CLPP

Summary

CLPP (caseinolytic mitochondrial matrix peptidase proteolytic subunit, HGNC:2084) is a protein-coding gene on chromosome 19p13.3, encoding ATP-dependent Clp protease proteolytic subunit, mitochondrial (Q16740). Protease component of the ClpXP complex that cleaves peptides and various proteins in an ATP-dependent process.

The protein encoded by this gene belongs to the peptidase family S14 and hydrolyzes proteins into small peptides in the presence of ATP and magnesium. The protein is transported into mitochondrial matrix and is associated with the inner mitochondrial membrane.

Source: NCBI Gene 8192 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Perrault syndrome 3 (Definitive, ClinGen)
• Clinical variants (ClinVar): 245 total — 12 pathogenic, 11 likely-pathogenic
• GTEx eGene: eQTL in 42 tissues, sQTL in 6 (q < 0.05)
• Phenotypes (HPO): 11
• ChEMBL bioactivity: 2 clinical-phase molecules tested; no curated mechanism-of-action drug
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• Constraint (gnomAD): pLI 0.01 (LoF-tolerant), LOEUF 0.94 (unconstrained)
• MANE Select transcript: NM_006012
• Interaction hub: 3,172 STRING partners (top 2% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2084
Approved symbol	CLPP
Name	caseinolytic mitochondrial matrix peptidase proteolytic subunit
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000125656
Ensembl biotype	protein_coding
OMIM	601119
Entrez	8192

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 9 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

MANE Select: ENST00000245816

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 3, TSL 5: 2

ENST00000245816, ENST00000594780, ENST00000596070, ENST00000596149, ENST00000596605, ENST00000597326, ENST00000646643, ENST00000715787, ENST00000926271, ENST00000926272, ENST00001035395, ENST00001125460

RefSeq mRNA: 1 — MANE Select: NM_006012 NM_006012

CCDS: CCDS12162

Canonical transcript exons

ENST00000245816 — 6 exons

Exon	Start	End
ENSE00002987749	6368538	6370242
ENSE00003484252	6366258	6366363
ENSE00003540033	6362446	6362542
ENSE00003667614	6361869	6361940
ENSE00003689024	6364452	6364639
ENSE00004027934	6361531	6361772

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 97.45.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 61.2497 / max 273.6877, expressed in 1823 samples.

Highest expression (Bgee): hindlimb stylopod muscle, gastrocnemius, mucosa of transverse colon, apex of heart, muscle of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CLPP is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 42 tissues and its splicing (sQTL) in 6 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 48 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Esophagus Muscularis	eqtl	5.4e-21	+0.40	19:6368863:C:G
Heart Atrial Appendage	eqtl	4.5e-20	+0.54	19:6368863:C:G
Cells Cultured fibroblasts	eqtl	1.8e-19	+0.27	19:6368863:C:G
Artery Tibial	eqtl	4.7e-19	+0.31	19:6368863:C:G
Whole Blood	eqtl	2.1e-18	+0.37	19:6327237:C:T
Thyroid	eqtl	3.9e-16	+0.27	19:6370255:C:T
Nerve Tibial	eqtl	3.2e-15	+0.32	19:6368863:C:G
Artery Aorta	eqtl	3.9e-15	+0.45	19:6368863:C:G
Esophagus Gastroesophageal Junction	eqtl	4.5e-14	+0.42	19:6368863:C:G
Brain Putamen basal ganglia	eqtl	5.8e-14	+0.61	19:6370259:C:T
Heart Left Ventricle	eqtl	1.7e-13	+0.41	19:6368863:C:G
Colon Sigmoid	eqtl	4.1e-13	+0.47	19:6368863:C:G
Brain Caudate basal ganglia	eqtl	2.4e-11	+0.46	19:6370255:C:T
Adipose Subcutaneous	eqtl	2.8e-11	+0.28	19:6357758:G:A
Lung	eqtl	4.1e-11	+0.41	19:6340165:CA:C
Skin Not Sun Exposed Suprapubic	eqtl	4.4e-11	+0.32	19:6368863:C:G
Cells EBV-transformed lymphocytes	eqtl	6.2e-11	+0.43	19:6368863:C:G
Brain Hippocampus	eqtl	1.1e-10	+0.55	19:6370255:C:T
Esophagus Mucosa	eqtl	1.3e-10	+0.30	19:6368863:C:G
Brain Frontal Cortex BA9	eqtl	7.4e-10	+0.55	19:6369698:G:T

FANTOM5 promoters

10 alternative TSS:

Promoter ID	TPM avg	Samples expressed
173462	37.6618	1812
173463	11.9723	1739
173461	4.4571	1643
173468	2.1750	1128
173466	1.7752	1135
173470	0.9027	523
173465	0.6495	429
173469	0.6249	341
173464	0.5888	294
173467	0.4424	226

