On this page
CTSD
cathepsin D
The CTSD gene provides instructions for making cathepsin D, a crucial enzyme found in lysosomes that helps break down and recycle cellular components, playing a vital role in cellular health. The CTSD gene encodes cathepsin D, an aspartyl protease enzyme active within lysosomes, the cellular compartments responsible for digestion and waste recycling.
CTSD is located on the short (p) arm of chromosome 11, at band 11p15.5. Arm ratio per GRCh38 - banding schematic.
Explore chromosome 11 in the library →Available at Jeen Health
Clinical tests that include this
Overview
The CTSD gene, or cathepsin D, is responsible for producing an enzyme that plays a critical role in cellular metabolism and waste management. This enzyme is a member of the cathepsin family, a group of proteases that modify proteins by cleaving them.
Cathepsin D is particularly active within lysosomes, which are organelles often referred to as the 'recycling centres' of the cell. Its function in these compartments is vital for breaking down various molecules and maintaining overall cellular health.
What the gene does
The cathepsin D enzyme, encoded by the CTSD gene, performs important proteolytic activities within cells. As a protease, it cleaves other proteins, which can lead to their degradation, activation, or regulation of processes like programmed cell death (apoptosis).
Cathepsin D is initially produced as an inactive preproenzyme and undergoes several processing steps to become mature and active. This activation involves the removal of extra protein segments and further modifications. The fully active enzyme comprises two distinct parts: a light chain and a heavy chain. Its primary role in lysosomes is to break down proteins, contributing to the digestion and recycling of cellular components.
Video: Genetics 101
Chromosome location
The CTSD gene is situated on chromosome 11, specifically located at position 11p15.5. This chromosomal address indicates its precise position within the human genome.
Protein structure
The cathepsin D protein, encoded by the CTSD gene, is 412 amino acids in length. It features a key functional region known as the Peptidase A1 domain, which spans amino acids 79 to 407. This domain is crucial for the enzyme's proteolytic activity.
Key variants
Genetic variations within the CTSD gene can alter the function of the cathepsin D enzyme. These changes may impact the enzyme's ability to properly process proteins within lysosomes, potentially leading to cellular dysfunction. Different types of genetic changes can occur, including substitutions, deletions, or insertions within the gene sequence.
Sample of pathogenic variants
10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.
| Variant (HGVS) | Protein change | Classification | Evidence | Associated condition |
|---|---|---|---|---|
c.17_30dup | p.Leu11fs | Pathogenic | ★★☆☆ | Neuronal ceroid lipofuscinosis |
c.244G>T | p.Glu82Ter | Pathogenic/Likely pathogenic | ★★☆☆ | CTSD-related disorder |
c.268del | p.Gln90fs | Pathogenic/Likely pathogenic | ★★☆☆ | CTSD-related disorder |
c.268dup | p.Gln90fs | Pathogenic | ★★☆☆ | Neuronal ceroid lipofuscinosis |
c.952del | p.Val318fs | Pathogenic/Likely pathogenic | ★★☆☆ | Neuronal ceroid lipofuscinosis |
c.1028del | p.Gly343fs | Pathogenic | ★☆☆☆ | Neuronal ceroid lipofuscinosis |
c.451del | p.Tyr150_Leu151insTer | Pathogenic | ★☆☆☆ | Neuronal ceroid lipofuscinosis |
c.457C>T | p.Gln153Ter | Pathogenic | ★☆☆☆ | Neuronal ceroid lipofuscinosis |
c.464_465del | p.Thr155fs | Pathogenic | ★☆☆☆ | Neuronal ceroid lipofuscinosis |
c.519dup | p.Val174fs | Pathogenic | ★☆☆☆ | Neuronal ceroid lipofuscinosis |
Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.
Associated conditions
Mutations in the CTSD gene are known to cause CLN10 disease, a severe neurological disorder. This condition is characterised by symptoms such as muscle rigidity, severe seizures, and respiratory failure, typically manifesting shortly after birth and often leading to death in infancy. In rare instances, CLN10 disease can present later in life with symptoms like poor coordination, balance issues (ataxia), and progressive intellectual decline.
No disease links recorded for this gene in our reference set.
Inheritance pattern
Conditions caused by pathogenic CTSD variants typically follow autosomal recessive inheritance.
When both parents are carriers, each child has a 25% chance of being affected, 50% of being a carrier, and 25% of being unaffected.
UK clinical status
The CTSD gene is included in several Green RAG status panels within the NHS Genomic Medicine Service's PanelApp. These include panels for DDG2P, Early onset or syndromic epilepsy, Foetal anomalies (R21), Intellectual disability, Likely inborn error of metabolism (R98), Lysosomal storage disorder (R276), Neuronal ceroid lipofuscinosis (R231), Retinal disorders (R32), and Undiagnosed metabolic disorders.
Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory
Frequently asked questions
What is the primary function of the CTSD gene?
The CTSD gene provides instructions for making cathepsin D, an enzyme located in lysosomes. This enzyme is essential for breaking down and recycling various cellular components, playing a key role in cellular waste management and protein processing.
What is CLN10 disease?
CLN10 disease is a severe neurological disorder caused by mutations in the CTSD gene. It typically presents at birth with symptoms like muscle rigidity, severe seizures, and respiratory failure, and can rarely have a later onset with progressive neurological decline.
How does cathepsin D become active in the cell?
Cathepsin D is initially produced as an inactive preproenzyme. It undergoes several processing steps, including the removal of extra protein segments, to become mature and fully active within the lysosomes, where it performs its proteolytic functions.
References
- Kollmann K, Uusi-Rauva K, Scifo E. Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. Biochimica et biophysica acta. 2013. PMID: 23402926
- Kousi M, Lehesjoki AE, Mole SE. Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. Human mutation. 2012. PMID: 21990111
- Masson O, Bach AS, Derocq D. Pathophysiological functions of cathepsin D: Targeting its catalytic activity versus its protein binding activity? Biochimie. 2010. PMID: 20493920
- Benes P, Vetvicka V, Fusek M. Cathepsin D--many functions of one aspartic protease. Critical reviews in oncology/hematology. 2008. PMID: 18396408
- Steinfeld R, Reinhardt K, Schreiber K. Cathepsin D deficiency is associated with a human neurodegenerative disorder. American journal of human genetics. 2006. PMID: 16685649