CTSA

Summary

CTSA (cathepsin A, HGNC:9251) is a protein-coding gene on chromosome 20q13.12, encoding Lysosomal protective protein (P10619). Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity.

This gene encodes a member of the peptidase S10 family of serine carboxypeptidases. Alternative splicing results in multiple transcript variants, at least one of which encodes a preproprotein that is proteolytically processed to generate two chains that comprise the heterodimeric active enzyme. This enzyme possesses deamidase, esterase and carboxypeptidase activities and acts as a scaffold in the lysosomal multienzyme complex. Mutations in this gene are associated with galactosialidosis.

Source: NCBI Gene 5476 — RefSeq curated summary.

At a glance

• Gene–disease (curated): galactosialidosis (Definitive, ClinGen)
• Clinical variants (ClinVar): 624 total — 41 pathogenic, 23 likely-pathogenic
• Phenotypes (HPO): 48
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_000308

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9251
Approved symbol	CTSA
Name	cathepsin A
Location	20q13.12
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000064601
Ensembl biotype	protein_coding
OMIM	613111
Entrez	5476

Gene structure

Transcript identifiers

Ensembl transcripts: 61 — 30 protein_coding, 19 retained_intron, 12 nonsense_mediated_decay

ENST00000191018, ENST00000354880, ENST00000372459, ENST00000372484, ENST00000419493, ENST00000480961, ENST00000484855, ENST00000485627, ENST00000493522, ENST00000606000, ENST00000606066, ENST00000606394, ENST00000606782, ENST00000606788, ENST00000607187, ENST00000607212, ENST00000607482, ENST00000607814, ENST00000607841, ENST00000646241, ENST00000676526, ENST00000676597, ENST00000676657, ENST00000676967, ENST00000677394, ENST00000677525, ENST00000677755, ENST00000678025, ENST00000678078, ENST00000678217, ENST00000678331, ENST00000678443, ENST00000678512, ENST00000678622, ENST00000678691, ENST00000678939, ENST00000678988, ENST00000679053, ENST00000679343, ENST00000684198, ENST00000867513, ENST00000867514, ENST00000867515, ENST00000867516, ENST00000867517, ENST00000867518, ENST00000867519, ENST00000867520, ENST00000867521, ENST00000867522, ENST00000958422, ENST00000958423, ENST00000958424, ENST00000958425, ENST00000958426, ENST00000958427, ENST00000958428, ENST00000958429, ENST00000958430, ENST00000958431, ENST00000958432

RefSeq mRNA: 3 — MANE Select: NM_000308 NM_000308, NM_001127695, NM_001167594

CCDS: CCDS46609

Canonical transcript exons

ENST00000646241 — 15 exons

Exon	Start	End
ENSE00000662429	45891916	45892027
ENSE00000845061	45892273	45892323
ENSE00001664035	45896965	45897040
ENSE00001684826	45897717	45897806
ENSE00001708661	45898005	45898109
ENSE00003486697	45893988	45894072
ENSE00003489474	45894823	45894901
ENSE00003582242	45894994	45895133
ENSE00003602327	45893220	45893311
ENSE00003617430	45892398	45892484
ENSE00003653142	45892725	45892880
ENSE00003702443	45894650	45894741
ENSE00003755203	45891569	45891762
ENSE00003900720	45898367	45898820
ENSE00003904098	45891335	45891379

Expression profiles

Bgee: expression breadth ubiquitous, 297 present calls, max score 99.48.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 120.7872 / max 986.7108, expressed in 1826 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
184959	99.8432	1825
184961	10.5440	1726
184960	8.2558	1674
184962	1.3904	803
184958	0.7538	430

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right adrenal gland	UBERON:0001233	99.48	gold quality
right adrenal gland cortex	UBERON:0035827	99.48	gold quality
left adrenal gland	UBERON:0001234	99.41	gold quality
left adrenal gland cortex	UBERON:0035825	99.36	gold quality
adrenal cortex	UBERON:0001235	99.34	gold quality
mucosa of transverse colon	UBERON:0004991	99.06	gold quality
stromal cell of endometrium	CL:0002255	99.03	gold quality
adrenal gland	UBERON:0002369	99.03	gold quality
monocyte	CL:0000576	98.78	gold quality
mononuclear cell	CL:0000842	98.60	gold quality
leukocyte	CL:0000738	98.57	gold quality
rectum	UBERON:0001052	98.56	gold quality
adult mammalian kidney	UBERON:0000082	98.38	gold quality
transverse colon	UBERON:0001157	98.26	gold quality
adrenal tissue	UBERON:0018303	98.26	gold quality
gall bladder	UBERON:0002110	98.00	gold quality
granulocyte	CL:0000094	97.89	gold quality
type B pancreatic cell	CL:0000169	97.77	gold quality
right coronary artery	UBERON:0001625	97.59	gold quality
descending thoracic aorta	UBERON:0002345	97.55	gold quality
small intestine Peyer’s patch	UBERON:0003454	97.51	gold quality
islet of Langerhans	UBERON:0000006	97.50	gold quality
colonic mucosa	UBERON:0000317	97.40	gold quality
spleen	UBERON:0002106	97.38	gold quality
metanephros cortex	UBERON:0010533	97.38	gold quality
renal medulla	UBERON:0000362	97.34	gold quality
thoracic aorta	UBERON:0001515	97.30	gold quality
ascending aorta	UBERON:0001496	97.26	gold quality
left coronary artery	UBERON:0001626	97.26	gold quality
ileal mucosa	UBERON:0000331	97.20	gold quality

Single-cell (SCXA)

Detected in 10 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-HCAD-4	yes	36.85
E-CURD-122	yes	21.41
E-MTAB-9221	yes	21.24
E-HCAD-10	yes	15.90
E-HCAD-13	yes	14.60
E-CURD-112	yes	13.60
E-HCAD-1	yes	8.04
E-MTAB-9543	yes	5.95
E-MTAB-7606	no	1365.35
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): FOXK1, SRF

miRNA regulators (miRDB)

42 targeting CTSA, 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-23B-5P	99.98	66.07	587
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-23A-5P	99.94	65.39	468
HSA-MIR-106A-5P	99.90	73.94	2683
HSA-MIR-6783-3P	99.89	67.92	2059
HSA-MIR-1343-3P	99.89	66.78	1815
HSA-MIR-17-5P	99.89	73.83	2665
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-106B-5P	99.88	74.72	2795
HSA-MIR-20A-5P	99.88	74.76	2769
HSA-MIR-20B-5P	99.88	74.01	2621
HSA-MIR-519D-3P	99.88	73.97	2607
HSA-MIR-526B-3P	99.88	74.06	2587
HSA-MIR-93-5P	99.88	73.98	2606
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-587	99.64	70.86	2611
HSA-MIR-3609	99.52	69.89	2587

Literature-anchored findings (GeneRIF, showing 21)

• mutations in early infantile galactosialidosis in two Dutch patients (PMID:12649068)
• Increased activity of beta-galactosidase in the peritoneal fluid is associated with gynecologic cancers and pelvic inflammatory disease (PMID:15785934)
• effects of GLB1, PPCA and NEU1 gene mutations on elastogenesis in skin fibroblasts (PMID:16538002)
• Results describe the hydrodynamic properties of PPCA, NEU1, and a complex of the two proteins and identified multiple binding sites on both proteins. (PMID:19666471)
• Our data suggest that CatA is involved in the C-terminal fine-tuning of antigenic T cell epitopes in human APC. (PMID:19954752)
• The Cathepsin C releases the glycosidases from complexes formed with cathepsin A, and reinstates their activity. (PMID:22532132)
• Catalytic function, tissue distribution and substrates of cathepsin A are discussed as well as inhibition of cathepsin A as an emerging strategy for the treatment of heart failure. (PMID:23495688)
• correct nomenclature of mutations for this gene is discussed; clinical and mutational analyses of 4 cases with rare infantile form of galactosialidosis; identified 3 novel nucleotide changes, 2 resulting in missense mutations and the third, resulting in the p.Gln406* stop codon; complexity of the clinical phenotypes in GS reflects dual functions of PPCA/CTSA (PMID:23915561)
• We identified compound heterozygous mutations in the CTSA gene, responsible for causing galactosialidosis (PMID:24769197)
• Case Report: galactosialidosis with novel mutations of CTSA gene diagnosed using placental pathology. (PMID:25075748)
• Galactosialidosis is a rare lysosomal storage disease caused by a combined deficiency of GM1 beta-galactosidase (beta-gal) and neuraminidase secondary to a defect of a lysosomal enzyme protective protein/cathepsin A (PPCA) and mutation in CTSA gene. (PMID:26259553)
• The gene signature of OPA1, CTSA, NDUFA1, STK10 and PRDX1 was able to identify patients post-implant with a sensitivity of 91% and a specificity of 86% in discrimination between post-implant group and healthy controls. (PMID:27177495)
• The usefulness of modified U1 snRNA for rescue from exon 7 skipping caused by the IVS7 +3a>g mutation of the CTSA gene. (PMID:30010039)
• Higher contents of cathepsin A, D, and E in the wall of the aortic aneurysms and a positive correlation between the concentration of cathepsin A and D and the width of the aneurysmal widening, suggests the participation of these enzymes in the pathogenesis of the aneurysm. (PMID:30278264)
• CTSA expression in the left atrium in mitral regurgitation patients significantly differed from those in aortic valve disease patients and normal controls. (PMID:30581499)
• Paired Carboxylic Acids in Enzymes and Their Role in Selective Substrate Binding, Catalysis, and Unusually Shifted pKa Values (PMID:31192586)
• Cathepsin A knockdown decreases the proliferation and invasion of A549 lung adenocarcinoma cells. (PMID:32323791)
• Enhanced carboxypeptidase efficacies and differentiation of peptide epimers. (PMID:34774536)
• Identification of the prognostic, diagnostic, and biological significance of the miR-148a-3p/cathepsin A axis in hepatocellular carcinoma. (PMID:36065643)
• Combining WGCNA and machine learning to construct basement membrane-related gene index helps to predict the prognosis and tumor microenvironment of HCC patients and verifies the carcinogenesis of key gene CTSA. (PMID:37287981)
• Proteomics analysis of serum and urine identifies VCP and CTSA as potential biomarkers associated with multiple myeloma. (PMID:38081446)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	ctsa	ENSDARG00000098114
mus_musculus	Ctsa	ENSMUSG00000017760
rattus_norvegicus	Ctsa	ENSRNOG00000015857

Paralogs (2): CPVL (ENSG00000106066), SCPEP1 (ENSG00000121064)

Protein

Protein identifiers

Lysosomal protective protein — P10619 (reviewed: P10619)

Alternative names: Carboxypeptidase C, Carboxypeptidase L, Cathepsin A, Protective protein cathepsin A, Protective protein for beta-galactosidase

All UniProt accessions (16): P10619, A0A7I2V2E2, A0A7I2V3B2, A0A7I2V3M2, A0A7I2V4D1, A0A7I2V4K5, A0A7I2V4Q9, A0A7I2V4R8, A0A7I2V504, A0A7I2YQT8, Q5JZH0, U3KQ41, U3KQF1, U3KQU6, X6R5C5, X6R8A1

UniProt curated annotations — full annotation on UniProt →

Function. Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins.

Subunit / interactions. Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide-linked.

Subcellular location. Lysosome.

Disease relevance. Galactosialidosis (GSL) [MIM:256540] A lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, intellectual disability, neurologic deterioration, absence of visceromegaly, and long survival. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S10 family.

Isoforms (2)

UniProt ID	Names	Canonical?
P10619-1	1	yes
P10619-2	2

RefSeq proteins (3): NP_000299, NP_001121167, NP_001161066 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001563	Peptidase_S10	Family
IPR018202	Ser_caboxypep_ser_AS	Active_site
IPR029058	AB_hydrolase_fold	Homologous_superfamily
IPR033124	Ser_caboxypep_his_AS	Active_site

Pfam: PF00450

Enzyme classification (BRENDA):

• EC 3.4.16.5 — carboxypeptidase C (BRENDA: 25 organisms, 271 substrates, 189 inhibitors, 113 Km, 113 kcat entries)

Substrate kinetics (BRENDA)

62 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
BENZYLOXYCARBONYL-PHE-LEU	0.07–3	8
BENZYLOXYCARBONYL-GLY-LEU	0.83–9.1	6
BENZYLOXYCARBONYL-GLY-PHE	0.41–19	6
9-FLUORENYLMETHOXYCARBONYL-GLU-GLU-ALA	0.0082–0.21	4
BENZYLOXYCARBONYL-ALA-PHE	0.57–4.2	4
BENZYLOXYCARBONYL-LEU-PHE	0.1–0.5	4
BENZYLOXYCARBONYL-PHE-GLU	0.36–16.5	4
BENZYLOXYCARBONYL-PHE-NH2	10–15	4
BENZYLOXYCARBONYL-GLU-PHE	0.053–3.3	3
BENZYLOXYCARBONYL-GLU-TYR	0.14–3	3
BENZYLOXYCARBONYL-HIS-PHE	0.1–0.38	3
BENZYLOXYCARBONYL-HIS-TYR	0.83–1.82	3
BENZYLOXYCARBONYL-TYR-GLU	0.86–1.55	3
9-FLUORENYLMETHOXYCARBONYL-GLU-GLU-GLU-ALA	0.0024–0.009	2
9-FLUORENYLMETHOXYCARBONYL-GLU-GLU-GLU-GLU-ALA	0.0006–0.0025	2

UniProt features (72 total): strand 21, helix 19, sequence variant 12, disulfide bond 4, chain 3, active site 3, mutagenesis site 2, sequence conflict 2, turn 2, glycosylation site 2, signal peptide 1, splice variant 1

Structure

Experimental structures (PDB)

12 structures.

PDB	Method	Resolution (Å)
4CI9	X-RAY DIFFRACTION	1.58
3BP7	X-RAY DIFFRACTION	1.8
3BP4	X-RAY DIFFRACTION	1.85
3BXN	X-RAY DIFFRACTION	1.86
4CIB	X-RAY DIFFRACTION	1.89
4CIA	X-RAY DIFFRACTION	1.98
4AZ3	X-RAY DIFFRACTION	2.04
4AZ0	X-RAY DIFFRACTION	2.17
1IVY	X-RAY DIFFRACTION	2.2
6WIA	X-RAY DIFFRACTION	2.21
4MWS	X-RAY DIFFRACTION	2.8
4MWT	X-RAY DIFFRACTION	3.85

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P10619-F1	94.59	0.87

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): 178; 400; 457

Disulfide bonds (4): 240–256, 241–246, 281–331, 88–362

Glycosylation sites (2): 145, 333

Mutagenesis-validated functional residues (2):

Position	Phenotype
178	inactivates the enzyme.
457	inactivates the enzyme.

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2132295	MHC class II antigen presentation
R-HSA-4085001	Sialic acid metabolism
R-HSA-4341670	Defective NEU1 causes sialidosis
R-HSA-6798695	Neutrophil degranulation
R-HSA-9840310	Glycosphingolipid catabolism

MSigDB gene sets: 357 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GOBP_REGULATION_OF_AUTOPHAGY, REACTOME_INNATE_IMMUNE_SYSTEM, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOCC_VACUOLAR_MEMBRANE, GOCC_SECRETORY_GRANULE, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, KEGG_LYSOSOME, AP2_Q3, GOBP_NEGATIVE_REGULATION_OF_PROTEIN_CATABOLIC_PROCESS, PATIL_LIVER_CANCER, MODULE_492

GO Biological Process (5): proteolysis (GO:0006508), intracellular protein transport (GO:0006886), regulation of protein stability (GO:0031647), regulation of chaperone-mediated autophagy (GO:1904714), negative regulation of chaperone-mediated autophagy (GO:1904715)

GO Molecular Function (5): carboxypeptidase activity (GO:0004180), serine-type carboxypeptidase activity (GO:0004185), enzyme activator activity (GO:0008047), 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), azurophil granule lumen (GO:0035578), lysosomal lumen (GO:0043202), extracellular exosome (GO:0070062), lumenal side of lysosomal membrane (GO:0098575)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Adaptive Immune System	1
Synthesis of substrates in N-glycan biosythesis	1
Diseases associated with N-glycosylation of proteins	1
Innate Immune System	1
Glycosphingolipid metabolism	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chaperone-mediated autophagy	2
catalytic activity	2
cellular anatomical structure	2
vacuolar lumen	2
protein metabolic process	1
intracellular protein localization	1
protein transport	1
intracellular transport	1
regulation of biological quality	1
regulation of autophagy	1
regulation of protein catabolic process	1
negative regulation of autophagy	1
negative regulation of protein catabolic process	1
regulation of chaperone-mediated autophagy	1
exopeptidase activity	1
carboxypeptidase activity	1
serine-type exopeptidase activity	1
enzyme regulator activity	1
molecular function activator activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
lytic vacuole	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
secretory granule lumen	1
azurophil granule	1
lysosome	1
extracellular vesicle	1
lysosomal membrane	1
lumenal side of membrane	1

Protein interactions and networks

STRING

2761 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CTSA	GLB1	P16278	999
CTSA	NEU1	Q99519	999
CTSA	ELN	P15502	847
CTSA	CTSS	P25774	769
CTSA	NEDD8	Q15843	755
CTSA	HINT1	P49773	744
CTSA	GALNS	P34059	734
CTSA	CES1	P23141	717
CTSA	NEU4	Q8WWR8	689
CTSA	MEI1	Q5TIA1	649
CTSA	CTSD	P07339	633
CTSA	UBE2M	P61081	605
CTSA	CTSB	P07858	598
CTSA	NAE1	Q13564	598
CTSA	NEU3	Q9UQ49	584

IntAct

60 interactions, top by confidence:

A	B	Type	Score
RHOA	ARHGEF11	psi-mi:“MI:0914”(association)	0.900
CDK2	CCNB2	psi-mi:“MI:0914”(association)	0.860
VIM	NEFL	psi-mi:“MI:0914”(association)	0.840
RHOA	CTSA	psi-mi:“MI:0914”(association)	0.730
SFXN5	CTSA	psi-mi:“MI:0914”(association)	0.640
RHOC	ARHGEF11	psi-mi:“MI:0914”(association)	0.530
MAD2L1BP	KIF20A	psi-mi:“MI:0914”(association)	0.530
FZR1	TK1	psi-mi:“MI:0914”(association)	0.530
LAGE3	CTSA	psi-mi:“MI:0914”(association)	0.530
YPEL5	SYNCRIP	psi-mi:“MI:0914”(association)	0.510
CTSA	LTB4R2	psi-mi:“MI:0915”(physical association)	0.370
Bcas2	PEX10	psi-mi:“MI:0914”(association)	0.350
VAPA		psi-mi:“MI:0914”(association)	0.350
KIE-1	GTPBP10	psi-mi:“MI:0914”(association)	0.350
FBXO6	GNS	psi-mi:“MI:0914”(association)	0.350
RORC	ANKHD1	psi-mi:“MI:0914”(association)	0.350
DNAJB2	UBB	psi-mi:“MI:0914”(association)	0.350
KLHDC9	CTSA	psi-mi:“MI:0914”(association)	0.350
TEX101	NDUFA4	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CTBP1	TAF15	psi-mi:“MI:0914”(association)	0.350
CAMKK1	CTSA	psi-mi:“MI:0914”(association)	0.350
TAOK2	AIP	psi-mi:“MI:0914”(association)	0.350

BioGRID (143): CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), APOA1BP (Co-fractionation), TIMM9 (Co-fractionation), TRNT1 (Co-fractionation), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS), CTSA (Affinity Capture-MS)

ESM2 similar proteins: A7YWG4, O35448, O35502, O35573, O35632, O35724, O35840, O70489, O88531, P04066, P08819, P0DPD9, P10619, P16301, P16675, P17164, P18424, P45478, P45479, P48300, P55747, Q05A56, Q12891, Q1JQA0, Q2M3T9, Q3MI05, Q5RFE4, Q60HF8, Q675A5, Q6AYS4, Q6PCJ9, Q6T3U4, Q6W3E9, Q6W3F0, Q71DJ5, Q8HXW6, Q8K1F9, Q8SQG7, Q8SQG8, Q8VEB4

Diamond homologs: A0A0C3VJP4, A1CUJ5, A1D3I1, A1DP75, A2QPW5, A4RPY8, A5AB21, A5YCB8, A6RUD7, A7F4H5, B0XQ16, B2WKF1, B6QAN5, B6QQZ9, B8M044, B8M719, B8NXS9, C0SGX7, C1GG77, C1GP85, C1GXD8, C4JNM2, C5FTV7, C5FWJ1, C5P212, C5P635, C7YQJ2, C9WMM5, D1ZEM2, E4USS9, E5A7I6, E9CS37, O04084, O23364, O64810, O64811, O81009, O82229, P07519, P08818

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
TFEB	“up-regulates quantity by expression”	CTSA	“transcriptional regulation”
ACSS2	“up-regulates quantity by expression”	CTSA	“transcriptional regulation”
TFE3	“up-regulates quantity by expression”	CTSA	“transcriptional regulation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	41
Likely pathogenic	23
Uncertain significance	179
Likely benign	298
Benign	25

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100724	NM_000308.4(CTSA):c.230del (p.Pro77fs)	Pathogenic
1073864	NM_000308.4(CTSA):c.991del (p.Cys331fs)	Pathogenic
1098801	NM_000308.4(CTSA):c.60del (p.Ser21fs)	Pathogenic
1322173	NM_000308.4(CTSA):c.1104dup (p.Gln369fs)	Pathogenic
1452908	NM_000308.4(CTSA):c.130C>T (p.Gln44Ter)	Pathogenic
1698376	NM_000308.4(CTSA):c.580G>A (p.Asp194Asn)	Pathogenic
1705554	NM_000308.4(CTSA):c.1294del (p.Asp432fs)	Pathogenic
2101801	NM_000308.4(CTSA):c.143del (p.Arg48fs)	Pathogenic
2236616	NM_000308.4(CTSA):c.990del (p.Cys331fs)	Pathogenic
225877	NM_000308.4(CTSA):c.833_834del (p.Tyr278fs)	Pathogenic
2727241	NM_000308.4(CTSA):c.518del (p.Phe173fs)	Pathogenic
2747132	NM_000308.4(CTSA):c.275_278del (p.Asp92fs)	Pathogenic
2748967	NM_000308.4(CTSA):c.15_19dup (p.Pro7fs)	Pathogenic
2753341	NM_000308.4(CTSA):c.463G>T (p.Glu155Ter)	Pathogenic
2755044	NM_000308.4(CTSA):c.253_254dup (p.Pro86fs)	Pathogenic
2797688	NM_000308.4(CTSA):c.242G>A (p.Trp81Ter)	Pathogenic
2827278	NM_000308.4(CTSA):c.1215_1216insTTTTTTTTTTTTTTTTTTTTNNNNNNNNNNGAGGGGCTCCTCACTTCCCAGAAGGGGCGGCCGGGCAGAGGCGCCCCTCACCTCCCAGACGGGGCGGCTGGCATGGCCTGCAATTTC (p.Phe405_Met406insPhePhePhePhePhePheXaaXaaXaaXaaGluGlyLeuLeuThrSerGlnLysGlyArgProGlyArgGlyAlaProHisLeuProAspGlyAlaAlaGlyMetAlaCysAsnPhe)	Pathogenic
2836788	NM_000308.4(CTSA):c.1106del (p.Gln369fs)	Pathogenic
2841707	NM_000308.4(CTSA):c.94C>T (p.Gln32Ter)	Pathogenic
2845062	NM_000308.4(CTSA):c.873T>G (p.Tyr291Ter)	Pathogenic
2888905	NM_000308.4(CTSA):c.31_34del (p.Leu11fs)	Pathogenic
2901872	NM_000308.4(CTSA):c.1063C>T (p.Gln355Ter)	Pathogenic
2968562	NM_000308.4(CTSA):c.350G>A (p.Trp117Ter)	Pathogenic
3013332	NM_000308.4(CTSA):c.1035C>A (p.Tyr345Ter)	Pathogenic
338531	NM_000308.4(CTSA):c.699G>A (p.Trp233Ter)	Pathogenic
3621616	NM_000308.4(CTSA):c.963_964del (p.Gly322_Asp323insTer)	Pathogenic
3644356	NM_000308.4(CTSA):c.501C>G (p.Tyr167Ter)	Pathogenic
3686079	NM_000308.4(CTSA):c.188del (p.His63fs)	Pathogenic
376	NM_000308.4(CTSA):c.692+3A>G	Pathogenic
378	NM_000308.4(CTSA):c.193T>C (p.Trp65Arg)	Pathogenic

SpliceAI

1966 predictions. Top by Δscore:

Variant	Effect	Δscore
20:45890248:A:AC	donor_gain	1.0000
20:45890249:C:CC	donor_gain	1.0000
20:45891715:G:GG	donor_gain	1.0000
20:45892392:CTCTA:C	acceptor_loss	1.0000
20:45892393:TCTAG:T	acceptor_loss	1.0000
20:45892394:CTAG:C	acceptor_loss	1.0000
20:45892395:TA:T	acceptor_loss	1.0000
20:45892396:A:AG	acceptor_gain	1.0000
20:45892396:A:AT	acceptor_loss	1.0000
20:45892397:G:GG	acceptor_gain	1.0000
20:45892397:GA:G	acceptor_gain	1.0000
20:45892397:GATT:G	acceptor_gain	1.0000
20:45892481:TGAGG:T	donor_loss	1.0000
20:45892482:GAG:G	donor_gain	1.0000
20:45892483:AGG:A	donor_loss	1.0000
20:45892484:GGT:G	donor_loss	1.0000
20:45892485:G:GC	donor_loss	1.0000
20:45892485:G:GG	donor_gain	1.0000
20:45892486:T:G	donor_loss	1.0000
20:45892713:T:TA	acceptor_gain	1.0000
20:45892717:A:AG	acceptor_gain	1.0000
20:45892718:T:G	acceptor_gain	1.0000
20:45892720:CCCA:C	acceptor_loss	1.0000
20:45892721:CCA:C	acceptor_loss	1.0000
20:45892723:A:AG	acceptor_gain	1.0000
20:45892723:AGGTC:A	acceptor_gain	1.0000
20:45892724:G:GC	acceptor_gain	1.0000
20:45892724:GGTC:G	acceptor_gain	1.0000
20:45892724:GGTCG:G	acceptor_gain	1.0000
20:45892860:G:GT	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000072914 (20:45895992 C>A,T), RS1000126499 (20:45896252 C>A,G), RS1000460046 (20:45889581 T>A), RS1000947010 (20:45889848 A>G), RS1001165990 (20:45898283 G>A), RS1001306470 (20:45896628 G>A), RS1001326045 (20:45898586 A>G), RS1001455876 (20:45890406 G>A,T), RS1003163687 (20:45895610 G>A,C), RS1003334266 (20:45889358 T>C), RS1003422166 (20:45894266 A>ACCT), RS1003594643 (20:45897693 C>T), RS1003805541 (20:45891628 G>A,T), RS1004921234 (20:45895635 T>C), RS1005121712 (20:45889434 C>A,T)

Disease associations

OMIM: gene MIM:613111 | disease phenotypes: MIM:256540, MIM:621394, MIM:236750, MIM:120435

GenCC curated gene-disease

Disease	Classification	Inheritance
galactosialidosis	Definitive	Autosomal recessive

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
galactosialidosis	Definitive	AR

Mondo (5): galactosialidosis (MONDO:0009737), cathepsin a-related arteriopathy-strokes-leukoencephalopathy (MONDO:0035551), brain small vessel disease 6 with leukoencephalopathy (MONDO:0980711), non-immune hydrops fetalis (MONDO:0009369), Lynch syndrome 1 (MONDO:0007356)

Orphanet (4): Galactosialidosis (Orphanet:351), Cathepsin A-related arteriopathy-strokes-leukoencephalopathy (Orphanet:575553), Non-immune hydrops fetalis (Orphanet:363999), Lynch syndrome (Orphanet:144)

HPO phenotypes

48 total (30 of 48 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000280	Coarse facial features
HP:0000360	Tinnitus
HP:0000365	Hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000524	Conjunctival telangiectasia
HP:0000571	Hypometric saccades
HP:0000716	Depression
HP:0000822	Hypertension
HP:0000925	Abnormality of the vertebral column
HP:0000943	Dysostosis multiplex
HP:0001028	Hemangioma
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001260	Dysarthria
HP:0001268	Mental deterioration
HP:0001278	Orthostatic hypotension
HP:0001279	Syncope
HP:0001310	Dysmetria
HP:0001433	Hepatosplenomegaly
HP:0001790	Nonimmune hydrops fetalis
HP:0002015	Dysphagia
HP:0002066	Gait ataxia
HP:0002075	Dysdiadochokinesis
HP:0002076	Migraine
HP:0002090	Pneumonia
HP:0002136	Broad-based gait
HP:0002166	Impaired vibration sensation in the lower limbs
HP:0002354	Memory impairment

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
C537261	Lynch syndrome I (site-specific colonic cancer) (supp.)
C536411	Neuraminidase deficiency with beta-galactosidase deficiency (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6115 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 26,257 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1025	ISOFLUROPHATE	4	13,137
CHEMBL325041	BORTEZOMIB	4	13,120

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — S10: Carboxypeptidase Y

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
compound 8a [PMID: 22861813]	Inhibition	7.42	pIC50
example 166 [WO2014154727]	Inhibition	7.04	pIC50
telaprevir	Inhibition	7.0	pIC50
boceprevir	Inhibition	6.0	pIC50

Binding affinities (BindingDB)

749 measured of 846 human assays (846 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
3-[3-(2,6-dimethoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	2 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-[5-(2-cyanopropan-2-yl)-2-methoxyphenyl]-5-fluorophenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	4 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxyphenyl)-5-fluorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	5 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,6-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	5 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxy-4-methylphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	6 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,6-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	7 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,6-dimethoxy-4-methylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	8 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-fluoro-6-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	8 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-methoxyphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	10 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(6-methoxy-2,2-dimethyl-3H-1-benzofuran-7-yl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	10 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	11 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(5-fluoro-2-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	12 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	13 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-fluoro-5-[4-(hydroxymethyl)-2,6-dimethoxyphenyl]phenyl]-3-(1,3-oxazol-2-yl)propanoic acid	IC50	14 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,5-dimethoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	14 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-ethoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	14 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-fluoro-6-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	16 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxy-4-methylphenyl)-5-fluorophenyl]-3-(1,3-oxazol-2-yl)propanoic acid	IC50	16 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(6-methoxy-2,2-dimethyl-3H-1-benzofuran-7-yl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-methoxy-5-methylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-methoxy-5-methylphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(5-tert-butyl-2-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(5-chloro-2-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-chloro-6-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	17 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,3,6-trimethoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	18 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(5-hydroxy-2-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	18 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxyphenyl)-5-fluorophenyl]-3-(1,3-oxazol-2-yl)propanoic acid	IC50	18 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,6-dimethoxy-4-methylphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	19 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	21 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-[5-(hydroxymethyl)-2-methoxyphenyl]-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	22 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	23 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-methoxy-5-methylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	24 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxy-4-methylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	24 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-ethoxyphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	24 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2-methoxy-5-propan-2-ylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	25 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
(3R)-3-[3-(2-methoxy-5-propan-2-ylphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	27 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,5-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	28 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxy-4-methylphenyl)-5-fluorophenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	28 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-[5-(hydroxymethyl)-2-methoxyphenyl]phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	29 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
(3S)-3-[[6-(2,3-dimethylphenyl)pyridine-2-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	IC50	29.4 nM	US-9029559: Substituted 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2,6-dimethoxyphenyl)phenyl]-3-(1,3-thiazol-2-yl)propanoic acid	IC50	30 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(2-methoxy-5-propan-2-ylphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	31 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,4-dimethoxyphenyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	33 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(5-chloro-2-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	34 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
(3S)-3-[3-(5-tert-butyl-2-methoxyphenyl)phenyl]-3-(1,3-thiazol-2-yl)propanoic acid	IC50	35 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-(4-fluoro-2-methoxyphenyl)-5-(trifluoromethyl)phenyl]-3-(5-methyl-1,3,4-oxadiazol-2-yl)propanoic acid	IC50	35 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
(3S)-3-[[6-(2,3-dimethylphenyl)-5-methoxypyridine-2-carbonyl]amino]-3-(4-methylphenyl)propanoic acid	IC50	37 nM	US-9029559: Substituted 3-heteroaroylamino-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(2,3-difluoro-6-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	37 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals
3-[3-chloro-5-(5-fluoro-2-methoxyphenyl)phenyl]-3-(5-methyl-1,3-thiazol-2-yl)propanoic acid	IC50	38 nM	US-9150526: Biaryl-propionic acid derivatives and their use as pharmaceuticals

