CTSO

Summary

CTSO (cathepsin O, HGNC:2542) is a protein-coding gene on chromosome 4q32.1, encoding Cathepsin O (P43234). Proteolytic enzyme possibly involved in normal cellular protein degradation and turnover.

The protein encoded by the gene is a cysteine proteinase and a member of the papain superfamily. This proteolytic enzyme is involved in cellular protein degradation and turnover. The recombinant form of this enzyme was shown to degrade synthetic peptides typically used as substrates for cysteine proteinases and its proteolytic activity was abolished by an inhibitor of cyteine proteinase.

Source: NCBI Gene 1519 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 56 total
• MANE Select transcript: NM_001334

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2542
Approved symbol	CTSO
Name	cathepsin O
Location	4q32.1
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000256043
Ensembl biotype	protein_coding
OMIM	600550
Entrez	1519

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 4 nonsense_mediated_decay

ENST00000433477, ENST00000676791, ENST00000678374, ENST00000679136, ENST00000679625, ENST00000679942, ENST00000679996, ENST00000680553, ENST00000680741, ENST00000681379, ENST00000859966, ENST00000859967, ENST00000952268

RefSeq mRNA: 1 — MANE Select: NM_001334 NM_001334

CCDS: CCDS3794

Canonical transcript exons

ENST00000433477 — 8 exons

Exon	Start	End
ENSE00001612008	155924118	155926070
ENSE00001751842	155929542	155929705
ENSE00001753351	155928336	155928428
ENSE00002080357	155953713	155953866
ENSE00002218314	155937362	155937483
ENSE00002435290	155943156	155943264
ENSE00002444303	155942317	155942456
ENSE00002524268	155939371	155939538

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 96.11.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 10.4204 / max 109.1830, expressed in 1543 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
54542	10.0461	1527
54543	0.3743	211

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	96.11	gold quality
gall bladder	UBERON:0002110	95.18	gold quality
endometrium	UBERON:0001295	94.19	gold quality
right coronary artery	UBERON:0001625	93.20	gold quality
smooth muscle tissue	UBERON:0001135	93.07	gold quality
placenta	UBERON:0001987	92.81	gold quality
mucosa of stomach	UBERON:0001199	92.68	gold quality
liver	UBERON:0002107	92.62	gold quality
duodenum	UBERON:0002114	92.54	gold quality
monocyte	CL:0000576	92.35	gold quality
right lobe of liver	UBERON:0001114	92.31	gold quality
leukocyte	CL:0000738	92.23	gold quality
fallopian tube	UBERON:0003889	92.00	gold quality
descending thoracic aorta	UBERON:0002345	91.89	gold quality
left coronary artery	UBERON:0001626	91.56	gold quality
right lung	UBERON:0002167	91.45	gold quality
colonic epithelium	UBERON:0000397	91.08	gold quality
thoracic aorta	UBERON:0001515	90.91	gold quality
rectum	UBERON:0001052	90.84	gold quality
ascending aorta	UBERON:0001496	90.83	gold quality
endocervix	UBERON:0000458	90.33	gold quality
lung	UBERON:0002048	89.91	gold quality
body of uterus	UBERON:0009853	89.91	gold quality
metanephros cortex	UBERON:0010533	89.91	gold quality
left adrenal gland	UBERON:0001234	89.76	gold quality
left adrenal gland cortex	UBERON:0035825	89.68	gold quality
lymph node	UBERON:0000029	89.46	gold quality
tibial artery	UBERON:0007610	89.42	gold quality
popliteal artery	UBERON:0002250	89.39	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.31	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

73 targeting CTSO, 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-6873-3P	100.00	71.42	2626
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-4747-5P	100.00	67.90	2681
HSA-MIR-5196-5P	100.00	67.98	2761
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-218-5P	99.93	72.22	2103
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-5680	99.91	69.83	3421
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-153-5P	99.89	73.86	6317
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-3133	99.81	70.92	3506
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-1303	99.65	69.77	1662
HSA-MIR-105-5P	99.54	69.24	2060
HSA-MIR-7853-5P	99.54	69.30	2055

Literature-anchored findings (GeneRIF, showing 3)

• In this study, various molecular dynamics (MD) simulations of pro- and mature human cathepsins L and O were performed. (PMID:23009386)
• a single-nucleotide polymorphism near the CTSO gene is a poor prognostic factor in breast cancer although further research might help to reveal the factors linking this genotype and prognosis. (PMID:26482374)
• We report that CTSO reduces the protein levels of BRCA1 and ZNF423 through cysteine proteinase-mediated degradation. We also have identified a series of transcription factors of BRCA1 that are regulated by CTSO at the protein level. (PMID:28968398)

Cross-species orthologs

16 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctso	ENSDARG00000052855
mus_musculus	Ctso	ENSMUSG00000028015
rattus_norvegicus	Ctso	ENSRNOG00000066128
caenorhabditis_elegans		WBGENE00000781
caenorhabditis_elegans		WBGENE00000782
caenorhabditis_elegans		WBGENE00000784
caenorhabditis_elegans		WBGENE00000785
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), CTSW (ENSG00000172543), CTSF (ENSG00000174080)

Protein

Protein identifiers

Cathepsin O — P43234 (reviewed: P43234)

All UniProt accessions (10): A0A7I2V4E3, A0A7I2V4S1, A0A7P0T898, A0A7P0T8T8, A0A7P0T996, A0A7P0Z4C4, A0A7P0Z4D8, A0A7P0Z4I5, A0A7P0Z4L5, P43234

UniProt curated annotations — full annotation on UniProt →

Function. Proteolytic enzyme possibly involved in normal cellular protein degradation and turnover.

