CASP12

Summary

CASP12 (caspase 12 (gene/pseudogene), HGNC:19004) is a protein-coding gene on chromosome 11q22.3, encoding Inactive caspase-12 (Q6UXS9). May function as a negative regulator of inflammatory responses and innate immunity.

Caspases are cysteine proteases that cleave C-terminal aspartic acid residues on their substrate molecules. This gene is most highly related to members of the ICE subfamily of caspases that process inflammatory cytokines. In rodents, the homolog of this gene mediates apoptosis in response to endoplasmic reticulum stress. However, in humans this gene contains a polymorphism for the presence or absence of a premature stop codon. The majority of human individuals have the premature stop codon and produce a truncated non-functional protein. The read-through codon occurs primarily in individuals of African descent and carriers have endotoxin hypo-responsiveness and an increased susceptibility to severe sepsis. Several alternatively spliced transcript variants have been noted for this gene.

Source: NCBI Gene 100506742 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 63 total
• Druggable target: yes

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:19004
Approved symbol	CASP12
Name	caspase 12 (gene/pseudogene)
Location	11q22.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000204403
Ensembl biotype	protein_coding
OMIM	608633
Entrez	100506742

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 10 protein_coding_LoF, 2 nonsense_mediated_decay

ENST00000375726, ENST00000417998, ENST00000433738, ENST00000441710, ENST00000446862, ENST00000447913, ENST00000448103, ENST00000458137, ENST00000494737, ENST00000508062, ENST00000613512, ENST00000703420

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000375726 — 7 exons

Exon	Start	End
ENSE00001468155	104897217	104897468
ENSE00001468157	104898408	104898670
ENSE00003530546	104887196	104887305
ENSE00003569524	104890374	104890523
ENSE00003582070	104886690	104886812
ENSE00003599230	104891170	104891404
ENSE00003672718	104892331	104892503

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 79.48.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.1575 / max 97.5743, expressed in 46 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
122069	0.1291	39
122070	0.0284	6

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	79.48	silver quality
right lung	UBERON:0002167	78.41	gold quality
left ovary	UBERON:0002119	76.32	gold quality
mucosa of stomach	UBERON:0001199	76.18	gold quality
ascending aorta	UBERON:0001496	75.83	gold quality
thoracic aorta	UBERON:0001515	75.83	gold quality
aorta	UBERON:0000947	74.99	gold quality
descending thoracic aorta	UBERON:0002345	74.90	gold quality
popliteal artery	UBERON:0002250	74.68	gold quality
tibial artery	UBERON:0007610	74.65	gold quality
buccal mucosa cell	CL:0002336	72.96	gold quality
left coronary artery	UBERON:0001626	72.49	gold quality
right ovary	UBERON:0002118	72.34	gold quality
body of uterus	UBERON:0009853	71.89	gold quality
right coronary artery	UBERON:0001625	70.92	gold quality
coronary artery	UBERON:0001621	70.62	gold quality
ovary	UBERON:0000992	69.96	gold quality
smooth muscle tissue	UBERON:0001135	69.69	gold quality
upper lobe of left lung	UBERON:0008952	69.13	gold quality
left uterine tube	UBERON:0001303	68.67	gold quality
left lobe of thyroid gland	UBERON:0001120	68.21	gold quality
right lobe of thyroid gland	UBERON:0001119	68.18	gold quality
gall bladder	UBERON:0002110	67.77	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	67.61	gold quality
upper lobe of lung	UBERON:0008948	67.34	gold quality
thyroid gland	UBERON:0002046	67.19	gold quality
cerebellar hemisphere	UBERON:0002245	66.91	gold quality
secondary oocyte	CL:0000655	66.78	silver quality
cerebellar cortex	UBERON:0002129	66.69	gold quality
tibial nerve	UBERON:0001323	66.64	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	3.25

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): ATF4, ESR1

Literature-anchored findings (GeneRIF, showing 26)

• caspase 12 has acquired deleterious mutations (PMID:12054529)
• Pathways involving this enzyme are involved in a neurodegenerative disease in vivo, and thus offer novel potential targets for the treatment of prion disorders. (PMID:14532116)
• Na/Ca exchanger overexpression activates caspase-12 (PMID:15033764)
• Csp12-L attenuates the inflammatory and innate immune response to endotoxins and in doing so may constitute a risk factor for developing sepsis (PMID:15129283)
• The activation of caspase-9 and depolarization of mitochondrial membrane potential were induced by BIK, which were decreased concomitant with caspase-12 silenced. (PMID:17574210)
• proteolytic activity of caspase-12 is confined to its own proenzyme (PMID:18332441)
• hRPE cells express a high level of caspase-12S. The regulated expression of caspase-12S suggests that this caspase recruitment domain (CARD)-only protein may be an endogenous dominant negative regulator that modulates inflammatory responses in hRPE cells. (PMID:18791174)
• estrogen-mediated inhibition of Csp-12L expression is a built-in mechanism that has evolved to protect females from Listeria monocytogenes infection. (PMID:19447924)
• the NOD2/RIP2 pathway has a role in recognition of Yersinia, but caspase-12 does not modulate innate host defense against Y. pestis (PMID:19721713)
• The calcium-calpain-caspase-12-caspase-3 cascade is altered in F508del-CFTR expressing cells. (PMID:20041182)
• Reactive oxygen species promote caspase-12 expression and tubular apoptosis in diabetic nephropathy. (PMID:20299359)
• Constitutively active forms of caspase-12 (rev-Deltapro1 and rev-Deltapro2) could induce cell death in cells transfected with the corresponding expression vectors. (PMID:20646990)
• CASPASE-12 does not influence the susceptibility to Candida sepsis, nor has any effect on the serum cytokine concentrations in Candida sepsis patients during the course of infection. (PMID:21706251)
• examines the role that CASP12 plays in down-regulating inflammation, we hypothesize that pathogens which exploit the inflammatory response are restrained by an active CASP12 gene product (PMID:21872999)
• EtOH-induced activation of caspase-12 could be one of the underlying mechanisms of hepatocyte apoptosis. (PMID:24224909)
• Distribution of CASP12 alleles (#rs497116) in African-Americans (AA) with rheumatoid arthritis (RA). There was no difference in the overall distribution of genotypes within AA with RA, but homozygous patients had lower baseline joint-narrowing scores. (PMID:24515649)
• conclude that the functional CASP12L allele is not a marker for susceptibility and/or severity of CAP (PMID:24586588)
• We found that RNA interference-induced Caspase-12 silencing increased NOD1, hBD1 and hBD2 expression (PMID:25503380)
• Endoplasmic reticulum stress related factor ATF6 and caspase-12 trigger apoptosis in neonatal hypoxic-ischemic encephalopathy. (PMID:26261584)
• Expression of caspase-12 was linked to decreased systemic and adipose tissue inflammation in a cohort of African American obese children. (PMID:26582949)
• CASP12 genotype thus does not influence the phenotype of systemic lupus erythematosus in African-Americans (PMID:26973091)
• Endoplasmic reticulum stress may be associated with apoptosis of LECs, resulting in cataract formation in diabetic patients. (PMID:27130368)
• study indicated the potential effect of Casp12 was on the activation of NF-kappaB by the degradation of IkappaBalpha in NPC cells. (PMID:28380444)
• The expression of three genes (STK26, KCNT2, CASP12) was correlated with the prognosis of skin cutaneous melanoma (SCM). STK26 and KCNT2 were significantly different between normal skin and SCM. These three hub genes have potential value as predictors for accurate diagnosis and prognosis of SCM in the future. (PMID:31557882)
• Analysis of CASP12 diagnostic and prognostic values in cervical cancer based on TCGA database. (PMID:31804677)
• Human Caspase 12 Enhances NF-kappaB Activity through Activation of IKK in Nasopharyngeal Carcinoma Cells. (PMID:33924755)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	casp8	ENSDARG00000058325
danio_rerio	casp3l	ENSDARG00000086266
danio_rerio		ENSDARG00000112575
mus_musculus	Casp12	ENSMUSG00000025887
rattus_norvegicus	Casp12	ENSRNOG00000033434
drosophila_melanogaster	Dronc	FBGN0026404
drosophila_melanogaster	Decay	FBGN0028381
caenorhabditis_elegans		WBGENE00000417
caenorhabditis_elegans		WBGENE00000819
caenorhabditis_elegans		WBGENE00000820
caenorhabditis_elegans	csp-3	WBGENE00000821

