosome organization (GO:0007040), lysosomal lumen acidification (GO:0007042), learning or memory (GO:0007611), associative learning (GO:0008306), intracellular water homeostasis (GO:0009992), regulation of fibroblast migration (GO:0010762), regulation of autophagosome size (GO:0016243), protein processing (GO:0016485), actin cytoskeleton organization (GO:0030036), regulation of synaptic transmission, GABAergic (GO:0032228), ionotropic glutamate receptor signaling pathway (GO:0035235), ceramide transport (GO:0035627), lysosomal lumen pH elevation (GO:0035752), renal potassium excretion (GO:0036359), amyloid precursor protein catabolic process (GO:0042987), positive regulation of Golgi to plasma membrane protein transport (GO:0042998), negative regulation of apoptotic process (GO:0043066), negative regulation of neuron apoptotic process (GO:0043524), blood vessel endothelial cell migration (GO:0043534), plasma membrane raft organization (GO:0044857), negative regulation of proteolysis (GO:0045861), glycerophospholipid biosynthetic process (GO:0046474), glycolipid transport (GO:0046836), vesicle transport along microtubule (GO:0047496), regulation of short-term neuronal synaptic plasticity (GO:0048172), positive regulation of pinocytosis (GO:0048549), neuromuscular process controlling balance (GO:0050885), regulation of cytosolic calcium ion concentration (GO:0051480), regulation of filopodium assembly (GO:0051489), regulation of cytoskeleton organization (GO:0051493), regulation of synaptic transmission, glutamatergic (GO:0051966), membrane organization (GO:0061024), autophagosome-lysosome fusion (GO:0061909), regulation of protein processing (GO:0070613), protein localization to plasma membrane (GO:0072659), Golgi to lysosome transport (GO:0090160), obsolete phagosome-lysosome docking (GO:0090384), phagosome-lysosome fusion (GO:0090385)

GO Molecular Function (5): glycolipid transfer activity (GO:0017089), calcium-dependent protein binding (GO:0048306), glycolipid binding (GO:0051861), sulfatide binding (GO:0120146), protein binding (GO:0005515)

GO Cellular Component (29): Golgi membrane (GO:0000139), nucleus (GO:0005634), cytoplasm (GO:0005737), lysosome (GO:0005764), lysosomal membrane (GO:0005765), early endosome (GO:0005769), late endosome (GO:0005770), autophagosome (GO:0005776), endoplasmic reticulum (GO:0005783), endoplasmic reticulum membrane (GO:0005789), Golgi apparatus (GO:0005794), Golgi stack (GO:0005795), trans-Golgi network (GO:0005802), cytosol (GO:0005829), plasma membrane (GO:0005886), caveola (GO:0005901), synaptic vesicle (GO:0008021), membrane (GO:0016020), early endosome membrane (GO:0031901), late endosome membrane (GO:0031902), neuron projection (GO:0043005), autolysosome (GO:0044754), membrane raft (GO:0045121), recycling endosome (GO:0055037), endosome (GO:0005768), vacuole (GO:0005773), endomembrane system (GO:0012505), cytoplasmic vesicle (GO:0031410), synapse (GO:0045202)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Transport of small molecules	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
cellular anatomical structure	3
cytoplasm	3
glycolipid binding	2
endosome	2
endomembrane system	2
Golgi apparatus subcompartment	2
endosome membrane	2
regulation of membrane potential	1
endocytosis	1
lytic vacuole organization	1
vacuolar acidification	1
behavior	1
cognition	1
learning	1
cell volume homeostasis	1
intracellular chemical homeostasis	1
fibroblast migration	1
regulation of cell migration	1
regulation of cellular component size	1
autophagosome organization	1
proteolysis	1
protein maturation	1
cytoskeleton organization	1
actin filament-based process	1
modulation of chemical synaptic transmission	1
synaptic transmission, GABAergic	1
glutamate-gated receptor activity	1
glutamate receptor signaling pathway	1
ligand-gated ion channel signaling pathway	1
lipid transport	1
nitrogen compound transport	1
intracellular pH elevation	1
renal tubular secretion	1
amyloid precursor protein metabolic process	1
regulation of Golgi to plasma membrane protein transport	1
Golgi to plasma membrane protein transport	1
positive regulation of protein transport	1
positive regulation of protein localization to plasma membrane	1
apoptotic process	1

