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
• GTEx eGene: eQTL in 45 tissues, sQTL in 2 (q < 0.05)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.14 (unconstrained)
• MANE Select transcript: NM_001335
• Notable: 78 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 13 — 10 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

MANE Select: ENST00000307886

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 2, TSL 5: 1

ENST00000307886, ENST00000524681, ENST00000526034, ENST00000528419, ENST00000679584, ENST00000680443, ENST00000680670, ENST00000681512, ENST00000894912, ENST00000894913, ENST00000959479, ENST00001055491, ENST00001136783

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.

Highest expression (Bgee): granulocyte, blood, bone marrow cell, spleen, decidua.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CTSW is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 45 tissues and its splicing (sQTL) in 2 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 47 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	eqtl	2.3e-114	+0.78	11:65882513:T:C
Whole Blood	eqtl	1.3e-88	+0.34	11:65878360:G:C
Esophagus Mucosa	eqtl	2.3e-81	+0.87	11:65882513:T:C
Colon Transverse	eqtl	1.2e-75	+0.78	11:65877883:A:G
Adipose Visceral Omentum	eqtl	3.7e-75	+0.66	11:65876556:T:C
Nerve Tibial	eqtl	4.7e-68	+0.76	11:65879086:C:A
Artery Aorta	eqtl	2.4e-66	+0.80	11:65877883:A:G
Stomach	eqtl	4.6e-64	+0.88	11:65877883:A:G
Esophagus Muscularis	eqtl	8.6e-62	+0.83	11:65877883:A:G
Lung	eqtl	2.3e-61	+0.67	11:65876556:T:C
Skin Sun Exposed Lower leg	eqtl	2.9e-61	-0.64	11:65894185:T:C
Adipose Subcutaneous	eqtl	2.7e-60	+0.58	11:65877883:A:G
Skin Not Sun Exposed Suprapubic	eqtl	1.8e-56	+0.66	11:65876556:T:C
Spleen	eqtl	4.9e-53	+0.92	11:65877883:A:G
Artery Tibial	eqtl	1.6e-50	+0.61	11:65876556:T:C
Breast Mammary Tissue	eqtl	3.2e-42	+0.62	11:65876556:T:C
Prostate	eqtl	1.7e-38	+0.86	11:65876556:T:C
Pancreas	eqtl	7.0e-37	+0.82	11:65878360:G:C
Esophagus Gastroesophageal Junction	eqtl	5.8e-34	+0.84	11:65876556:T:C
Colon Sigmoid	eqtl	1.7e-32	+0.73	11:65876556:T:C

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
115229	19.0823	357

Top tissues by expression

showing 100 of 287 tissues 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
smooth muscle tissue	UBERON:0001135	67.83	gold quality
body of stomach	UBERON:0001161	67.54	gold quality
trabecular bone tissue	UBERON:0002483	67.27	gold quality
liver	UBERON:0002107	67.02	gold quality
amniotic fluid	UBERON:0000173	66.87	gold quality
lower esophagus mucosa	UBERON:0035834	66.49	gold quality
ascending aorta	UBERON:0001496	66.42	gold quality
thoracic aorta	UBERON:0001515	66.42	gold quality
right coronary artery	UBERON:0001625	66.42	gold quality
duodenum	UBERON:0002114	66.14	gold quality
urinary bladder	UBERON:0001255	66.00	gold quality
subcutaneous adipose tissue	UBERON:0002190	65.99	gold quality
right lobe of thyroid gland	UBERON:0001119	65.85	gold quality
triceps brachii	UBERON:0001509	65.76	gold quality
stomach	UBERON:0000945	65.68	gold quality
transverse colon	UBERON:0001157	65.63	gold quality
ectocervix	UBERON:0012249	65.38	gold quality
left lobe of thyroid gland	UBERON:0001120	65.37	gold quality
gluteal muscle	UBERON:0002000	65.03	gold quality
thyroid gland	UBERON:0002046	65.00	gold quality
adipose tissue	UBERON:0001013	64.77	gold quality
placenta	UBERON:0001987	64.76	gold quality
nasal cavity mucosa	UBERON:0001826	64.61	gold quality
mucosa of stomach	UBERON:0001199	64.55	gold quality
fundus of stomach	UBERON:0001160	64.46	gold quality
vagina	UBERON:0000996	64.45	gold quality
connective tissue	UBERON:0002384	64.26	gold quality
secondary oocyte	CL:0000655	64.18	gold quality
left coronary artery	UBERON:0001626	63.93	gold quality
descending thoracic aorta	UBERON:0002345	63.93	gold quality
left uterine tube	UBERON:0001303	63.84	gold quality
periodontal ligament	UBERON:0008266	63.50	gold quality
intestine	UBERON:0000160	63.40	gold quality
tonsil	UBERON:0002372	63.37	gold quality
coronary artery	UBERON:0001621	62.84	gold quality
minor salivary gland	UBERON:0001830	62.82	gold quality
right atrium auricular region	UBERON:0006631	62.71	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	62.68	gold quality
esophagus mucosa	UBERON:0002469	62.64	gold quality
esophagus	UBERON:0001043	62.57	gold quality
saliva-secreting gland	UBERON:0001044	62.56	gold quality
lower esophagus	UBERON:0013473	62.54	gold quality
lower esophagus muscularis layer	UBERON:0035833	62.45	gold quality
aorta	UBERON:0000947	62.21	gold quality
heart right ventricle	UBERON:0002080	62.19	gold quality
body of uterus	UBERON:0009853	62.18	gold quality
large intestine	UBERON:0000059	62.17	gold quality
endocervix	UBERON:0000458	62.02	gold quality
endometrium	UBERON:0001295	62.02	gold quality
colon	UBERON:0001155	62.01	gold quality
anatomical system	UBERON:0000467	61.81	gold quality
multicellular organism	UBERON:0000468	61.70	gold quality
material anatomical entity	UBERON:0000465	61.68	gold quality
cardiac atrium	UBERON:0002081	61.61	gold quality
prostate gland	UBERON:0002367	61.46	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	61.46	gold quality
biceps brachii	UBERON:0001507	61.44	gold quality
skin of abdomen	UBERON:0001416	61.04	gold quality
skin of leg	UBERON:0001511	61.03	gold quality
mouth mucosa	UBERON:0003729	60.92	gold quality
uterus	UBERON:0000995	60.79	gold quality
esophagus squamous epithelium	UBERON:0006920	60.64	gold quality
spinal cord	UBERON:0002240	60.59	gold quality
female reproductive system	UBERON:0000474	60.32	gold quality
zone of skin	UBERON:0000014	60.05	gold quality
tibial nerve	UBERON:0001323	59.97	gold quality
heart	UBERON:0000948	59.93	gold quality
muscle of leg	UBERON:0001383	59.70	gold quality
left adrenal gland cortex	UBERON:0035825	59.56	gold quality
palpebral conjunctiva	UBERON:0001812	59.55	silver 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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 77 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	109.6	medium
Spleen	tissue	40.0	medium
Lymph node	tissue	27.6	medium
Lung	tissue	22.6	medium
Tonsil	tissue	13.0	medium
Appendix	tissue	12.2	low
Salivary gland	tissue	8.6	not detected
Urinary bladder	tissue	8.1	low
Stomach 1	tissue	7.9	not detected
Thymus	tissue	7.3
Spinal cord	tissue	7.1
Endometrium 1	tissue	6.3	not detected
Liver	tissue	6.1	not detected
Rectum	tissue	6.0	not detected
Gallbladder	tissue	5.9	not detected
Small intestine	tissue	5.8	not detected
Duodenum	tissue	5.7	not detected
Colon	tissue	5.2	not detected
Adipose tissue	tissue	4.8	not detected
Fallopian tube	tissue	3.8	not detected
Substantia nigra	tissue	3.7
Seminal vesicle	tissue	3.6	not detected
Breast	tissue	3.4	not detected
Medulla oblongata	tissue	3.3
Placenta	tissue	3.1	not detected
Esophagus	tissue	2.9	low
Corpus callosum	tissue	2.9
Adrenal gland	tissue	2.8	not detected
Heart muscle	tissue	2.7	not detected
Epididymis	tissue	2.7	not detected
Superior colliculi	tissue	2.7
Periaqueductal gray	tissue	2.7
Skin 1	tissue	2.6	low
Smooth muscle	tissue	2.6	not detected
Cervix	tissue	2.5	not detected
Vagina	tissue	2.4	not detected
Olfactory bulb	tissue	2.3
Pons	tissue	2.2
Midbrain	tissue	2.2
Thalamus	tissue	2.2
Hypothalamus	tissue	2.1
Thyroid gland	tissue	1.9	not detected
Cerebellum	tissue	1.8	not detected
Prostate	tissue	1.8	not detected
Pancreas	tissue	1.7	not detected
Hippocampal formation	tissue	1.7
Entorhinal cortex	tissue	1.7
Septum	tissue	1.7
Locus coeruleus	tissue	1.6
Choroid plexus	tissue	1.5
Ovary	tissue	1.4	not detected
Basal ganglia	tissue	1.4	not detected
Hippocampus	tissue	1.4	not detected
Ventral forebrain	tissue	1.4
Cerebral cortex	tissue	1.3	not detected
Temporal cortex	tissue	1.3
Testis	tissue	1.2	medium
Skeletal muscle	tissue	1.2	not detected
Nucleus accumbens	tissue	1.2
Retrosplenial and cingulate cortex	tissue	1.2

Brain sub-regions (HPA Brain Atlas): detected in 189; highest nTPM — Dorsal spinal cord (7.1), Ventral spinal cord (5.2), Flocculonodular lobe (4.0), Cerebellar cortex (3.6), Nucleus gracilis (3.5).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CTSW by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

14 miRNAs:

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

Functional genomics

gnomAD constraint: pLI 1.5e-12, LOEUF 1.14, missense Z 0.434 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000307886 — one region, missense o/e 0.99.

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)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Carica papaya	P05993	90.0%	Diamond
Arabidopsis thaliana	Q9SUL1	71.7%	Diamond
Felis catus	Q9TST1	71.5%	Diamond
Zea mays	Q10716	69.9%	Diamond
Lathyrus oleraceus	P25804	69.4%	Diamond
Schistosoma mansoni	Q26534	50.5%	Diamond
Theileria parva	P22497	41.5%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
OVOL1-AS1	ncRNA	101927828
SNX32	protein-coding	254122
EFEMP2	protein-coding	30008
OVOL1	protein-coding	5017
MUS81	protein-coding	80198
FIBP	protein-coding	9158
FOSL1	protein-coding	8061
C11orf68	protein-coding	83638
CFL1	protein-coding	1072
DRAP1	protein-coding	10589
CCDC85B	protein-coding	11007

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

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Enzymes, Peptidases, Cysteine-type peptidases, Metabolic proteins, Predicted intracellular proteins, Plasma proteins

Protein evidence: Evidence at protein level

Antibody reliability (HPA): IH enhanced

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)

Position	Role
153
291
331

Disulfide bonds (3)

Type	Positions
Disulfide bond	284–352, 150–191, 184–226

Glycosylation sites (2)

Type	Positions
N-linked (glcnac…) asparagine	50, 205

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 4; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

4 pathways:

ID	Pathway	Evidence
R-HSA-114608	Platelet degranulation	curated
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 (3): immune response (GO:0006955), 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 (8): extracellular region (GO:0005576), 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

3 top-level categories:

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

GO top-level categories

22 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 1 of 17 annotations. The rest are phylogenetic / computational / electronic (IEA).

1 experimentally-supported GO terms:

GO term	NS	Evidence
membrane	CC	high-throughput assay

Protein interactions and networks

STRING

showing 15 of 878 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSW	NKG7	Q16617	601
CTSW	GZMH	P20718	572
CTSW	CD8A	P01732	550
CTSW	GNLY	P09325	543
CTSW	GZMA	P12544	523
CTSW	MS4A1	P08984	513
CTSW	CST7	O76096	509
CTSW	GZMM	P51124	496
CTSW	PRF1	P14222	476
CTSW	KLRD1	Q13241	452
CTSW	KLRB1	Q12918	449
CTSW	KLRK1	P26718	442
CTSW	CD247	P20963	433
CTSW	GZMB	P10144	432
CTSW	GZMK	P49863	432

IntAct

Human interaction partners of CTSW in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

2 partners by confidence:

Partner	Interaction type	MIscore	Records
EMX2	physical association	0.400	1
CREB3	physical association	0.370	1

BioGRID (1 interactions; top human partners by supporting records): CREB3 (Two-hybrid)

Disease & clinical

Genetic variants

Variant evidence for CTSW: 78 ClinVar records (0 pathogenic / likely pathogenic); 4 GWAS associations.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 24 predictions of 878):

Position(s)	Effect	Δscore	Sites
11:65882363	donor_gain	1.0000
11:65882601	acceptor_gain	1.0000
11:65882605	acceptor_gain	1.0000
11:65882607–65882608	acceptor_loss	1.0000	6
11:65882690	donor_loss	1.0000	2
11:65882921	donor_gain	1.0000
11:65882940	donor_gain	1.0000
11:65883067–65883068	acceptor_loss	1.0000	5
11:65883134–65883135	donor_loss	1.0000	4
11:65879942	donor_loss	0.9900	2

AlphaMissense

639 missense substitutions predicted likely pathogenic (of 2,467 scored), across 164 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
N331	8	0.936	0.985
F66	8	0.920	0.986
D93	8	0.899	0.943
D133	8	0.881	0.950
H291	8	0.862	0.931
D183	8	0.827	0.891
W327	7	0.968	0.994
F45	7	0.964	0.987
C284	7	0.961	0.980
C352	7	0.959	0.984
F86	7	0.956	0.991
F298	7	0.955	0.994
W337	7	0.942	0.991
W134	7	0.939	0.993
F42	7	0.929	0.976
F91	7	0.925	0.979
W154	7	0.915	0.986
C184	7	0.913	0.947
C374	7	0.913	0.953
W333	7	0.908	0.969

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Breast Invasive Carcinoma (TCGA)	favorable	8.49e-05
Liver Hepatocellular Carcinoma (validation)	favorable	0.000793

Disease associations

OMIM: gene MIM:602364 | disease phenotypes:

GWAS associations

4 associations:

Study	Trait	p-value
GCST90002393_454	Monocyte count	7e-14
GCST002481_8	Acne (severe)	3e-11
GCST001725_13	Inflammatory bowel disease	3e-10
GCST009798_50	Asthma	2e-9

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0005091	monocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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)

Via MONDO — disease-level, not drug-specific.