CTSW

Summary

CTSW (cathepsin W, HGNC:2546) is a protein-coding gene on chromosome 11q13.1, encoding Cathepsin W (P56202). May have a specific function in the mechanism or regulation of T-cell cytolytic activity.

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.

Source: NCBI Gene 1521 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 78 total
• MANE Select transcript: NM_001335

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2546
Approved symbol	CTSW
Name	cathepsin W
Location	11q13.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000172543
Ensembl biotype	protein_coding
OMIM	602364
Entrez	1521

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 9 protein_coding, 1 retained_intron, 1 nonsense_mediated_decay

ENST00000307886, ENST00000524681, ENST00000526034, ENST00000528419, ENST00000679584, ENST00000680443, ENST00000680670, ENST00000681512, ENST00000894912, ENST00000894913, ENST00000959479

RefSeq mRNA: 1 — MANE Select: NM_001335 NM_001335

CCDS: CCDS8117

Canonical transcript exons

ENST00000307886 — 10 exons

Exon	Start	End
ENSE00001190463	65883215	65883424
ENSE00001190470	65883069	65883133
ENSE00001190475	65882779	65882904
ENSE00001190483	65882609	65882689
ENSE00001190494	65882430	65882526
ENSE00001190505	65882175	65882329
ENSE00001190516	65881407	65881520
ENSE00001190530	65880202	65880286
ENSE00001219070	65883508	65883741
ENSE00001219076	65879837	65879941

Expression profiles

Bgee: expression breadth ubiquitous, 171 present calls, max score 99.46.

FANTOM5 (CAGE): breadth broad, TPM avg 19.0823 / max 2662.2613, expressed in 357 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
115229	19.0823	357

Top tissues by expression

287 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
granulocyte	CL:0000094	99.46	gold quality
blood	UBERON:0000178	93.26	gold quality
bone marrow cell	CL:0002092	91.89	gold quality
spleen	UBERON:0002106	88.29	gold quality
decidua	UBERON:0002450	88.10	gold quality
bone marrow	UBERON:0002371	86.54	gold quality
leukocyte	CL:0000738	85.22	gold quality
mononuclear cell	CL:0000842	83.94	gold quality
monocyte	CL:0000576	83.58	gold quality
lymph node	UBERON:0000029	83.12	gold quality
upper lobe of left lung	UBERON:0008952	80.42	gold quality
right lung	UBERON:0002167	80.38	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.20	gold quality
vermiform appendix	UBERON:0001154	78.45	gold quality
gall bladder	UBERON:0002110	77.50	gold quality
upper lobe of lung	UBERON:0008948	77.48	gold quality
right lobe of liver	UBERON:0001114	77.27	gold quality
mucosa of transverse colon	UBERON:0004991	76.28	gold quality
rectum	UBERON:0001052	75.03	gold quality
caecum	UBERON:0001153	73.49	gold quality
right uterine tube	UBERON:0001302	72.26	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	71.46	gold quality
apex of heart	UBERON:0002098	71.06	gold quality
omental fat pad	UBERON:0010414	70.67	gold quality
peritoneum	UBERON:0002358	70.59	gold quality
lung	UBERON:0002048	70.58	gold quality
adipose tissue of abdominal region	UBERON:0007808	70.22	gold quality
colonic epithelium	UBERON:0000397	70.17	gold quality
small intestine Peyer’s patch	UBERON:0003454	69.12	gold quality
small intestine	UBERON:0002108	68.25	gold quality

Single-cell (SCXA)

Detected in 43 experiment(s), a significant marker in 40.

Experiment	Marker?	Max mean expression
E-MTAB-6701	yes	6114.17
E-HCAD-24	yes	5242.71
E-MTAB-6678	yes	4396.27
E-CURD-120	yes	2840.47
E-MTAB-6505	yes	2443.67
E-GEOD-70580	yes	2206.72
E-CURD-55	yes	2087.42
E-HCAD-4	yes	1888.59
E-GEOD-149689	yes	1847.03
E-CURD-122	yes	1800.08
E-HCAD-15	yes	1650.75
E-MTAB-8207	yes	1594.69
E-MTAB-9467	yes	1560.42
E-GEOD-139324	yes	1499.90
E-CURD-112	yes	1495.46

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

14 targeting CTSW, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-4999-5P	99.35	69.15	926
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-506-5P	98.02	67.41	1065
HSA-MIR-5186	94.63	66.76	627

Literature-anchored findings (GeneRIF, showing 7)

• Endogenous cathepsin W is expressed predominantly in NK cells, is up-regulated by IL-2, and is mainly targeted to the endoplasmic reticulum. (PMID:11490002)
• Cathepsin W-positive cells had a ’lymphocyte phenotype’, but the relative portion of cathepsin W-positive cells among the infiltrating leukocytes in gastrointestinal disease differed remarkably. (PMID:12437118)
• a genetic variant and a novel isoform of cathepsin W are present in about 14% and 12%, respectively, within the Caucasian population (PMID:15358123)
• Despite being expressed in the effector subset of CD8(+) and NK cells and of being released during target cell killing, our functional inhibition studies exclude an essential role of CatW in the process of cytotoxicity. (PMID:19100676)
• The predominant expression of wildtype form by infiltrating immune cells was confirmed in 116 patients with gastroesophageal reflux disease and 27 reflux-negative individuals demonstrating that cathepsin W expression is not altered in this disease. (PMID:22050231)
• These results establish CtsW as an important host factor for entry of influenza A virus into target cells and suggest that CtsW could be a promising target for the development of future antiviral drugs. (PMID:26060270)
• Proteomic Identification of Potential Target Proteins of Cathepsin W for Its Development as a Drug Target for Influenza. (PMID:35867415)

Cross-species orthologs

23 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctsl.1	ENSDARG00000003902
danio_rerio	ctss1	ENSDARG00000036940
danio_rerio	tinagl1	ENSDARG00000061231
danio_rerio	ctsbb	ENSDARG00000101051
mus_musculus	Ctsw	ENSMUSG00000024910
rattus_norvegicus	Ctsw	ENSRNOG00000027096
drosophila_melanogaster	CtsB	FBGN0030521
drosophila_melanogaster	Swim	FBGN0034709
caenorhabditis_elegans		WBGENE00000781
caenorhabditis_elegans		WBGENE00000782
caenorhabditis_elegans		WBGENE00000784
caenorhabditis_elegans		WBGENE00000785
caenorhabditis_elegans	cpz-1	WBGENE00000788
caenorhabditis_elegans	F26E4.3	WBGENE00009158
caenorhabditis_elegans		WBGENE00013072
caenorhabditis_elegans		WBGENE00013076
caenorhabditis_elegans		WBGENE00013764
caenorhabditis_elegans		WBGENE00016300
caenorhabditis_elegans		WBGENE00016306
caenorhabditis_elegans		WBGENE00019314
caenorhabditis_elegans		WBGENE00019986
caenorhabditis_elegans		WBGENE00022189
caenorhabditis_elegans		WBGENE00044760

Paralogs (12): CTSZ (ENSG00000101160), CTSH (ENSG00000103811), CTSC (ENSG00000109861), CTSL (ENSG00000135047), CTSV (ENSG00000136943), TINAG (ENSG00000137251), TINAGL1 (ENSG00000142910), CTSK (ENSG00000143387), CTSS (ENSG00000163131), CTSB (ENSG00000164733), CTSF (ENSG00000174080), CTSO (ENSG00000256043)

Protein

Protein identifiers

Cathepsin W — P56202 (reviewed: P56202)

Alternative names: Lymphopain

All UniProt accessions (7): P56202, A0A7P0T817, A0A7P0T8B4, A0A7P0T8L7, A0A7P0TAB1, E9PI30, H0YDT2

UniProt curated annotations — full annotation on UniProt →

Function. May have a specific function in the mechanism or regulation of T-cell cytolytic activity. (Microbial infection) Plays a role during influenza virus infection in lungs cells ex vivo. Acts at the level of virus entering host cytoplasm from late endosome.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Expressed predominantly in natural killer cells, and in cytotoxic T cells.

Similarity. Belongs to the peptidase C1 family.

RefSeq proteins (1): NP_001326* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000668	Peptidase_C1A_C	Domain
IPR013128	Peptidase_C1A	Family
IPR013201	Prot_inhib_I29	Domain
IPR025660	Pept_his_AS	Active_site
IPR025661	Pept_asp_AS	Active_site
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR039417	Peptidase_C1A_papain-like	Domain

Pfam: PF00112, PF08246

UniProt features (14 total): disulfide bond 3, active site 3, sequence variant 2, glycosylation site 2, signal peptide 1, propeptide 1, sequence conflict 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P56202-F1	84.28	0.69