Subcellular location. Lysosome.

Tissue specificity. Expressed in all tissues examined. High levels seen in the ovary, kidney and placenta while low levels seen in thymus and skeletal muscle.

Similarity. Belongs to the peptidase C1 family.

RefSeq proteins (1): NP_001325* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000169	Pept_cys_AS	Active_site
IPR000668	Peptidase_C1A_C	Domain
IPR013128	Peptidase_C1A	Family
IPR025660	Pept_his_AS	Active_site
IPR038765	Papain-like_cys_pep_sf	Homologous_superfamily
IPR039417	Peptidase_C1A_papain-like	Domain

Pfam: PF00112

UniProt features (11 total): disulfide bond 3, active site 3, glycosylation site 2, signal peptide 1, propeptide 1, chain 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P43234-F1	89.69	0.80

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): 132; 269; 289

Disulfide bonds (3): 262–310, 129–170, 163–204

Glycosylation sites (2): 62, 105

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-1280218	Adaptive Immune System
R-HSA-168256	Immune System

MSigDB gene sets: 158 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_DN, MODULE_172, chr4q32, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_LYSOSOME, CHANDRAN_METASTASIS_DN, CAIRO_HEPATOBLASTOMA_CLASSES_DN, LI_WILMS_TUMOR_VS_FETAL_KIDNEY_1_UP, HOSHIDA_LIVER_CANCER_SUBCLASS_S3, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_AND_CANCER_BOX4_DN, BROWNE_HCMV_INFECTION_24HR_DN

GO Biological Process (2): proteolysis (GO:0006508), obsolete proteolysis involved in protein catabolic process (GO:0051603)

GO Molecular Function (5): cysteine-type endopeptidase activity (GO:0004197), protein binding (GO:0005515), peptidase activity (GO:0008233), cysteine-type peptidase activity (GO:0008234), hydrolase activity (GO:0016787)

GO Cellular Component (2): obsolete extracellular space (GO:0005615), lysosome (GO:0005764)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Adaptive Immune System	1
Immune System	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein metabolic process	1
endopeptidase activity	1
cysteine-type peptidase activity	1
binding	1
hydrolase activity	1
catalytic activity, acting on a protein	1
peptidase activity	1
catalytic activity	1
lytic vacuole	1

Protein interactions and networks

STRING

994 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSO	ZNF423	Q2M1K9	541
CTSO	RBM46	Q8TBY0	460
CTSO	KLHL2	O95198	431
CTSO	LGMN	Q99538	412
CTSO	TDO2	P48775	411
CTSO	GUCY1B1	Q02153	407
CTSO	ESPL1	Q14674	390
CTSO	CDCP1	Q9H5V8	388
CTSO	MAEA	Q7L5Y9	373
CTSO	PSMA1	P25786	365
CTSO	CTSD	P07339	338
CTSO	GNB1L	Q9BYB4	334
CTSO	DDX59	Q5T1V6	315
CTSO	GUCY1A1	Q02108	314
CTSO	BLMH	Q13867	313
CTSO	BCS1L	Q9Y276	313

IntAct

27 interactions, top by confidence:

A	B	Type	Score
CTSO	PRKCA	psi-mi:“MI:0915”(physical association)	0.560
CTSO	YWHAG	psi-mi:“MI:0915”(physical association)	0.560
CTSO	SETDB1	psi-mi:“MI:0915”(physical association)	0.560
CTSO	KAT5	psi-mi:“MI:0915”(physical association)	0.560
CTSO	LMO3	psi-mi:“MI:0915”(physical association)	0.560
KNG1	CTSV	psi-mi:“MI:0914”(association)	0.530
MTFR1	CTSO	psi-mi:“MI:0915”(physical association)	0.400
KNG1	CTSV	psi-mi:“MI:0914”(association)	0.350
CTSO	LYPLA1	psi-mi:“MI:0914”(association)	0.350
CSTA	CTSV	psi-mi:“MI:0914”(association)	0.350
CST3	CTSV	psi-mi:“MI:0914”(association)	0.350
CSTB	CTSH	psi-mi:“MI:0914”(association)	0.350
CTSO	hldE	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (20): LYPLA1 (Affinity Capture-MS), GRN (Affinity Capture-MS), AMZ2 (Affinity Capture-MS), CTSO (Affinity Capture-MS), CTSO (Affinity Capture-MS), LYPLA1 (Affinity Capture-MS), GRN (Affinity Capture-MS), CTSO (Synthetic Lethality), CTSO (Affinity Capture-MS), LYPLA1 (Affinity Capture-MS), CTSO (Affinity Capture-MS), GRN (Affinity Capture-MS), PGLYRP3 (Affinity Capture-MS), CTSO (Affinity Capture-MS), CTSO (Affinity Capture-MS)

