CLN2
MCID: CRD183
MIFTS: 56

Ceroid Lipofuscinosis, Neuronal, 2 (CLN2)

Categories: Eye diseases, Genetic diseases, Mental diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Ceroid Lipofuscinosis, Neuronal, 2

MalaCards integrated aliases for Ceroid Lipofuscinosis, Neuronal, 2:

Name: Ceroid Lipofuscinosis, Neuronal, 2 57 72 13 70
Jansky-Bielschowsky Disease 57 73 20 43 72 36 6
Cln2 57 12 20 72
Neuronal Ceroid Lipofuscinosis 2 12 20 15
Lincl 43 72 54
Late-Infantile Neuronal Ceroid Lipofuscinosis 43 72
Ceroid Lipofuscinosis Neuronal 2 29 6
Cln2 Disease 43 58
Neuronal Ceroid Lipofuscinosis 2 with Variable Age at Onset 72
Ceroid Lipofuscinosis, Neuronal, 2, Variable Age at Onset 57
Neuronal Ceroid Lipofuscinosis 2 Variable Age at Onset 12
Classic Late Infantile Neuronal Ceroid Lipofuscinosis 58
Neuronal Ceroid Lipofuscinosis, Late-Infantile 43
Late-Infantile Neuronal Ceroid Lipfuscinosis 70
Lipofuscinosis, Ceroid, Neuronal, Type 2 39
Late-Infantile Batten Disease 43
Cln2 Disease, Late Infantile 20
Classic Late Infantile Ncl 58
Cln2 Disease, Juvenile 20

Characteristics:

Orphanet epidemiological data:

58
cln2 disease
Inheritance: Autosomal recessive; Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset at 2 to 4 years
death at 10 to 15 years


HPO:

31
ceroid lipofuscinosis, neuronal, 2:
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Inborn errors of metabolism


External Ids:

Disease Ontology 12 DOID:0110726
OMIM® 57 204500
OMIM Phenotypic Series 57 PS256730
KEGG 36 H02278
MeSH 44 D009472
ICD10 32 E75.4
ICD10 via Orphanet 33 E75.4
UMLS via Orphanet 71 C1876161
Orphanet 58 ORPHA228349
UMLS 70 C0022340 C1876161

Summaries for Ceroid Lipofuscinosis, Neuronal, 2

MedlinePlus Genetics : 43 CLN2 disease is an inherited disorder that primarily affects the nervous system. The signs and symptoms of this condition typically begin between ages 2 and 4. The initial features usually include recurrent seizures (epilepsy) and difficulty coordinating movements (ataxia). Affected children also develop muscle twitches (myoclonus) and vision loss. CLN2 disease affects motor skills, such as sitting and walking, and speech development. This condition also causes the loss of previously acquired skills (developmental regression), intellectual disability that gradually gets worse, and behavioral problems. Individuals with this condition often require the use of a wheelchair by late childhood and typically do not survive past their teens.Some children with CLN2 disease do not develop symptoms until later in childhood, typically after age 4. These individuals tend to have milder features overall compared to those diagnosed earlier, but with more severe ataxia. They have a shortened life expectancy, although they tend to survive into adulthood.CLN2 disease is one of a group of disorders known as neuronal ceroid lipofuscinoses (NCLs), which may also be collectively referred to as Batten disease. All these disorders affect the nervous system and typically cause worsening problems with vision, movement, and thinking ability. The different NCLs are distinguished by their genetic cause. Each disease type is given the designation "CLN," meaning ceroid lipofuscinosis, neuronal, and then a number to indicate its subtype.

MalaCards based summary : Ceroid Lipofuscinosis, Neuronal, 2, also known as jansky-bielschowsky disease, is related to ceroid lipofuscinosis, neuronal, 10 and ceroid lipofuscinosis, neuronal, 8, northern epilepsy variant, and has symptoms including seizures, ataxia and myoclonus. An important gene associated with Ceroid Lipofuscinosis, Neuronal, 2 is TPP1 (Tripeptidyl Peptidase 1), and among its related pathways/superpathways are Cell cycle Role of SCF complex in cell cycle regulation and Ubiquitin mediated proteolysis. Affiliated tissues include eye and brain, and related phenotypes are ataxia and developmental regression

Disease Ontology : 12 A neuronal ceroid lipofuscinosis that is characterized by 'curvilinear' profile lipopigment pattern and has material basis in homozygous or compound heterozygous mutation in the TPP1 gene on chromosome 11p15.