Paralogs (16): CASP10 (ENSG00000003400), CFLAR (ENSG00000003402), CASP8 (ENSG00000064012), PYCARD (ENSG00000103490), CASP14 (ENSG00000105141), CASP2 (ENSG00000106144), CASP9 (ENSG00000132906), CASP1 (ENSG00000137752), CASP5 (ENSG00000137757), CASP6 (ENSG00000138794), CASP3 (ENSG00000164305), CASP7 (ENSG00000165806), PYDC1 (ENSG00000169900), CASP4 (ENSG00000196954), CARD16 (ENSG00000204397), CARD18 (ENSG00000255501)

Protein

Protein identifiers

Inactive caspase-12 — Q6UXS9 (reviewed: Q6UXS9)

All UniProt accessions (1): Q6UXS9

UniProt curated annotations — full annotation on UniProt →

Function. May function as a negative regulator of inflammatory responses and innate immunity. May reduce cytokine release in response to bacterial lipopolysaccharide during infection. Reduces activation of NF-kappa-B in response to TNF. May lack protease activity.

Tissue specificity. Widely expressed, with highest levels in lung.

Polymorphism. The sequence shown in this entry differs from the translation of the reference genome assembly (GRCh38/hg38) due to a nonsense variant creating stop codon at position 125 in the reference genome, giving rise to a truncated protein (Csp12-S). The sequence shown in this entry is that of variant p.Ter125Arg. This variant gives rise to a full length protein (Csp12-L). It occurs in the human population at a frequence of about 4% according to the Genome Aggregation Database (gnomAD v3.1.2), with highest frequency observed in people of African descent (up to 60% in certain sub-Saharan populations). Csp12-L expression may increase the susceptibility to severe sepsis, and may result in higher mortality rates (up to 3-fold) once severe sepsis develop.

Similarity. Belongs to the peptidase C14A family.

Isoforms (8)

UniProt ID	Names	Canonical?
Q6UXS9-1	1, Epsilon, Gamma	yes
Q6UXS9-2	2, Alpha, Beta
Q6UXS9-3	3, Iota
Q6UXS9-4	4, Zeta, Epsilon
Q6UXS9-5	5, Eta, Delta
Q6UXS9-6	6, Gamma, Zeta
Q6UXS9-7	7, Theta, Eta
Q6UXS9-8	8, Delta, Theta

RefSeq proteins (0): (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001309	Pept_C14_p20	Domain
IPR001315	CARD	Domain
IPR002138	Pept_C14_p10	Domain
IPR002398	Pept_C14	Family
IPR011029	DEATH-like_dom_sf	Homologous_superfamily
IPR011600	Pept_C14_caspase	Domain
IPR015917	Pept_C14A	Domain
IPR029030	Caspase-like_dom_sf	Homologous_superfamily
IPR033139	Caspase_cys_AS	Active_site

Pfam: PF00619, PF00656

Enzyme classification (BRENDA):

• EC 3.4.22.B66 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

UniProt features (17 total): splice variant 7, sequence variant 3, active site 2, modified residue 2, chain 1, domain 1, sequence conflict 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q6UXS9-F1	77.13	0.31

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 (2): 172; 220

Post-translational modifications (2): 85, 90

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 87 (showing top): GSE45365_NK_CELL_VS_BCELL_DN, GOBP_INFLAMMATORY_RESPONSE, chr11q22, GOBP_POSITIVE_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, FOSTER_TOLERANT_MACROPHAGE_UP, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM1, GOMF_CYSTEINE_TYPE_PEPTIDASE_ACTIVITY, GOBP_REGULATION_OF_RESPONSE_TO_STRESS, SCHAEFFER_PROSTATE_DEVELOPMENT_6HR_UP, GOBP_NEURON_APOPTOTIC_PROCESS, GOBP_REGULATION_OF_RESPONSE_TO_EXTERNAL_STIMULUS, GOBP_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_REGULATION_OF_DEFENSE_RESPONSE, GOBP_POSITIVE_REGULATION_OF_INFLAMMATORY_RESPONSE, GOBP_POSITIVE_REGULATION_OF_NEURON_APOPTOTIC_PROCESS

GO Biological Process (4): proteolysis (GO:0006508), positive regulation of neuron apoptotic process (GO:0043525), positive regulation of inflammatory response (GO:0050729), regulation of apoptotic process (GO:0042981)

GO Molecular Function (1): cysteine-type peptidase activity (GO:0008234)

GO Cellular Component (4): cytoplasm (GO:0005737), endoplasmic reticulum (GO:0005783), cytosol (GO:0005829), NLRP1 inflammasome complex (GO:0072558)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
cytoplasm	2
protein metabolic process	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
inflammatory response	1
positive regulation of defense response	1
positive regulation of response to external stimulus	1
regulation of inflammatory response	1
apoptotic process	1
regulation of programmed cell death	1
peptidase activity	1
intracellular anatomical structure	1
endomembrane system	1
intracellular membrane-bounded organelle	1
canonical inflammasome complex	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

8 interactions, top by confidence:

A	B	Type	Score
MYC	MAX	psi-mi:“MI:0914”(association)	0.980
STAT1	STAT3	psi-mi:“MI:0914”(association)	0.910
CFTR	CNOT1	psi-mi:“MI:0914”(association)	0.480
MYOD1	TCF4	psi-mi:“MI:0914”(association)	0.420
NEK10		psi-mi:“MI:0914”(association)	0.350
ATG16L1		psi-mi:“MI:0914”(association)	0.350
HSPA5	CASP7	psi-mi:“MI:0914”(association)	0.350

BioGRID (21): CASP12 (Biochemical Activity), CASP9 (Biochemical Activity), MAGEA3 (Two-hybrid), MAGEA3 (Affinity Capture-Western), CASP12 (Affinity Capture-Western), CASP12 (Affinity Capture-Western), CASP12 (Affinity Capture-Western), CASP12 (Affinity Capture-Western), CASP12 (Affinity Capture-MS), CASP12 (Affinity Capture-MS), CASP12 (Affinity Capture-MS), CASP12 (Affinity Capture-MS), CASP12 (Proximity Label-MS), CASP12 (Affinity Capture-MS), CASP12 (Affinity Capture-MS)

ESM2 similar proteins: A0A140LIF8, B1ARD6, B1ARD8, G1SRW8, O08736, O14862, O35368, O89110, P0C7P3, P0DOV1, P13504, P29452, P41218, P43527, P51878, P55865, P55867, P70343, Q02955, Q075B4, Q08AF3, Q153Z0, Q16666, Q3UX83, Q4R7Q1, Q504J1, Q504N7, Q5RCZ8, Q5U311, Q60766, Q62929, Q6AYC2, Q6IEE8, Q6UXS9, Q7Z7L1, Q8BV49, Q8CGE8, Q8IXQ6, Q8IYM2, Q8SPH9

Diamond homologs: O08736, O35397, O75601, P29452, P29466, P42574, P43527, P49662, P51878, P55212, P55213, P55865, P55867, P70343, P70677, Q075B4, Q08DY9, Q153Z0, Q2PFV2, Q504J1, Q5E9C1, Q5IS54, Q5IS99, Q60431, Q6UXS9, Q8MJC3, Q8MJU1, Q8MKI5, Q920D5, Q95ND5, Q9I9L7, Q9MZV6, Q9MZV7, Q9N2I1, Q9TV13, A0A1D5PPP7, F1NV61, G5ECW5, O01382, O02002

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
CASP12	up-regulates	CASP9	cleavage

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	42
Likely benign	8
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1122 predictions. Top by Δscore:

Variant	Effect	Δscore
11:104887190:CCCTA:C	donor_loss	1.0000
11:104887191:CCTA:C	donor_loss	1.0000
11:104887192:CTACC:C	donor_loss	1.0000
11:104887193:TACCT:T	donor_loss	1.0000
11:104887195:C:CA	donor_loss	1.0000
11:104887302:TTAT:T	acceptor_gain	1.0000
11:104887303:TAT:T	acceptor_gain	1.0000
11:104887303:TATC:T	acceptor_loss	1.0000
11:104887304:ATCT:A	acceptor_loss	1.0000
11:104887305:TCT:T	acceptor_loss	1.0000
11:104887306:C:CC	acceptor_gain	1.0000
11:104887307:T:A	acceptor_loss	1.0000
11:104890373:T:C	donor_gain	1.0000
11:104891168:A:AC	donor_gain	1.0000
11:104891168:ACTG:A	donor_gain	1.0000
11:104891169:C:CC	donor_gain	1.0000
11:104891169:CTGC:C	donor_gain	1.0000
11:104886811:ACCTA:A	acceptor_loss	0.9900
11:104886814:T:G	acceptor_loss	0.9900
11:104887301:ATTAT:A	acceptor_gain	0.9900
11:104887312:A:AC	acceptor_gain	0.9900
11:104887312:A:C	acceptor_gain	0.9900
11:104890372:A:AC	donor_gain	0.9900
11:104890520:CCAT:C	acceptor_gain	0.9900
11:104890521:CATC:C	acceptor_gain	0.9900
11:104891147:CAG:C	donor_gain	0.9900
11:104891168:ACTGC:A	donor_gain	0.9900
11:104891169:CTG:C	donor_gain	0.9900
11:104891169:CTGCC:C	donor_gain	0.9900
11:104891171:G:GA	donor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000133900 (11:104893817 T>C), RS1000414834 (11:104896191 A>T), RS1000742290 (11:104895088 A>G), RS1000749196 (11:104889774 G>A), RS1000799111 (11:104896485 T>C), RS1000818106 (11:104891303 G>T), RS1001153477 (11:104894780 C>A,G), RS1001191635 (11:104899365 A>G), RS1001855705 (11:104897738 A>G), RS1001864031 (11:104892424 A>G,T), RS1002247185 (11:104891788 A>T), RS1002253553 (11:104886706 T>A,G), RS1002435537 (11:104885818 G>T), RS1002926528 (11:104889479 C>T), RS1003250601 (11:104893377 T>C)