Protein interactions and networks

STRING

1427 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLN3	CLN5	O75503	996
CLN3	PPT1	P50897	985
CLN3	CLN6	Q9NWW5	979
CLN3	CLN8	Q9UBY8	966
CLN3	MFSD8	Q8NHS3	951
CLN3	HOOK1	Q9UJC3	936
CLN3	DNAJC5	Q9H3Z4	911
CLN3	TPP1	O14773	909
CLN3	KCNIP3	Q9Y2W7	850
CLN3	CTSD	P07339	818
CLN3	PPT2	Q9UMR5	753
CLN3	KCTD7	Q96MP8	728
CLN3	ATG7	O95352	713
CLN3	SBDS	Q9Y3A5	679
CLN3	CTSF	Q9UBX1	673

IntAct

43 interactions, top by confidence:

A	B	Type	Score
IFT20	CLN3	psi-mi:“MI:0915”(physical association)	0.560
MAGEB6	CLN3	psi-mi:“MI:0915”(physical association)	0.560
CDHR3	CLN3	psi-mi:“MI:0915”(physical association)	0.560
SLC22A9	GPR89A	psi-mi:“MI:0914”(association)	0.530
SYP	APBB1	psi-mi:“MI:0914”(association)	0.530
FUCA2	HSPA5	psi-mi:“MI:0914”(association)	0.530
ARMC6	SLC27A2	psi-mi:“MI:0914”(association)	0.530
CLN5	CLN3	psi-mi:“MI:0915”(physical association)	0.520
ZYG11B	CLN3	psi-mi:“MI:0915”(physical association)	0.400
Prdm16	ESYT2	psi-mi:“MI:0914”(association)	0.350
Mecom	ESYT2	psi-mi:“MI:0914”(association)	0.350
CLN3	ESYT2	psi-mi:“MI:0914”(association)	0.350
Npc1	ESYT2	psi-mi:“MI:0914”(association)	0.350
MLNR	NBAS	psi-mi:“MI:0914”(association)	0.350
LRRC25	POTEF	psi-mi:“MI:0914”(association)	0.350
C5AR1	TCAF2	psi-mi:“MI:0914”(association)	0.350
OPRL1	METTL15	psi-mi:“MI:0914”(association)	0.350
GLMP	RTL8C	psi-mi:“MI:0914”(association)	0.350
GRPR	GPR89A	psi-mi:“MI:0914”(association)	0.350
GCGR	GPR89A	psi-mi:“MI:0914”(association)	0.350
TPRA1	BMPR1B	psi-mi:“MI:0914”(association)	0.350
TMPRSS11B	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Proximity Label-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS), CLN3 (Affinity Capture-MS)

ESM2 similar proteins: A0A3Q2HW92, A6NDV4, A6NFX1, A6QLK4, B1AWJ5, F1NCD6, F1NJ67, F1PZV2, O35308, O35595, O70461, O95907, Q08DX7, Q0IHM1, Q0P5C0, Q0P5M9, Q13286, Q14728, Q29611, Q2YDU8, Q3T9M1, Q3U481, Q501I9, Q5R8G5, Q5R9A1, Q5U419, Q60HH0, Q61124, Q66H95, Q6NUT3, Q6UXD7, Q6ZMD2, Q7RTT9, Q8BFQ6, Q8CE47, Q8NA29, Q8R0G7, Q8R139, Q8TB61, Q8VCW4

Diamond homologs: P0CM42, P0CM43, P47040, Q13286, Q29611, Q2GN49, Q4HX89, Q4P4U7, Q4X0S3, Q59LX9, Q60HH0, Q61124, Q6BZ39, Q6BZW3, Q6CLN9, Q6FPB6, Q758C3, Q7SC45, Q9US09

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CDK1	“down-regulates activity”	CLN3	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

1266 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	103
Likely pathogenic	106
Uncertain significance	365
Likely benign	530
Benign	31

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100719	NM_001042432.2(CLN3):c.371_372insT (p.Ser125fs)	Pathogenic
1067645	NM_001042432.2(CLN3):c.962+2T>G	Pathogenic
1070933	NM_001042432.2(CLN3):c.392del (p.Ser131fs)	Pathogenic
1072038	NM_001042432.2(CLN3):c.43G>T (p.Glu15Ter)	Pathogenic
1072910	NM_001042432.2(CLN3):c.592del (p.Ser198fs)	Pathogenic
1073957	NC_000016.9:g.(?_28484798)_28497560del	Pathogenic
1073958	NC_000016.9:g.(?28493426)(28493993_?)del	Pathogenic
1073959	NC_000016.9:g.(?28502803)(28503080_?)del	Pathogenic
1076288	NM_001042432.2(CLN3):c.1198-2A>C	Pathogenic
1120167	Single allele	Pathogenic
1387336	NM_001042432.2(CLN3):c.105del (p.His34_Trp35insTer)	Pathogenic
1402913	NM_001042432.2(CLN3):c.482C>T (p.Ser161Leu)	Pathogenic
1417871	NC_000016.9:g.(?28495307)(28495459_?)del	Pathogenic
1429184	NM_001042432.2(CLN3):c.985_988del (p.Gly329fs)	Pathogenic
1431853	NM_001042432.2(CLN3):c.709C>T (p.Gln237Ter)	Pathogenic
1451800	NM_001042432.2(CLN3):c.30del (p.Ser12fs)	Pathogenic
1452129	NM_001042432.2(CLN3):c.825G>A (p.Trp275Ter)	Pathogenic
1452713	NC_000016.9:g.(?28488837)(28495459_?)del	Pathogenic
1685639	NM_001042432.2(CLN3):c.382dup (p.Val128fs)	Pathogenic
1767342	NM_001042432.2(CLN3):c.954dup (p.Tyr319fs)	Pathogenic
183669	NM_001042432.2(CLN3):c.494G>A (p.Gly165Glu)	Pathogenic
2002289	NM_001042432.2(CLN3):c.317dup (p.Thr108fs)	Pathogenic
2008352	NM_001042432.2(CLN3):c.413del (p.Ser138fs)	Pathogenic
2081574	NM_001042432.2(CLN3):c.967C>T (p.Gln323Ter)	Pathogenic
2118627	NM_001042432.2(CLN3):c.828_829del (p.Phe278fs)	Pathogenic
2423566	NC_000016.9:g.(?28488827)(28489208_?)del	Pathogenic
2423568	NC_000016.9:g.(?28495317)(28500717_?)del	Pathogenic
2423571	NC_000016.9:g.(?28493416)(28494003_?)del	Pathogenic
2431547	NC_000016.10:g.(28485964_28486930)del	Pathogenic
2435726	NM_001042432.2(CLN3):c.354_355insG (p.Leu119fs)	Pathogenic

SpliceAI

2446 predictions. Top by Δscore:

Variant	Effect	Δscore
16:28477498:T:TA	donor_gain	1.0000
16:28477631:CTGGT:C	acceptor_gain	1.0000
16:28477636:C:CC	acceptor_gain	1.0000
16:28477732:CTGA:C	donor_loss	1.0000
16:28477733:TGAC:T	donor_loss	1.0000
16:28477733:TGACC:T	donor_loss	1.0000
16:28477734:GACC:G	donor_loss	1.0000
16:28477735:ACCT:A	donor_gain	1.0000
16:28477736:CCTC:C	donor_gain	1.0000
16:28477738:T:TA	donor_gain	1.0000
16:28477873:AGGCA:A	acceptor_gain	1.0000
16:28477874:GGCA:G	acceptor_gain	1.0000
16:28477875:GCA:G	acceptor_gain	1.0000
16:28477876:CA:C	acceptor_gain	1.0000
16:28477876:CAC:C	acceptor_gain	1.0000
16:28477878:C:CC	acceptor_gain	1.0000
16:28482383:C:CC	acceptor_gain	1.0000
16:28484116:TAG:T	acceptor_gain	1.0000
16:28484119:C:CC	acceptor_gain	1.0000
16:28486341:GCTCA:G	donor_loss	1.0000
16:28486342:CTCA:C	donor_loss	1.0000
16:28486343:TCACC:T	donor_loss	1.0000
16:28486344:CACCT:C	donor_loss	1.0000
16:28486345:ACCTG:A	donor_loss	1.0000
16:28486346:C:CT	donor_loss	1.0000
16:28486346:C:G	donor_loss	1.0000
16:28486573:CTTA:C	donor_loss	1.0000
16:28486574:TTA:T	donor_loss	1.0000
16:28486574:TTACC:T	donor_loss	1.0000
16:28486575:TA:T	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000408917 (16:28475162 AC>A), RS1000909741 (16:28476347 A>T), RS1000997750 (16:28486829 A>G), RS1001151881 (16:28488790 C>T), RS1001282630 (16:28487311 C>T), RS1001749269 (16:28481177 C>G), RS1001999703 (16:28489308 T>C,G), RS1002000641 (16:28477088 A>G,T), RS1002041670 (16:28482770 G>A,C), RS1002088630 (16:28472784 G>A,T), RS1002193211 (16:28486084 G>A), RS1002353803 (16:28479874 G>A), RS1002435103 (16:28476823 G>T), RS1002544742 (16:28473218 C>T), RS1003102333 (16:28479501 C>T)

Disease associations

OMIM: gene MIM:607042 | disease phenotypes: MIM:256730, MIM:204200, MIM:268000, MIM:611726, MIM:120970

GenCC curated gene-disease

Disease	Classification	Inheritance
neuronal ceroid lipofuscinosis 3	Definitive	Autosomal recessive
inherited retinal dystrophy	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
neuronal ceroid lipofuscinosis	Definitive	AR

Mondo (8): neuronal ceroid lipofuscinosis (MONDO:0016295), neuronal ceroid lipofuscinosis 3 (MONDO:0008767), juvenile neuronal ceroid lipofuscinosis (MONDO:0019262), retinitis pigmentosa (MONDO:0019200), inherited retinal dystrophy (MONDO:0019118), progressive myoclonic epilepsy type 3 (MONDO:0012721), cone-rod dystrophy (MONDO:0015993), intellectual disability (MONDO:0001071)

Orphanet (10): Neuronal ceroid lipofuscinosis (Orphanet:216), OBSOLETE: Infantile neuronal ceroid lipofuscinosis (Orphanet:79263), CLN3 disease (Orphanet:228346), OBSOLETE: Juvenile neuronal ceroid lipofuscinosis (Orphanet:79264), Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862), Progressive myoclonic epilepsy type 3 (Orphanet:263516), Cone rod dystrophy (Orphanet:1872), CLN14 disease (Orphanet:699708), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

32 total (30 of 32 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000501	Glaucoma
HP:0000510	Rod-cone dystrophy
HP:0000518	Cataract
HP:0000529	Progressive visual loss
HP:0000546	Retinal degeneration
HP:0000550	Undetectable electroretinogram
HP:0000608	Macular degeneration
HP:0000618	Blindness
HP:0000648	Optic atrophy
HP:0000709	Psychosis
HP:0000726	Dementia
HP:0000739	Anxiety
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001300	Parkinsonism
HP:0001317	Abnormal cerebellum morphology
HP:0001336	Myoclonus
HP:0001922	Vacuolated lymphocytes
HP:0002059	Cerebral atrophy
HP:0002069	Bilateral tonic-clonic seizure
HP:0002071	Abnormality of extrapyramidal motor function
HP:0002074	Increased neuronal autofluorescent lipopigment
HP:0002361	Psychomotor deterioration
HP:0002505	Loss of ambulation
HP:0003205	Curvilinear intracellular accumulation of autofluorescent lipopigment storage material
HP:0003208	Fingerprint intracellular accumulation of autofluorescent lipopigment storage material
HP:0003463	Increased extraneuronal autofluorescent lipopigment
HP:0003621	Juvenile onset

