CTSL
protein-codingcathepsin L, the group of Cathepsins
Gene summary
The protein encoded by this gene is a lysosomal cysteine proteinase that plays a major role in intracellular protein catabolism. Its substrates include collagen and elastin, as well as alpha-1 protease inhibitor, a major controlling element of neutrophil elastase activity. The encoded protein has been implicated in several pathologic processes, including myofibril necrosis in myopathies and in myocardial ischemia, and in the renal tubular response to proteinuria. This protein, which is a member of the peptidase C1 family, is a dimer composed of disulfide-linked heavy and light chains, both produced from a single protein precursor. Additionally, this protein cleaves the S1 subunit of the SARS-CoV-2 spike protein, which is necessary for entry of the virus into the cell. [provided by RefSeq, Aug 2020]
- CTSL1
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~7.4 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to CTSL variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001912.5. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 1 | 1 | ||||
| missense | 47 | 3 | 1 | 51 | ||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 3 | 3 | ||||
| Total | 0 | 0 | 50 | 4 | 1 | 55 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001903.1 | 7 | MANE Select | |
| Ensembl | ENSP00000345344.5 | 7 | MANE Select | |
| RefSeq | NP_001244900.1 | 7 | Standard | |
| RefSeq | NP_001244901.1 | 7 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- Antigen processing and presentation - Homo sapiens (human)
- Phagosome - Homo sapiens (human)
- Autophagy - animal - Homo sapiens (human)
- Lysosome - Homo sapiens (human)
- Fluid shear stress and atherosclerosis - Homo sapiens (human)
Biological Process
- adaptive immune response
- proteolysis
- antigen processing and presentation
- antigen processing and presentation of exogenous peptide antigen via MHC class II
- extracellular matrix disassembly
Molecular Function
- fibronectin binding
- cysteine-type endopeptidase activity
- serine-type endopeptidase activity
- protein binding
- collagen binding
Cellular Component
- extracellular region
- extracellular space
- nucleus
- lysosome
- endolysosome lumen
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000343150
- Coding exons
- 7
- Length
- 5875
- Individuals with no LoFs
- 125678
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 70
- Defined
- 125748
- p
- 0.000278
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.361 | 167 | 181 | 0.924 | 0.00000891 | 2222 |
| Missense (PolyPhen) | 44 | 65.928 | 0.66739 | 865 | ||
| Synonymous | 0.514 | 59 | 64.2 | 0.918 | 0.00000343 | 592 |
| Loss of Function | 2.18 | 6 | 15.2 | 0.396 | 6.45e-7 | 190 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0 | 0.0 | absent |
| Latino/Admixed American | 0.000029 | 0.000029 | rare |
| Ashkenazi Jewish | 0 | 0.0 | absent |
| East Asian | 0.000054 | 0.000054 | rare |
| Finnish | 0 | 0.0 | absent |
| European (Non-Finnish) | 0.000044 | 0.000044 | rare |
| South Asian | 0.0021 | 0.0021 | notable |
| Other | 0 | 0.0 | absent |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Important for the overall degradation of proteins in lysosomes.;
Recessive Scores
- pRec
- 0.763
Intolerance Scores
- RVIS EVS
- 0.13
- RVIS percentile EVS
- 63.2
Essentials
- Essential (CRISPR)
- N
- Essential (gene trap)
- N
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |