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TPP1 Gene

protein-coding GIFtS: 66
GCID: GC11M006634

Tripeptidyl Peptidase I

(Previous names: ceroid-lipofuscinosis, neuronal 2, late infantile (Jansky-Bielschowsky...)
(Previous symbols: CLN2, SCAR7)

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(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, ¹⁰fRNAdb, ¹²H-InvDB, ¹³NCBI, ¹⁴NONCODE, and/or ¹⁵RNAdb)
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Aliases
Tripeptidyl Peptidase I¹ ²		Spinocerebellar Ataxia, Autosomal Recessive 7¹
CLN2¹ ² ³ ⁵		TPP I¹
SCAR7¹ ² ⁵		Growth-Inhibiting Protein 1²
Cell Growth-Inhibiting Gene 1 Protein² ³		Lysosomal Pepstatin Insensitive Protease²
Tripeptidyl Aminopeptidase² ³		Tripeptidyl-Peptidase 1²
LPIC² ³		TPP-I³
TPP-1² ³		Lysosomal Pepstatin-Insensitive Protease³
EC 3.4.14.9³ ⁸		Tripeptidyl-Peptidase I³
Ceroid-Lipofuscinosis, Neuronal 2, Late Infantile (Jansky-Bielschowsky Disease)¹

External Ids:	HGNC: 2073¹	Entrez Gene: 1200²	Ensembl: ENSG00000166340⁷	OMIM: 607998⁵	UniProtKB: O14773³

Export aliases for TPP1 gene to outside databases

Previous GC identifers: GC11M006591 GC11M006292

(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for TPP1 Gene:

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. (provided by RefSeq, Jul 2008)

GeneCards Summary for TPP1 Gene:

TPP1 (tripeptidyl peptidase I) is a protein-coding gene. Diseases associated with TPP1 include childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia, and ceroid lipofuscinosis neuronal 2. GO annotations related to this gene include serine-type peptidase activity and serine-type endopeptidase activity.

UniProtKB/Swiss-Prot: TPP1_HUMAN, O14773

Function: Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal

peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires

substrates with an unsubstituted N-terminus (By similarity)

Gene Wiki entry for TPP1 (Tripeptidyl peptidase I) Gene

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence:

NC_000011.10 NC_018922.2 NT_009237.19

Regulatory elements:

Regulatory transcription factor binding sites in the TPP1 gene promoter:
CRE-BP1 HOXA5 ATF-2 ATF
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: TPP1 promoter sequence

Search Chromatin IP Primers for TPP1

Epigenetics:

DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat TPP1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 11p15 Ensembl cytogenetic band: 11p15.4 HGNC cytogenetic band: 11p15.4

TPP1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TPP1 gene location

GeneLoc information about chromosome 11 GeneLoc Exon Structure

GeneLoc location for GC11M006634: view genomic region (about GC identifiers)

Start:	6,633,997 bp from pter	End:	6,640,692 bp from pter
Size:	6,696 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, ²neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Cloud-Clone Corp.,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Cloud-Clone Corp., Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, and/or Cloud-Clone Corp.)
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UniProtKB/Swiss-Prot: TPP1_HUMAN, O14773 (See protein sequence)

Recommended Name: Tripeptidyl-peptidase 1 precursor

Size: 563 amino acids; 61248 Da

Cofactor: Binds 1 calcium ion per subunit

Subunit: Monomer

Sequence caution: Sequence=AAM08412.1; Type=Miscellaneous discrepancy; Note=Incorrectly indicated as originating

from bovine; Sequence=AAQ88866.1; Type=Frameshift; Positions=551;

3 PDB 3D structures from and Proteopedia for TPP1:

1R60 (3D)

3EDY (3D)

3EE6 (3D)

Secondary accessions: Q53HT1 Q5JAK6 Q6UX56 Q71JP6 Q96C37

Alternative splicing: 2 isoforms: O14773-1 O14773-2 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for TPP1: NX_O14773

Explore proteomics data for TPP1 at MOPED

Post-translational modifications:

Activated by autocatalytic proteolytical processing upon acidification. N-glycosylation is required for processing

and activity¹

Glycosylation² at Asn210, Asn222, Asn286, Asn313, Asn443

Modification sites at PhosphoSitePlus

Selected DME Specific Peptides for TPP1 (O14773) (see all 26)

