# CTSW > Gene · canonical: https://sugi.bio/atlas/gene/CTSW/ > Atlas v1.12.2 · generated 2026-10-13T13:32:47+00:00 ## 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](https://www.ncbi.nlm.nih.gov/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](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-6701) | yes | 6114.17 | | [E-HCAD-24](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-24) | yes | 5242.71 | | [E-MTAB-6678](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-6678) | yes | 4396.27 | | [E-CURD-120](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-120) | yes | 2840.47 | | [E-MTAB-6505](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-6505) | yes | 2443.67 | | [E-GEOD-70580](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-70580) | yes | 2206.72 | | [E-CURD-55](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-55) | yes | 2087.42 | | [E-HCAD-4](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-4) | yes | 1888.59 | | [E-GEOD-149689](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-149689) | yes | 1847.03 | | [E-CURD-122](https://www.ebi.ac.uk/gxa/sc/experiments/E-CURD-122) | yes | 1800.08 | | [E-HCAD-15](https://www.ebi.ac.uk/gxa/sc/experiments/E-HCAD-15) | yes | 1650.75 | | [E-MTAB-8207](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-8207) | yes | 1594.69 | | [E-MTAB-9467](https://www.ebi.ac.uk/gxa/sc/experiments/E-MTAB-9467) | yes | 1560.42 | | [E-GEOD-139324](https://www.ebi.ac.uk/gxa/sc/experiments/E-GEOD-139324) | yes | 1499.90 | | [E-CURD-112](https://www.ebi.ac.uk/gxa/sc/experiments/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](https://gnomad.broadinstitute.org/) **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](https://www.uniprot.org/uniprotkb/P05993/entry) | 90.0% | Diamond | | Arabidopsis thaliana | [Q9SUL1](https://www.uniprot.org/uniprotkb/Q9SUL1/entry) | 71.7% | Diamond | | Felis catus | [Q9TST1](https://www.uniprot.org/uniprotkb/Q9TST1/entry) | 71.5% | Diamond | | Zea mays | [Q10716](https://www.uniprot.org/uniprotkb/Q10716/entry) | 69.9% | Diamond | | Lathyrus oleraceus | [P25804](https://www.uniprot.org/uniprotkb/P25804/entry) | 69.4% | Diamond | | Schistosoma mansoni | [Q26534](https://www.uniprot.org/uniprotkb/Q26534/entry) | 50.5% | Diamond | | Theileria parva | [P22497](https://www.uniprot.org/uniprotkb/P22497/entry) | 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](/atlas/gene/OVOL1-AS1/) | ncRNA | 101927828 | | [SNX32](/atlas/gene/SNX32/) | protein-coding | 254122 | | [EFEMP2](/atlas/gene/EFEMP2/) | protein-coding | 30008 | | [OVOL1](/atlas/gene/OVOL1/) | protein-coding | 5017 | | [MUS81](/atlas/gene/MUS81/) | protein-coding | 80198 | | [FIBP](/atlas/gene/FIBP/) | protein-coding | 9158 | | [FOSL1](/atlas/gene/FOSL1/) | protein-coding | 8061 | | [C11orf68](/atlas/gene/C11orf68/) | protein-coding | 83638 | | [CFL1](/atlas/gene/CFL1/) | protein-coding | 1072 | | [DRAP1](/atlas/gene/DRAP1/) | protein-coding | 10589 | | [CCDC85B](/atlas/gene/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 →](https://www.uniprot.org/uniprotkb/P56202/entry) **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](https://amigo.geneontology.org/amigo/term/GO:0016020) | 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](#clinvar) (0 pathogenic / likely pathogenic); [4 GWAS associations](#gwas-assoc). #### 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. ## Related Atlas pages *No linked Atlas pages yet — the cross-entity mesh grows as the corpus expands.*