CTSC

cathepsin C, the group of Cathepsins

Basic information

Region (hg38): 11:88265068-88359684

Previous symbols: [ "PLS", "PALS" ]

Links

ENSG00000109861 ∙ NCBI:1075 ∙ OMIM:602365 ∙ HGNC:2528 ∙ Uniprot:P53634 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Papillon-Lefevre disease (Definitive), mode of inheritance: AR
• Haim-Munk syndrome (Moderate), mode of inheritance: AR
• Haim-Munk syndrome (Supportive), mode of inheritance: AR
• Papillon-Lefevre disease (Supportive), mode of inheritance: AR
• ectodermal dysplasia syndrome (Strong), mode of inheritance: AR
• periodontitis, aggressive 1 (Limited), mode of inheritance: Unknown
• Haim-Munk syndrome (Strong), mode of inheritance: AR
• Haim-Munk syndrome (Limited), mode of inheritance: Unknown
• Papillon-Lefevre disease (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Haim-Munk syndrome; Papillon-Lefevre syndrome; Periodontitis 1, juvenile	AR	Allergy/Immunology/Infectious	Early diagnosis to allow control of oral infections may preserve dentition	Allergy/Immunology/Infectious; Dental; Dermatologic; Musculoskeletal	14244097; 14252683; 162525; 2943312; 2965550; 7623262; 9085215; 10593994; 10581027; 11106356; 10662807; 12509601; 12637913; 14974080; 15606524; 18945301; 19816003; 20359428; 21393975

ClinVar

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

• Haim-Munk syndrome;Periodontitis, aggressive 1;Papillon-Lefèvre syndrome (89 variants)
• Papillon-Lefèvre syndrome (63 variants)
• Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome (53 variants)
• not provided (48 variants)
• Haim-Munk syndrome (47 variants)
• Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome (45 variants)
• Papillon-Lefèvre syndrome;Haim-Munk syndrome;Periodontitis, aggressive 1 (28 variants)
• Inborn genetic diseases (18 variants)
• Haim-Munk syndrome;Papillon-Lefèvre syndrome;Periodontitis, aggressive 1 (13 variants)
• Papillon-Lefèvre syndrome;Periodontitis, aggressive 1;Haim-Munk syndrome (11 variants)
• not specified (10 variants)
• - (4 variants)
• Periodontitis, aggressive 1 (3 variants)
• CTSC-Related Disorders (3 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTSC gene is commonly pathogenic or not.

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			2	58	2	62
missense	3	5	124	4	1	137
nonsense	9	1				10
start loss						0
frameshift	10	1	1			12
inframe indel			2			2
splice donor/acceptor (+/-2bp)	2	1				3
splice region			10	8	1	19
non coding	1		10	16	35	62
Total	25	8	139	78	38

Highest pathogenic variant AF is 0.0000591

Variants in CTSC

This is a list of pathogenic ClinVar variants found in the CTSC region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
11-88291569-TGAAAGAAA-T			Uncertain significance (-)
11-88291569-T-TGAAAGAAAGAAAGAAAGAAA			Uncertain significance (-)
11-88293592-T-C		Haim-Munk syndrome • Papillon-Lefèvre syndrome	Uncertain significance (Jan 12, 2018)
11-88293625-T-C		Papillon-Lefèvre syndrome • Haim-Munk syndrome	Uncertain significance (Feb 16, 2018)
11-88293656-T-C		Papillon-Lefèvre syndrome • Haim-Munk syndrome	Uncertain significance (Jan 13, 2018)
11-88293727-T-C		Papillon-Lefèvre syndrome • Haim-Munk syndrome	Benign (Jan 13, 2018)
11-88293753-A-G		Papillon-Lefèvre syndrome • Haim-Munk syndrome	Benign (Jan 13, 2018)
11-88294006-C-T		Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome • CTSC-related disorder	Likely benign (Jan 31, 2024)
11-88294021-T-C		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Likely benign (Jul 30, 2023)
11-88294041-T-C		not specified • Papillon-Lefèvre syndrome • Haim-Munk syndrome • Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome	Benign/Likely benign (Jan 31, 2024)
11-88294047-C-G		Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome	Uncertain significance (Dec 31, 2022)
11-88294049-A-G		Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome	Uncertain significance (Jun 27, 2022)
11-88294052-G-A		Haim-Munk syndrome;Periodontitis, aggressive 1;Papillon-Lefèvre syndrome	Uncertain significance (Dec 30, 2019)
11-88294052-GCA-G		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Uncertain significance (Apr 21, 2022)
11-88294053-C-T		Haim-Munk syndrome;Papillon-Lefèvre syndrome;Periodontitis, aggressive 1	Uncertain significance (Nov 08, 2022)
11-88294054-A-G		Haim-Munk syndrome;Periodontitis, aggressive 1;Papillon-Lefèvre syndrome	Likely benign (Jan 11, 2024)
11-88294057-C-T		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Likely benign (Sep 24, 2023)
11-88294057-CTCA-C		Haim-Munk syndrome;Periodontitis, aggressive 1;Papillon-Lefèvre syndrome	Uncertain significance (Feb 04, 2022)
11-88294060-A-G		Periodontitis, aggressive 1;Haim-Munk syndrome;Papillon-Lefèvre syndrome	Likely benign (Jul 21, 2023)
11-88294061-T-G			Uncertain significance (Jan 17, 2020)
11-88294073-C-A		Inborn genetic diseases	Uncertain significance (Jun 22, 2021)
11-88294073-C-T		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Uncertain significance (Jul 19, 2022)
11-88294074-G-A		Haim-Munk syndrome • Papillon-Lefèvre syndrome • Haim-Munk syndrome;Periodontitis, aggressive 1;Papillon-Lefèvre syndrome	Uncertain significance (Aug 06, 2022)
11-88294075-G-A		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Likely benign (Apr 26, 2023)
11-88294078-C-T		Periodontitis, aggressive 1;Papillon-Lefèvre syndrome;Haim-Munk syndrome	Likely benign (Jul 25, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTSC	protein_coding	protein_coding	ENST00000227266	7	44196

