Gene: TPP1

Alternate names for this Gene: CLN2|GIG1|LPIC|SCAR7|TPP-1

Gene Summary: This gene encodes a member of the sedolisin family of serine proteases. The protease functions in the lysosome to cleave N-terminal tripeptides from substrates, and has weaker endopeptidase activity. It is synthesized as a catalytically-inactive enzyme which is activated and auto-proteolyzed upon acidification. Mutations in this gene result in late-infantile neuronal ceroid lipofuscinosis, which is associated with the failure to degrade specific neuropeptides and a subunit of ATP synthase in the lysosome.

Gene is located in Chromosome: 11

Location in Chromosome : 11p15.4

Description of this Gene: tripeptidyl peptidase 1

Type of Gene: protein-coding

rs1184563885 in TPP1 gene and CEROID LIPOFUSCINOSIS, NEURONAL, 2 PMID 10862088 2000 A novel nonsense mutation (Q509X) in three Italian late-infantile neuronal ceroid-lipofuscinosis children.

PMID 19038967 2009 Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis.

PMID 10330339 1999 Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

PMID 9295267 1997 Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.

PMID 19038966 2009 Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis.

PMID 19246452 2009 Lysosomal serine protease CLN2 regulates tumor necrosis factor-alpha-mediated apoptosis in a Bid-dependent manner.

PMID 21990111 2012 Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

PMID 23539563 2013 The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis.

PMID 15317752 2004 Mutations in classical late infantile neuronal ceroid lipofuscinosis disrupt transport of tripeptidyl-peptidase I to lysosomes.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 12950156 2003 R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis.

PMID 28464005 2017 Collectively, these assessments indicate that the Cln2R207X/R207X mouse is a valid CLN2 disease model which can be used for the preclinical evaluation of all therapeutic approaches including mutation guided therapies.

PMID 9788728 1998 Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis.

PMID 20340139 2010 Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.

PMID 12414822 2002 Identification of novel CLN2 mutations shows Canadian specific NCL2 alleles.

PMID 18684116 2008 The clinical and genetic epidemiology of neuronal ceroid lipofuscinosis in Newfoundland.

PMID 11339651 2001 Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.

PMID 22221116 2012 Progressive conduction defects and cardiac death in late infantile neuronal ceroid lipofuscinosis.

PMID 14736728 2004 Mutation of the glycosylated asparagine residue 286 in human CLN2 protein results in loss of enzymatic activity.

PMID 12376936 2002 Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.

PMID 22612257 2012 Targeted next generation sequencing as a diagnostic tool in epileptic disorders.

PMID 11589012 2001 New mutations in the neuronal ceroid lipofuscinosis genes.

PMID 19201763 2009 Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis.

PMID 12698559 2003 [Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation].

PMID 11241479 2001 Two novel CLN2 gene mutations in a Chinese patient with classical late-infantile neuronal ceroid lipofuscinosis.

PMID 10665500 2000 Prenatal testing for late infantile neuronal ceroid lipofuscinosis.

PMID 26633542 2016 Clinical application of whole-exome sequencing across clinical indications.

PMID 23418007 2013 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).

PMID 18411270 2008 Prosegment of tripeptidyl peptidase I is a potent, slow-binding inhibitor of its cognate enzyme.

PMID 11589013 2001 Tripeptidyl-peptidase I in neuronal ceroid lipofuscinoses and other lysosomal storage disorders.

PMID 11054422 2001 The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH.

PMID 23266810 2013 Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America.

PMID 17679671 2007 Neurological deterioration in late infantile neuronal ceroid lipofuscinosis.

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 19793312 2009 Genotype analysis of the TPP1 gene in the 'classical' CLN2 patients showed the presence of the known mutation p.Arg208X and the novel mutations p.Leu104X, p.Asp276Val, and p.Ala453Val.

PMID 10356316 1999 Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene.

PMID 22245569 2012 Clinical study in Chinese patients with late-infantile form neuronal ceroid lipofuscinoses.

PMID 20820830 2011 A novel CLN2/TPP1 mutation in a Chinese patient with late infantile neuronal ceroid lipofuscinosis.

PMID 23374165 2013 Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy.

PMID 26032578 2015 A novel CLN2/TPP1 mutation in a patient with late infantile neuronal ceroid lipofuscinosis.

PMID 12125808 2002 Neuronal ceroid lipofuscinoses caused by defects in soluble lysosomal enzymes (CLN1 and CLN2).

PMID 28554332 2017 Genomic diagnosis for children with intellectual disability and/or developmental delay.

rs113019349 in TPP1 gene and Neuronal Ceroid-Lipofuscinoses PMID 10330339 1999 Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

PMID 9788728 1998 Two common mutations in the CLN2 gene underlie late infantile neuronal ceroid lipofuscinosis.

PMID 26075876 2015 Lysoplex: An efficient toolkit to detect DNA sequence variations in the autophagy-lysosomal pathway.

PMID 23539563 2013 The role of nonsense-mediated decay in neuronal ceroid lipofuscinosis.

PMID 18283468 2008 Atypical CLN2 with later onset and prolonged course: a neuropathologic study showing different sensitivity of neuronal subpopulations to TPP1 deficiency.

PMID 15317752 2004 We analyzed the functional consequences of the mutations R127Q, R208X, N286S, I287N, T353P and Q422H, which were previously identified in patients with late infantile ceroid lipofuscinosis, with regard to enzymatic activity, stability, post-translational processing and intracellular localization of tripeptidyl-peptidase I.

PMID 9295267 1997 Association of mutations in a lysosomal protein with classical late-infantile neuronal ceroid lipofuscinosis.

PMID 20340139 2010 Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.

PMID 21990111 2012 Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

PMID 23266810 2013 Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America.

PMID 12698559 2003 [Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation].

PMID 25525159 2015 RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.

PMID 11339651 2001 Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.

PMID 26795593 2016 Diagnostic exome sequencing provides a molecular diagnosis for a significant proportion of patients with epilepsy.

PMID 19793312 2009 An integrated strategy for the diagnosis of neuronal ceroid lipofuscinosis types 1 (CLN1) and 2 (CLN2) in eleven Latin American patients.

PMID 23418007 2013 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).

PMID 10356316 1999 Late infantile neuronal ceroid lipofuscinosis is due to splicing mutations in the CLN2 gene.

PMID 12376936 2002 Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.

PMID 22832778 2013 Late infantile neuronal ceroid lipofuscinosis: mutations in the CLN2 gene and clinical course in Spanish patients.

rs398122959 in TPP1 gene and SPINOCEREBELLAR ATAXIA, AUTOSOMAL RECESSIVE 7 PMID 23418007 2013 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).

rs750428882 in TPP1 gene and Seizures PMID 24091540 2013 Diagnostic utility of whole exome sequencing in patients showing cerebellar and/or vermis atrophy in childhood.

PMID 19038967 2009 Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis.

PMID 21990111 2012 Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

PMID 19038966 2009 Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis.