Human Disease Model Report: neuronal ceroid lipofuscinosis 10

General Information

Name

neuronal ceroid lipofuscinosis 10

FlyBase ID

FBhh0000105

Disease Ontology Term

neuronal ceroid lipofuscinosis 10

Parent Disease

neuronal ceroid lipofuscinosis

OMIM

CEROID LIPOFUSCINOSIS, NEURONAL, 10; CLN10

Overview

This report describes neuronal ceroid lipofuscinosis 10 (CLN10), which is a subtype of neuronal ceroid lipofuscinosis; CLN10 exhibits autosomal recessive inheritance. The human gene implicated in this disease is Cathepsin D (CTSD), which is a ubiquitously expressed lysosomal protease. There is a single high-scoring fly ortholog, Dmel\cathD, for which loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated. Dmel\cathD is also a high-scoring ortholog of a second human gene, NAPSA.

The human Hsap\CTSD gene has been introduced into flies, but has not been characterized.

Loss-of-function mutations of Dmel\cathD are viable and fertile; aged animals exhibit a mild retinal defects; increased numbers of apoptotic nuclei are observed in the brains of aged animals. Phenotypic assays using an allele of the fly gene have allowed characterization of genetic interactions. Physical interactions for the cathD protein have been described; see below and in the cathD gene report.

[updated Oct. 2019 by FlyBase; FBrf0222196]

Disease Summary Information

Parent Disease Summary: neuronal ceroid lipofuscinosis

Symptoms and phenotype

The neuronal ceroid lipofuscinoses (NCLs or CLNs) are a clinically heterogeneous group of neurodegenerative disorders; the general clinical course includes progressive dementia, seizures, and progressive visual failure (Mole et al., 2005; pubmed:15965709). [from MIM:256730; 2016.01.05]

(OMIM, 2013-)

Individuals with all forms NCL have shortened life expectancy, but it is highly variable, depending upon the form of the disease (from Medscape, http://emedicine.medscape.com/article/1178391-overview; 2016.01.05).

(FlyBase Curators, 2013-)

The term Batten disease may refer specifically to the juvenile-onset form, but is also used to refer to any NCL.

(FlyBase Curators, 2013-)

Specific Disease Summary: neuronal ceroid lipofuscinosis 10

OMIM report

[CEROID LIPOFUSCINOSIS, NEURONAL, 10; CLN10](https://omim.org/entry/610127)

Human gene(s) implicated

[CATHEPSIN D; CTSD](https://omim.org/entry/116840)

Symptoms and phenotype

See general description of neuronal ceroid lipofuscinosis, above. Age of onset of neuronal ceroid lipofuscinosis 10 (CLN10) is variable. The congenital form is usually fatal within days after birth. [from MIM:610127; 2016.01.05]

(OMIM, 2013-)

Genetics

Neuronal ceroid lipofuscinosis 10 (CLN10) is inherited as an autosomal recessive and is caused by homozygous or compound heterozygous mutation in the cathepsin D gene (CTSD). [from MIM:610127; 2016.01.05]

(OMIM, 2013-)

Cellular phenotype and pathology

Molecular information

Cathepsin D (CTSD) is a lysosomal aspartyl protease; it is ubiquitously expressed and is involved in proteolytic degradation, cell invasion, and apoptosis (Steinfeld et al., 2006; pubmed:16685649). [from MIM:116840; 2016.01.05]

(OMIM, 2013-)

External links

Gene2Function (human gene): CTSD
Gene Cards: CTSD
GeneReviews, NCBI Bookshelf: Neuronal Ceroid-Lipofuscinoses
MedlinePlus (gene): CTSD
MARRVEL (human gene): CTSD
NCBI MedGen: Ceroid lipofuscinosis neuronal 10 (CLN10)
NCBI (Entrez) gene: CTSD; cathepsin D

Disease synonyms

ceroid lipofuscinosis, neuronal

ceroid lipofuscinosis, neuronal, 10

ceroid lipofuscinosis, neuronal, cathepsin D-deficient

CLN10

congenital neuronal ceroid lipofuscinosis

NCL10

NCL due to cathepsin D deficiency

neuronal ceroid lipofuscinosis

neuronal ceroid lipofuscinosis, congenital

Search term: lipid storage disease

Search term: lysosomal storage disorder

Related Diseases

Related human health report(s)

Related Specific Diseases

OMIM phenotypic series

Ceroid lipofuscinoses

Disease

Associated Human gene(s)

Drosophila model

Human transgene in Drosophila

[CLN1](https://omim.org/entry/256730)

[PPT1](https://omim.org/entry/600722)

neuronal ceroid lipofuscinosis 1

[CLN2](https://omim.org/entry/204500)

[TPP1](https://omim.org/entry/607998)

[CLN3](https://omim.org/entry/204200)

[CLN3](https://omim.org/entry/607042)

neuronal ceroid lipofuscinosis 3

[CLN4](https://omim.org/entry/162350)

[DNAJC5](https://omim.org/entry/611203)

neuronal ceroid lipofuscinosis 4

[CLN5](https://omim.org/entry/256731)

[CLN5](https://omim.org/entry/608102)

[CLN6A](https://omim.org/entry/601780)

[CLN6](https://omim.org/entry/606725)

[CLN6B](https://omim.org/entry/204300)

[CLN6](https://omim.org/entry/606725)

[CLN7](https://omim.org/entry/610951)

[MFSD8](https://omim.org/entry/611124)

neuronal ceroid lipofuscinosis 7

[CLN8](https://omim.org/entry/600143)

[CLN8](https://omim.org/entry/607837)

[CLN8](https://omim.org/entry/610003)

[CLN8](https://omim.org/entry/607837)

[CLN10](https://omim.org/entry/610127)

[CTSD](https://omim.org/entry/116840)

neuronal ceroid lipofuscinosis 10

[CLN11](https://omim.org/entry/614706)

[GRN](https://omim.org/entry/138945)

[CLN13](https://omim.org/entry/615362)

[CTSF](https://omim.org/entry/603539)

Ortholog Information

Human gene(s) in FlyBase

Hsap\CTSD

Human gene (HGNC)

Symbol / Name

CTSD; cathepsin D

D. melanogaster ortholog (based on DIOPT)

Dmel\cathD

(DIOPT, 2013-)

Comments on ortholog(s)

Many to one: 2 human to 1 Drosophila. The human gene CTSD is orthologous to the fly gene Dmel\cathD (reciprocal best hit); Dmel\cathD is also a high-scoring ortholog of the human gene NAPSA.

Other mammalian ortholog(s) used

D. melanogaster Gene Information (1)

Dmel\cathD

Gene Snapshot

cathD (cathD) encodes a protein involved in apoptosis and the defense response to Gram-negative bacteria. [Date last reviewed: 2019-09-19]

Molecular function (GO)

aspartic-type endopeptidase activity

Cellular component (GO)

Gene Groups / Pathways

Comments on ortholog(s)

High-scoring ortholog of CTSD; lower-scoring ortholog of second human gene, NAPSA (1 Drosphila to 2 human). Dmel\cathD shares 52% identity and 67% similarity with the human gene CTSD; it shares 48% identity and 62% similarity with the human gene NAPSA.