Top tissues by expression

showing 100 of 293 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
hindlimb stylopod muscle	UBERON:0004252	97.45	gold quality
gastrocnemius	UBERON:0001388	97.15	gold quality
mucosa of transverse colon	UBERON:0004991	97.04	gold quality
apex of heart	UBERON:0002098	96.92	gold quality
muscle of leg	UBERON:0001383	96.76	gold quality
right adrenal gland	UBERON:0001233	96.68	gold quality
left adrenal gland	UBERON:0001234	96.47	gold quality
right lobe of liver	UBERON:0001114	96.42	gold quality
right adrenal gland cortex	UBERON:0035827	96.42	gold quality
left adrenal gland cortex	UBERON:0035825	96.31	gold quality
body of stomach	UBERON:0001161	96.19	gold quality
lower esophagus mucosa	UBERON:0035834	95.99	gold quality
stromal cell of endometrium	CL:0002255	95.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	95.93	gold quality
mucosa of stomach	UBERON:0001199	95.92	gold quality
lower esophagus	UBERON:0013473	95.79	gold quality
lower esophagus muscularis layer	UBERON:0035833	95.79	gold quality
adenohypophysis	UBERON:0002196	95.71	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	95.62	gold quality
left coronary artery	UBERON:0001626	95.57	gold quality
right atrium auricular region	UBERON:0006631	95.57	gold quality
heart left ventricle	UBERON:0002084	95.55	gold quality
left uterine tube	UBERON:0001303	95.41	gold quality
muscle layer of sigmoid colon	UBERON:0035805	95.38	gold quality
adrenal cortex	UBERON:0001235	95.33	gold quality
ganglionic eminence	UBERON:0004023	95.29	gold quality
cardiac ventricle	UBERON:0002082	95.28	gold quality
esophagus	UBERON:0001043	95.19	gold quality
cortical plate	UBERON:0005343	95.19	gold quality
metanephros cortex	UBERON:0010533	95.18	gold quality
body of pancreas	UBERON:0001150	95.14	gold quality
esophagus mucosa	UBERON:0002469	95.02	gold quality
popliteal artery	UBERON:0002250	94.97	gold quality
muscle organ	UBERON:0001630	94.96	gold quality
tibial artery	UBERON:0007610	94.96	gold quality
right coronary artery	UBERON:0001625	94.94	gold quality
transverse colon	UBERON:0001157	94.89	gold quality
skin of leg	UBERON:0001511	94.86	gold quality
omental fat pad	UBERON:0010414	94.81	gold quality
aorta	UBERON:0000947	94.80	gold quality
ascending aorta	UBERON:0001496	94.80	gold quality
thoracic aorta	UBERON:0001515	94.78	gold quality
granulocyte	CL:0000094	94.77	gold quality
peritoneum	UBERON:0002358	94.76	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.75	gold quality
right testis	UBERON:0004534	94.74	gold quality
coronary artery	UBERON:0001621	94.72	gold quality
left testis	UBERON:0004533	94.71	gold quality
adrenal gland	UBERON:0002369	94.69	gold quality
ectocervix	UBERON:0012249	94.66	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.62	gold quality
pituitary gland	UBERON:0000007	94.44	gold quality
descending thoracic aorta	UBERON:0002345	94.43	gold quality
right ovary	UBERON:0002118	94.41	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	94.40	gold quality
gluteal muscle	UBERON:0002000	94.38	gold quality
ventricular zone	UBERON:0003053	94.32	gold quality
skin of abdomen	UBERON:0001416	94.31	gold quality
minor salivary gland	UBERON:0001830	94.30	gold quality
right lobe of thyroid gland	UBERON:0001119	94.24	gold quality
upper lobe of left lung	UBERON:0008952	94.24	gold quality
adipose tissue of abdominal region	UBERON:0007808	94.16	gold quality
prefrontal cortex	UBERON:0000451	94.15	gold quality
heart	UBERON:0000948	94.12	gold quality
triceps brachii	UBERON:0001509	94.10	gold quality
endocervix	UBERON:0000458	94.06	gold quality
cardiac atrium	UBERON:0002081	94.06	gold quality
left lobe of thyroid gland	UBERON:0001120	93.98	gold quality
body of uterus	UBERON:0009853	93.98	gold quality
right frontal lobe	UBERON:0002810	93.95	gold quality
stomach	UBERON:0000945	93.78	gold quality
left ovary	UBERON:0002119	93.77	gold quality
right lung	UBERON:0002167	93.72	gold quality
saliva-secreting gland	UBERON:0001044	93.58	gold quality
tibial nerve	UBERON:0001323	93.58	gold quality
nucleus accumbens	UBERON:0001882	93.58	gold quality
caudate nucleus	UBERON:0001873	93.50	gold quality
amygdala	UBERON:0001876	93.45	gold quality
spleen	UBERON:0002106	93.43	gold quality
small intestine	UBERON:0002108	93.42	gold quality
mouth mucosa	UBERON:0003729	93.22	gold quality
putamen	UBERON:0001874	93.20	gold quality
upper lobe of lung	UBERON:0008948	93.12	gold quality
right hemisphere of cerebellum	UBERON:0014890	93.11	gold quality
cingulate cortex	UBERON:0003027	92.99	gold quality
spinal cord	UBERON:0002240	92.93	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.91	gold quality
anterior cingulate cortex	UBERON:0009835	92.79	gold quality
cerebellar hemisphere	UBERON:0002245	92.78	gold quality
cerebellar cortex	UBERON:0002129	92.74	gold quality
testis	UBERON:0000473	92.64	gold quality
sigmoid colon	UBERON:0001159	92.62	gold quality
thyroid gland	UBERON:0002046	92.62	gold quality
colon	UBERON:0001155	92.60	gold quality
embryo	UBERON:0000922	92.52	gold quality
zone of skin	UBERON:0000014	92.29	gold quality
adult mammalian kidney	UBERON:0000082	92.22	gold quality
large intestine	UBERON:0000059	92.21	gold quality
intestine	UBERON:0000160	92.14	gold quality
lymph node	UBERON:0000029	92.07	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	12.27
E-MTAB-7052	no	78.42
E-HCAD-13	no	2.85
E-CURD-112	no	2.78

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Skeletal muscle	tissue	137.8	low
Frontal cortex	tissue	79.5
Caudate putamen	tissue	74.1
Choroid plexus	tissue	62.7
Pituitary gland	tissue	59.6
Tongue	tissue	55.2
Vagina	tissue	48.1	low
Pancreas	tissue	46.7	high
Hippocampus	tissue	46.3	medium
Liver	tissue	45.8	medium
Salivary gland	tissue	45.4	low
Duodenum	tissue	44.7	medium
Lymph node	tissue	44.5	medium
Locus coeruleus	tissue	44.5
Nucleus accumbens	tissue	43.3
Thymus	tissue	42.1
Bone marrow	tissue	40.5	low
Adrenal gland	tissue	39.9	high
Heart muscle	tissue	39.6	low
Adipose tissue	tissue	39.4	low
Appendix	tissue	39.1	high
Small intestine	tissue	38.5	high
Colon	tissue	34.6	medium
Parathyroid gland	tissue	34.4	medium
Stomach 1	tissue	33.7	high
Tonsil	tissue	33.4	high
Spleen	tissue	32.3	high
Kidney	tissue	32.1	medium
Ovary	tissue	32.0	low
Spinal cord	tissue	31.7
Medulla oblongata	tissue	30.4
Prostate	tissue	30.0	high
Superior colliculi	tissue	29.7
Postcentral gyrus	tissue	29.7
Pons	tissue	29.5
Seminal vesicle	tissue	29.4	high
Thalamus	tissue	29.2
Midbrain	tissue	27.6
Esophagus	tissue	27.2	high
Substantia nigra	tissue	26.9
Skin 1	tissue	25.9	medium
Testis	tissue	25.8	high
Hypothalamus	tissue	25.8
Urinary bladder	tissue	25.5	medium
Corpus callosum	tissue	24.9
Hippocampal formation	tissue	24.7
Fallopian tube	tissue	24.2	medium
Lung	tissue	24.0	medium
Ventral forebrain	tissue	23.9
Putamen	tissue	23.8
Placenta	tissue	23.8	medium
Periaqueductal gray	tissue	23.8
Smooth muscle	tissue	23.4	low
Septum	tissue	23.1
Basal ganglia	tissue	23.0	medium
Breast	tissue	21.6	not detected
Rectum	tissue	21.5	high
Cervix	tissue	21.2	high
Cerebral cortex	tissue	19.5	medium
Gallbladder	tissue	19.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (59.8), Posterior thalamic nucleus (56.1), Medial dorsal thalamic nucleus (53.7), Dorsal funiculus (white matter) (52.5), Supraoptic nucleus (51.9).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RELB

miRNA regulators (miRDB)