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (3): 153; 291; 331

Disulfide bonds (3): 284–352, 150–191, 184–226

Glycosylation sites (2): 50, 205

Function

Pathways and Gene Ontology

Reactome pathways

4 pathways

ID	Pathway
R-HSA-114608	Platelet degranulation
R-HSA-109582	Hemostasis
R-HSA-76002	Platelet activation, signaling and aggregation
R-HSA-76005	Response to elevated platelet cytosolic Ca2+

MSigDB gene sets: 253 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, GSE18804_SPLEEN_MACROPHAGE_VS_COLON_TUMORAL_MACROPHAGE_UP, GOCC_SECRETORY_GRANULE, REACTOME_PLATELET_ACTIVATION_SIGNALING_AND_AGGREGATION, GOLDRATH_IMMUNE_MEMORY, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_LYSOSOME, chr11q13, GNF2_ZAP70, DEURIG_T_CELL_PROLYMPHOCYTIC_LEUKEMIA_DN, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, WONG_ENDMETRIUM_CANCER_DN, GNF2_IL2RB, SANSOM_APC_TARGETS_DN, RYTTCCTG_ETS2_B

GO Biological Process (4): immune response (GO:0006955), obsolete proteolysis involved in protein catabolic process (GO:0051603), immune system process (GO:0002376), proteolysis (GO:0006508)

GO Molecular Function (4): cysteine-type endopeptidase activity (GO:0004197), cysteine-type peptidase activity (GO:0008234), peptidase activity (GO:0008233), hydrolase activity (GO:0016787)

GO Cellular Component (9): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), lysosome (GO:0005764), endoplasmic reticulum (GO:0005783), membrane (GO:0016020), platelet dense granule lumen (GO:0031089), cytoplasm (GO:0005737), endomembrane system (GO:0012505), intracellular organelle lumen (GO:0070013)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Response to elevated platelet cytosolic Ca2+	1
Hemostasis	1
Platelet activation, signaling and aggregation	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
immune system process	1
response to stimulus	1
biological_process	1
protein metabolic process	1
endopeptidase activity	1
cysteine-type peptidase activity	1
peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
catalytic activity	1
lytic vacuole	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
secretory granule lumen	1
platelet dense granule	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1
intracellular organelle	1
organelle lumen	1

Protein interactions and networks

STRING

1233 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSW	GZMH	P20718	540
CTSW	NKG7	Q16617	533
CTSW	CD8A	P01732	527
CTSW	LRRC8D	Q7L1W4	513
CTSW	GZMA	P12544	491
CTSW	TNFRSF18	Q9Y5U5	487
CTSW	GNLY	P09325	475
CTSW	CTSL	P07711	467
CTSW	PTPRCAP	Q14761	450
CTSW	CST7	O76096	447
CTSW	GZMK	P49863	444
CTSW	LGMN	Q99538	435
CTSW	PCSK4	Q6UW60	411
CTSW	IHH	Q14623	387
CTSW	KLRB1	Q12918	386

IntAct

3 interactions, top by confidence:

A	B	Type	Score
EMX2	CTSW	psi-mi:“MI:0915”(physical association)	0.400
CTSW	CREB3	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (2): CTSW (Two-hybrid), EMX2 (Proximity Label-MS)

ESM2 similar proteins: A0A068CNX1, A0A072UTP9, A0A0F7G352, D3ZZ07, F4JNL3, O35186, O46427, O60911, O70370, P00786, P06797, P07154, P07711, P09668, P15242, P25326, P25773, P25774, P43235, P43236, P49935, P55097, P56202, P56203, P61276, P61277, Q02765, Q3T0I2, Q3ZKN1, Q40143, Q5E968, Q63088, Q6YD92, Q80UB0, Q8H166, Q8HY81, Q8HY82, Q8RWQ9, Q8VYS0, Q90686

Diamond homologs: A0A068CNX1, A0A0F7G352, A0A1S4F2V5, D3ZZ07, O10364, O35186, O45734, O60911, O70370, O91466, O97578, P00786, P04988, P05993, P06797, P07154, P07711, P09648, P0DO76, P13277, P14658, P15242, P25326, P25773, P25774, P25775, P25778, P25779, P25782, P25783, P25784, P25804, P25975, P35591, P36400, P41715, P41721, P43234, P43235, P43236

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

78 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	65
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1632 predictions. Top by Δscore:

Variant	Effect	Δscore
11:65879938:CCAGG:C	donor_loss	1.0000
11:65879939:CAGG:C	donor_loss	1.0000
11:65879940:AGGT:A	donor_loss	1.0000
11:65879941:GGT:G	donor_loss	1.0000
11:65879942:G:GA	donor_loss	1.0000
11:65881399:T:TA	acceptor_gain	1.0000
11:65881439:AACCT:A	acceptor_gain	1.0000
11:65882173:A:AG	acceptor_gain	1.0000
11:65882174:G:GG	acceptor_gain	1.0000
11:65882174:GA:G	acceptor_gain	1.0000
11:65882174:GAGGA:G	acceptor_gain	1.0000
11:65882363:C:G	donor_gain	1.0000
11:65882601:T:A	acceptor_gain	1.0000
11:65882603:CACCA:C	acceptor_loss	1.0000
11:65882604:A:AG	acceptor_gain	1.0000
11:65882604:ACCAG:A	acceptor_loss	1.0000
11:65882605:C:G	acceptor_gain	1.0000
11:65882605:CCAGA:C	acceptor_loss	1.0000
11:65882606:CAGA:C	acceptor_loss	1.0000
11:65882607:A:AC	acceptor_loss	1.0000
11:65882607:A:AG	acceptor_gain	1.0000
11:65882608:G:GA	acceptor_gain	1.0000
11:65882608:GA:G	acceptor_gain	1.0000
11:65882608:GAACT:G	acceptor_gain	1.0000
11:65882685:CAACA:C	donor_gain	1.0000
11:65882686:AACA:A	donor_gain	1.0000
11:65882686:AACAG:A	donor_loss	1.0000
11:65882687:ACA:A	donor_gain	1.0000
11:65882687:ACAG:A	donor_loss	1.0000
11:65882688:CA:C	donor_gain	1.0000

AlphaMissense

2467 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:65883296:T:C	F298L	0.994
11:65883298:T:A	F298L	0.994
11:65883298:T:G	F298L	0.994
11:65883385:G:C	W327C	0.994
11:65883385:G:T	W327C	0.994
11:65882290:G:C	W134C	0.993
11:65882290:G:T	W134C	0.993
11:65881490:T:C	F86L	0.991
11:65881492:T:A	F86L	0.991
11:65881492:T:G	F86L	0.991
11:65883415:G:C	W337C	0.991
11:65883415:G:T	W337C	0.991
11:65880247:T:C	F45L	0.987
11:65880249:C:A	F45L	0.987
11:65880249:C:G	F45L	0.987
11:65880259:T:C	F49L	0.987
11:65880261:C:A	F49L	0.987
11:65880261:C:G	F49L	0.987
11:65882471:C:A	N161K	0.987
11:65882471:C:G	N161K	0.987
11:65881430:T:C	F66L	0.986
11:65881432:T:A	F66L	0.986
11:65881432:T:G	F66L	0.986
11:65881508:A:C	S92R	0.986
11:65881510:T:A	S92R	0.986
11:65881510:T:G	S92R	0.986
11:65882450:G:C	W154C	0.986
11:65882450:G:T	W154C	0.986
11:65883383:T:A	W327R	0.986
11:65883383:T:C	W327R	0.986

dbSNP variants (sampled 300 via entrez): RS1000433510 (11:65883003 G>C,T), RS1000583119 (11:65880911 C>G), RS1000765021 (11:65884006 G>A), RS1001059607 (11:65879009 A>G), RS1001830491 (11:65877952 G>C), RS1002057686 (11:65879652 G>A), RS1002179802 (11:65878232 T>A), RS1002554502 (11:65879393 T>C), RS1002556349 (11:65878589 T>G), RS1002587288 (11:65878381 A>G), RS1003017807 (11:65883785 C>G), RS1003824061 (11:65880614 C>T), RS1004325865 (11:65879766 C>T), RS1004500720 (11:65880325 C>T), RS1004564324 (11:65881314 G>A)

Disease associations

OMIM: gene MIM:602364 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001725_13	Inflammatory bowel disease	3.000000e-10
GCST002481_8	Acne (severe)	3.000000e-11
GCST009798_25	Asthma	2.000000e-09
GCST90002393_432	Monocyte count	7.000000e-14

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

18 total (human), top 18 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
aristolochic acid I	increases expression	1
GSK-J4	decreases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
(+)-JQ1 compound	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Atrazine	increases expression	1
Diuron	decreases expression	1
Endosulfan	increases expression	1
Estradiol	affects cotreatment, decreases expression	1
Nickel	increases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Progesterone	affects cotreatment, decreases expression	1
Dronabinol	decreases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.