CTSW

protein-coding

cathepsin W, the group of Cathepsins

Gene summary

The protein encoded by this gene, a member of the peptidase C1 family, is a cysteine proteinase that may have a specific function in the mechanism or regulation of T-cell cytolytic activity. The encoded protein is found associated with the membrane inside the endoplasmic reticulum of natural killer and cytotoxic T-cells. Expression of this gene is up-regulated by interleukin-2. [provided by RefSeq, Jul 2008]

MANE transcript

NM_001335.4

Inheritance

—

ClinVar variants

U:69B:3

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.93

Max pathogenic AF

—

Genomic locus

chr11:65,879,809-65,883,741

External References & Databases

Ensembl (ENSG00000172543)

Transcript & Mutation Effects

hg38 • Region Span ~3.9 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 CTSW variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 67

not providedTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001335.4. 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						0
missense			66 clinvar	2 clinvar		68
nonsense			1 clinvar			1
start loss						0
frameshift				1 clinvar		1
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	0	0	69	3	0	72

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001335.4	RefSeq	NP_001326.3	10	MANE Select
ENST00000307886.8	Ensembl	ENSP00000311300.3	10	MANE Select
ENST00000526034.2	Ensembl	ENSP00000434267.2	9	Standard
ENST00000526034.3	Ensembl	ENSP00000434267.2	9	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Lysosome - Homo sapiens (human)
Apoptosis - Homo sapiens (human)
Platelet degranulation
Response to elevated platelet cytosolic Ca2+
Platelet activation, signaling and aggregation

Biological Process

platelet degranulation
immune response
proteolysis involved in cellular protein catabolic process

Molecular Function

cysteine-type endopeptidase activity
cysteine-type peptidase activity

Cellular Component

extracellular region
extracellular space
lysosome
membrane
platelet dense granule lumen

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000307886
Coding exons: 10
Length: 3933
Individuals with no LoFs: 125007
Homozygous LoFs: 8
Heterozygous LoFs: 733
Defined: 125748
p: 0.00295

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	-0.674	247	219	1.13	0.0000127	2456
Missense (PolyPhen)		85	82.144	1.0348		928
Synonymous	0.0453	87	87.5	0.994	0.00000530	737
Loss of Function	0.293	18	19.4	0.928	8.31e-7	223

Population LoF Frequency

Population	CAF	p-value	Status
African	0.0020	0.0020	notable
Latino/Admixed American	0.019	0.019	notable
Ashkenazi Jewish	0.00079	0.00079	rare
East Asian	0.00050	0.00049	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00018	0.00018	rare
South Asian	0.00054	0.00052	rare
Other	0.0033	0.0033	notable

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May have a specific function in the mechanism or regulation of T-cell cytolytic activity.;

Recessive Scores

pRec: 0.162

Intolerance Scores

RVIS EVS: -0.75
RVIS percentile EVS: 13.58

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.152

Gene Damage Prediction

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