Targeting CLPP by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

11 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-128-3P	99.95	71.17	2484
HSA-MIR-216A-3P	99.95	71.19	2505
HSA-MIR-3681-3P	99.88	70.46	2254
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-516B-5P	99.56	66.33	1495
HSA-MIR-670-3P	99.03	68.88	2404
HSA-MIR-1207-3P	98.99	66.22	1532
HSA-MIR-4326	98.97	67.63	962
HSA-MIR-6801-3P	98.04	64.64	805
HSA-MIR-6810-3P	97.96	64.57	1023
HSA-MIR-6787-3P	97.75	66.17	1233

Functional genomics

gnomAD constraint: pLI 0.00616, LOEUF 0.936, missense Z 0.128 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000245816 splits into 2 regions with different missense tolerance; 0 are missense-constrained. Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
19:6,361,575–6,361,903	148 / 122.6	1.21	no
19:6,361,904–6,368,707	213 / 280.9	0.76	no
ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 24)

• the N-terminal peptide of ClpP is a structural component of the substrate translocation channel and may play an important functional role as well (PMID:15522782)
• hClpX can regulate the appearance of hClpP peptidase activity in mitochondria and might affect the nature of the degradation products released during ATP-dependent proteolytic cycles (PMID:16115876)
• We propose that decreased levels of mitochondrial proteases Lon and ClpP may allow heat shock protein 60 substrate proteins to go through more folding attempts (PMID:18378094)
• Deletion of PaClpP, leads to an unexpected healthy phenotype and increased lifespan of the fungal ageing model organism Podospora anserina and This phenotype can be reverted by expression of human ClpP. (PMID:23360988)
• Perrault syndrome is caused by recessive mutations in CLPP. (PMID:23541340)
• Optical trapping to assay single-molecule ClpXP unfolding and translocation of substrates consisting of domains with varying stabilities and sequences; find that ClpXP unfolds most domains by a single pathway, with kinetics that depend on the native fold and structural stability. (PMID:25083874)
• ClpP proteases from E. coli, S. aureus, and human mitochondria exhibit preferences for certain amino acids in the P1, P2, and P3 positions . (PMID:26606371)
• Mitochondrial overexpression of human ClpP protects HeLa cells from killing by cisplatin. Overexpression of human ClpP desensitizes cells to cisplatin. (PMID:26675528)
• ere we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2 (PMID:26970254)
• Data indicate endopeptidase Clp (ClpP) mutation identified in two patients with Perrault syndrome type 3 in a Turkish family. (PMID:27087618)
• we demonstrate that a strong mitochondrial cardiomyopathy and diminished respiration due to DARS2 deficiency can be alleviated by the loss of CLPP, leading to an increased de novo synthesis of individual OXPHOS subunits. (PMID:27154400)
• Data suggest that tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. (PMID:27389535)
• Autophagy compensates impaired energy metabolism in CLPXP-deficient Podospora anserina strains and extends healthspan. (PMID:28449241)
• ClpP is selectively decreased in alphaSyn-expressing cell culture and neurons derived from iPS cells of PD patient carrying alphaSyn A53T mutant, and in dopaminergic neurons of alphaSyn A53T mice and PD patient postmortem brains. ClpP loss damages mitochondria. Overexpression causes oxidative stress and suppresses alphaSyn phosphorylation. alphaSyn WT and A53T mutant interact with ClpP and suppress its peptidase activity. (PMID:30877431)
• Results found that CLPP influenced mitochondrial respiration only under conditions of oxidative stress. (PMID:30878663)
• Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease. (PMID:32342250)
• Genomic sequencing highlights the diverse molecular causes of Perrault syndrome: a peroxisomal disorder (PEX6), metabolic disorders (CLPP, GGPS1), and mtDNA maintenance/translation disorders (LARS2, TFAM). (PMID:32399598)
• Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer. (PMID:34207660)
• Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site-Specific Photocrosslinking Approach. (PMID:34847623)
• Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA. (PMID:34943861)
• CLPP deficiency ameliorates neurodegeneration caused by impaired mitochondrial protein synthesis. (PMID:35240691)
• Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma. (PMID:35905743)
• Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma. (PMID:37923710)
• HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells. (PMID:38419499)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	clpp	ENSDARG00000020679
mus_musculus	Clpp	ENSMUSG00000002660
rattus_norvegicus	Clpp	ENSRNOG00000047052
drosophila_melanogaster	ClpP	FBGN0032229
caenorhabditis_elegans		WBGENE00014172

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1858213) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 63 distinct phenotype terms.

Mouse phenotype (MP)	Records
decreased body length	2
male infertility	2
female infertility	2
decreased bone mineral density	1
increased leukocyte cell number	1
increased monocyte cell number	1
tremors	1
small ovary	1
small testis	1
arrest of spermatogenesis	1
dermatitis	1
decreased locomotor activity	1
decreased startle reflex	1
abnormal T cell activation	1
abnormal oogenesis	1
premature death	1
increased hematocrit	1
decreased corpora lutea number	1
decreased vertical activity	1
increased circulating serum albumin level	1
increased circulating alkaline phosphatase level	1
thrombocytopenia	1
increased circulating glycerol level	1
abnormal bone structure	1
increased lean body mass	1

+38 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Bos taurus	Q2KHU4	89.9%	Diamond
Caenorhabditis briggsae	A8WPG6	87.8%	Diamond
Arabidopsis thaliana	Q9FN42	66.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
MIR6790	ncRNA	102465473
GTF2F1	protein-coding	2962
PSPN	protein-coding	5623
ALKBH7	protein-coding	84266
ACER1	protein-coding	125981
RFX2-AS1	ncRNA	139281648
MLLT1	protein-coding	4298
RFX2	protein-coding	5990
ACSBG2	protein-coding	81616
MIR6885	ncRNA	102465533
MIR3940	ncRNA	100500888
KHSRP	protein-coding	8570

Protein

Protein identifiers

ATP-dependent Clp protease proteolytic subunit, mitochondrial — Q16740 (reviewed: Q16740)

Alternative names: Caseinolytic mitochondrial matrix peptidase proteolytic subunit, Endopeptidase Clp

All UniProt accessions (5): A0A2R8YEF5, M0QXE9, M0QYV5, M0R208, Q16740

UniProt curated annotations — full annotation on UniProt →

Function. Protease component of the ClpXP complex that cleaves peptides and various proteins in an ATP-dependent process. Has low peptidase activity in the absence of CLPX. The ClpXP complex can degrade CSN1S1, CSN2 and CSN3, as well as synthetic peptides (in vitro) and may be responsible for a fairly general and central housekeeping function rather than for the degradation of specific substrates. Cleaves PINK1 in the mitochondrion.

Subunit / interactions. Fourteen CLPP subunits assemble into 2 heptameric rings which stack back to back to give a disk-like structure with a central cavity. Component of the ClpXP complex formed by the assembly of two CLPP heptameric rings with two CLPX hexameric rings, giving rise to a symmetrical structure with two central CLPP rings flanked by a CLPX ring at either end of the complex.

Subcellular location. Mitochondrion matrix.

Tissue specificity. Detected in liver (at protein level). Predominantly expressed in skeletal muscle. Intermediate levels in heart, liver and pancreas. Low in brain, placenta, lung and kidney.

Disease relevance. Perrault syndrome 3 (PRLTS3) [MIM:614129] An autosomal recessive, sex-influenced disorder characterized by sensorineural deafness in both males and females, and ovarian dysgenesis in females. Affected females have primary amenorrhea, streak gonads, and infertility, whereas affected males show normal pubertal development and are fertile. A spectrum of additional clinical features, including cerebellar ataxia, learning disability, and peripheral neuropathy, have been described in some PRLTS3 affected individuals. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the peptidase S14 family.

RefSeq proteins (1): NP_006003* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001907	ClpP	Family
IPR018215	ClpP_Ser_AS	Active_site
IPR023562	ClpP/TepA	Family
IPR029045	ClpP/crotonase-like_dom_sf	Homologous_superfamily
IPR033135	ClpP_His_AS	Active_site

Pfam: PF00574

Enzyme classification (BRENDA)

• EC 3.4.21.92 — Endopeptidase Clp (BRENDA: 73 organisms, 159 substrates, 60 inhibitors, 27 Km, 17 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
N-SUCCINYL-LEU-TYR-7-AMIDO-4-METHYLCOUMARIN	0.52–1.1	5
ARC-SSRA	0.0005–0.14	4
LAMBDA O CM-TITIIN	0.011–0.041	4
INSULIN CHAIN B	0.04–0.3167	3
CM-TITIN-SSRA	0.0024–0.08	2
FEGFP-SSRA	—	2
LAMBDA O ARC	0.0044–0.013	2
SUC-LLVY-4-METHYLCOUMARIN-7-AMIDE	0.065	2
31-KNOTTED METHYLTRANSFERASE YBEA-SSRA	0.0013	1
ATP	0.21	1
N-SUCCINYL-LEU-TYR 4-METHYLCOUMARIN 7-AMIDE	1.3	1
GLUCAGON	—	0
OXIDIZED INSULIN B-CHAIN	—	0
PHE-ALA-PRO-HIS-MET-ALA-LEU-VAL-PRO-VAL	—	0
SUCCINYL-LLVY-7-AMIDO-4-METHYLCOUMARIN	—	0

UniProt features (35 total): strand 12, helix 9, sequence variant 3, mutagenesis site 2, active site 2, modified residue 2, transit peptide 1, chain 1, sequence conflict 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

showing 30 of 32 structures by resolution:

PDB	Title	Method	Resolution (Å)
8HGK	Crystal structure of human ClpP in complex with ZK53	X-RAY DIFFRACTION	1.9
8I7X	Crystal structure of human ClpP in complex with ZG36	X-RAY DIFFRACTION	1.99
6DL7	Human mitochondrial ClpP in complex with ONC201 (TIC10)	X-RAY DIFFRACTION	2
1TG6	Crystallography and mutagenesis point to an essential role for the N-terminus of human …	X-RAY DIFFRACTION	2.1
7WH5	Crystal structure of human ClpP in complex with ZG180	X-RAY DIFFRACTION	2.13
8YLB	Cocrystal structures of agonists compound 1 with HsClpP	X-RAY DIFFRACTION	2.15
7UVM	Crystal structure of human ClpP protease in complex with TR-27	X-RAY DIFFRACTION	2.19
9DW3	Human mitochondrial ClpP in complex with Bortezomib	ELECTRON MICROSCOPY	2.4
9KUF	Cryo-EM structure of HsClpP bound to CLPP-2068	ELECTRON MICROSCOPY	2.45
9DKW	Human mitochondrial ClpP in complex with Bortezomib	ELECTRON MICROSCOPY	2.49
7VP9	Crystal structure of human ClpP in complex with ZG111	X-RAY DIFFRACTION	2.55
8YPA	Human mitochondrial ClpP in complex with TR89	X-RAY DIFFRACTION	2.67
9PNC	Crystal structure of human mitochondrial ClpP protease C144R mutant in complex with …	X-RAY DIFFRACTION	2.7
9DQK	human ClpP - Apo - A192E / E196R	X-RAY DIFFRACTION	2.75
9Z3C	Human ClpP with drug	X-RAY DIFFRACTION	2.78
6BBA	Crystal structure of human mitochondrial ClpP complex with acyldepsipeptide ADEP-28	X-RAY DIFFRACTION	2.8
7UW0	Crystal structure of human ClpP protease in complex with TR-133	X-RAY DIFFRACTION	2.8
8W7E	Design, synthesis and biological evaluations of novel small molecular hyper-activators of …	X-RAY DIFFRACTION	2.8
9DW0	Human ClpX-bound ClpP	ELECTRON MICROSCOPY	2.8
9DKV	Human mitochondrial ClpP in Apo state	ELECTRON MICROSCOPY	2.81
7UVR	Crystal structure of human ClpP protease in complex with TR-65	X-RAY DIFFRACTION	2.86
8WUZ	Development of 2-imino-2,3,5,6,7,8-hexahydropyrido[4,3-d]pyrimidin-4(1H)-one derivatives …	X-RAY DIFFRACTION	2.9
8W7C	Activation of mitochondrial Caseinolytic Protease P (ClpP) induces selective cancer cell …	X-RAY DIFFRACTION	3
9PN7	Crystal structure of human mitochondrial ClpP protease C144R mutant	X-RAY DIFFRACTION	3.02
6H23	Crystal structure of the hClpP Y118A mutant with an activating small molecule	X-RAY DIFFRACTION	3.09
7UVN	Crystal structure of human ClpP protease in complex with TR-57	X-RAY DIFFRACTION	3.11
9DQL	human ClpP - Bortezomib - A192E / E196R	X-RAY DIFFRACTION	3.2
7UVU	Crystal structure of human ClpP protease in complex with TR-107	X-RAY DIFFRACTION	3.24
9DW1	Human mitochondrial ClpP protease	ELECTRON MICROSCOPY	3.4
9YKZ	Un-crosslinked hClpP	ELECTRON MICROSCOPY	3.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q16740-F1	82.68	0.62

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Peptidases, Serine-type peptidases, Predicted intracellular proteins, Disease related genes, Potential drug targets, Human disease related genes, Congenital malformations, Other congenital malformations

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): mitochondria

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
153	nucleophile
178

Post-translational modifications (2)

Type	Positions
N6-succinyllysine	200
N6-acetyllysine	211

Mutagenesis-validated functional residues (2)

Position	Phenotype
58–61	abolishes protease activity.
153	abolishes protease activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 curated (TAS) of 2; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

2 pathways:

ID	Pathway	Evidence
R-HSA-9837999	Mitochondrial protein degradation	curated
R-HSA-392499	Metabolism of proteins	—

MSigDB gene sets: 165 (showing top): MORF_DNMT1, MORF_ESPL1, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, ACEVEDO_NORMAL_TISSUE_ADJACENT_TO_LIVER_TUMOR_DN, MORF_BUB3, BOGNI_TREATMENT_RELATED_MYELOID_LEUKEMIA_UP, DOUGLAS_BMI1_TARGETS_UP, WONG_MITOCHONDRIA_GENE_MODULE, GOBP_MEMBRANE_PROTEIN_PROTEOLYSIS, GOBP_PROTEIN_CATABOLIC_PROCESS, RAMPON_ENRICHED_LEARNING_ENVIRONMENT_LATE_UP, GOCC_MITOCHONDRIAL_MATRIX, GOBP_PROTEOLYSIS, SMITH_TERT_TARGETS_UP

GO Biological Process (5): proteolysis (GO:0006508), protein quality control for misfolded or incompletely synthesized proteins (GO:0006515), membrane protein proteolysis (GO:0033619), mitochondrial protein catabolic process (GO:0035694), protein catabolic process (GO:0030163)

GO Molecular Function (9): endopeptidase activity (GO:0004175), ATP-dependent peptidase activity (GO:0004176), serine-type endopeptidase activity (GO:0004252), peptidase activity (GO:0008233), identical protein binding (GO:0042802), ATPase binding (GO:0051117), protein binding (GO:0005515), serine-type peptidase activity (GO:0008236), hydrolase activity (GO:0016787)

GO Cellular Component (3): mitochondrion (GO:0005739), mitochondrial matrix (GO:0005759), endopeptidase Clp complex (GO:0009368)

Reactome top-level categories

1 top-level categories:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

21 GO namespaces:

Category	Terms
peptidase activity	3
protein metabolic process	2
protein catabolic process	2
mitochondrion	2
proteolysis	1
mitochondrion organization	1
macromolecule catabolic process	1
ATP-dependent activity	1
endopeptidase activity	1
serine-type peptidase activity	1
hydrolase activity	1
catalytic activity, acting on a protein	1
protein binding	1
enzyme binding	1
binding	1
serine hydrolase activity	1
catalytic activity	1
cytoplasm	1
intracellular membrane-bounded organelle	1
intracellular organelle lumen	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 7 of 18 annotations. The rest are phylogenetic / computational / electronic (IEA).

7 experimentally-supported GO terms:

GO term	NS	Evidence
membrane protein proteolysis	BP	direct assay
proteolysis	BP	direct assay
endopeptidase Clp complex	CC	direct assay
mitochondrial matrix	CC	direct assay
mitochondrion	CC	direct assay
endopeptidase activity	MF	direct assay
serine-type endopeptidase activity	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 3,172 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLPP	CLPX	O76031	948
CLPP	TBX22	Q9Y458	942
CLPP	RPS16	P17008	890
CLPP	CLPB	Q9H078	835
CLPP	YME1L1	Q96TA2	825
CLPP	LONP1	P36776	811
CLPP	HSPE1	P61604	794
CLPP	HSPD1	P10809	792
CLPP	GRPEL1	Q9HAV7	764
CLPP	ERAL1	O75616	737
CLPP	ATF5	Q9Y2D1	721
CLPP	AFG3L2	Q9Y4W6	715
CLPP	HSPA9	P30036	712
CLPP	LARS2	Q15031	697
CLPP	SPX	Q9BT56	686

IntAct

Human interaction partners of CLPP in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

30 partners by confidence:

Partner	Interaction type	MIscore	Records
HTT	physical association	0.560	6
DTX2	physical association	0.560	5
ABI2	physical association	0.560	3
APP	physical association	0.560	3
ATXN3	physical association	0.560	3
C14orf119	physical association	0.560	3
DNM2	physical association	0.560	3
EFEMP1	physical association	0.560	3
EFEMP2	physical association	0.560	3
GDAP1	physical association	0.560	3
GRN	physical association	0.560	3
JPH3	physical association	0.560	3
NUTF2	physical association	0.560	3
P4HA3	physical association	0.560	3
PLSCR4	physical association	0.560	3
PPP2CA	physical association	0.560	3
PSMB1	physical association	0.560	3
RBPMS	physical association	0.560	3
SNCA	physical association	0.560	3
TARDBP	physical association	0.560	3
TNPO3	physical association	0.560	3
WFS1	physical association	0.560	3
HERC2	association	0.350	1
UQCC1	association	0.350	1
NDUFA4	proximity	0.270	1
GH1	physical association	0.000	1
HLA-B	physical association	0.000	1
RAB5IF	physical association	0.000	1
SAP18	physical association	0.000	1
TRIM54	physical association	0.000	1

BioGRID (845 interactions; top human partners by supporting records in a sample of 600 records): CS (Proximity Label-MS; 4 records), PPA2 (Affinity Capture-MS; 4 records), SSBP1 (Proximity Label-MS; 4 records), AARS2 (Proximity Label-MS; 3 records), ACAD9 (Proximity Label-MS; 3 records), ACADM (Proximity Label-MS; 3 records), ACADSB (Proximity Label-MS; 3 records), ACO2 (Proximity Label-MS; 3 records), AIFM1 (Proximity Label-MS; 3 records), AK3 (Proximity Label-MS; 3 records), ALDH4A1 (Proximity Label-MS; 3 records), CARS2 (Proximity Label-MS; 3 records), CLPX (Reconstituted Complex; 3 records), COX5A (Proximity Label-MS; 3 records), ECSIT (Affinity Capture-MS; 3 records)

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
★ ALAS1-CLPP-CLPX complex	3	CLPP, CLPX, ALAS1
ClpXP complex	2	CLPP, CLPX
ClpP complex, heptameric	1	CLPP

Disease & clinical

Genetic variants

Variant evidence for CLPP: 245 ClinVar records (23 pathogenic / likely pathogenic). Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	11
Uncertain significance	76
Likely benign	99
Benign	31

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 23 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2138190	NM_006012.4(CLPP):c.21del (p.Ala10fs)	Pathogenic	criteria provided, multiple submitters, no conflicts	3
593703	NM_006012.4(CLPP):c.367+2T>C	Pathogenic	criteria provided, single submitter	1
1356365	NM_006012.4(CLPP):c.12_33dup (p.Val12fs)	Pathogenic	criteria provided, single submitter	1
1411562	NM_006012.4(CLPP):c.491del (p.Pro164fs)	Pathogenic	criteria provided, single submitter	1
2031987	NM_006012.4(CLPP):c.585_586insAT (p.Glu196fs)	Pathogenic	criteria provided, single submitter	1
2579749	NM_006012.4(CLPP):c.383_399dup (p.Asp134fs)	Pathogenic	criteria provided, single submitter	1
3601032	NM_006012.4(CLPP):c.328del (p.Ser110fs)	Pathogenic	criteria provided, single submitter	1
3601044	NM_006012.4(CLPP):c.661G>T (p.Glu221Ter)	Pathogenic	criteria provided, single submitter	1
813818	NM_006012.4(CLPP):c.233G>C (p.Arg78Pro)	Likely pathogenic	criteria provided, single submitter	1
1332812	NM_006012.4(CLPP):c.299T>C (p.Ile100Thr)	Likely pathogenic	criteria provided, single submitter	1
2138191	NM_006012.4(CLPP):c.661G>A (p.Glu221Lys)	Likely pathogenic	criteria provided, single submitter	1
2171411	NM_006012.4(CLPP):c.199-1G>C	Likely pathogenic	criteria provided, single submitter	1
2584518	NM_006012.4(CLPP):c.484G>A (p.Gly162Ser)	Likely pathogenic	criteria provided, single submitter	1
3601043	NM_006012.4(CLPP):c.400G>C (p.Asp134His)	Likely pathogenic	criteria provided, single submitter	1
4855728	NM_006012.4(CLPP):c.661+2T>G	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore CLPP’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 35 predictions of 235):

Position(s)	Effect	Δscore	Sites
19:6361774	donor_loss	1.0000
19:6361867–6361868	acceptor_loss	1.0000	4
19:6362543–6362544	donor_loss	1.0000	5
19:6364450–6364451	acceptor_loss	1.0000	5
19:6364640–6364641	donor_loss	1.0000	5
19:6366244–6366245	acceptor_gain	1.0000	2
19:6361773	donor_loss	0.9900
19:6361867–6361868	acceptor_loss	0.9900	2
19:6361941–6361942	donor_loss	0.9900	5
19:6362444–6362445	acceptor_loss	0.9900	5

AlphaMissense

951 missense substitutions predicted likely pathogenic (of 1,794 scored), across 185 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M154	9	0.923	0.997
M176	9	0.923	0.998
M136	9	0.865	0.994
M88	9	0.860	0.981
D134	8	0.998	1.000
H178	8	0.998	1.000
D74	8	0.996	0.998
D227	8	0.991	0.998
S153	8	0.990	1.000
D190	8	0.988	0.998
D242	8	0.988	0.998
H212	8	0.969	0.995
D93	8	0.946	0.992
H116	8	0.930	0.993
S121	8	0.905	0.999
F105	7	0.997	0.999
R226	7	0.993	0.999
W146	7	0.986	0.999
F238	7	0.981	0.994
Q179	7	0.980	0.998

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

1 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	6.03e-05

Disease associations

OMIM: gene MIM:601119 | disease phenotypes: MIM:614129, MIM:233400

GenCC curated gene-disease

1 curated gene-disease records:

Disease	Classification	Inheritance	Records
Perrault syndrome 3	Definitive	Autosomal recessive	3

ClinGen Gene-Disease Validity

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

1 validity classifications:

Disease	Classification	Inheritance
Perrault syndrome 3	Definitive	AR

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (17 panels, 12 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

17 panels:

Panel	Rating
DDG2P	green
Hypotonic infant	green
Leukodystrophy, childhood onset	green
Likely inborn error of metabolism	green
Mitochondrial disorders	green
Monogenic hearing loss	green
Paediatric disorders	green
Possible mitochondrial disorder, nuclear genes	green
Primary ovarian insufficiency	green
Undiagnosed metabolic disorders	green
Unexplained death in infancy and sudden unexplained death in childhood	green
White matter disorders and cerebral calcification - childhood onset	green
Ataxia and cerebellar anomalies - childhood onset	amber
Fetal anomalies	amber
Hereditary ataxia and cerebellar anomalies, childhood onset	amber
Hypogonadotropic hypogonadism	amber
Hypogonadotropic hypogonadism (GMS)	amber

Mondo (3): Perrault syndrome 3 (MONDO:0013588), Perrault syndrome 1 (MONDO:0009300), Perrault syndrome (MONDO:0017312)

Orphanet (2): Perrault syndrome (Orphanet:2855), Perrault syndrome type 1 (Orphanet:642945)

HPO phenotypes

11 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000013	Hypoplasia of the uterus
HP:0000252	Microcephaly
HP:0000407	Sensorineural hearing impairment
HP:0000786	Primary amenorrhea
HP:0000815	Hypergonadotropic hypogonadism
HP:0001250	Seizure
HP:0004322	Short stature
HP:0008232	Elevated circulating follicle stimulating hormone level
HP:0010464	Streak ovary
HP:0011969	Elevated circulating luteinizing hormone level

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL4523305 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 940 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

2 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL4297310	DORDAVIPRONE	3	875
CHEMBL4650311	ONC-206	1	65

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — AAA ATPases

Most potent curated ligand interactions (1 total), top 1:

Ligand	Action	Affinity	Parameter
compound 16z [PMID: 35609303]	Activation	6.7	pEC50

Binding affinities (BindingDB)

201 measured of 254 human assays (264 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL4303616	EC50	11 nM
CHEMBL6177725	EC50	22 nM
CHEMBL6172967	EC50	27 nM
CHEMBL6172944	EC50	43 nM
CHEMBL6177581	EC50	45 nM
CHEMBL6166703	EC50	56 nM
CHEMBL6167082	EC50	59 nM
CHEMBL6173060	EC50	63 nM
CHEMBL6172920	EC50	65 nM
CHEMBL6164875	EC50	68 nM
CHEMBL5597011	EC50	80 nM
CHEMBL6177210	KD	88 nM
CHEMBL5597441	EC50	90 nM
CHEMBL5596220	EC50	90 nM
CHEMBL6170047	EC50	93 nM
CHEMBL5170429	EC50	100 nM
CHEMBL5176506	EC50	110 nM
CHEMBL6176209	EC50	113 nM
CHEMBL5287429	EC50	120 nM
CHEMBL5290620	EC50	120 nM
CHEMBL5283010	EC50	120 nM
CHEMBL5194447	EC50	120 nM
CHEMBL5596597	EC50	120 nM
CHEMBL5275131	EC50	130 nM
CHEMBL5173519	EC50	130 nM
CHEMBL5180553	EC50	130 nM
CHEMBL5597008	EC50	130 nM
CHEMBL5598515	EC50	130 nM
CHEMBL5426567	EC50	140 nM
CHEMBL5597414	EC50	140 nM
CHEMBL6176195	EC50	151 nM
CHEMBL5205960	EC50	160 nM
CHEMBL5197418	EC50	190 nM
CHEMBL5191392	EC50	200 nM
CHEMBL5572211	EC50	200 nM
CHEMBL5196310	EC50	210 nM
CHEMBL6192038	EC50	220 nM
CHEMBL5597713	EC50	230 nM
CHEMBL5598503	EC50	240 nM
CHEMBL6192577	EC50	240 nM
CHEMBL5193179	EC50	260 nM
CHEMBL5597740	EC50	260 nM
CHEMBL5596563	EC50	260 nM
CHEMBL6193410	EC50	260 nM
CHEMBL6193212	EC50	260 nM
CHEMBL6170822	EC50	266 nM
CHEMBL6176600	EC50	270 nM
CHEMBL6176529	EC50	272 nM
CHEMBL5185111	EC50	280 nM
CHEMBL6191999	EC50	280 nM

ChEMBL bioactivities

212 potent at pChembl≥5 of 243 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.98	EC50	10.5	nM	CHEMBL4303616
7.92	EC50	12.02	nM	DORDAVIPRONE
7.66	EC50	21.8	nM	CHEMBL6177725
7.57	EC50	26.9	nM	CHEMBL6172967
7.52	Kd	30.3	nM	CHEMBL5572211
7.36	EC50	43.4	nM	CHEMBL6172944
7.35	EC50	44.8	nM	CHEMBL6177581
7.28	Kd	53	nM	CHEMBL5597011
7.25	EC50	56.1	nM	CHEMBL6166703
7.23	EC50	59.2	nM	CHEMBL6167082
7.20	EC50	62.8	nM	CHEMBL6173060
7.19	EC50	65.1	nM	CHEMBL6172920
7.17	EC50	67.9	nM	CHEMBL6164875
7.10	EC50	80	nM	CHEMBL5597011
7.06	Kd	87.9	nM	CHEMBL6177210
7.05	EC50	90	nM	CHEMBL5597441
7.05	EC50	90	nM	CHEMBL5596220
7.03	EC50	93	nM	CHEMBL6170047
7.00	EC50	100	nM	CHEMBL5170429
6.96	EC50	110	nM	CHEMBL5176506
6.95	EC50	113.4	nM	CHEMBL6176209
6.92	EC50	120	nM	CHEMBL5194447
6.92	EC50	120	nM	CHEMBL5287429
6.92	EC50	120	nM	CHEMBL5290620
6.92	EC50	120	nM	CHEMBL5283010
6.92	EC50	120	nM	CHEMBL5596597
6.89	EC50	130	nM	CHEMBL5173519
6.89	EC50	130	nM	CHEMBL5180553
6.89	EC50	130	nM	CHEMBL5597008
6.89	EC50	130	nM	CHEMBL5598515
6.89	EC50	130	nM	CHEMBL5275131
6.87	EC50	135	nM	CHEMBL5275131
6.85	EC50	140	nM	CHEMBL5426567
6.85	EC50	140	nM	CHEMBL5597414
6.82	EC50	150.7	nM	CHEMBL6176195
6.81	Kd	155	nM	CHEMBL5597011
6.81	EC50	156	nM	CHEMBL5287669
6.80	EC50	160	nM	CHEMBL5205960
6.75	Kd	180	nM	CHEMBL5191392
6.74	Kd	181.1	nM	CHEMBL6192038
6.72	EC50	190	nM	CHEMBL5197418
6.70	EC50	200	nM	CHEMBL5191392
6.70	EC50	200	nM	CHEMBL5572211
6.68	EC50	210	nM	CHEMBL5196310
6.66	EC50	220	nM	CHEMBL6192038
6.64	EC50	230	nM	CHEMBL5597713
6.62	EC50	240	nM	CHEMBL5598503
6.62	EC50	240	nM	CHEMBL6192577
6.58	EC50	260	nM	CHEMBL5193179
6.58	EC50	260	nM	CHEMBL5597740