GCHESCL

GLHRFPP

RQRPEPQ

YGKYLTLE

See TPP1 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

REFSEQ proteins: NP_000382.3

ENSEMBL proteins:

ENSP00000299427 ENSP00000437066 ENSP00000398136 ENSP00000434647 ENSP00000435001

Reactome Protein details: O14773

TPP1 Human Recombinant Protein Products:

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TPP1 Antibody Products:

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	LSBio Antibodies in human, mouse, rat for TPP1

TPP1 Assay Products:

	Browse Kits and Assays available from EMD Millipore
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	GenScript Custom Assay Services for TPP1
	Browse Enzo Life Sciences for kits & assays
	Cloud-Clone Corp. ELISAs for TPP1 Cloud-Clone Corp. CLIAs for TPP1

(According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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3 InterPro protein domains:

IPR000209 Peptidase_S8/S53_dom

IPR009020 Prot_inh_propept

IPR015366 Peptidase_S53_propep

Graphical View of Domain Structure for InterPro Entry O14773

ProtoNet protein and cluster: O14773

UniProtKB/Swiss-Prot: TPP1_HUMAN, O14773

Similarity: Contains 1 peptidase S53 domain

TPP1 for domains About GeneDecksing

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Molecular Function:

UniProtKB/Swiss-Prot Summary: TPP1_HUMAN, O14773

Function: Lysosomal serine protease with tripeptidyl-peptidase I activity. May act as a non-specific lysosomal

peptidase which generates tripeptides from the breakdown products produced by lysosomal proteinases. Requires

substrates with an unsubstituted N-terminus (By similarity)

Catalytic activity: Release of an N-terminal tripeptide from a polypeptide, but also has endopeptidase activity

Enzyme Number (IUBMB): EC 3.4.14.9¹ ²

Gene Ontology (GO): Selected molecular function terms (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004175	endopeptidase activity	IMP	10679303
GO:0004252	serine-type endopeptidase activity	IEA	--
GO:0005515	protein binding	IPI	12134079
GO:0008233	peptidase activity	IMP	9295267
GO:0008236	serine-type peptidase activity	IMP	11054422

TPP1 for ontologies About GeneDecksing

Phenotypes:
8 MGI mutant phenotypes (inferred from 4 alleles) (MGI details for Tpp1):

behavior/neurological	cellular	homeostasis/metabolism	integument	mortality/aging
muscle	nervous system	respiratory system

TPP1 for phenotypes About GeneDecksing

Animal Models:
MGI mouse knock-out Tpp1^tm1Plob for TPP1

inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for TPP1

inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for TPP1

genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for TPP1

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		Block miRNA regulation of human, mouse, rat TPP1 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate TPP1 (see all 36):
		hsa-miR-4291 hsa-miR-3938 hsa-let-7d hsa-miR-301a hsa-miR-3162-5p hsa-let-7g hsa-miR-1184 hsa-let-7a

		SwitchGear 3'UTR luciferase reporter plasmid: TPP1 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for TPP1
		Predesigned siRNA for gene silencing in human, mouse, rat TPP1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TPP1

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		GenScript: all cDNA clones in your preferred vector: TPP1 (NM_000391)
		Sino Biological Human cDNA Clone for TPP1
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TPP1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TPP1

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		Browse ESI BIO Cell Lines and PureStem Progenitors for TPP1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TPP1

(According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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Subcellular locations from UniProtKB/Swiss-Prot

TPP1_HUMAN, O14773: Lysosome. Melanosome. Note=Identified by mass spectrometry in melanosome fractions from

stage I to stage IV

Subcellular locations from COMPARTMENTS:

Compartment	Confidence
lysosome	5
vacuole	5
extracellular	2
mitochondrion	2
endoplasmic reticulum	1

About this image

Gene Ontology (GO): 5 cellular component terms: About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005739	mitochondrion	IEA	--
GO:0005764	lysosome	IMP	9295267
GO:0042470	melanosome	IEA	--
GO:0043202	lysosomal lumen	TAS	--
GO:0070062	extracellular vesicular exosome	IDA	19056867

TPP1 for ontologies About GeneDecksing

(SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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SuperPaths for TPP1 About

See pathways by source

SuperPath

Contained pathways About

Unfolded Protein Response

	Unfolded Protein Response	0.61			Activation of Chaperone Genes by XBP1(S)	0.59
	Activation of Chaperones by IRE1alpha	0.61

Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein

Metabolism of proteins

0.30

Lysosome

Lysosome

Pathways by source See SuperPaths
Show all pathways

1 Reactome Pathway for TPP1

XBP1(S) activates chaperone genes

1 Kegg Pathway (Kegg details for TPP1):

Lysosome

TPP1 for pathways About GeneDecksing

Pathway & Disease-focused RT² Profiler PCR Array including TPP1:

Telomeres & Telomerase in human mouse rat

Interactions:

GeneGlobe Interaction Network for TPP1

STRING Interaction Network Preview (showing 5 interactants - click image to see 11)

Selected Interacting proteins for TPP1 (O14773^{2, 3} ENSP00000299427⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 56)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
NMB	P08949³, ENSP00000378089⁴	I2D: score=2 STRING: ENSP00000378089
MYC	P01106³, ENSP00000367207⁴	I2D: score=1 STRING: ENSP00000367207
POT1	Q9NUX5³, ENSP00000350249⁴	I2D: score=1 STRING: ENSP00000350249
ATP6V1B2	P21281², ENSP00000276390⁴	MINT-4054731 STRING: ENSP00000276390
ATG10	Q9H0Y0³	I2D: score=1

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Gene Ontology (GO): Selected biological process terms (see all 13): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006508	proteolysis	IMP	10965052
GO:0006629	lipid metabolic process	TAS	9295267
GO:0006987	activation of signaling protein activity involved in unfolded protein response	TAS	--
GO:0007040	lysosome organization	ISS	--
GO:0007399	nervous system development	IMP	9295267

TPP1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse compounds at ApexBio

Browse Tocris compounds for TPP1

3 HMDB Compounds for TPP1 About this table

Compound	Synonyms	CAS #	PubMed Ids
Neuromedin B	Gly-Asn-Leu-Trp-Ala-Thr-Gly-His-Phe-Met-NH2	87096-84-2	--
Neuromedin B (1-3)	Gly-Asn-Leu	--	--
Neuromedin B (4-10)	Trp-Ala-Thr-Gly-His-Phe-Met-NH2	--	--

6 Novoseek inferred chemical compound relationships for TPP1 gene About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
tripeptide s	82.5	29	11589011 (1), 16869297 (1), 10470035 (1), 11445074 (1) (see all 16)
serine	31.6	17	11054422 (3), 12488460 (2), 12025857 (1), 16869297 (1) (see all 9)
mannose 6-phosphate	30.5	1	10428067 (1)
atp	10.2	7	10965052 (2), 11332778 (1), 11415435 (1), 10349869 (1)
oligonucleotide	6.89	4	17237767 (1), 17237768 (1), 20404094 (1)
aspartate	0	1	15733845 (1)

TPP1 for compounds About GeneDecksing

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
Conferences by KenesGroup, exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, and/or QIAGEN )
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REFSEQ mRNAs for TPP1 gene:

NM_000391.3

Unigene Cluster for TPP1:

Tripeptidyl peptidase I

Hs.523454 [show with all ESTs]

Unigene Representative Sequence: NM_000391

16 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000299427(uc001mel.1) ENST00000533371(uc001mek.1) ENST00000524611

ENST00000532191 ENST00000524924 ENST00000436873 ENST00000528807 ENST00000524788

ENST00000528571 ENST00000428886(uc010rar.1) ENST00000534644 ENST00000530040

ENST00000528917 ENST00000531754 ENST00000524903 ENST00000528657

miRNA Products:		Block miRNA regulation of human, mouse, rat TPP1 using miScript Target Protectors
		Selected qRT-PCR Assays for microRNAs that regulate TPP1 (see all 36):
		hsa-miR-4291 hsa-miR-3938 hsa-let-7d hsa-miR-301a hsa-miR-3162-5p hsa-let-7g hsa-miR-1184 hsa-let-7a

		SwitchGear 3'UTR luciferase reporter plasmid: TPP1 3' UTR sequence

Inhib. RNA Products:		OriGene RNAi products in human, mouse, rat for TPP1
		Predesigned siRNA for gene silencing in human, mouse, rat TPP1

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		GenScript: all cDNA clones in your preferred vector: TPP1 (NM_000391)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TPP1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TPP1

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		Pre-validated RT² qPCR Primer Assay in human, mouse, rat TPP1
		QuantiTect SYBR Green Assays in human, mouse, rat TPP1
		QuantiFast Probe-based Assays in human, mouse, rat TPP1

Additional mRNA sequence:

AF017456.1 AK222499.1 AK222538.1 AK293518.1 AK293741.1 AK295801.1 AK299703.1 AK300998.1

AK303323.1 AK312388.1 AY268890.1 AY358502.1 BC014863.1

Selected DOTS entries (see all 32):

DT.447122 DT.100701567 DT.97763427 DT.100836516 DT.97852548 DT.100788035 DT.100788046 DT.92455901

DT.97764994 DT.120724803 DT.91799575 DT.120724847 DT.92455900 DT.95244240 DT.120724830 DT.100788034

DT.120724870 DT.100788043 DT.120724857 DT.120724873 DT.87079500 DT.95244243 DT.95244254 DT.100788042

Selected AceView cDNA sequences (see all 676):

AA191412 BI764893 AW969542 BG163596 AB000895 BI757298 BQ003496 AL547629

BQ682389 BM971099 BU622851 AA861148 BQ267771 AW590772 AW235673 AL543280

AA287327 BF966046 AI678796 H99523 BM310213 NM_000391 T54160 AB053446

GeneLoc Exon Structure

Selected Alternative Splicing Database (ASD) splice patterns (SP) for TPP1 (see all 19) About this scheme

ExUns:	1a	·	1b	·	1c	^	2a	·	2b	·	2c	·	2d	^	3a	·	3b	·	3c	·	3d	^	4a	·	4b	·	4c	^	5a	·	5b	^	6a	·	6b	·	6c	·	6d	^	7a	·	7b	·	7c	·	7d	·	7e	·	7f	·
SP1:							-		-		-										-														-		-		-
SP2:																					-														-		-		-
SP3:							-		-		-										-				-		-		-		-		-		-		-		-		-		-		-		-		-		-
SP4:							-		-		-								-		-		-		-		-		-		-		-		-		-		-		-		-		-		-		-		-
SP5:							-		-		-										-												-		-		-		-

ExUns:	7g	·	7h	·	7i	^	8a	·	8b	^	9a	·	9b	^	10a	·	10b	^	11a	·	11b	^	12a	·	12b	^	13a	·	13b	^	14a	·	14b	·	14c
SP1:															-
SP2:															-
SP3:	-		-		-		-		-		-		-		-		-		-
SP4:	-		-		-		-		-		-		-		-		-		-
SP5:

ECgene alternative splicing isoforms for TPP1

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE ¹MOPED, ²PaxDb, and ³MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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TPP1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS <intensity>^2/3
CGAP TAG: GAATGCTGAC

About this image

TPP1 expression in embryonic tissues and stem cells About this table

Data from LifeMap, the Embryonic Development and Stem Cells Database
selected tissues (see all 17) fully expand


Brain (Nervous System) fully expand to see all 3 entries
Cerebral Cortex

Neural Tube (Nervous System) fully expand to see all 2 entries
Metencephalon

Liver (Hepatobiliary System)
Hepatocytes Liver Lobule

Trophoblast (Extraembryonic Tissues)
Trophoblast Cells Trophoblast

Testis (Reproductive System)
Leydig Cells Testis Interstitium

TPP1 Protein expression data from MOPED¹, PaxDb² and MaxQB³:

About this image

TPP1 Protein Expression

SOURCE GeneReport for Unigene cluster: Hs.523454

UniProtKB/Swiss-Prot: TPP1_HUMAN, O14773

Tissue specificity: Detected in all tissues examined with highest levels in heart and placenta and relatively

similar levels in other tissues

Pathway & Disease-focused RT² Profiler PCR Array including TPP1:

Telomeres & Telomerase in human mouse rat

Primer Products:		OriGene qSTAR qPCR primer pairs in human, mouse for TPP1
		Pre-validated RT² qPCR Primer Assay in human, mouse, rat TPP1
		QuantiTect SYBR Green Assays in human, mouse, rat TPP1
		QuantiFast Probe-based Assays in human, mouse, rat TPP1

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TPP1

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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This gene was present in the common ancestor of chordates.