ChEMBL bioactivities

756 potent at pChembl≥5 of 790 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	IC50	2	nM	CHEMBL3913129
8.52	IC50	3	nM	CHEMBL2171390
8.40	IC50	4	nM	CHEMBL3947662
8.30	IC50	5	nM	CHEMBL2171392
8.30	IC50	5	nM	CHEMBL3959487
8.30	IC50	5	nM	CHEMBL3900996
8.22	IC50	6	nM	CHEMBL3945914
8.15	IC50	7	nM	CHEMBL3975529
8.10	IC50	8	nM	CHEMBL3977104
8.10	IC50	8	nM	CHEMBL3944726
8.00	IC50	10	nM	CHEMBL2171394
8.00	IC50	10	nM	CHEMBL3898095
8.00	IC50	10	nM	CHEMBL3920300
7.96	IC50	11	nM	CHEMBL3907904
7.92	IC50	12	nM	CHEMBL3895656
7.89	IC50	13	nM	CHEMBL3985600
7.85	IC50	14	nM	CHEMBL3980117
7.85	IC50	14	nM	CHEMBL3916226
7.85	IC50	14	nM	CHEMBL3946844
7.82	IC50	15	nM	CHEMBL2171398
7.82	IC50	15	nM	CHEMBL2171397
7.80	IC50	16	nM	CHEMBL3914540
7.80	IC50	16	nM	CHEMBL3981058
7.77	IC50	17	nM	CHEMBL3985437
7.77	IC50	17	nM	CHEMBL3985175
7.77	IC50	17	nM	CHEMBL3982519
7.77	IC50	17	nM	CHEMBL3900002
7.77	IC50	17	nM	CHEMBL3942847
7.77	IC50	17	nM	CHEMBL3900041
7.77	IC50	17	nM	CHEMBL3969663
7.75	IC50	18	nM	CHEMBL3946014
7.75	IC50	18	nM	CHEMBL3901611
7.75	IC50	18	nM	CHEMBL3902645
7.72	IC50	19	nM	CHEMBL3941265
7.68	IC50	21	nM	CHEMBL3945253
7.66	IC50	22	nM	CHEMBL3962665
7.64	IC50	23	nM	CHEMBL3915744
7.62	IC50	24	nM	CHEMBL3953436
7.62	IC50	24	nM	CHEMBL3893164
7.62	IC50	24	nM	CHEMBL3933072
7.60	IC50	25	nM	CHEMBL3145342
7.60	IC50	25	nM	CHEMBL3985962
7.58	IC50	26	nM	CHEMBL2171396
7.57	IC50	27	nM	CHEMBL3908185
7.55	IC50	28	nM	CHEMBL3935782
7.55	IC50	28	nM	CHEMBL3891945
7.54	IC50	29	nM	CHEMBL3889674
7.53	IC50	29.4	nM	CHEMBL3682847
7.52	IC50	30	nM	CHEMBL2171399
7.52	IC50	30	nM	CHEMBL3942531