GARD : 20 Neuronal ceroid lipofuscinosis 2 (CLN2) is a type of neuronal ceroid lipofuscinosis (NCL), a group of severe diseases that affect the nervous system. Symptoms of the CLN2 generally develop between ages two and four years, although later onset cases have been reported. Children with CLN2 may experience speech delay, seizures that do not respond to medications, loss of muscle coordination ( ataxia ), muscle twitches (myoclonus), loss of vision, developmental delay, and intellectual disability. Symptoms of CLN2 worsen as the child gets older (progressive). CLN2 is caused by changes (pathogenic variations) in the TPP1 gene and is inherited in an autosomal recessive manner. Although there is no medication that can currently cure CLN2, in the Spring of 2017 both the United States Food and Drug Administration (FDA) and the European Commission approved the use of c erliponase alfa (brand name: Brineura ) for children with CLN2. In clinical studies, cerliponase alfa was shown to slow down the progression of the disease. In addition, other medications and therapies can help relieve some of the symptoms of CLN2. Please note : Batten disease originally referred specifically to the juvenile and most common form of NCL, now known as CLN3. However, the term Batten disease is increasingly used to describe all forms of NCL. All types of NCL also belong to a larger group of diseases known as lysosomal storage disorders.

OMIM® : 57 The neuronal ceroid lipofuscinoses (NCL; CLN) are a clinically and genetically heterogeneous group of neurodegenerative disorders characterized by the intracellular accumulation of autofluorescent lipopigment storage material in different patterns ultrastructurally. The clinical course includes progressive dementia, seizures, and progressive visual failure. The lipopigment pattern seen most often in CLN2 consists of 'curvilinear' profiles (Mole et al., 2005). For a general phenotypic description and a discussion of genetic heterogeneity of CLN, see CLN1 (256730). (204500) (Updated 05-Apr-2021)

KEGG : 36 Jansky-Bielschowsky disease, a classical late infantile neuronal ceroid lipofuscinosis (LINCL), is an autosomal recessive neurodegenerative disease with onset of symptoms between 2 and 4 years of age. Clinical symptoms include seizures, progressive encephalopathy, visual failure, and motor abnormalities. Mutations in the TPP1 gene, that encodes the lysosomal enzyme tripeptidyl-peptidase 1, cause this disease.

UniProtKB/Swiss-Prot : 72 Ceroid lipofuscinosis, neuronal, 2: 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 lipopigment pattern seen most often in CLN2 consists of curvilinear profiles.

Wikipedia : 73 Jansky-Bielschowsky disease is an extremely rare autosomal recessive genetic disorder that is part of... more...

Related Diseases for Ceroid Lipofuscinosis, Neuronal, 2

Diseases in the Neuronal Ceroid Lipofuscinosis family:

Ceroid Lipofuscinosis, Neuronal, 4b, Autosomal Dominant Ceroid Lipofuscinosis, Neuronal, 3
Ceroid Lipofuscinosis, Neuronal, 4a, Autosomal Recessive Ceroid Lipofuscinosis, Neuronal, 2
Ceroid Lipofuscinosis, Neuronal, 1 Ceroid Lipofuscinosis, Neuronal, 5
Ceroid Lipofuscinosis, Neuronal, 8 Ceroid Lipofuscinosis, Neuronal, 6
Ceroid Lipofuscinosis, Neuronal, 9 Ceroid Lipofuscinosis, Neuronal, 10
Ceroid Lipofuscinosis, Neuronal, 7 Ceroid Lipofuscinosis, Neuronal, 11
Ceroid Lipofuscinosis, Neuronal, 13 Adult Neuronal Ceroid Lipofuscinosis

Diseases related to Ceroid Lipofuscinosis, Neuronal, 2 via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 80)
# Related Disease Score Top Affiliating Genes
1 ceroid lipofuscinosis, neuronal, 10 31.3 TPP1 PPT1 MFSD8 CTSD CLN8 CLN6
2 ceroid lipofuscinosis, neuronal, 8, northern epilepsy variant 31.1 PPT1 MFSD8 CLN8 CLN6 CLN5 CLN3
3 ceroid lipofuscinosis, neuronal, 4a, autosomal recessive 31.1 TPP1 PPT1 CTSD CLN6 CLN3
4 ceroid lipofuscinosis, neuronal, 7 31.0 TPP1 PPT1 MFSD8 CTSD CLN8 CLN6
5 neuronal ceroid-lipofuscinoses 31.0 TPP1 PPT1 MFSD8 CTSD CLN8 CLN6
6 ceroid lipofuscinosis, neuronal, 6 30.9 TPP1 MFSD8 CLN8 CLN6 CLN5
7 progressive myoclonus epilepsy 30.7 TPP1 CLN6 CLN5 CLN3
8 ceroid lipofuscinosis, neuronal, 3 30.7 TPP1 PPT1 MFSD8 CTSD CLN8 CLN6
9 lysosomal storage disease 30.4 TPP1 PPT1 H2AC18 CTSD CLN6 CLN5
10 adult neuronal ceroid lipofuscinosis 30.1 TPP1 PPT1 CLN6
11 ceroid lipofuscinosis, neuronal, 1 29.9 TPP1 SWI5 SRF PPT1 MFSD8 H2AC18
12 spinocerebellar ataxia, autosomal recessive 7 29.6 TPP1 PPT1 MFSD8 CTSD CLN8 CLN6
13 neuronal ceroid lipofuscinosis 29.6 TPP1 SWI5 SRF PPT1 MFSD8 H2AC18
14 ceroid lipofuscinosis, neuronal, 8 10.7
15 myoclonus 10.6
16 encephalopathy 10.6
17 seizure disorder 10.5
18 3-methylglutaconic aciduria, type iii 10.4
19 ataxia and polyneuropathy, adult-onset 10.3
20 yemenite deaf-blind hypopigmentation syndrome 10.3
21 cone-rod dystrophy 2 10.3
22 stargardt disease 1 10.3
23 retinitis pigmentosa 10.3
24 rett syndrome 10.3
25 macular dystrophy with central cone involvement 10.3
26 chorea, childhood-onset, with psychomotor retardation 10.3
27 stargardt disease 10.3
28 leukodystrophy 10.3
29 choreatic disease 10.3
30 early myoclonic encephalopathy 10.3
31 retinal disease 10.3
32 fundus dystrophy 10.3
33 pathologic nystagmus 10.3
34 myoclonus epilepsy 10.3
35 precocious puberty 10.3
36 dysphagia 10.3
37 rare neurodegenerative disease 10.3
38 retinal degeneration 10.3
39 peripheral retinal degeneration 10.2 CLN5 CLN3
40 aspartylglucosaminuria 10.2 CLN6 CLN5 CLN3
41 tay-sachs disease 10.2 TPP1 CLN6 CLN3
42 macular degeneration, age-related, 1 10.2
43 mucolipidosis 10.2 CTSD CLN6 CLN3
44 western equine encephalitis 10.2 H2AC18 CDK1
45 ceroid lipofuscinosis, neuronal, 9 10.1 MFSD8 CLN8 CLN6 CLN5 CLN3
46 central core myopathy 10.1 PPT1 CLN8
47 progressive myoclonus epilepsy 3 10.1 TPP1 PPT1 MFSD8 CLN8 CLN6
48 mucopolysaccharidosis, type iiia 10.1 TPP1 PPT1 CLN6 CLN5 CLN3
49 unverricht-lundborg syndrome 10.1 PPT1 MFSD8 CLN6 CLN5 CLN3
50 visual epilepsy 10.1 PPT1 MFSD8 CLN8 CLN6 CLN5 CLN3

Graphical network of the top 20 diseases related to Ceroid Lipofuscinosis, Neuronal, 2:



Diseases related to Ceroid Lipofuscinosis, Neuronal, 2

Symptoms & Phenotypes for Ceroid Lipofuscinosis, Neuronal, 2

Human phenotypes related to Ceroid Lipofuscinosis, Neuronal, 2:

31 (show all 13)
# Description HPO Frequency HPO Source Accession
1 ataxia 31 HP:0001251
2 developmental regression 31 HP:0002376
3 delayed speech and language development 31 HP:0000750
4 progressive visual loss 31 HP:0000529
5 myoclonus 31 HP:0001336
6 cerebral atrophy 31 HP:0002059
7 retinal degeneration 31 HP:0000546
8 seizure 31 HP:0001250
9 increased neuronal autofluorescent lipopigment 31 HP:0002074
10 curvilinear intracellular accumulation of autofluorescent lipopigment storage material 31 HP:0003205
11 undetectable electroretinogram 31 HP:0000550
12 increased extraneuronal autofluorescent lipopigment 31 HP:0003463
13 abnormal nervous system electrophysiology 31 HP:0001311

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
ataxia
myoclonus
cerebral atrophy
autofluorescent lipopigment in neurons
more
Laboratory Abnormalities:
lipopigment in extraneuronal cells
'curvilinear profiles' ultrastructurally

Head And Neck Eyes:
retinal degeneration
vision loss, progressive
abolished electroretinogram (erg)

Clinical features from OMIM®:

204500 (Updated 05-Apr-2021)

UMLS symptoms related to Ceroid Lipofuscinosis, Neuronal, 2:


seizures; ataxia; myoclonus

GenomeRNAi Phenotypes related to Ceroid Lipofuscinosis, Neuronal, 2 according to GeneCards Suite gene sharing:

26
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Decreased Hepatitis C Virus pseudoparticles (HCVpp; H77; genotype 1a) infection GR00234-A-1 8.8 CDK1 CHKA CKS1B

MGI Mouse Phenotypes related to Ceroid Lipofuscinosis, Neuronal, 2:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 mortality/aging MP:0010768 9.83 CDC14A CDC20 CDC34 CDK1 CHKA CKS1B
2 liver/biliary system MP:0005370 9.7 CDK1 CHKA CLN3 FBXW7 FLI1 MFSD8
3 vision/eye MP:0005391 9.32 CDC14A CDK1 CLN3 CLN5 CLN6 CLN8

Drugs & Therapeutics for Ceroid Lipofuscinosis, Neuronal, 2

Interventional clinical trials:

(show all 17)
# Name Status NCT ID Phase Drugs
1 A Phase 1/2 Open-Label Dose-Escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Intracerebroventricular BMN 190 in Patients With Late-Infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Disease Completed NCT01907087 Phase 1, Phase 2
2 Direct CNS Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children With LINCL With Uncommon Genotypes and/or Moderate to Severe Impairment Completed NCT01414985 Phase 1, Phase 2
3 A Multicenter, Multinational, Extension Study to Evaluate the Long-Term Efficacy and Safety of BMN 190 in Patients With CLN2 Disease Completed NCT02485899 Phase 1, Phase 2
4 A Phase 2, Open-Label, Multicenter Study to Evaluate Safety, Tolerability, and Efficacy of Intracerebroventricular BMN 190 in Pediatric Patients < 18 Years of Age With CLN2 Disease Active, not recruiting NCT02678689 Phase 2
5 Phase I/IIa Gene Transfer Clinical Trial for Variant Late Infantile Neuronal Ceroid Lipofuscinosis, Delivering the CLN6 Gene by Self-Complementary AAV9 Active, not recruiting NCT02725580 Phase 1, Phase 2
6 Direct CNS Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Serotype rh.10 Expressing the Human CLN2 cDNA to Children With Late Infantile Neuronal Ceroid Lipofuscinosis (LINCL) Completed NCT01161576 Phase 1
7 Administration of a Replication Deficient Adeno-associated Virus Gene Transfer Vector Expressing the Human CLN2 cDNA to the Brain of Children With Late Infantile Neuronal Ceroid Lipofuscinosis Completed NCT00151216 Phase 1
8 A Phase Ib Study of the Safety and Preliminary Efficacy of Allogeneic Intracerebral Human Central Nervous System Stem Cell Transplantation in Subjects With Non-Refractory Infantile and Late Infantile Neuronal Ceroid Lipofuscinosis Withdrawn NCT01238315 Phase 1
9 A Multicenter, Multi-national Open-label Program to Provide BMN 190 to Patients Diagnosed With CLN2 Disease Approved for marketing NCT02963350 BMN190, recombinant human tripeptidyl peptidase-1 (rhTPP1)
10 Genotype - Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis Completed NCT00151268
11 Genotype-Phenotype Correlations of Late Infantile Neuronal Ceroid Lipofuscinosis Completed NCT01035424
12 A Natural History and Outcome Measure Discovery Study of Variant Late Infantile Neuronal Ceroid Lipofuscinosis Type 5 (CLN5) and Variant Late Infantile Neuronal Ceroid Lipofuscinosis Type 7 (CLN7) Recruiting NCT03822650
13 Cerliponase Alfa Observational Study Recruiting NCT04476862 Cerliponase Alfa
14 Examining Developmental Outcomes of Children Diagnosed With CLN2 Disease Recruiting NCT03862274
15 A Retrospective, Chart Review Study to Evaluate Ocular Disease Progression in Children With Late-infantile Neuronal Ceroid Lipofuscinosis Type 2 (CLN2) Not yet recruiting NCT04480476
16 A Prospective, Observational Study to Evaluate Ocular Disease Progression in Children With CLN2 Batten Disease Not yet recruiting NCT04462692
17 Collection of Cerebrospinal Fluid in Healthy Children Terminated NCT01698229

Search NIH Clinical Center for Ceroid Lipofuscinosis, Neuronal, 2

Genetic Tests for Ceroid Lipofuscinosis, Neuronal, 2

Genetic tests related to Ceroid Lipofuscinosis, Neuronal, 2:

# Genetic test Affiliating Genes
1 Ceroid Lipofuscinosis Neuronal 2 29 TPP1

Anatomical Context for Ceroid Lipofuscinosis, Neuronal, 2

MalaCards organs/tissues related to Ceroid Lipofuscinosis, Neuronal, 2:

40
Eye, Brain

Publications for Ceroid Lipofuscinosis, Neuronal, 2

Articles related to Ceroid Lipofuscinosis, Neuronal, 2:

(show top 50) (show all 152)
# Title Authors PMID Year
1
Prenatal testing for late infantile neuronal ceroid lipofuscinosis. 57 6 54
10665500 2000
2
Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis. 57 54 6
9788728 1998
3
The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland. 6 57
18684116 2008
4
CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype. 6 57
17959406 2008
5
Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations. 6 57
12376936 2002
6
Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder. 57 6
10330339 1999
7
Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis. 57 6
9295267 1997
8
Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner. 54 6
19246452 2009
9
Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. 54 6
19038966 2009
10
Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. 6 54
19038967 2009
11
Residual levels of tripeptidyl-peptidase I activity dramatically ameliorate disease in late-infantile neuronal ceroid lipofuscinosis. 57 54
18343701 2008
12
Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes. 54 6
15317752 2004
13
Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity. 54 6
14736728 2004
14
R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. 54 6
12950156 2003
15
The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. 54 6
11054422 2001
16
Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. 6 54
11339651 2000
17
A novel nonsense mutation (Q509X) in three Italian late-infantile neuronal ceroid-lipofuscinosis children. 6 54
10862088 2000
18
Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene. 6 54
10356316 1999
19
Chromosomal localization of two genes underlying late-infantile neuronal ceroid lipofuscinosis. 57 54
10737126 1998
20
Loci for classical and a variant late infantile neuronal ceroid lipofuscinosis map to chromosomes 11p15 and 15q21-23. 57 54
9097964 1997
21
Genetic heterogeneity in neuronal ceroid lipofuscinosis (NCL): evidence that the late-infantile subtype (Jansky-Bielschowsky disease; CLN2) is not an allelic form of the juvenile or infantile subtypes. 57 61
8213822 1993
22
Mutation update: Review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease. 6
31283065 2019
23
Homozygous missense TPP1 mutation associated with mild late infantile neuronal ceroid lipofuscinosis and the genotype-phenotype correlation. 6
31059981 2019
24
Study of Intraventricular Cerliponase Alfa for CLN2 Disease. 57
29688815 2018
25
Genomic diagnosis for children with intellectual disability and/or developmental delay. 6
28554332 2017
26
A tailored mouse model of CLN2 disease: A nonsense mutant for testing personalized therapies. 6
28464005 2017
27
Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy. 6
26795593 2016
28
Clinical application of whole-exome sequencing across clinical indications. 6
26633542 2016
29
A novel CLN2/TPP1 mutation in a patient with late infantile neuronal ceroid lipofuscinosis. 6
26032578 2015
30
TPP1 deficiency: Rare cause of isolated childhood-onset progressive ataxia. 6
26224725 2015
31
Multifocal retinopathy in Dachshunds with CLN2 neuronal ceroid lipofuscinosis. 57
25697710 2015
32
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
33
The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis. 6
23539563 2013
34
Autosomal recessive spinocerebellar ataxia 7 (SCAR7) is caused by variants in TPP1, the gene involved in classic late-infantile neuronal ceroid lipofuscinosis 2 disease (CLN2 disease). 6
23418007 2013
35
Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America. 6
23266810 2013
36
Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. 6
23374165 2013
37
Clinical study in Chinese patients with late-infantile form neuronal ceroid lipofuscinoses. 6
22245569 2012
38
Targeted next generation sequencing as a diagnostic tool in epileptic disorders. 6
22612257 2012
39
Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis. 6
22221116 2012
40
Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. 6
21990111 2012
41
A novel CLN2/TPP1 mutation in a Chinese patient with late infantile neuronal ceroid lipofuscinosis. 6
20820830 2011
42
Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I. 6
20340139 2010
43
An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients. 6
19793312 2009
44
Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme. 6
18411270 2008
45
Neurological deterioration in late infantile neuronal ceroid lipofuscinosis. 6
17679671 2007
46
Correlations between genotype, ultrastructural morphology and clinical phenotype in the neuronal ceroid lipofuscinoses. 57
15965709 2005
47
A new locus for a childhood onset, slowly progressive autosomal recessive spinocerebellar ataxia maps to chromosome 11p15. 6
15520412 2004
48
A mouse model of classical late-infantile neuronal ceroid lipofuscinosis based on targeted disruption of the CLN2 gene results in a loss of tripeptidyl-peptidase I activity and progressive neurodegeneration. 57
15483130 2004
49
Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles. 6
12414822 2002
50
Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2). 6
12125808 2002

Variations for Ceroid Lipofuscinosis, Neuronal, 2

ClinVar genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 2:

6 (show top 50) (show all 244)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 TPP1 NM_000391.4(TPP1):c.616C>T (p.Arg206Cys) SNV Pathogenic 2646 rs28940573 GRCh37: 11:6638277-6638277
GRCh38: 11:6617046-6617046
2 TPP1 NM_000391.4(TPP1):c.640C>T (p.Gln214Ter) SNV Pathogenic 371293 rs752164603 GRCh37: 11:6638253-6638253
GRCh38: 11:6617022-6617022
3 MFSD8 NM_001371596.2(MFSD8):c.103C>T (p.Arg35Ter) SNV Pathogenic 846459 GRCh37: 4:128878707-128878707
GRCh38: 4:127957552-127957552
4 TPP1 NM_000391.4(TPP1):c.1098G>A (p.Trp366Ter) SNV Pathogenic 561135 rs1564854729 GRCh37: 11:6637283-6637283
GRCh38: 11:6616052-6616052
5 TPP1 NM_000391.4(TPP1):c.688-1G>T SNV Pathogenic 996031 GRCh37: 11:6638091-6638091
GRCh38: 11:6616860-6616860
6 TPP1 NM_000391.4(TPP1):c.229G>A (p.Gly77Arg) SNV Pathogenic 68744 rs121908195 GRCh37: 11:6640007-6640007
GRCh38: 11:6618776-6618776
7 TPP1 NM_000391.4(TPP1):c.1093T>C (p.Cys365Arg) SNV Pathogenic 2641 rs119455953 GRCh37: 11:6637288-6637288
GRCh38: 11:6616057-6616057
8 TPP1 NM_000391.4(TPP1):c.1340G>A (p.Arg447His) SNV Pathogenic 2645 rs119455956 GRCh37: 11:6636487-6636487
GRCh38: 11:6615256-6615256
9 TPP1 NM_000391.4(TPP1):c.851G>T (p.Gly284Val) SNV Pathogenic 2647 rs119455957 GRCh37: 11:6637927-6637927
GRCh38: 11:6616696-6616696
10 TPP1 NM_000391.4(TPP1):c.887-10A>G SNV Pathogenic 2649 rs755445790 GRCh37: 11:6637744-6637744
GRCh38: 11:6616513-6616513
11 TPP1 NM_000391.4(TPP1):c.1266G>C (p.Gln422His) SNV Pathogenic 68738 rs121908200 GRCh37: 11:6636673-6636673
GRCh38: 11:6615442-6615442
12 TPP1 NM_000391.4(TPP1):c.509-1G>A SNV Pathogenic 207574 rs56144125 GRCh37: 11:6638385-6638385
GRCh38: 11:6617154-6617154
13 TPP1 NM_000391.4(TPP1):c.380+5G>A SNV Pathogenic 599035 rs1564855725 GRCh37: 11:6638852-6638852
GRCh38: 11:6617621-6617621
14 TPP1 NM_000391.4(TPP1):c.851G>T (p.Gly284Val) SNV Pathogenic 2647 rs119455957 GRCh37: 11:6637927-6637927
GRCh38: 11:6616696-6616696
15 TPP1 NM_000391.4(TPP1):c.311T>A (p.Leu104Ter) SNV Pathogenic 207561 rs202189057 GRCh37: 11:6638926-6638926
GRCh38: 11:6617695-6617695
16 TPP1 NM_000391.4(TPP1):c.622C>T (p.Arg208Ter) SNV Pathogenic 2643 rs119455955 GRCh37: 11:6638271-6638271
GRCh38: 11:6617040-6617040
17 TPP1 NM_000391.4(TPP1):c.509-1G>C SNV Pathogenic 2644 rs56144125 GRCh37: 11:6638385-6638385
GRCh38: 11:6617154-6617154
18 MFSD8 NM_001371596.2(MFSD8):c.863+1G>A SNV Pathogenic 504888 rs200319160 GRCh37: 4:128854139-128854139
GRCh38: 4:127932984-127932984
19 TPP1 NM_000391.4(TPP1):c.827A>T (p.Asp276Val) SNV Pathogenic 207581 rs763162812 GRCh37: 11:6637951-6637951
GRCh38: 11:6616720-6616720
20 TPP1 NM_000391.4(TPP1):c.622C>T (p.Arg208Ter) SNV Pathogenic 2643 rs119455955 GRCh37: 11:6638271-6638271
GRCh38: 11:6617040-6617040
21 TPP1 NM_000391.4(TPP1):c.509-1G>C SNV Pathogenic 2644 rs56144125 GRCh37: 11:6638385-6638385
GRCh38: 11:6617154-6617154
22 TPP1 NM_000391.4(TPP1):c.379C>T (p.Arg127Ter) SNV Pathogenic 207569 rs756564767 GRCh37: 11:6638858-6638858
GRCh38: 11:6617627-6617627
23 TPP1 NM_000391.4(TPP1):c.379C>T (p.Arg127Ter) SNV Pathogenic 207569 rs756564767 GRCh37: 11:6638858-6638858
GRCh38: 11:6617627-6617627
24 MFSD8 NM_152778.3(MFSD8):c.754+2T>A SNV Pathogenic 65897 rs587778809 GRCh37: 4:128859936-128859936
GRCh38: 4:127938781-127938781
25 MFSD8 NM_152778.3(MFSD8):c.1141G>T (p.Glu381Ter) SNV Pathogenic 162379 rs724159970 GRCh37: 4:128842888-128842888
GRCh38: 4:127921733-127921733
26 TPP1 NM_000391.4(TPP1):c.1015C>T (p.Arg339Trp) SNV Pathogenic 207586 rs750428882 GRCh37: 11:6637606-6637606
GRCh38: 11:6616375-6616375