Orthologs for TPP1 gene from Selected species (see all 14) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Tpp1^{1 , 5}	tripeptidyl peptidase I^{1, 5}	86.42(n)¹ 88.43(a)¹		7 (55.97 cM)⁵ 12751¹ NM_009906.5¹ NP_034036.1¹ 105744847⁵
chicken (Gallus gallus)	Aves	TPP1¹	tripeptidyl peptidase I	64.7(n) 63.18(a)		425576 XM_423326.4 XP_423326.3
lizard (Anolis carolinensis)	Reptilia	TPP1⁶	tripeptidyl peptidase I	52(a)	1 ↔ 1	GL344198.1(2428-26016)
African clawed frog (Xenopus laevis)	Amphibia	Xl.23928²	Xenopus laevis transcribed sequence with moderate similarity more	77.06(n)		BQ737450.1
zebrafish (Danio rerio)	Actinopterygii	wufa01b09²	wufa01b09	74.33(n)		334714 CA787388.1

ENSEMBL Gene Tree for TPP1 (if available)
TreeFam Gene Tree for TPP1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, ⁴UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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SNP ID	Valid	Clinical significance	Chr 11 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs121908202^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ untested¹	6550573(-)	`AACCTC/TGGTGA`	2	S L	mis¹		0	--	--	--	--
rs119455956^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6550657(-)	`TGGCCA/GTGCCT`	2	H R	mis¹		0	--	--	--	--
rs121908200^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ untested¹	6550843(-)	`TACCAG/CGTACG`	2	/H /Q	mis¹		1		NA	4548
rs119455954^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6551457(-)	`CGGGTA/GTTGGT`	2	Y C	mis¹		0	--	--	--	--
rs119455953^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6551458(-)	`CCGGGC/TGTTGG`	2	R C	mis¹		0	--	--	--	--
rs119455958^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6552090(-)	`TGCCAA/GCATCT`	2	N S	mis¹		0	--	--	--	--
rs119455957^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6552096(-)	`TGCTGG/TTGCCA`	2	G V	mis¹		0	--	--	--	--
rs28940573^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ pathogenic¹	6552446(-)	`TGATCC/TGTAAG`	2	R C	mis¹ ese³		0	--	--	--	--
rs121908204^1,2,,4	C	Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴ untested¹	6553026(-)	`CATCCA/GGTGAG`	2	Q R	mis¹		0	--	--	--	--
VAR_066885⁴		Ceroid lipofuscinosis, neuronal, 2 (CLN2)⁴	--	see VAR_066885	2	R Q	mis⁴		0	--	--	--	--

HapMap Linkage Disequilibrium report for TPP1 (6633997 - 6640692 bp)

Structural Variations
Database of Genomic Variants (DGV) 3 variations for TPP1: About this table

Variant ID	Type	Subtype	PubMed ID
nsv896972	CNV	Loss	21882294
nsv896971	CNV	Loss	21882294
nsv825755	CNV	Gain	20364138

Human Gene Mutation Database (HGMD): TPP1
Locus Specific Mutation Databases (LSDB): TPP1

Site Specific Mutation Identification with PCR Assays

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(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Conferences by KenesGroup, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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OMIM gene information: 607998
OMIM disorders: 204500 609270
UniProtKB/Swiss-Prot: TPP1_HUMAN, O14773

Ceroid lipofuscinosis, neuronal, 2 (CLN2) [MIM:204500]: 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.

Note=The disease is caused by mutations affecting the gene represented in this entry

Selected diseases for TPP1 (see all 29):
About MalaCards

childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia ceroid lipofuscinosis neuronal 2 late-infantile neuronal ceroid lipofuscinosis visual epilepsy

malignant migrating partial seizures of infancy neuronal ceroid lipofuscinosis adult neuronal ceroid lipofuscinosis batten disease

neuronal ceroid-lipofuscinoses cerebral atrophy myoclonus epilepsy developmental disabilities

progressive myoclonus epilepsy myoclonus lysosomal storage disease neuronitis

blindness sjogren's syndrome brain injury cerebritis

2 diseases from the University of Copenhagen DISEASES database for TPP1:

Neuronal ceroid lipofuscinosis Visual epilepsy

TPP1 for disorders About GeneDecksing

Congresses - knowledge worth sharing:
Alzheimer's & Parkinson's Diseases Congress (ADPD) 18 - 22 March 2015