PubChem BioAssay actives

36 with measured affinity, of 69 total; 36 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
(3S)-3-[[5-(3,3-dimethyl-2-oxobutoxy)-1-(2-fluorophenyl)pyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0030	uM
(3S)-3-[[1-(2-fluorophenyl)-5-[(2R)-2-hydroxy-3,3-dimethylbutoxy]pyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0050	uM
(3S)-3-[[1-(2-fluorophenyl)-5-[(2S)-2-hydroxy-3,3-dimethylbutoxy]pyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0100	uM
(3S)-3-[[5-ethoxy-1-(2-fluorophenyl)pyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0150	uM
(3S)-3-[[5-(cyclopropylmethoxy)-1-(2-fluorophenyl)pyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0150	uM
3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-[4-(4-fluorophenyl)phenyl]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0250	uM
(3S)-3-[[1-(2-fluorophenyl)-5-methoxypyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0260	uM
(3S)-3-[[4-fluoro-1-(2-fluorophenyl)-5-methoxypyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0300	uM
(3S)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0380	uM
(3S)-3-(2,4-dichlorophenyl)-3-[[1-(2-fluorophenyl)-5-[(2R)-2-hydroxy-3,3-dimethylbutoxy]pyrazole-3-carbonyl]amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0500	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148174: Binding affinity to human CTSA incubated for 45 mins by Kinobead based pull down assay	kd	0.0553	uM
(3S)-3-[[2-(2-chlorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0570	uM
(3S)-3-[[2-(3-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0590	uM
(3S)-3-(2,4-dichlorophenyl)-3-[[5-(3,3-dimethyl-2-oxobutoxy)-1-(2-fluorophenyl)pyrazole-3-carbonyl]amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0600	uM
(3S)-3-(2,4-dichlorophenyl)-3-[[1-(2-fluorophenyl)-5-[(2S)-2-hydroxy-3,3-dimethylbutoxy]pyrazole-3-carbonyl]amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0700	uM
(3S)-3-(2-methylphenyl)-3-[(3-oxo-2-phenyl-1H-pyrazole-5-carbonyl)amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0700	uM
3-(5-fluoro-2-methylphenyl)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0760	uM
(3S)-3-[[2-(4-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.0870	uM
3-(2,3-dichlorophenyl)-3-[(3-oxo-2-phenyl-1H-pyrazole-5-carbonyl)amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1000	uM
(3S)-3-[(4-methoxy-1-phenylpyrazole-3-carbonyl)amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1000	uM
(3S)-3-[[2-(3-chlorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1020	uM
(3S)-3-[[4-chloro-1-(2-fluorophenyl)-5-methoxypyrazole-3-carbonyl]amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1100	uM
(3S)-3-[(4-hydroxy-1-phenylpyrazole-3-carbonyl)amino]-3-(2-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1100	uM
3-(2,3-dichlorophenyl)-3-[[2-(2,4-difluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.1200	uM
3-[(3-oxo-2-phenyl-1H-pyrazole-5-carbonyl)amino]-3-(4-phenoxyphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.2000	uM
3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-phenylpropanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.2260	uM
(3S)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(3-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.2520	uM
(3S)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(4-methylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.2740	uM
(3S)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(2-methoxyphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.3570	uM
(3S)-3-[[2-(2-fluorophenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-[2-(trifluoromethyl)phenyl]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.3750	uM
3,4-dichloroisochromen-1-one	279732: Inhibition of recombinant CatA using [14C]GS-7340 substrate	ic50	0.6000	uM
3-[[2-(2,5-dimethylphenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(4-phenylphenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	0.8030	uM
3-[[2-(2,5-dimethylphenyl)-3-oxo-1H-pyrazole-5-carbonyl]amino]-3-(4-fluorophenyl)propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	5.3800	uM
(3R)-3-(2-methylphenyl)-3-[(3-oxo-2-phenyl-1H-pyrazole-5-carbonyl)amino]propanoic acid	702511: Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric analysis	ic50	7.8000	uM
Bortezomib	1128236: Inhibition of recombinant cathepsin A (unknown origin) using Mca-Arg-Pro-Pro-Gly-Phe-Ser-Ala-Phe-Lys(Dnp)-OH as substrate incubated with enzyme for 5 mins prior to substrate challenge for 2 hrs by spectrofluorometer analysis	ic50	9.2000	uM
2-[fluoro(propan-2-yloxy)phosphoryl]oxypropane	279732: Inhibition of recombinant CatA using [14C]GS-7340 substrate	ic50	10.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, decreases methylation, increases expression	3
sodium arsenite	affects expression, increases expression	2
Arsenic Trioxide	increases expression	2
Doxorubicin	affects expression	2
Smoke	decreases expression	2
Tetrachlorodibenzodioxin	increases expression	2
Tobacco Smoke Pollution	affects expression, increases expression	2
Tretinoin	increases expression	2
Valproic Acid	increases expression	2
aristolochic acid I	decreases expression	1
spautin-1	affects cotreatment, affects localization, increases transport	1
remdesivir	increases hydrolysis	1
bisphenol F	increases expression	1
glycidyl methacrylate	decreases expression	1
beta-lapachone	decreases expression, increases expression	1
butyraldehyde	decreases expression	1
leucyl-leucine-methyl ester	increases expression	1
tamibarotene	increases expression	1
di-n-butylphosphoric acid	affects expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
bisphenol S	increases expression	1
jinfukang	affects cotreatment, increases expression	1
quizartinib	affects cotreatment, affects localization, increases transport	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Temozolomide	decreases expression	1
Acetaminophen	increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Atrazine	decreases expression	1

ChEMBL screening assays

19 unique, capped per target: 13 binding, 6 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL2176198	Binding	Inhibition of human recombinant Myc-His10-tagged cathepsin A expressed in baculovirus infected Sf9 cells using BodipyFL labeled bradykinin as substrate incubated for 15 mins prior to substrate addition measured after 15 mins by fluorimetric	Novel β-amino acid derivatives as inhibitors of cathepsin A. — J Med Chem
CHEMBL4046686	ADMET	Drug metabolism assessed as CatA (unknown origin)-mediated monophosphate formation after 18 hrs relative to control	The discovery of IDX21437: Design, synthesis and antiviral evaluation of 2’-α-chloro-2’-β-C-methyl branched uridine pronucleotides as potent liver-targeted HCV polymerase inhibitors. — Bioorg Med Chem Lett

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_D5FD	HeLa::TMEM192-3xHA CTSA partial KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01416467	Not specified	COMPLETED	Characterization of the Patient Population With Galactosialidosis
NCT01891422	Not specified	COMPLETED	Longitudinal Studies of the Glycoproteinoses
NCT04624789	Not specified	UNKNOWN	Registry Gangliosidoses
NCT04308603	Not specified	COMPLETED	Multicentric Prospective Study to Screen Inborn Errors of Metabolism in Non-immune Hydrops (NIH) Fetalis by Massively Parallel Sequencing
NCT05528796	Not specified	ENROLLING_BY_INVITATION	Uncovering the Etiologies of Non-immune Hydrops Fetalis