CAPNS1

Summary

CAPNS1 (calpain small subunit 1, HGNC:1481) is a protein-coding gene on chromosome 19q13.12, encoding Calpain small subunit 1 (P04632). Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction.

This gene is a member of the calpain small subunit family. Calpains are calcium-dependent cysteine proteinases that are widely distributed in mammalian cells. Calpains operate as heterodimers, comprising a specific large catalytic subunit (calpain 1 subunit in Calpain I, and calpain 2 subunit in Calpain II), and a common small regulatory subunit encoded by this gene. This encoded protein is essential for the stability and function of both calpain heterodimers, whose proteolytic activities influence various cellular functions including apoptosis, proliferation, migration, adhesion, and autophagy. Calpains have been implicated in neurodegenerative processes, such as myotonic dystrophy. A pseudogene of this gene has been defined on chromosome 1. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 826 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 73 total — 1 pathogenic, 2 likely-pathogenic
• Phenotypes (HPO): 21
• Druggable target: yes
• MANE Select transcript: NM_001749

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1481
Approved symbol	CAPNS1
Name	calpain small subunit 1
Location	19q13.12
Locus type	gene with protein product
Status	Approved
Aliases	CANP, CANPS, 30K, CDPS
Ensembl gene	ENSG00000126247
Ensembl biotype	protein_coding
OMIM	114170
Entrez	826

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 23 protein_coding, 1 retained_intron, 1 non_stop_decay

ENST00000246533, ENST00000586851, ENST00000586963, ENST00000587718, ENST00000588780, ENST00000588815, ENST00000589146, ENST00000589162, ENST00000590049, ENST00000590211, ENST00000590874, ENST00000591041, ENST00000592354, ENST00000592483, ENST00000628018, ENST00000628306, ENST00000856038, ENST00000940675, ENST00000940676, ENST00000940677, ENST00000959930, ENST00000959931, ENST00000959932, ENST00000959933, ENST00000959934

RefSeq mRNA: 4 — MANE Select: NM_001749 NM_001003962, NM_001302632, NM_001302633, NM_001749

CCDS: CCDS12489

Canonical transcript exons

ENST00000246533 — 11 exons

Exon	Start	End
ENSE00000862923	36149578	36149636
ENSE00001057386	36140997	36141220
ENSE00002800711	36140066	36140157
ENSE00003685060	36146196	36146312
ENSE00003695778	36142909	36142966
ENSE00003698742	36145976	36146054
ENSE00003699477	36142300	36142333
ENSE00003700110	36143064	36143128
ENSE00003701014	36142652	36142741
ENSE00003702045	36145806	36145874
ENSE00003762668	36149813	36150353

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 250.3443 / max 1110.9650, expressed in 1829 samples.

FANTOM5 promoters (15 alternative TSS)

Promoter ID	TPM avg	Samples expressed
175475	227.5219	1828
175477	11.7314	1752
175474	3.6795	1392
175473	2.5569	1364
175478	2.4872	1337
175493	1.7053	1135
175476	0.2034	81
175483	0.1132	54
175485	0.1122	30
175486	0.0701	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
metanephros cortex	UBERON:0010533	99.66	gold quality
stromal cell of endometrium	CL:0002255	99.64	gold quality
granulocyte	CL:0000094	99.63	gold quality
ileal mucosa	UBERON:0000331	99.63	gold quality
lower esophagus mucosa	UBERON:0035834	99.61	gold quality
prefrontal cortex	UBERON:0000451	99.58	gold quality
right frontal lobe	UBERON:0002810	99.57	gold quality
right uterine tube	UBERON:0001302	99.56	gold quality
right lung	UBERON:0002167	99.56	gold quality
right lobe of thyroid gland	UBERON:0001119	99.55	gold quality
left lobe of thyroid gland	UBERON:0001120	99.55	gold quality
mucosa of transverse colon	UBERON:0004991	99.55	gold quality
upper lobe of left lung	UBERON:0008952	99.55	gold quality
apex of heart	UBERON:0002098	99.54	gold quality
adenohypophysis	UBERON:0002196	99.54	gold quality
left testis	UBERON:0004533	99.53	gold quality
endocervix	UBERON:0000458	99.52	gold quality
right coronary artery	UBERON:0001625	99.52	gold quality
right testis	UBERON:0004534	99.52	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	99.52	gold quality
ectocervix	UBERON:0012249	99.51	gold quality
lower esophagus	UBERON:0013473	99.51	gold quality
lower esophagus muscularis layer	UBERON:0035833	99.51	gold quality
esophagus	UBERON:0001043	99.50	gold quality
ascending aorta	UBERON:0001496	99.50	gold quality
thoracic aorta	UBERON:0001515	99.50	gold quality
left coronary artery	UBERON:0001626	99.50	gold quality
esophagus mucosa	UBERON:0002469	99.50	gold quality
upper lobe of lung	UBERON:0008948	99.50	gold quality
peripheral nervous system	UBERON:0000010	99.49	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-13	yes	24.95
E-ANND-3	yes	15.37
E-MTAB-5061	no	3.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, NFKB, NRF1

miRNA regulators (miRDB)

23 targeting CAPNS1, 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-4455	100.00	65.48	1587
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-6722-3P	99.45	67.62	1919
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6837-5P	99.25	65.47	1632
HSA-MIR-4758-3P	99.12	63.96	869
HSA-MIR-6749-3P	99.00	65.73	1443
HSA-MIR-939-3P	98.97	65.07	2347
HSA-MIR-6761-5P	98.71	68.03	1504
HSA-MIR-5589-5P	98.34	64.82	1148
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-1278	97.75	67.55	628
HSA-MIR-296-5P	97.61	64.02	851
HSA-MIR-6773-5P	97.04	64.30	595
HSA-MIR-3192-5P	96.98	65.76	1926
HSA-MIR-6724-5P	96.41	63.11	507
HSA-MIR-7160-3P	96.40	64.15	462
HSA-MIR-1291	96.28	65.89	1224
HSA-MIR-2861	95.24	65.47	1056

Literature-anchored findings (GeneRIF, showing 31)

• calpain-mediated XIAP degradation contributes to initiation of apoptosis in normal neutrophils and dysfunction of this regulatory pathway can lead to pathological neutrophil accumulation. (PMID:12121983)
• Whereas alphaPIX guanine nucleotide exchange factor activity contributes to enhanced formation of cellular protrusions, the GEF-independent association with calpain 4 leads to induction of a yet unknown signaling cascade resulting in cell spreading. (PMID:15611136)
• results reveal that especially NRF-1, along with AP-1 and, to a minor extent, an Sp1 site, is essential for human CAPNS1 promoter activity and gene expression (PMID:18234454)
• c-Myc regulates calpain activity through calpastatin; apoptosis induced by calpain inhibition is dependent on c-Myc, and calpastatin knockdown promotes transformation in c-Myc-negative cells (PMID:18544539)
• RasGAP and Capns1 interaction in oncogenic Ras cells is involved in regulating migration and cell survival. (PMID:18761085)
• Genetic variations in LEP, CAPNS1 and ALOX15 show significant association with IL-6 expression. (PMID:19942621)
• CAPNS1 depletion is coupled to reduced levels of H2AX phosphorylation, not only in Ras(v12) induced BJ-ET fibroblasts, but also in a number of cellular systems upon genotoxic stress (PMID:20107320)
• The authors conclude that hepatitis B virus X protein upregulate Capn4 through NF-kappaB/p65 to promote migration of hepatoma cells. (PMID:20419804)
• The expression of both CAPN 1 and CAPNS 1 is increased in transplant kidneys with acute rejection, and increased expression of CAPN 1 alone was observed in kidneys with chronic rejection. (PMID:21268016)
• Capn4 overexpression was implicated in ICC metastasis/invasion, and Capn4 overexpression may be used as a molecular therapeutic target for intrahepatic cholangiocarcinoma (PMID:23349941)
• This study suggests that augmented calpain activity is associated with increased incidence of thrombosis under hypoxic environments. (PMID:24297866)
• Capn4 mRNA and protein are increased in human clear cell renal cell carcinoma tissues and higher Capn4 levels are associated with advanced clinical tumour stage and shorter overall survival. (PMID:24514433)
• The overexpression of Capn4 is a novel negative prognostic marker, and Capn4 may be used as a new target in therapeutic strategies for human glioma. (PMID:24628706)
• Capn4 can contribute to hepatocellular carcinoma growth and metastasis (PMID:24962955)
• HBXIP was able to up-regulate Capn4 at the levels of promoter. (PMID:25304384)
• High levels of Capn4 expression were associated with lymph node metastasis and large tumor size in non-small cell lung cancer patients.Capn4 promotes non-small cell lung cancer progression via upregulation of matrix metalloproteinase 2. (PMID:25636510)
• CAPNS1 depletion is coupled to impairment of breast cancer cell growth. (PMID:26771715)
• Capn4 promotes epithelial-mesenchymal transition in human melanoma cells through activation of the Wnt/beta-catenin pathway. (PMID:27878263)
• MALAT1 and Capn4 were up-regulated while miR-124 expression was down-regulated in nasopharyngeal carcinoma cell lines. (PMID:28857668)
• that Capn4 promotes cell proliferation by increasing MAPK7 expression (PMID:29331389)
• Capn4 and miR-1271 may serve as potential therapeutic targets for the treatment of colorectal cancer. (PMID:29331762)
• Calpain small subunit 1 (Capn4) overexpression increased the protein level of cleaved talin and and activated the focal adhesion kinase (FAK)/AKT/MAPK signaling in 786-O cells, while Capn4 silencing decreased the protein level of cleaved talin in Caki-1 cells. (PMID:29648579)
• Suppression of Capn4 by miR-520b inhibits the growth and invasion of prostate cancer cells associated with downregulated Wnt/beta-catenin signaling. (PMID:30241050)
• our results show that enhanced Capn4 expression activates the Wnt/beta-catenin signaling pathway, resulting in increased ZEB1 expression and the promotion of esophageal squamous cell carcinoma (ESCC) cell metastasis. (PMID:30444080)
• Low calpain 4 expression is associated with ovarian cancer. (PMID:30448882)
• Collectively, these data suggested the tumor suppressive role of miR-337-3p in ccRCC. MiR-337-3p suppressed cell proliferation and metastasis in lear cell renal cell carcinoma partially via targeting Capn4. (PMID:30452399)
• Capn4 coordination with LMP1 enhances NPC migration. (PMID:31691433)
• Capn4 contributes to tumor invasion and metastasis in gastric cancer via activation of the Wnt/beta-catenin/MMP9 signalling pathways. (PMID:32777225)
• Circular RNA ABCB10 promotes cell proliferation and invasion, but inhibits apoptosis via regulating the microRNA1271mediated Capn4/Wnt/betacatenin signaling pathway in epithelial ovarian cancer. (PMID:33760208)
• Overexpression of Capns1 Predicts Poor Prognosis and Correlates with Tumor Progression in Renal Cell Carcinoma. (PMID:33887737)
• Identification of Crucial Genes and Key Functions in Type 2 Diabetic Hearts by Bioinformatic Analysis. (PMID:35242109)

Cross-species orthologs

13 orthologs

Organism	Symbol	Gene ID
danio_rerio	capns1b	ENSDARG00000013804
danio_rerio	capns1a	ENSDARG00000035329
mus_musculus	Capns1	ENSMUSG00000001794
rattus_norvegicus	Capns1	ENSRNOG00000067065
caenorhabditis_elegans		WBGENE00000542
caenorhabditis_elegans	clp-3	WBGENE00000544
caenorhabditis_elegans		WBGENE00000546
caenorhabditis_elegans		WBGENE00000547
caenorhabditis_elegans		WBGENE00006606
caenorhabditis_elegans	clp-8	WBGENE00009695
caenorhabditis_elegans	clpr-3	WBGENE00010417
caenorhabditis_elegans	clpr-1	WBGENE00012233
caenorhabditis_elegans	clpr-3	WBGENE00013184

Paralogs (20): CAPN1 (ENSG00000014216), SRI (ENSG00000075142), CAPN6 (ENSG00000077274), CAPN3 (ENSG00000092529), CAPN15 (ENSG00000103326), GCA (ENSG00000115271), ADGB (ENSG00000118492), CAPN7 (ENSG00000131375), CAPN9 (ENSG00000135773), CAPN11 (ENSG00000137225), CAPN10 (ENSG00000142330), CAPN5 (ENSG00000149260), PEF1 (ENSG00000162517), CAPN2 (ENSG00000162909), CAPN13 (ENSG00000162949), CAPN12 (ENSG00000182472), CAPN8 (ENSG00000203697), CAPN14 (ENSG00000214711), PDCD6 (ENSG00000249915), CAPNS2 (ENSG00000256812)

Protein

Protein identifiers

Calpain small subunit 1 — P04632 (reviewed: P04632)

Alternative names: Calcium-activated neutral proteinase small subunit, Calcium-dependent protease small subunit, Calcium-dependent protease small subunit 1, Calpain regulatory subunit

All UniProt accessions (12): P04632, A0A075B7C0, A0A0C4DGQ5, K7EIV0, K7EKD8, K7ELJ7, K7EM73, K7EMQ1, K7ES78, S4R3F9, U3KPR7, U3KQE2

UniProt curated annotations — full annotation on UniProt →

Function. Regulatory subunit of the calcium-regulated non-lysosomal thiol-protease which catalyzes limited proteolysis of substrates involved in cytoskeletal remodeling and signal transduction. Essential for embryonic development.

Subunit / interactions. Homodimer or heterodimer of a large (catalytic) and a small (regulatory) subunit. In presence of calcium, the heterodimer dissociates.

Subcellular location. Cytoplasm. Cell membrane.

Disease relevance. Pulmonary hypertension, primary, 6 (PPH6) [MIM:620777] A form of primary pulmonary hypertension, a disease defined by plexiform lesions of proliferating endothelial cells in pulmonary arterioles. The lesions lead to elevated pulmonary arterial pression, right ventricular failure, and death. Primary pulmonary hypertension exhibits incomplete penetrance, sex bias and variable age of onset, both within and between families. PPH6 is an autosomal recessive form. The disease may be caused by variants affecting the gene represented in this entry.

Domain organisation. The contact of the 5th EF-hand domain from each monomer allows the formation of the homodimer and also appears to mediate the contact between the large catalytic subunit and small regulatory subunit for the formation of the heterodimer. EF-hand domains are paired. EF-hand 1 is paired with EF-hand 2 and EF-hand 3 is paired with EF-hand 4. The fifth EF-hand domain, left unpaired, does not bind the calcium but is responsible of the dimerization by EF-embrace. The first four EF-hand domains bind calcium, however it is not sure if the binding of EF-hand 4 to calcium is physiologically relevant.

RefSeq proteins (4): NP_001003962, NP_001289561, NP_001289562, NP_001740* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002048	EF_hand_dom	Domain
IPR011992	EF-hand-dom_pair	Homologous_superfamily
IPR018247	EF_Hand_1_Ca_BS	Binding_site

Enzyme classification (BRENDA):

• EC 3.4.22.53 — calpain-2 (BRENDA: 21 organisms, 189 substrates, 162 inhibitors, 17 Km, 12 kcat entries)
• EC 3.4.22.B24 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
SUCCINYL-LEU-TYR-7-AMIDO-4-METHYLCOUMARIN	0.431–3.18	4
SUCCINYL-LEU-LEU-VAL-TYR-7-AMIDO-4-METHYLCOUMARI	0.459–0.461	2
SUCCINYL-LEU-MET-7-AMIDO-4-METHYLCOUMARIN	4.66–4.68	2
T-BUTYLOXYCARBONYL-VAL-LEU-LYS-7-AMIDO-4-METHYLC	8.11–8.12	2
BOC-VAL-LEU-LYS-METHYLCOUMARIN	7.5	1
SUCCINYL-BOVINE SERUM ALBUMIN	2.2	1
SUCCINYL-CASEIN	10	1
SUCCINYL-INSULIN B	453.7	1
SUCCINYL-LEU-LEU-VAL-TYR-METHYLCOUMARIN	19.32	1
SUCCINYL-PROTAMINE	101.3	1
T-BOC-LEU-MET-METHYLCOUMARIN	5.33	1

UniProt features (46 total): binding site 16, helix 9, domain 5, sequence conflict 5, strand 4, modified residue 3, turn 2, chain 1, sequence variant 1

Structure

Experimental structures (PDB)

9 structures.

PDB	Method	Resolution (Å)
4PHJ	X-RAY DIFFRACTION	1.6
4WQ2	X-RAY DIFFRACTION	1.64
4WQ3	X-RAY DIFFRACTION	1.79
5D69	X-RAY DIFFRACTION	1.97
4PHM	X-RAY DIFFRACTION	2.03
4PHK	X-RAY DIFFRACTION	2.05
6QLB	X-RAY DIFFRACTION	2.32
1KFU	X-RAY DIFFRACTION	2.5
1KFX	X-RAY DIFFRACTION	3.15

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P04632-F1	78.90	0.58

Functional residue map

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

Ligand- & substrate-binding residues (16): 137; 152; 154; 156; 158; 163; 182; 184; 186; 188; 193; 225 …

Post-translational modifications (3): 1, 6, 179

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-1474228	Degradation of the extracellular matrix
R-HSA-6809371	Formation of the cornified envelope
R-HSA-8862803	Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer’s disease models
R-HSA-9856530	High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells
R-HSA-9860927	Turbulent (oscillatory, disturbed) flow shear stress activates signaling by PIEZO1 and integrins in endothelial cells

MSigDB gene sets: 240 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, MODULE_151, DAZARD_UV_RESPONSE_CLUSTER_G4, HSIAO_HOUSEKEEPING_GENES, GOBP_MACROAUTOPHAGY, BROWNE_HCMV_INFECTION_48HR_DN, WANG_ESOPHAGUS_CANCER_VS_NORMAL_DN, BIOCARTA_P35ALZHEIMERS_PATHWAY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, ZHAN_V2_LATE_DIFFERENTIATION_GENES, BIOCARTA_UCALPAIN_PATHWAY, BACH2_01, MORF_PPP2R4, TGANTCA_AP1_C

GO Biological Process (3): proteolysis (GO:0006508), positive regulation of cell population proliferation (GO:0008284), regulation of macroautophagy (GO:0016241)

GO Molecular Function (4): calcium-dependent cysteine-type endopeptidase activity (GO:0004198), calcium ion binding (GO:0005509), protein binding (GO:0005515), metal ion binding (GO:0046872)

GO Cellular Component (7): cytosol (GO:0005829), plasma membrane (GO:0005886), membrane (GO:0016020), extracellular exosome (GO:0070062), calpain complex (GO:0110158), cytoplasm (GO:0005737), endomembrane system (GO:0012505)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Response of endothelial cells to shear stress	2
Extracellular matrix organization	1
Keratinization	1
Neurodegenerative Diseases	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
cytoplasm	2
protein metabolic process	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
regulation of autophagy	1
macroautophagy	1
cysteine-type endopeptidase activity	1
metal ion binding	1
binding	1
cation binding	1
membrane	1
cell periphery	1
extracellular vesicle	1
caspase complex	1
intracellular anatomical structure	1
vacuole	1
plasma membrane	1

Protein interactions and networks

STRING

1352 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CAPNS1	CAPN2	P17655	981
CAPNS1	CAPN1	P07384	981
CAPNS1	CAST	P20810	914
CAPNS1	CAPN6	Q9Y6Q1	826
CAPNS1	TLN1	Q9Y490	613
CAPNS1	CAPN7	Q9Y6W3	567
CAPNS1	CAPN5	O15484	559
CAPNS1	EEF2	P13639	556
CAPNS1	CALM1	P02593	514
CAPNS1	CALML6	Q8TD86	510
CAPNS1	CALML3	P27482	510
CAPNS1	CALML5	Q9NZT1	510
CAPNS1	CALML4	Q96GE6	510
CAPNS1	ARHGEF6	Q15052	507
CAPNS1	CAPN10	Q9HC96	463

IntAct

91 interactions, top by confidence:

A	B	Type	Score
CAPN1	CAPNS1	psi-mi:“MI:0914”(association)	0.840
CAPN1	CAPNS1	psi-mi:“MI:0194”(cleavage reaction)	0.840
CAPN1	CAPNS1	psi-mi:“MI:0915”(physical association)	0.840
CAPNS1	CAPN2	psi-mi:“MI:0407”(direct interaction)	0.810
CAPN2	CAPNS1	psi-mi:“MI:0915”(physical association)	0.810
CFTR	XPO1	psi-mi:“MI:0914”(association)	0.710
CFTR	ESYT2	psi-mi:“MI:0914”(association)	0.710
AGTRAP	CAPNS1	psi-mi:“MI:0915”(physical association)	0.560
CAPNS1	AGTRAP	psi-mi:“MI:0915”(physical association)	0.560
CFAP418	CAPNS1	psi-mi:“MI:0915”(physical association)	0.530
CAPNS2	CAPNS1	psi-mi:“MI:0914”(association)	0.530
GRB2	ARHGEF35	psi-mi:“MI:0914”(association)	0.530
CAPN2	MYO9A	psi-mi:“MI:0914”(association)	0.530
TNF	B4GALT5	psi-mi:“MI:0914”(association)	0.530
RASA1	CAPNS1	psi-mi:“MI:0915”(physical association)	0.520
CAPNS1	RASA1	psi-mi:“MI:0915”(physical association)	0.520
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
CAST	CAPNS1	psi-mi:“MI:0915”(physical association)	0.400
CAPNS1	E2	psi-mi:“MI:0915”(physical association)	0.370

BioGRID (152): CAPNS1 (Affinity Capture-MS), AGTRAP (Two-hybrid), USP1 (Affinity Capture-MS), USP1 (Affinity Capture-Western), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS), CAPNS1 (Affinity Capture-MS)

ESM2 similar proteins: A0PJX0, A1L1L6, A4IG32, B1A8Z2, B1H2N3, C7A278, D2HZB0, O88456, P04632, P06813, P07090, P22676, P47728, Q08331, Q0IIL1, Q17QE5, Q1RMX9, Q2HJF8, Q2KI69, Q32L26, Q32LU1, Q3T0E8, Q3ZBY3, Q4R518, Q5PPL2, Q5RDF9, Q5ZM73, Q6NVC5, Q6P6Q9, Q6P8Y1, Q6PHZ8, Q6PIL6, Q8BG51, Q8HYN7, Q8IXI2, Q8R426, Q8VCX5, Q8WWF8, Q99828, Q99MG9

Diamond homologs: A6NHC0, A8MX76, G3V7W1, O08529, O08688, O14815, O15484, O23184, O35350, O35646, O35920, O75808, O88456, O88501, P00789, P04574, P04632, P05044, P06813, P06814, P06815, P07384, P13135, P16259, P17655, P20807, P27398, P27730, P28676, P30626, P34308, P35750, P43367, P43368, P51186, P97571, Q07009, Q11002, Q22036, Q27970

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 71 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

GO biological processes:

GO term	Partners	Fold	FDR
response to ethanol	5	12.8×	9e-03
response to hypoxia	6	10.1×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	2
Uncertain significance	36
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
3066189	NM_001749.4(CAPNS1):c.210-2A>G	Pathogenic
3066188	NM_001749.4(CAPNS1):c.721+1G>A	Likely pathogenic
4849418	NM_001749.4(CAPNS1):c.605-2A>C	Likely pathogenic

SpliceAI

1387 predictions. Top by Δscore:

Variant	Effect	Δscore
19:36141217:TCAGG:T	donor_loss	1.0000
19:36141219:AGG:A	donor_loss	1.0000
19:36141221:GTA:G	donor_loss	1.0000
19:36142295:C:CA	acceptor_gain	1.0000
19:36142295:CGCA:C	acceptor_loss	1.0000
19:36142296:GCAG:G	acceptor_loss	1.0000
19:36142297:CAG:C	acceptor_loss	1.0000
19:36142298:A:AG	acceptor_gain	1.0000
19:36142298:AGC:A	acceptor_gain	1.0000
19:36142299:G:GC	acceptor_gain	1.0000
19:36142299:GC:G	acceptor_gain	1.0000
19:36142299:GCG:G	acceptor_gain	1.0000
19:36142299:GCGA:G	acceptor_gain	1.0000
19:36142331:CCGGT:C	donor_loss	1.0000
19:36142332:CGGT:C	donor_loss	1.0000
19:36142333:GGTA:G	donor_loss	1.0000
19:36142334:G:GC	donor_loss	1.0000
19:36142334:G:GG	donor_gain	1.0000
19:36142335:TAAG:T	donor_loss	1.0000
19:36142649:CAGC:C	acceptor_loss	1.0000
19:36142650:A:AG	acceptor_gain	1.0000
19:36142651:G:GT	acceptor_gain	1.0000
19:36142651:GC:G	acceptor_gain	1.0000
19:36142651:GCC:G	acceptor_gain	1.0000
19:36142651:GCCC:G	acceptor_gain	1.0000
19:36142651:GCCCC:G	acceptor_gain	1.0000
19:36142737:GAGAT:G	donor_gain	1.0000
19:36142738:AGAT:A	donor_gain	1.0000
19:36142739:GAT:G	donor_gain	1.0000
19:36142739:GATG:G	donor_gain	1.0000

AlphaMissense

1768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:36142721:T:C	F105L	1.000
19:36142723:T:A	F105L	1.000
19:36142723:T:G	F105L	1.000
19:36142934:T:C	L120P	1.000
19:36143102:T:C	C144R	1.000
19:36143103:G:A	C144Y	1.000
19:36143104:T:G	C144W	1.000
19:36143106:G:C	R145P	1.000
19:36143117:G:C	A149P	1.000
19:36143126:G:C	D152H	1.000
19:36143127:A:C	D152A	1.000
19:36143127:A:T	D152V	1.000
19:36145825:T:C	L159P	1.000
19:36145839:T:C	F164L	1.000
19:36145841:C:A	F164L	1.000
19:36145841:C:G	F164L	1.000
19:36145851:T:A	W168R	1.000
19:36145851:T:C	W168R	1.000
19:36145869:T:A	W174R	1.000
19:36145869:T:C	W174R	1.000
19:36146199:T:C	F203S	1.000
19:36146287:C:G	C232W	1.000
19:36146292:T:A	V234D	1.000
19:36146295:G:T	R235M	1.000
19:36146298:T:C	L236P	1.000
19:36149583:T:C	F243L	1.000
19:36149585:C:A	F243L	1.000
19:36149585:C:G	F243L	1.000
19:36149813:T:A	W261R	1.000
19:36149813:T:C	W261R	1.000

dbSNP variants (sampled 300 via entrez): RS1000092115 (19:36141787 G>A,C), RS1000130897 (19:36145025 A>G), RS1000436841 (19:36145447 C>A,T), RS1000644142 (19:36148036 C>A), RS1000676557 (19:36143680 T>G), RS1001005563 (19:36146565 C>G,T), RS1001134137 (19:36142603 T>C), RS1001231160 (19:36141679 A>C,G), RS1001412527 (19:36150161 C>A,T), RS1001662629 (19:36141353 C>G,T), RS1003182884 (19:36140045 C>A,T), RS1003410890 (19:36145170 T>C), RS1003873822 (19:36140240 G>A), RS1004197360 (19:36142515 A>G), RS1004308111 (19:36148892 G>A)

Disease associations

OMIM: gene MIM:114170 | disease phenotypes: MIM:620777

GenCC curated gene-disease

Mondo (1): pulmonary hypertension, primary, 6 (MONDO:0958334)

Orphanet (0):

HPO phenotypes

21 total (21 of 21 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000961	Cyanosis
HP:0001508	Failure to thrive
HP:0001622	Premature birth
HP:0001639	Hypertrophic cardiomyopathy
HP:0001667	Right ventricular hypertrophy
HP:0001678	Atrioventricular block
HP:0001708	Right ventricular failure
HP:0002092	Pulmonary arterial hypertension
HP:0002093	Respiratory insufficiency
HP:0002094	Dyspnea
HP:0002104	Apnea
HP:0003593	Infantile onset
HP:0004749	Atrial flutter
HP:0005954	Pulmonary capillary hemangiomatosis
HP:0011462	Young adult onset
HP:0011463	Childhood onset
HP:0025179	Ground-glass opacification
HP:0031185	Elevated circulating NT-proBNP concentration
HP:0032979	Hemosiderin-laden macrophages in bronchoalveolar fluid
HP:0033376	Alveolar septal thickening

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL2111357 (PROTEIN COMPLEX), CHEMBL4962 (SINGLE PROTEIN)

