CTSB

protein-coding

cathepsin B, the group of Cathepsins

Gene summary

This gene encodes a member of the C1 family of peptidases. Alternative splicing of this gene results in multiple transcript variants. At least one of these variants encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cathepsin B light and heavy chains, which can dimerize to form the double chain form of the enzyme. This enzyme is a lysosomal cysteine protease with both endopeptidase and exopeptidase activity that may play a role in protein turnover. It is also known as amyloid precursor protein secretase and is involved in the proteolytic processing of amyloid precursor protein (APP). Incomplete proteolytic processing of APP has been suggested to be a causative factor in Alzheimer's disease, the most common cause of dementia. Overexpression of the encoded protein has been associated with esophageal adenocarcinoma and other tumors. Both Cathepsin B and Cathepsin L are involved in the cleavage of the spike protein from the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) upon its entry to the human host cell. Multiple pseudogenes of this gene have been identified. [provided by RefSeq, Sep 2020]

MANE transcript

NM_001908.5

Inheritance

ClinVar variants

U:97B:50

Top phenotype

Keratolytic winter erythema

gnomAD constraint

pLI —, LoF o/e 0.89

Max pathogenic AF

—

Genomic locus

chr8:11,842,524-11,869,533

External References & Databases

Ensembl (ENSG00000164733)

Transcript & Mutation Effects

hg38 • Region Span ~27.0 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

keratolytic winter erythemaSTRONG

Inheritance Pattern: AD

Disease ID:MONDO:0007854

Submitter: Labcorp Genetics (formerly Invitae)

keratolytic winter erythemaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007854

Submitter: G2P

keratolytic winter erythemaLIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0007854

Submitter: Ambry Genetics

Clinical Genomic Database (CGD)

Keratolytic winter erythemaAD

Manifestation: Dermatologic

Intervention: General

Rationale: 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

Comments: Reported variants involved duplications upstream of the gene (and which disrupted CTSB gene function)

Refs: 28457472

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to CTSB variants in ClinVar

4 Conditions Cataloged

not providedTotal: 104

not specifiedTotal: 74

CTSB-related disorderTotal: 9

Keratolytic winter erythemaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001908.5. 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 clinvar	24 clinvar	5 clinvar	30
missense			88 clinvar	15 clinvar	6 clinvar	109
nonsense			1 clinvar			1
start loss						0
frameshift			2 clinvar			2
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	97	39	11	147

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 395 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001908.5	RefSeq	NP_001899.1	9	MANE Select
ENST00000353047.11	Ensembl	ENSP00000345672.5	9	MANE Select
NM_001317237.2	RefSeq	NP_001304166.1	6	Standard
NM_001384714.1	RefSeq	NP_001371643.1	9	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
ctsba	Danio rerio	Structure: whole organism Quality: wholly dorsalized abnormal

Gene / Model

Organism

Observed Phenotype

ctsba

Danio rerio

Structure: whole organism

Quality: wholly dorsalized

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

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)

Biological Process

proteolysis
collagen catabolic process
epithelial cell differentiation
regulation of apoptotic process
neutrophil degranulation

Molecular Function

cysteine-type endopeptidase activity
serine-type endopeptidase activity
protein binding
collagen binding
peptidase activity

Cellular Component

extracellular region
extracellular space
nucleolus
lysosome
endolysosome lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000353047
Coding exons: 9
Length: 26925
Individuals with no LoFs: 125667
Homozygous LoFs: 0
Heterozygous LoFs: 80
Defined: 125747
p: 0.000318

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-3.35	344	208	1.65	0.0000126	2204
Missense (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

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00049	0.00049	rare
Latino/Admixed American	0.00026	0.00023	rare
Ashkenazi Jewish	0.00020	0.00020	rare
East Asian	0.00016	0.00016	rare
Finnish	0.00056	0.00055	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00016	0.00016	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

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.;

Recessive Scores

pRec: 0.666

Intolerance Scores

LoFtool: 0.0421
RVIS EVS: 0
RVIS percentile EVS: 54.07

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.841

Gene Damage Prediction

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