CTSB

cathepsin B, the group of Cathepsins

Basic information

Region (hg38): 8:11842524-11869533

Links

ENSG00000164733 ∙ NCBI:1508 ∙ OMIM:116810 ∙ HGNC:2527 ∙ Uniprot:P07858 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• keratolytic winter erythema (Strong), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Keratolytic winter erythema	AD	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	Dermatologic	28457472
Reported variants involved duplications upstream of the gene (and which disrupted CTSB gene function)

ClinVar

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

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the CTSB 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				15	10	25
missense			51	9	9	69
nonsense						0
start loss						0
frameshift			2			2
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region			3	6		9
non coding				9	12	21
Total	0	0	53	33	31

Variants in CTSB

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

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

Position	Type	Phenotype	Significance	ClinVar
8-11845130-T-C			Uncertain significance (Dec 22, 2021)
8-11845144-T-G			Benign (Aug 09, 2022)
8-11845145-G-C		not specified	Uncertain significance (Jul 26, 2022)
8-11845148-C-A			Uncertain significance (Mar 23, 2022)
8-11845148-C-T			Uncertain significance (Oct 13, 2021)
8-11845149-G-A			Likely benign (Mar 07, 2021)
8-11845151-T-C			Uncertain significance (Mar 18, 2022)
8-11845153-C-G			Uncertain significance (Nov 08, 2022)
8-11845154-G-A		not specified	Uncertain significance (Dec 10, 2020)
8-11845178-A-C		not specified	Uncertain significance (Sep 17, 2021)
8-11845182-G-A			Benign (Jul 25, 2022)
8-11845191-G-C			Uncertain significance (Nov 01, 2022)
8-11845196-C-T			Benign (Nov 15, 2022)
8-11845231-A-T			Likely benign (Jan 15, 2024)
8-11845645-G-C			Likely benign (Nov 23, 2021)
8-11845647-G-C			Benign (Dec 22, 2020)
8-11845648-G-A			Benign (Aug 31, 2022)
8-11845649-G-A			Likely benign (Aug 04, 2021)
8-11845678-G-C		not specified	Uncertain significance (Mar 20, 2023)
8-11845715-C-T		not specified	Uncertain significance (Aug 14, 2024)
8-11845718-T-G			Uncertain significance (Jul 12, 2022)
8-11845734-C-T		CTSB-related disorder	Benign (Jun 12, 2023)
8-11845737-G-C		not specified	Uncertain significance (Apr 09, 2024)
8-11845742-G-A			Uncertain significance (Jul 11, 2022)
8-11845763-T-A		not specified	Conflicting classifications of pathogenicity (Dec 06, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
CTSB	protein_coding	protein_coding	ENST00000353047	9	26925

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
5.88e-11	0.122	125667	0	80	125747	0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-3.35	344	208	1.65	0.0000126	2204
Missense in Polyphen		101	83.461	1.2101		841
Synonymous	-7.39	168	82.6	2.03	0.00000577	612
Loss of Function	0.457	17	19.2	0.887	8.16e-7	222

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000753	0.000753
Ashkenazi Jewish	0.000199	0.000198
East Asian	0.000163	0.000163
Finnish	0.000557	0.000554
European (Non-Finnish)	0.000370	0.000360
Middle Eastern	0.000163	0.000163
South Asian	0.000164	0.000163
Other	0.000163	0.000163

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Thiol protease which is believed to participate in intracellular degradation and turnover of proteins. Has also been implicated in tumor invasion and metastasis.
• Pathway: Antigen processing and presentation - Homo sapiens (human);Autophagy - animal - Homo sapiens (human);Lysosome - Homo sapiens (human);NOD-like receptor signaling pathway - Homo sapiens (human);Renin secretion - Homo sapiens (human);Apoptosis - Homo sapiens (human);Ebola Virus Pathway on Host;Ebola Virus Pathway on Host;Neutrophil degranulation;Assembly of collagen fibrils and other multimeric structures;Trafficking and processing of endosomal TLR;Toll-Like Receptors Cascades;Collagen degradation;Collagen formation;Extracellular matrix organization;MHC class II antigen presentation;Innate Immune System;Immune System;Adaptive Immune System;Degradation of the extracellular matrix (Consensus)

Recessive Scores

• pRec: 0.666

Intolerance Scores

• loftool: 0.0421
• rvis_EVS: 0
• rvis_percentile_EVS: 54.07

Haploinsufficiency Scores

• pHI: 0.138
• ghis: 0.467

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.841

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Ctsb
• 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); homeostasis/metabolism phenotype; cellular phenotype; digestive/alimentary 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); neoplasm; 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); normal phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype

Zebrafish Information Network

• Gene name: ctsba
• Affected structure: whole organism
• Phenotype tag: abnormal
• Phenotype quality: wholly dorsalized

Gene ontology

• Biological process: proteolysis;collagen catabolic process;epithelial cell differentiation;regulation of apoptotic process;neutrophil degranulation;decidualization;viral entry into host cell;regulation of catalytic activity;proteolysis involved in cellular protein catabolic process;cellular response to thyroid hormone stimulus
• Cellular component: extracellular region;extracellular space;nucleolus;lysosome;endolysosome lumen;melanosome;intracellular membrane-bounded organelle;perinuclear region of cytoplasm;collagen-containing extracellular matrix;extracellular exosome;ficolin-1-rich granule lumen
• Molecular function: cysteine-type endopeptidase activity;serine-type endopeptidase activity;protein binding;collagen binding;peptidase activity;cysteine-type peptidase activity;proteoglycan binding