Disease associations

OMIM: gene MIM:608633 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST006461_1	Self-reported risk-taking behaviour	4.000000e-08
GCST007325_4	General risk tolerance (MTAG)	5.000000e-09
GCST011768_8	Schizophrenia	1.000000e-08
GCST011769_21	Schizophrenia	3.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0008579	risk-taking behaviour

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3831289 (PROTEIN FAMILY)

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
7.80	EC50	16	nM	CHEMBL1091826

PubChem BioAssay actives

1 with measured affinity, of 2 total; 1 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
N-(4-methoxyphenyl)-N-methyl-1,2,3-benzotriazin-4-amine	1393168: Activation of caspase cascade in human T47D cells using N-(Ac-DEVD)-N’-ethoxycarbonyl-R110 fluorogenic substrate incubated for 48 hrs by fluorescent plate reader based assay	ec50	0.0160	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Arsenic Trioxide	increases activity, increases expression, decreases reaction, increases cleavage, increases reaction	4
4-phenylbutyric acid	increases expression, decreases cleavage, decreases reaction, increases cleavage	3
7-methyl-5-(1-((3-(trifluoromethyl)phenyl)acetyl)-2,3-dihydro-1H-indol-5-yl)-7H-pyrrolo(2,3-d)pyrimidin-4-amine	increases cleavage, increases expression, decreases cleavage, decreases expression, affects cotreatment (+4 more)	3
Thapsigargin	decreases reaction, increases expression, increases activity, increases cleavage	3
Resveratrol	increases activity, increases expression, decreases reaction, increases cleavage	2
Acetylcysteine	decreases reaction, increases abundance, increases cleavage, increases reaction	2
Cadmium	increases cleavage, increases abundance, decreases reaction, increases activity	2
Cisplatin	affects cotreatment, increases activity, increases reaction	2
Methamphetamine	increases expression, decreases expression, decreases reaction, affects reaction	2
Tunicamycin	affects cotreatment, increases activity, increases reaction, decreases reaction	2
1-Methyl-4-phenylpyridinium	decreases reaction, increases cleavage, increases expression	2
Paclitaxel	decreases expression, increases expression, affects cotreatment	2
SC-66 compound	decreases expression	1
CB-5083	affects cotreatment, increases cleavage	1
methylgerambullin	increases cleavage	1
ML385	decreases reaction, increases cleavage	1
thymoquinone	decreases expression	1
bufotalin	decreases reaction, increases activity, increases cleavage	1
naringin	increases expression	1
methylselenic acid	decreases reaction, increases cleavage	1
tetrandrine	increases cleavage	1
antibiotic G 418	increases cleavage	1
2,4,5,2’,4’,5’-hexachlorobiphenyl	increases reaction, increases expression	1
arsenite	increases expression	1
zinc chloride	increases activity, affects cotreatment	1
fisetin	decreases reaction, increases expression	1
sodium arsenite	affects reaction, increases cleavage	1
manganese chloride	increases activity, increases cleavage, increases reaction	1
1,2-bis(2-aminophenoxy)ethane-N,N,N’,N’-tetraacetic acid	decreases reaction, increases expression	1
benzo(e)pyrene	increases activity	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4199992	Binding	Activation of caspase (unknown origin)	MK-8353: Discovery of an Orally Bioavailable Dual Mechanism ERK Inhibitor for Oncology. — ACS Med Chem Lett

Clinical trials (associated diseases)

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