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

ChEMBL bioactivities

71 potent at pChembl≥5 of 79 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.31	IC50	4.9	nM	CHEMBL203568
8.10	IC50	8	nM	CHEMBL204883
8.07	Ki	8.5	nM	CHEMBL117023
7.70	IC50	20	nM	CHEMBL341222
7.60	IC50	25	nM	CHEMBL340020
7.60	IC50	25	nM	CHEMBL439155
7.52	IC50	30	nM	CHEMBL338859
7.46	IC50	35	nM	CHEMBL341014
7.42	IC50	38	nM	CHEMBL201990
7.40	IC50	40	nM	CHEMBL286722
7.40	IC50	40	nM	CHEMBL423112
7.31	IC50	48.7	nM	CHEMBL383110
7.28	Ki	52	nM	CHEMBL331850
7.26	IC50	55	nM	CHEMBL419423
7.26	IC50	55.4	nM	CHEMBL206235
7.16	Ki	69	nM	CHEMBL117840
7.12	IC50	75.9	nM	CHEMBL203570
7.12	Ki	75	nM	CHEMBL118908
7.10	Ki	80	nM	CHEMBL441280
7.07	IC50	85.5	nM	CHEMBL203244
7.05	IC50	88.6	nM	CHEMBL204229
7.02	Ki	96	nM	CHEMBL116429
7.00	IC50	100	nM	CHEMBL128775
7.00	IC50	100	nM	CHEMBL129657
7.00	IC50	100	nM	CHEMBL127613
7.00	IC50	100	nM	CHEMBL339000
7.00	Ki	100	nM	CHEMBL117776
6.98	IC50	105	nM	CHEMBL203632
6.92	Ki	120	nM	CHEMBL331322
6.86	IC50	138	nM	CHEMBL204046
6.85	IC50	140	nM	CHEMBL128776
6.82	IC50	150.9	nM	CHEMBL412566
6.82	IC50	150	nM	CHEMBL206453
6.80	Ki	160	nM	CHEMBL326290
6.70	Ki	200	nM	CHEMBL444594
6.70	Ki	200	nM	CHEMBL420872
6.70	Ki	200	nM	CHEMBL118025
6.70	Ki	200	nM	CHEMBL117336
6.68	Ki	210	nM	CHEMBL116894
6.65	IC50	222	nM	CHEMBL203448
6.60	Ki	250	nM	CHEMBL325147
6.57	IC50	270	nM	CHEMBL129458
6.55	Ki	280	nM	CHEMBL325401
6.50	Ki	320	nM	CHEMBL116256
6.50	Ki	320	nM	CHEMBL115701
6.50	Ki	320	nM	CHEMBL325223
6.45	IC50	354.1	nM	CHEMBL206126
6.40	IC50	400	nM	CHEMBL128135
6.30	IC50	500	nM	CHEMBL129823
6.30	Ki	500	nM	CHEMBL432443

