CTSZ

protein-coding

cathepsin Z, the group of Cathepsins

Gene summary

The protein encoded by this gene is a lysosomal cysteine proteinase and member of the peptidase C1 family. It exhibits both carboxy-monopeptidase and carboxy-dipeptidase activities. The encoded protein has also been known as cathepsin X and cathepsin P. This gene is expressed ubiquitously in cancer cell lines and primary tumors and, like other members of this family, may be involved in tumorigenesis. [provided by RefSeq, Oct 2008]

MANE transcript

NM_001336.4

Inheritance

—

ClinVar variants

U:50B:7

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 1.5

Max pathogenic AF

—

Genomic locus

chr20:58,985,686-59,008,238

External References & Databases

Ensembl (ENSG00000101160)

Transcript & Mutation Effects

hg38 • Region Span ~22.6 kb

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GenCC 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 CTSZ variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 47

not providedTotal: 4

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001336.4. 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		1
missense			45 clinvar	4 clinvar	2 clinvar	51
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			5 clinvar			5
Total	0	0	50	5	2	57

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 28 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001336.4	RefSeq	NP_001327.2	6	MANE Select
ENST00000217131.6	Ensembl	ENSP00000217131.5	6	MANE Select
ENST00000503833.7	Ensembl	ENSP00000506414.1	5	Standard
ENST00000679948.1	Ensembl	ENSP00000505895.1	5	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Apoptosis - Homo sapiens (human)
Lysosome Vesicle Biogenesis
Clathrin derived vesicle budding
Neutrophil degranulation

Biological Process

angiotensin maturation
proteolysis
endoplasmic reticulum to Golgi vesicle-mediated transport
negative regulation of plasminogen activation
negative regulation of neuron projection development

Molecular Function

carboxypeptidase activity
cysteine-type endopeptidase activity
protein binding
cysteine-type peptidase activity

Cellular Component

Golgi membrane
extracellular region
extracellular space
lysosome
endoplasmic reticulum

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000217131
Coding exons: 6
Length: 12063
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	0.600	150	172	0.871	0.0000102	1953
Missense (PolyPhen)		50	62.318	0.80234		660
Synonymous	-0.178	75	73.1	1.03	0.00000503	585
Loss of Function	-1.70	20	13.3	1.50	5.68e-7	154

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00074	0.00074	rare
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0.00010	0.000099	rare
East Asian	0.00011	0.00011	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00028	0.00027	rare
South Asian	0.00046	0.00046	rare
Other	0.00049	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Exhibits carboxy-monopeptidase as well as carboxy- dipeptidase activity.;

Recessive Scores

pRec: 0.149

Intolerance Scores

LoFtool: 0.573
RVIS EVS: 0.62
RVIS percentile EVS: 83.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.713

Gene Damage Prediction

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