PubChem BioAssay actives

212 with measured affinity, of 547 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
N-[1-(4-chloroanilino)-1-oxopropan-2-yl]oxy-3,5-bis(trifluoromethyl)benzamide	2089290: Agonist activity at human ClpP expressed in Escherichia coli using AC-WLA-AMC as substrate measured every 5 mins for 1 hr by fluorescence based analysis	ec50	0.0105	uM
11-benzyl-7-[(2-methylphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one	2089290: Agonist activity at human ClpP expressed in Escherichia coli using AC-WLA-AMC as substrate measured every 5 mins for 1 hr by fluorescence based analysis	ec50	0.0120	uM
(12R)-11-benzyl-12-methyl-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0218	uM
3-[[(7R)-7-methyl-2-[(4-methylphenyl)methylamino]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0269	uM
1-[(3-cyanophenyl)methyl]-N-[[4-(trifluoromethyl)phenyl]methyl]-3,6-dihydro-2H-pyridine-5-carboxamide	2089293: Binding affinity to human ClpP expressed in Escherichia coli assessed as dissociation constant by ITC method	kd	0.0303	uM
3-[[(7R)-7-methyl-2-[(2-methylphenyl)methylamino]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0434	uM
3-[[(7R)-2-[(3-bromophenyl)methylamino]-7-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0448	uM
11-[(3-chlorophenyl)methyl]-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122731: Binding affinity to human recombinant N-terminal 6his/sumo tagged ClpP (57 to 277 residues) assessed as dissociation constant incubated for 30 mins by MST assay	kd	0.0530	uM
3-[[(7R)-7-methyl-4-oxo-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0561	uM
3-[[(7R)-2-[(4-chlorophenyl)methylamino]-7-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0592	uM
(7R)-6-[(3-bromophenyl)methyl]-7-methyl-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0628	uM
(7R)-6-benzyl-7-methyl-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0651	uM
3-[[(7R)-7-methyl-2-(naphthalen-1-ylmethylamino)-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0679	uM
3-[[(7R)-2-[(4-bromophenyl)methylamino]-7-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269301: Binding affinity to human ClpP extracted from Escherichia coli assessed as equilibrium dissociation constant by biolayer interferometry technique	kd	0.0879	uM
11-[(3-chlorophenyl)methyl]-7-[(4-chlorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.0900	uM
3-[[7-[(4-chlorophenyl)methyl]-8-oxo-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-11-yl]methyl]benzonitrile	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.0900	uM
3-[[(7R)-2-[(4-bromo-2-methylphenyl)methylamino]-7-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.0930	uM
11-benzyl-5-[(3-methoxyphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1000	uM
11-benzyl-5-[(2-methoxyphenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1100	uM
3-[[(7R)-7-methyl-2-[(3-methylphenyl)methylamino]-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.1134	uM
3-[[7-[(4-chlorophenyl)methyl]-8-oxo-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-11-yl]methyl]benzonitrile	1920623: Agonist activity at human recombinant CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1200	uM
3-[[8-oxo-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-11-yl]methyl]benzonitrile	1920623: Agonist activity at human recombinant CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1200	uM
5,11-dibenzyl-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1200	uM
11-[(3-chlorophenyl)methyl]-7-[(4-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.1200	uM
1-(3-aminopropyl)-6-[(3-methylphenyl)methyl]-3-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-5H-pyrido[4,3-d]pyrimidine-2,4-dione	1920623: Agonist activity at human recombinant CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1200	uM
3-[[3-[(4-chlorophenyl)methyl]-1-methyl-2,4-dioxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2233653: Activation of recombinant human ClpP using Ac-WLA-AMC as substrate by plate reader analysis	ec50	0.1300	uM
11-benzyl-5-[(4-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1300	uM
11-benzyl-5-(cyclohexylmethyl)-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1300	uM
11-[(3-fluorophenyl)methyl]-7-[(4-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.1300	uM
7-[(4-chlorophenyl)methyl]-11-[(3-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.1300	uM
3-[[3-[(4-chlorophenyl)methyl]-4-oxo-7,8-dihydro-5H-pyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2022458: Activation of recombinant human CLpP using casein-FITC as substrate preincubated for 30 mins followed by substrate addition by spectra max i3x fluorescence based assay	ec50	0.1400	uM
11-[(3-fluorophenyl)methyl]-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.1400	uM
(7R)-6-[(3-chlorophenyl)methyl]-7-methyl-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.1507	uM
11-benzyl-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),5-dien-8-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.1560	uM
11-benzyl-5-[(2,4-difluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1600	uM
11-benzyl-5-[(3-bromo-4-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911139: Binding affinity to human CLpP assessed as dissociation constant by ITC method	kd	0.1800	uM
(6R)-2-[(3,5-difluorophenyl)methyl]-6-(hydroxymethyl)-5-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one	2278817: Binding affinity to human recombinant ClpP assessed as dissociation constant by microscale thermophoresis (MST) assay	kd	0.1811	uM
11-benzyl-5-[(2-chlorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.1900	uM
11-benzyl-5-[(4-bromo-3-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.2100	uM
11-benzyl-7-[(4-chlorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.2300	uM
11-benzyl-7-[[4-(trifluoromethyl)phenyl]methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.2400	uM
2-[(3,5-difluorophenyl)methyl]-5-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one	2278815: Agonist activity at human ClpP expressed in Escherichia coli BL21(DE3) using FITC-casein substrate assessed as fluorescence of FITC	ec50	0.2400	uM
11-benzyl-5-[(3-fluorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),6-dien-8-one	1911131: Agonist activity at human CLpP (57 to 277 amino acids) expressed in Escherichia coli using fluorogenic peptide AC-WLA-AMC as substrate incubated for 10 mins by fluorescence based assay	ec50	0.2600	uM
7-benzyl-11-[(3-chlorophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.2600	uM
11-benzyl-7-[(4-bromophenyl)methyl]-2,5,7,11-tetrazatricyclo[7.4.0.02,6]trideca-1(9),3,5-trien-8-one	2122727: Activation of human recombinant his-sumo tagged ClpP expressed in Escherichia coli BL21 (DE3) using FITC-casein as substrate preincubated for 30 mins followed by substrate addition and measured every 60 secs for 30 mins by fluorescence based microplate reader analysis	ec50	0.2600	uM
(7S)-2-[(3,5-difluorophenyl)methyl]-7-hydroxy-5-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one	2278815: Agonist activity at human ClpP expressed in Escherichia coli BL21(DE3) using FITC-casein substrate assessed as fluorescence of FITC	ec50	0.2600	uM
(7R)-2-[(3,5-difluorophenyl)methyl]-7-hydroxy-5-[[4-(trifluoromethyl)phenyl]methyl]-7,8-dihydro-6H-pyrazolo[1,5-a][1,4]diazepin-4-one	2278815: Agonist activity at human ClpP expressed in Escherichia coli BL21(DE3) using FITC-casein substrate assessed as fluorescence of FITC	ec50	0.2600	uM
3-[[(7R)-2-[(4-bromo-3-fluorophenyl)methylamino]-7-methyl-4-oxo-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-6-yl]methyl]benzonitrile	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.2655	uM
(7R)-7-methyl-6-[[3-(trifluoromethoxy)phenyl]methyl]-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.2699	uM
(7R)-6-[(3-fluorophenyl)methyl]-7-methyl-2-[[4-(trifluoromethyl)phenyl]methylamino]-3,5,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-one	2269299: Activation of human ClpP extracted from Escherichia coli using Ac-WLA-AMC as substrate assessed as fluorescence signal measured after 10 mins incubation	ec50	0.2720	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases expression	4
sodium arsenite	decreases expression, affects cotreatment, increases abundance, increases expression	2
Arsenic	increases expression, affects methylation, affects cotreatment, increases abundance	2
AKT activator SC79	increases expression, affects reaction, decreases reaction	1
triphenyl phosphate	affects expression	1
alpha-pinene	increases abundance, affects cotreatment, increases oxidation	1
lead acetate	increases expression, affects reaction, increases abundance	1
trichostatin A	affects expression	1
arsenite	affects binding, increases reaction	1
afimoxifene	affects response to substance	1
perfluorooctanoic acid	increases expression	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
ochratoxin A	decreases expression, affects cotreatment	1
methacrylaldehyde	increases abundance, affects cotreatment, increases oxidation	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
bisphenol B	increases expression	1
10-(octyloxy)decyl-2-(trimethylammonium)ethyl phosphate	decreases expression	1
bisphenol AF	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1
Anisomycin	affects reaction, decreases reaction, increases expression	1
Citrinin	decreases expression, affects cotreatment	1
Doxorubicin	decreases expression	1
Ivermectin	decreases expression	1
Lead	affects reaction, increases abundance, increases expression	1
Manganese	increases expression, affects cotreatment, increases abundance	1
Ozone	affects cotreatment, increases oxidation, increases abundance	1
Smoke	decreases expression	1

ChEMBL screening assays

96 unique, capped per target: 96 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4305800	Binding	Inhibition of C-terminal recombinant human ClpP (57 to 277 amino acids) expressed in Escherichia coli Rosetta2 cells using Suc-Leu-Tyr-AMC as substrate incubated for 1 hr and measured for 90 mins by fluorescence assay	De Novo Design of Boron-Based Peptidomimetics as Potent Inhibitors of Human ClpP in the Presence of Human ClpX. — *J Med Chem*

Cellosaurus cell lines

6 cell lines: 6 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D1M1	Abcam K-562 CLPP KO	Cancer cell line	Female
CVCL_D2IL	Abcam Raji CLPP KO	Cancer cell line	Male
CVCL_E1TW	HAP1 CLPP (-) 2	Cancer cell line	Male
CVCL_E1TX	HAP1 CLPP (-) 3	Cancer cell line	Male
CVCL_UQ33	Abcam Jurkat CLPP KO	Cancer cell line	Male
CVCL_XM85	HAP1 CLPP (-) 1	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CLPP across ~30M SureChEMBL compounds — explore on Sugi Predict.