PubChem BioAssay actives

56 with measured affinity, of 111 total; 50 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
(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoic acid	262308: Inhibition of isolated human calpain1	ic50	0.0049	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]acetyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0080	uM
3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoic acid	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0085	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2S)-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]propanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0250	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-2-[[(2S)-3-hydroxy-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]butanoyl]amino]-4-methylpentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0380	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-2-[[(2S)-3-hydroxy-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]propanoyl]amino]-4-methylpentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0487	uM
benzyl N-[1-[[3,4-dioxo-1-phenyl-4-(2-phenylethylamino)butan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0520	uM
(2S)-N-[(2S)-1-[[(3S)-2-hydroxyoxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methyl-2-[[2-(10H-phenothiazin-2-yl)acetyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0554	uM
benzyl N-[1-[(1-amino-1,2-dioxohexan-3-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0690	uM
3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxopentanoic acid	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0750	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2S)-3-methyl-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]butanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0759	uM
benzyl N-[4-methyl-1-[[4-(2-methylpropylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0800	uM
N-[(2S)-1-[[(2S)-1-[[(3S)-2-hydroxyoxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]-10H-phenothiazine-2-carboxamide	262308: Inhibition of isolated human calpain1	ic50	0.0855	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2S)-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]butanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.0886	uM
benzyl N-[1-[[1-(heptylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.0960	uM
ethyl 3-[[2-[(2,2-diphenylacetyl)amino]-4-methylpentanoyl]amino]-2-oxopentanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.1000	uM
(2S)-N-[(2S)-1-[[(3S)-2-hydroxyoxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methyl-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.1050	uM
benzyl N-[4-methyl-1-[[1-(nonylamino)-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.1200	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[2-methyl-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]propanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.1380	uM
(2S)-N-[(2S)-1-[[(3S)-2-hydroxyoxolan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]-4-methyl-2-[3-(10H-phenothiazin-2-yl)propanoylamino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.1500	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2S)-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]pentanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.1509	uM
benzyl N-[1-[[1-(2,2-diphenylethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.1600	uM
benzyl N-[1-[[1,2-dioxo-1-(2-phenylethylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2000	uM
benzyl N-[1-[[4-(ethylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2000	uM
benzyl N-[1-[[1-(benzylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2000	uM
benzyl N-[1-[[1-(butylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2000	uM
benzyl N-[1-[[1-(ethylamino)-1,2-dioxohexan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2100	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2S)-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]-2-phenylacetyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.2220	uM
benzyl N-[1-[[1-(ethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2500	uM
benzyl N-[1-[(1-amino-1,2-dioxopentan-3-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.2800	uM
benzyl N-[4-methyl-1-[[1-(octylamino)-1,2-dioxopentan-3-yl]amino]-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.3200	uM
benzyl N-[1-[[1,2-dioxo-1-(2-phenylpropylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.3200	uM
benzyl N-[1-[[1,2-dioxo-1-(4-phenylbutylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.3200	uM
(2S)-2-[[(2S)-3,3-dimethyl-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]butanoyl]amino]-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methylpentanamide	262308: Inhibition of isolated human calpain1	ic50	0.3541	uM
benzyl N-[1-[[4-(butylamino)-3,4-dioxo-1-phenylbutan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.5000	uM
(2S)-N-[(3S)-2-hydroxyoxolan-3-yl]-4-methyl-2-[[(2R)-3-methyl-2-[[2-(10H-phenothiazin-2-yloxy)acetyl]amino]butanoyl]amino]pentanamide	262308: Inhibition of isolated human calpain1	ic50	0.5532	uM
benzyl N-[1-[[1-(cyclohexylmethylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.6800	uM
benzyl N-[1-[[1,2-dioxo-1-(3-phenylpropylamino)pentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	0.8000	uM
[(3S)-3-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(10H-phenothiazine-2-carbonylamino)pentanoyl]amino]pentanoyl]amino]oxolan-2-yl] acetate	262308: Inhibition of isolated human calpain1	ic50	0.9050	uM
ethyl 3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-methylsulfanyl-2-oxopentanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.0000	uM
benzyl N-[1-[(4-amino-3,4-dioxo-1-phenylbutan-2-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.0000	uM
ethyl (3S)-3-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(naphthalene-2-carbonylamino)pentanoyl]amino]pentanoyl]amino]-2-oxopentanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.3000	uM
ethyl 3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxohexanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.4000	uM
ethyl (3S)-3-[[(2S)-4-methyl-2-[[(2S)-4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]pentanoyl]amino]-2-oxo-4-phenylbutanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.4000	uM
ethyl 3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.8000	uM
butyl 3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxopentanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.8000	uM
benzyl N-[(2S)-1-[[(2S)-1-[[(3S)-4,5-dioxoheptan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	1.8000	uM
benzyl N-[1-[[1-(butan-2-ylamino)-1,2-dioxopentan-3-yl]amino]-4-methyl-1-oxopentan-2-yl]carbamate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	2.0000	uM
benzyl 3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxo-4-phenylbutanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	3.4000	uM
ethyl 4-(4-chlorophenyl)-3-[[4-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-2-oxobutanoate	46528: Inhibitory activity of alpha-keto esters towards calpain 1 at pH 8.0.	ki	4.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects cotreatment, increases methylation, decreases expression, increases expression	3
Valproic Acid	decreases expression, increases expression, affects expression	3
Cadmium Chloride	decreases expression, increases expression	3
cadmium acetate	increases expression, affects reaction, increases activity, increases cleavage	2
Arsenic Trioxide	increases expression, decreases response to substance	2
bisphenol F	affects cotreatment, increases expression	1
alpha phellandrene	increases expression	1
triphenyl phosphate	affects expression	1
sodium arsenate	decreases expression	1
pyrogallol 1,3-dimethyl ether	decreases expression, affects cotreatment, affects localization	1
beta-lapachone	decreases expression	1
arsenite	affects binding, increases reaction	1
sulforaphane	affects binding	1
sodium arsenite	decreases expression	1
ochratoxin A	increases expression	1
4-hydroxy-2-nonenal	decreases expression	1
homosalate	affects cotreatment, decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
nutlin 3	affects cotreatment, increases secretion	1
bisphenol B	increases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	decreases expression	1
bisphenol AF	increases expression	1
Temozolomide	decreases expression	1
Sunitinib	decreases expression	1
Fulvestrant	affects cotreatment, increases methylation	1
Aspirin	decreases expression	1
Cisplatin	increases response to substance	1
Dactinomycin	affects cotreatment, increases secretion	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL653673	Binding	Inhibition of Calpain 1 by [3H]acetyl-casein assay	Characterization of a continuous fluorogenic assay for calpain I. Kinetic evaluation of peptide aldehydes, halomethyl ketones and (acyloxy)methyl ketones as inhibitors of the enzyme — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_E1CA	Ubigene SK-N-SH CAPNS1 KO	Cancer cell line	Female
CVCL_SG78	HAP1 CAPNS1 (-) 1	Cancer cell line	Male
CVCL_SG79	HAP1 CAPNS1 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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