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.15e-7	0.801	125704	0	44	125748	0.000175

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.143	252	246	1.03	0.0000123	3026
Missense in Polyphen		92	83.927	1.0962		1097
Synonymous	-0.909	105	93.8	1.12	0.00000469	889
Loss of Function	1.44	14	21.1	0.662	0.00000104	246

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000272	0.000264
Ashkenazi Jewish	0.00	0.00
East Asian	0.000163	0.000163
Finnish	0.000222	0.000185
European (Non-Finnish)	0.000210	0.000202
Middle Eastern	0.000163	0.000163
South Asian	0.000196	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thiol protease. Has dipeptidylpeptidase activity. Active against a broad range of dipeptide substrates composed of both polar and hydrophobic amino acids. Proline cannot occupy the P1 position and arginine cannot occupy the P2 position of the substrate. Can act as both an exopeptidase and endopeptidase. Activates serine proteases such as elastase, cathepsin G and granzymes A and B. Can also activate neuraminidase and factor XIII. {ECO:0000269|PubMed:1586157}.
• Disease: DISEASE: Papillon-Lefevre syndrome (PLS) [MIM:245000]: An autosomal recessive disorder characterized by palmoplantar keratosis and severe periodontitis affecting deciduous and permanent dentitions and resulting in premature tooth loss. The palmoplantar keratotic phenotype vary from mild psoriasiform scaly skin to overt hyperkeratosis. Keratosis also affects other sites such as elbows and knees. {ECO:0000269|PubMed:10581027, ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:11106356, ECO:0000269|PubMed:11158173, ECO:0000269|PubMed:11180012, ECO:0000269|PubMed:11180601, ECO:0000269|PubMed:11886537, ECO:0000269|PubMed:12112662, ECO:0000269|PubMed:12809647, ECO:0000269|PubMed:14974080, ECO:0000269|PubMed:15108292, ECO:0000269|PubMed:15991336, ECO:0000269|PubMed:25799584}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Haim-Munk syndrome (HMS) [MIM:245010]: An autosomal recessive disorder characterized by palmoplantar keratosis, onychogryphosis and periodontitis. Additional features are pes planus, arachnodactyly, and acroosteolysis. {ECO:0000269|PubMed:10662807}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Periodontititis, aggressive, 1 (AP1) [MIM:170650]: A disease characterized by severe and protracted gingival infections, generalized or localized, leading to tooth loss. Amounts of microbial deposits are generally inconsistent with the severity of periodontal tissue destruction and the progression of attachment and bone loss may be self arresting. {ECO:0000269|PubMed:10662808, ECO:0000269|PubMed:14974080}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Lysosome - Homo sapiens (human);Apoptosis - Homo sapiens (human);miR-targeted genes in epithelium - TarBase;miR-targeted genes in leukocytes - TarBase;miR-targeted genes in lymphocytes - TarBase;miR-targeted genes in muscle cell - TarBase;Neutrophil degranulation;Vesicle-mediated transport;Membrane Trafficking;Post-translational protein modification;Metabolism of proteins;MHC class II antigen presentation;Innate Immune System;Immune System;Adaptive Immune System;Cargo concentration in the ER;Transport to the Golgi and subsequent modification;Asparagine N-linked glycosylation;COPII-mediated vesicle transport;ER to Golgi Anterograde Transport (Consensus)

Recessive Scores

• pRec: 0.665

Intolerance Scores

• loftool: 0.165
• rvis_EVS: -0.45
• rvis_percentile_EVS: 24.33

Haploinsufficiency Scores

• pHI: 0.256
• hipred: N
• hipred_score: 0.229
• ghis: 0.535

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.277

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctsc
• Phenotype: cellular phenotype; homeostasis/metabolism 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); growth/size/body region phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system 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); normal phenotype; hematopoietic system phenotype

Gene ontology

• Biological process: T cell mediated cytotoxicity;proteolysis;endoplasmic reticulum to Golgi vesicle-mediated transport;apoptotic process;immune response;aging;response to organic substance;neutrophil degranulation;COPII vesicle coating;proteolysis involved in cellular protein catabolic process;positive regulation of proteolysis involved in cellular protein catabolic process;positive regulation of apoptotic signaling pathway
• Cellular component: Golgi membrane;extracellular region;extracellular space;nucleoplasm;lysosome;endoplasmic reticulum lumen;centrosome;membrane;COPII-coated ER to Golgi transport vesicle;endoplasmic reticulum-Golgi intermediate compartment membrane;azurophil granule lumen;intracellular membrane-bounded organelle;collagen-containing extracellular matrix;extracellular exosome
• Molecular function: cysteine-type endopeptidase activity;serine-type endopeptidase activity;protein binding;cysteine-type peptidase activity;peptidase activator activity involved in apoptotic process;phosphatase binding;chloride ion binding;identical protein binding;protein self-association;chaperone binding