CTSD

cathepsin D, the group of Cathepsins|Peptidase family A1

Basic information

Region (hg38): 11:1752752-1764573

Previous symbols: [ "CPSD" ]

Links

ENSG00000117984

∙ NCBI:1509 ∙ OMIM:116840 ∙ HGNC:2529 ∙ Uniprot:P07339 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

neuronal ceroid lipofuscinosis 10 (Definitive), mode of inheritance: AR
neuronal ceroid lipofuscinosis 10 (Strong), mode of inheritance: AR
neuronal ceroid lipofuscinosis 10 (Strong), mode of inheritance: AR
neuronal ceroid lipofuscinosis 10 (Supportive), mode of inheritance: AR
neuronal ceroid lipofuscinosis (Definitive), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Ceroid lipofuscinosis, neuronal, 10	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Biochemical; Neurologic; Ophthalmologic	16670177; 16685649; 25298308

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the CTSD gene.

Neuronal ceroid lipofuscinosis (24 variants)
Neuronal ceroid lipofuscinosis 10 (2 variants)
not provided (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTSD gene is commonly pathogenic or not. These statistics are base on transcript: . Only rare variants are included in the table.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			4 clinvar	197 clinvar	4 clinvar	205
missense		1 clinvar	210 clinvar	4 clinvar		215
nonsense	8 clinvar	1 clinvar				9
start loss			1			1
frameshift	17 clinvar	1 clinvar	3 clinvar			21
splice donor/acceptor (+/-2bp)		10 clinvar	1 clinvar			11
Total	25	13	219	201	4

Highest pathogenic variant AF is 0.0000197259

Loading clinvar variants...

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTSD	protein_coding	protein_coding	ENST00000236671	9	11241

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000917	0.987	125700	0	16	125716	0.0000636

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	1.38	190	252	0.755	0.0000168	2648
Missense in Polyphen		72	110.36	0.65239		1123
Synonymous	-0.909	134	121	1.10	0.00000958	865
Loss of Function	2.21	8	18.2	0.441	8.85e-7	210

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000580	0.0000580
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000925	0.0000924
European (Non-Finnish)	0.0000898	0.0000879
Middle Eastern	0.00	0.00
South Asian	0.0000657	0.0000653
Other	0.00	0.00

dbNSFP

Source: dbNSFP

Function: FUNCTION: Acid protease active in intracellular protein breakdown. Plays a role in APP processing following cleavage and activation by ADAM30 which leads to APP degradation (PubMed:27333034). Involved in the pathogenesis of several diseases such as breast cancer and possibly Alzheimer disease. {ECO:0000269|PubMed:27333034}.;
Disease: DISEASE: Ceroid lipofuscinosis, neuronal, 10 (CLN10) [MIM:610127]: A form of neuronal ceroid lipofuscinosis with onset at birth or early childhood. 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. {ECO:0000269|PubMed:16670177, ECO:0000269|PubMed:16685649, ECO:0000269|PubMed:21990111}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
Pathway: Autophagy - animal - Homo sapiens (human);Lysosome - Homo sapiens (human);Estrogen signaling pathway - Homo sapiens (human);Tuberculosis - Homo sapiens (human);Sphingolipid signaling pathway - Homo sapiens (human);Apoptosis - Homo sapiens (human);Prolactin Signaling Pathway;Neutrophil degranulation;Signal Transduction;Peptide hormone metabolism;downregulated of mta-3 in er-negative breast tumors;Prolactin;Metabolism of proteins;Metabolism of Angiotensinogen to Angiotensins;MHC class II antigen presentation;thyroid hormone biosynthesis;Innate Immune System;Immune System;Adaptive Immune System;Signaling by Nuclear Receptors;Direct p53 effectors;Estrogen-dependent gene expression;ESR-mediated signaling;Validated nuclear estrogen receptor alpha network;Ceramide signaling pathway;LKB1 signaling events (Consensus)

Recessive Scores

pRec: 0.909

Intolerance Scores

loftool: 0.533
rvis_EVS: -0.58
rvis_percentile_EVS: 18.72

Haploinsufficiency Scores

pHI: 0.741
hipred: Y
hipred_score: 0.725
ghis: 0.518

Essentials

essential_gene_CRISPR: N
essential_gene_CRISPR2: N
essential_gene_gene_trap: N
gene_indispensability_pred: E
gene_indispensability_score: 0.970

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

Gene name: Ctsd
Phenotype: homeostasis/metabolism phenotype; cellular phenotype; endocrine/exocrine gland phenotype; growth/size/body region phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); immune system phenotype; vision/eye phenotype; digestive/alimentary phenotype; hearing/vestibular/ear phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); hematopoietic system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan);

Zebrafish Information Network

Gene name: ctsd
Affected structure: muscle
Phenotype tag: abnormal
Phenotype quality: decreased thickness

Gene ontology

Biological process: proteolysis;antigen processing and presentation of exogenous peptide antigen via MHC class II;protein catabolic process;collagen catabolic process;neutrophil degranulation
Cellular component: extracellular region;extracellular space;lysosome;specific granule lumen;melanosome;lysosomal lumen;membrane raft;collagen-containing extracellular matrix;extracellular exosome;tertiary granule lumen;ficolin-1-rich granule lumen
Molecular function: aspartic-type endopeptidase activity;cysteine-type endopeptidase activity;serine-type endopeptidase activity;protein binding