ESM2 similar proteins: A1E295, O65493, O70370, P00787, P05689, P06797, P07154, P07688, P07711, P07858, P10605, P10619, P16675, P25326, P25773, P25774, P25775, P25804, P35591, P43233, P43234, P43295, P43296, P83205, Q02765, Q10716, Q13219, Q16819, Q26534, Q3MI05, Q3SZI1, Q3ZKN1, Q4R5M2, Q5R6D1, Q7TN16, Q8BM88, Q8HY81, Q8R4K8, Q8VYS0, Q920A5

Diamond homologs: A0A509APV9, A5YVK8, A8DS38, B2LSD2, D3ZZ07, F4JNL3, O10364, O23791, O35186, O45734, O60911, O65039, O70370, O91466, O97397, O97578, P04989, P05994, P06797, P07154, P09648, P12412, P14080, P14518, P20721, P25249, P25250, P25251, P25326, P25773, P25775, P25776, P25777, P25781, P25783, P25784, P25803, P25805, P35591, P36184

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	44
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

0 predictions. Top by Δscore:

AlphaMissense

2103 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:155928394:C:A	W291C	0.997
4:155928394:C:G	W291C	0.997
4:155928396:A:G	W291R	0.996
4:155928396:A:T	W291R	0.996
4:155929632:A:G	W250R	0.996
4:155929632:A:T	W250R	0.996
4:155928338:C:G	C310S	0.995
4:155928339:A:T	C310S	0.995
4:155928382:C:A	W295C	0.995
4:155928382:C:G	W295C	0.995
4:155939455:A:C	S156R	0.995
4:155939455:A:T	S156R	0.995
4:155939457:T:G	S156R	0.995
4:155939524:C:A	W133C	0.995
4:155939524:C:G	W133C	0.995
4:155943160:A:C	F80L	0.994
4:155943160:A:T	F80L	0.994
4:155943162:A:G	F80L	0.994
4:155928338:C:T	C310Y	0.993
4:155928400:A:C	N289K	0.993
4:155928400:A:T	N289K	0.993
4:155928384:A:G	W295R	0.992
4:155928384:A:T	W295R	0.992
4:155929594:G:C	C262W	0.992
4:155939414:C:G	C170S	0.992
4:155939415:A:T	C170S	0.992
4:155939515:G:C	S136R	0.992
4:155939515:G:T	S136R	0.992
4:155939517:T:G	S136R	0.992
4:155939526:A:G	W133R	0.992

dbSNP variants (sampled 300 via entrez): RS10000523 (4:155939953 C>A,G,T), RS1000091125 (4:155934438 G>A), RS1000174042 (4:155949685 G>C), RS10002427 (4:155951679 C>A,T), RS1000247612 (4:155949430 G>A,T), RS1000247920 (4:155955124 A>G), RS1000462546 (4:155950370 C>T), RS10005054 (4:155952026 C>G,T), RS10005559 (4:155952505 C>A,G,T), RS1000576932 (4:155950092 A>G), RS10006015 (4:155947016 C>T), RS10006268 (4:155947099 G>A,C,T), RS1000808558 (4:155954907 T>C), RS1000854154 (4:155945657 C>T), RS1000878040 (4:155929022 C>T)

Disease associations

OMIM: gene MIM:600550 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

46 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression, decreases methylation, affects cotreatment	7
Estradiol	decreases reaction, increases expression, decreases expression	2
GSK-J4	decreases expression	1
afuresertib	increases expression	1
sotorasib	affects cotreatment, increases expression	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
deoxynivalenol	decreases expression	1
2-methyl-4-isothiazolin-3-one	decreases expression	1
arsenite	decreases reaction, increases expression	1
methylparaben	decreases expression	1
sulforaphane	increases expression	1
sodium arsenite	increases expression	1
butyraldehyde	decreases expression	1
zinc chromate	increases abundance, increases expression	1
1-aminomethylphosphonic acid	increases expression	1
phenethyl isothiocyanate	increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
perfluorooctane sulfonic acid	increases expression	1
scriptaid	affects expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression, increases expression	1
belinostat	decreases expression	1
ICG 001	increases expression	1
abrine	decreases expression	1
dorsomorphin	decreases expression, increases expression, affects cotreatment	1
NSC 689534	increases expression	1
trametinib	affects cotreatment, increases expression	1
MT19c compound	increases expression	1
NVP-BKM120	affects cotreatment, increases expression	1

Clinical trials (associated diseases)

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