Selected Novoseek inferred disease relationships for TPP1 gene (see all 12) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
lincl	98.9	201	9097964 (5), 10737126 (5), 10762513 (4), 16052206 (4) (see all 60)
neuronal ceroid lipofuscinoses	95.6	12	10428067 (1), 15719035 (1), 16869297 (1), 10191110 (1) (see all 10)
batten disease	84.7	7	15158442 (1), 11504071 (1), 11579433 (1), 10446748 (1)
lysosomal storage diseases	79.9	8	10470035 (1), 11445074 (1), 15158442 (1), 10762513 (1) (see all 6)
neurodegenerative diseases	73.5	25	10428067 (1), 12608292 (1), 16091586 (1), 16869297 (1) (see all 16)
neurodegeneration	49.2	6	15483130 (1), 16452657 (1), 11339651 (1), 11921051 (1) (see all 5)
visual loss	34.7	1	16720047 (1)
blindness	22.5	2	18344450 (1), 18850119 (1)
developmental disabilities	15	2	11332767 (1), 11073228 (1)
atrophy	12.7	4	11071145 (1), 11462245 (1), 11579433 (1)

GeneTests: TPP1
GeneReviews: TPP1
Genetic Association Database (GAD): TPP1
Human Genome Epidemiology (HuGE) Navigator: TPP1 (2 documents)

Export disorders for TPP1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for TPP1 gene, integrated from 10 sources (see all 176):
(articles sorted by number of sources associating them with TPP1)

Utopia: connect your pdf to the dynamic
world of online information

Structural organization and sequence of CLN2, the defective gene in classical late infantile neuronal ceroid lipofuscinosis. (PubMed id 9653647)^{1, 2, 3, 9} Liu C.-G.... Lobel P. (Genomics 1998)
Mutations in CLN7/MFSD8 are a common cause of variant late-infantile neuronal ceroid lipofuscinosis. (PubMed id 19201763)^{1, 2, 4} Kousi M....Lehesjoki A.-E. (Brain 2009)
Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I. (PubMed id 20340139)^{1, 2, 9} Walus M.... Golabek A.A. (Hum. Mutat. 2010)
Structure of tripeptidyl-peptidase I provides insight into the molecular basis of late infantile neuronal ceroid lipofuscinosis. (PubMed id 19038966)^{1, 2, 9} Pal A....Steinfeld R. (J. Biol. Chem. 2009)
Crystal structure and autoactivation pathway of the precursor form of human tripeptidyl-peptidase 1, the enzyme deficient in late infantile ceroid lipofuscinosis. (PubMed id 19038967)^{1, 2, 9} Guhaniyogi J.... Lobel P. (J. Biol. Chem. 2009)
The human CLN2 protein/tripeptidyl-peptidase I is a serine protease that autoactivates at acidic pH. (PubMed id 11054422)^{1, 2, 9} Lin L.... Lobel P. (J. Biol. Chem. 2001)
R208X mutation in CLN2 gene associated with reduced cerebrospinal fluid pterins in a girl with classic late infantile neuronal ceroid lipofuscinosis. (PubMed id 12950156)^{1, 4, 9} BarisiA8 N....Blau N. (Croat. Med. J. 2003)
Expression and analysis of CLN2 variants in CHO cells: Q100R represents a polymorphism, and G389E and R447H represent loss-of- function mutations. (PubMed id 11462245)^{1, 2, 9} Lin L. and Lobel P. (Hum. Mutat. 2001)
Heterogeneity of late-infantile neuronal ceroid lipofuscinosis. (PubMed id 11339651)^{1, 2, 9} Zhong N.... Brown W.T. (Genet. Med. 2000)
Tripeptidyl peptidase 1 deficiency in neuronal ceroid lipofuscinosis. A novel mutation. (PubMed id 12698559)^{1, 2, 9} Bukina A.M.... Il'ina E.S. (Vopr. Med. Khim. 2002)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 1200	HGNC: 2073	AceView: CLN2andDCHS1	Ensembl:ENSG00000166340	euGenes: HUgn1200
ECgene: TPP1	Kegg: 1200	H-InvDB: TPP1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for TPP1	Pharmacogenomics, SNPs, Pathways
NCL CLN2	http://www.ucl.ac.uk/ncl/cln2.shtml
GeneReviews	http://www.ncbi.nlm.nih.gov/books/NBK1116/?term=TPP1[genesymbol]

Intellectual Property for TPP1 gene
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Patent Information for TPP1 gene:
Search GeneIP for patents involving TPP1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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Tripeptidyl Peptidase I

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Tripeptidyl Peptidase I

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