27 TPP1 NM_000391.4(TPP1):c.1551+1G>A SNV Pathogenic/Likely pathogenic 188909 rs786204553 GRCh37: 11:6636096-6636096
GRCh38: 11:6614865-6614865
28 TPP1 NM_000391.4(TPP1):c.1094G>A (p.Cys365Tyr) SNV Pathogenic/Likely pathogenic 2642 rs119455954 GRCh37: 11:6637287-6637287
GRCh38: 11:6616056-6616056
29 TPP1 NM_000391.4(TPP1):c.972_979del (p.Ser324fs) Deletion Pathogenic/Likely pathogenic 188850 rs778232650 GRCh37: 11:6637642-6637649
GRCh38: 11:6616411-6616418
30 TPP1 NM_000391.4(TPP1):c.833A>G (p.Gln278Arg) SNV Pathogenic/Likely pathogenic 207582 rs796053439 GRCh37: 11:6637945-6637945
GRCh38: 11:6616714-6616714
31 TPP1 NM_000391.4(TPP1):c.1525C>T (p.Gln509Ter) SNV Pathogenic/Likely pathogenic 551316 rs1184563885 GRCh37: 11:6636123-6636123
GRCh38: 11:6614892-6614892
32 TPP1 NM_000391.4(TPP1):c.1076-2A>G SNV Likely pathogenic 552401 rs1424116749 GRCh37: 11:6637307-6637307
GRCh38: 11:6616076-6616076
33 TPP1 NM_000391.4(TPP1):c.605C>T (p.Pro202Leu) SNV Likely pathogenic 68747 rs121908205 GRCh37: 11:6638288-6638288
GRCh38: 11:6617057-6617057
34 TPP1 NM_000391.4(TPP1):c.1611_1621del (p.Cys537fs) Deletion Likely pathogenic 552881 rs1554901463 GRCh37: 11:6635848-6635858
GRCh38: 11:6614617-6614627
35 TPP1 NM_000391.4(TPP1):c.17+1G>A SNV Likely pathogenic 553258 rs779615685 GRCh37: 11:6640614-6640614
GRCh38: 11:6619383-6619383
36 TPP1 NM_000391.4(TPP1):c.357dup (p.Leu120fs) Duplication Likely pathogenic 554563 rs1554902085 GRCh37: 11:6638879-6638880
GRCh38: 11:6617648-6617649
37 TPP1 NM_000391.4(TPP1):c.1076-2A>T SNV Likely pathogenic 555109 rs1424116749 GRCh37: 11:6637307-6637307
GRCh38: 11:6616076-6616076
38 TPP1 NM_000391.4(TPP1):c.1449del (p.Ile484fs) Deletion Likely pathogenic 557022 rs1057516264 GRCh37: 11:6636199-6636199
GRCh38: 11:6614968-6614968
39 TPP1 NM_000391.4(TPP1):c.1392_1393del (p.Asn464fs) Deletion Likely pathogenic 557053 rs1407106889 GRCh37: 11:6636434-6636435
GRCh38: 11:6615203-6615204
40 TPP1 NM_000391.4(TPP1):c.1551+1G>T SNV Likely pathogenic 558183 rs786204553 GRCh37: 11:6636096-6636096
GRCh38: 11:6614865-6614865
41 TPP1 NM_000391.4(TPP1):c.689del (p.Phe230fs) Deletion Likely pathogenic 559477 rs1554901898 GRCh37: 11:6638089-6638089
GRCh38: 11:6616858-6616858
42 TPP1 NM_000391.4(TPP1):c.184del (p.Ser62fs) Deletion Likely pathogenic 559497 rs1554902217 GRCh37: 11:6640052-6640052
GRCh38: 11:6618821-6618821
43 TPP1 NM_000391.4(TPP1):c.533del (p.Pro178fs) Deletion Likely pathogenic 974574 GRCh37: 11:6638360-6638360
GRCh38: 11:6617129-6617129
44 TPP1 NM_000391.4(TPP1):c.1259C>A (p.Ser420Ter) SNV Likely pathogenic 370212 rs1057516319 GRCh37: 11:6636680-6636680
GRCh38: 11:6615449-6615449
45 TPP1 NM_000391.4(TPP1):c.687+2T>G SNV Likely pathogenic 371022 rs1057516945 GRCh37: 11:6638204-6638204
GRCh38: 11:6616973-6616973
46 TPP1 NM_000391.4(TPP1):c.1205A>G (p.Glu402Gly) SNV Likely pathogenic 523039 rs1471156821 GRCh37: 11:6636734-6636734
GRCh38: 11:6615503-6615503
47 TPP1 NM_000391.4(TPP1):c.422dup (p.Tyr141Ter) Duplication Likely pathogenic 550623 rs1554902043 GRCh37: 11:6638617-6638618
GRCh38: 11:6617386-6617387
48 TPP1 NM_000391.4(TPP1):c.1367_1368del (p.Leu455_Ser456insTer) Deletion Likely pathogenic 551005 rs1554901576 GRCh37: 11:6636459-6636460
GRCh38: 11:6615228-6615229
49 TPP1 NM_000391.4(TPP1):c.1552-1G>A SNV Likely pathogenic 370467 rs1057516511 GRCh37: 11:6635918-6635918
GRCh38: 11:6614687-6614687
50 TPP1 NM_000391.4(TPP1):c.609dup (p.Val204fs) Duplication Likely pathogenic 370272 rs1057516366 GRCh37: 11:6638283-6638284
GRCh38: 11:6617052-6617053

UniProtKB/Swiss-Prot genetic disease variations for Ceroid Lipofuscinosis, Neuronal, 2:

72 (show all 36)
# Symbol AA change Variation ID SNP ID
1 TPP1 p.Cys365Arg VAR_005643 rs119455953
2 TPP1 p.Cys365Tyr VAR_005644 rs119455954
3 TPP1 p.Arg447His VAR_005645 rs119455956
4 TPP1 p.Gly77Arg VAR_009603 rs121908195
5 TPP1 p.Arg206Cys VAR_009605 rs28940573
6 TPP1 p.Ile287Asn VAR_009606 rs121908196
7 TPP1 p.Glu343Lys VAR_009607 rs121908197
8 TPP1 p.Val385Asp VAR_009608 rs121908198
9 TPP1 p.Gly389Glu VAR_009609 rs121908199
10 TPP1 p.Gln422His VAR_009610 rs121908200
11 TPP1 p.Ala454Glu VAR_009611 rs121908201
12 TPP1 p.Ser475Leu VAR_009612 rs121908202
13 TPP1 p.Arg127Gln VAR_016790 rs121908204
14 TPP1 p.Ser153Pro VAR_016791 rs155490202
15 TPP1 p.Arg206His VAR_016792 rs121908209
16 TPP1 p.Val277Met VAR_016793 rs121908207
17 TPP1 p.Gln278Pro VAR_016794 rs796053439
18 TPP1 p.Gly284Val VAR_016795 rs119455957
19 TPP1 p.Asn286Ser VAR_016796 rs119455958
20 TPP1 p.Thr353Pro VAR_016797 rs121908206
21 TPP1 p.Lys428Asn VAR_016798
22 TPP1 p.Gly473Arg VAR_016799 rs121908203
23 TPP1 p.Phe481Cys VAR_016800
24 TPP1 p.Gly482Arg VAR_058435 rs121908208
25 TPP1 p.Pro202Leu VAR_063640 rs121908205
26 TPP1 p.Pro544Ser VAR_063641 rs121908210
27 TPP1 p.Ser62Thr VAR_066883
28 TPP1 p.Tyr209His VAR_066884 rs121867862
29 TPP1 p.Arg266Gln VAR_066885 rs757953998
30 TPP1 p.Arg339Gln VAR_066886 rs765380155
31 TPP1 p.Ser382Arg VAR_066887
32 TPP1 p.Ala448Val VAR_066888
33 TPP1 p.Gly501Cys VAR_066889
34 TPP1 p.Asn504Tyr VAR_066890
35 TPP1 p.Trp548Arg VAR_066891 rs134896726
36 TPP1 p.Gln278Arg VAR_072749 rs796053439

Expression for Ceroid Lipofuscinosis, Neuronal, 2

Search GEO for disease gene expression data for Ceroid Lipofuscinosis, Neuronal, 2.

Pathways for Ceroid Lipofuscinosis, Neuronal, 2

Pathways related to Ceroid Lipofuscinosis, Neuronal, 2 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.7 FBXW7 CKS1B CDK1 CDC34
2 11.58 FBXW7 CDC34 CDC20
3 11.21 TPP1 PPT1 MFSD8 CTSD CLN5 CLN3
4 10.99 CKS1B CDK1 CDC20 CDC14A

GO Terms for Ceroid Lipofuscinosis, Neuronal, 2

Cellular components related to Ceroid Lipofuscinosis, Neuronal, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lysosomal membrane GO:0005765 9.56 MFSD8 CTSD CLN5 CLN3
2 membrane raft GO:0045121 9.35 TPP1 PPT1 CTSD CLN6 CLN3
3 lysosomal lumen GO:0043202 9.33 TPP1 PPT1 CTSD
4 lysosome GO:0005764 9.1 TPP1 PPT1 MFSD8 CTSD CLN5 CLN3

Biological processes related to Ceroid Lipofuscinosis, Neuronal, 2 according to GeneCards Suite gene sharing:

(show all 16)
# Name GO ID Score Top Affiliating Genes
1 cell cycle GO:0007049 9.95 CKS1B CDK1 CDC34 CDC20 CDC14A
2 cell division GO:0051301 9.85 CKS1B CDK1 CDC34 CDC20 CDC14A
3 response to toxic substance GO:0009636 9.69 SRF CHKA CDK1
4 neuron development GO:0048666 9.65 SRF PPT1 MFSD8
5 associative learning GO:0008306 9.62 SRF PPT1 CLN8 CLN3
6 mitotic cell cycle phase transition GO:0044772 9.56 CKS1B CDK1
7 protein catabolic process GO:0030163 9.55 TPP1 PPT1 CLN8 CLN6 CLN5
8 cellular protein catabolic process GO:0044257 9.54 PPT1 CLN8
9 neuromuscular process controlling balance GO:0050885 9.54 TPP1 CLN8 CLN3
10 megakaryocyte development GO:0035855 9.52 SRF FLI1
11 glycerophospholipid biosynthetic process GO:0046474 9.49 FAR1 CLN3
12 lysosomal protein catabolic process GO:1905146 9.43 TPP1 CLN3
13 cellular macromolecule catabolic process GO:0044265 9.43 PPT1 CLN8 CLN6
14 positive regulation of pinocytosis GO:0048549 9.4 PPT1 CLN3
15 lysosomal lumen acidification GO:0007042 9.26 PPT1 CLN6 CLN5 CLN3
16 lysosome organization GO:0007040 9.17 TPP1 PPT1 MFSD8 CLN8 CLN6 CLN5

Molecular functions related to Ceroid Lipofuscinosis, Neuronal, 2 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 ubiquitin-protein transferase activator activity GO:0097027 9.16 FBXW7 CDC20
2 lysophosphatidic acid binding GO:0035727 9.13 TPP1 PPT1 CLN6
3 sulfatide binding GO:0120146 8.92 TPP1 PPT1 CLN6 CLN3

Sources for Ceroid Lipofuscinosis, Neuronal, 2

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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