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST000531_2	Inflammatory bowel disease (early onset)	2.000000e-09
GCST004131_83	Inflammatory bowel disease	2.000000e-12
GCST004132_69	Crohn’s disease	3.000000e-10
GCST004616_67	Platelet distribution width	1.000000e-10
GCST005316_516	Intelligence (MTAG)	2.000000e-08
GCST006269_329	General cognitive ability	3.000000e-10
GCST007044_23	Extremely high intelligence	2.000000e-08
GCST007293_116	Body fat distribution (arm fat ratio)	2.000000e-08
GCST007293_16	Body fat distribution (arm fat ratio)	4.000000e-09
GCST007293_43	Body fat distribution (arm fat ratio)	2.000000e-12
GCST007294_71	Body fat distribution (trunk fat ratio)	2.000000e-12
GCST007294_97	Body fat distribution (trunk fat ratio)	1.000000e-11
GCST007295_20	Body fat distribution (leg fat ratio)	3.000000e-06
GCST007295_44	Body fat distribution (leg fat ratio)	1.000000e-21
GCST007295_79	Body fat distribution (leg fat ratio)	2.000000e-24
GCST009875_15	Type 1 diabetes	1.000000e-10
GCST010133_15	Lamb consumption	3.000000e-08
GCST010703_152	Brain morphology (MOSTest)	3.000000e-09
GCST011940_5	Bullous pemphigoid	2.000000e-09
GCST90002395_190	Mean platelet volume	1.000000e-73
GCST90002402_180	Platelet count	1.000000e-72

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0007984	platelet component distribution width
EFO:0004337	intelligence
EFO:0004341	body fat distribution
EFO:0008111	diet measurement
EFO:0004346	neuroimaging measurement
EFO:0004309	platelet count

MeSH disease descriptors (5)

Descriptor	Name	Tree numbers
D000071700	Cone-Rod Dystrophies	C11.270.152; C11.768.585.658.250; C16.320.290.152
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C567095	Epilepsy, Progressive Myoclonic 3 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

52 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, increases expression, increases methylation	3
Air Pollutants	affects cotreatment, increases abundance, increases expression, increases oxidation, affects expression	2
Ozone	affects expression, affects cotreatment, increases expression, increases oxidation, increases abundance	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Cyclosporine	decreases expression	2
p-Chloromercuribenzoic Acid	affects cotreatment, increases expression	2
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases expression, increases oxidation, increases abundance	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
pyrrolidine dithiocarbamic acid	affects cotreatment, decreases expression, decreases reaction	1
methacrylaldehyde	affects cotreatment, increases expression, increases oxidation, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
jinfukang	increases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
PP242	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
2,3,5-trichloro-6-phenyl-(1,4)benzoquinone	decreases expression	1
Sunitinib	decreases expression	1
Zoledronic Acid	increases expression	1
Arsenic Trioxide	decreases response to substance	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases expression, increases oxidation, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Atrazine	increases expression	1

Cellosaurus cell lines

28 cell lines: 17 induced pluripotent stem cell, 6 cancer cell line, 4 transformed cell line, 1 embryonic stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D4FV	HCT116-CLN3-KO-c10	Cancer cell line	Male
CVCL_D4FW	HCT116-CLN3-KO-c12	Cancer cell line	Male
CVCL_D5EL	HeLa::TMEM192-3xHA CLN3 KO	Cancer cell line	Female
CVCL_DA93	GM20381	Transformed cell line	Female
CVCL_DA94	GM20382	Transformed cell line	Female
CVCL_DA95	GM20383	Transformed cell line	Female
CVCL_DA96	GM20384	Transformed cell line	Male
CVCL_E0AC	Ubigene HeLa CLN3 KO	Cancer cell line	Female
CVCL_E3T1	CHDTRi001-B	Induced pluripotent stem cell	Male
CVCL_E3T2	CHDTRi002-B	Induced pluripotent stem cell	Female

Clinical trials (associated diseases)

290 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT04637282	PHASE3	NOT_YET_RECRUITING	Safety, Tolerability, and Efficacy of PLX-200 in Patients With CLN3
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT01399047	PHASE2	COMPLETED	Cellcept for Treatment of Juvenile Neuronal Ceroid Lipofuscinosis
NCT02678689	PHASE2	COMPLETED	A Safety, Tolerability, and Efficacy Study of BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)