Orthologs and Alignments from DRSC

DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans

H. sapiens (Human)

Other Genes Used: Viral, Bacterial, Synthetic (0)

Summary of Physical Interactions (27 groups)

cathD

protein-protein

Interacting group

Assay

References

cathD - Akt

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cathD - CCT3

experimental knowledge based

(Guruharsha et al., 2011)

cathD - CCT6

experimental knowledge based

(Guruharsha et al., 2011)

cathD - CG5854

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Cnx99A

experimental knowledge based

(Guruharsha et al., 2011)

cathD - CtsL1

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Cyp12d1-p

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Droj2

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Gfat2

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Gp93

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Hel25E

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Ldh

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Mcad

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Mec2

experimental knowledge based

(Guruharsha et al., 2011)

cathD - MED4

anti tag coimmunoprecipitation, peptide massfingerprinting, experimental knowledge based

(Rhee et al., 2014)

cathD - Nfs1

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Ost1

experimental knowledge based

(Guruharsha et al., 2011)

cathD - Pdk1

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cathD - Rab5

experimental knowledge based

(Guruharsha et al., 2011)

cathD - S6k

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cathD - ScsβA

experimental knowledge based

(Guruharsha et al., 2011)

cathD - ScsβG

experimental knowledge based

(Guruharsha et al., 2011)

cathD - SERCA

experimental knowledge based

(Guruharsha et al., 2011)

cathD - sima

anti tag coimmunoprecipitation, Identification by mass spectrometry

(Vinayagam et al., 2016)

cathD - Tapδ

experimental knowledge based

(Guruharsha et al., 2011)

cathD - UQCR-C2

experimental knowledge based

(Guruharsha et al., 2011)

cathD - wal

experimental knowledge based

(Guruharsha et al., 2011)

Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)

cathD

Models Based on Experimental Evidence ( 1 )

Allele

Disease

Evidence

References

cathD¹

model of neuronal ceroid lipofuscinosis

CEA

(Myllykangas et al., 2005)

CEC

(Kuronen et al., 2009)

Modifiers Based on Experimental Evidence ( 2 )

Allele

Disease

Interaction

References

cathD¹

exacerbates tauopathy

modeled by Hsap\MAPT^R406W.UAS

(Khurana et al., 2010)

model of neuronal ceroid lipofuscinosis

is exacerbated by schlank^G0061

(Kuronen et al., 2009)

is exacerbated by shi¹

(Kuronen et al., 2009)

is exacerbated by Trxr1^G0481

(Kuronen et al., 2009)

is exacerbated by Hmgcr^UAS.cvDa

(Kuronen et al., 2009)

is exacerbated by Hsc70-4^L3929

(Kuronen et al., 2009)

is exacerbated by mTor^{WT.UAS.Tag:FLAG}

(Kuronen et al., 2009)

is exacerbated by CtsB^PG148

(Kuronen et al., 2009)

cathD^UAS.cUa

ameliorates tauopathy

modeled by Hsap\MAPT^GMR.Ex.PJ

(Bakhoum et al., 2014)

Alleles Representing Disease-Implicated Variants

Genetic Tools, Stocks and Reagents

Sources of Stocks

Contact lab of origin for a reagent not available from a public stock center.

Bloomington Stock Center Disease Page

Neuronal ceroid lipofuscinosis

Related mammalian, viral, bacterial, or synthetic transgenes

Allele

Transgene

Publicly Available Stocks

Hsap\CTSD^UAS.Tag:HA

PBac{UAS-hCTSD.HA}

y¹ w^*; PBac{UAS-hCTSD.HA}VK00033

Selected Drosophila transgenes

Allele

Transgene

Publicly Available Stocks

cathD^UAS.cUa

P{UAS-cathD.U}

RNAi constructs available

Allele

Transgene

Publicly Available Stocks

cathD^GD5487

P{GD5487}

w¹¹¹⁸; P{GD5487}v31012

cathD^HM05189

P{TRiP.HM05189}

y¹ v¹; P{TRiP.HM05189}attP2

y¹ v¹; P{TRiP.HMJ21197}attP40/CyO

cathD^HMC03859

P{TRiP.HMC03859}

y¹ sc^* v¹ sev²¹; P{TRiP.HMC03859}attP40

Selected Drosophila classical alleles

Allele

Allele class

Mutagen

Publicly Available Stocks

cathD¹

P-element activity

References (6)

Report Sections

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