CLPX

Summary

CLPX (caseinolytic mitochondrial matrix peptidase chaperone subunit X, HGNC:2088) is a protein-coding gene on chromosome 15q22.31, encoding ATP-dependent clpX-like chaperone, mitochondrial (O76031). ATP-dependent chaperone that functions as an unfoldase.

The protein encoded by this gene is part of a protease found in mitochondria. This protease is ATP-dependent and targets specific proteins for degradation. The protease consists of two heptameric rings of the CLPP catalytic subunit sandwiched between two hexameric rings of the chaperone subunit encoded by this gene. Targeted proteins are unwound by this protein and then passed on to the CLPP subunit for degradation. Two transcript variants, one protein-coding and the other non-protein coding, have been found for this gene.

Source: NCBI Gene 10845 — RefSeq curated summary.

At a glance

• Gene–disease (curated): protoporphyria, erythropoietic, 2 (Strong, GenCC)
• Clinical variants (ClinVar): 166 total — 1 likely-pathogenic
• Phenotypes (HPO): 5
• Druggable target: yes
• MANE Select transcript: NM_006660

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:2088
Approved symbol	CLPX
Name	caseinolytic mitochondrial matrix peptidase chaperone subunit X
Location	15q22.31
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000166855
Ensembl biotype	protein_coding
OMIM	615611
Entrez	10845

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 9 protein_coding, 3 retained_intron, 1 nonsense_mediated_decay

ENST00000300107, ENST00000558103, ENST00000558958, ENST00000559152, ENST00000559218, ENST00000560166, ENST00000858712, ENST00000858713, ENST00000858714, ENST00000935106, ENST00000935107, ENST00000935108, ENST00000969231

RefSeq mRNA: 1 — MANE Select: NM_006660 NM_006660

CCDS: CCDS10202

Canonical transcript exons

ENST00000300107 — 14 exons

Exon	Start	End
ENSE00001107292	65156844	65156932
ENSE00001200922	65148219	65150913
ENSE00003462105	65180044	65180204
ENSE00003480714	65154782	65155081
ENSE00003490572	65152430	65152536
ENSE00003492161	65164029	65164188
ENSE00003538680	65153547	65153639
ENSE00003574426	65178934	65179051
ENSE00003601283	65158575	65158751
ENSE00003613017	65166631	65166785
ENSE00003616163	65157746	65157910
ENSE00003627303	65185075	65185342
ENSE00003690031	65162604	65162645
ENSE00003693372	65155692	65155856

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.15.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.8537 / max 110.1213, expressed in 1811 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
150531	16.4438	1811
150532	0.1538	52
150533	0.1382	32
150530	0.0878	18
150534	0.0302	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	98.15	gold quality
male germ cell	CL:0000015	95.76	gold quality
calcaneal tendon	UBERON:0003701	95.41	gold quality
secondary oocyte	CL:0000655	94.74	gold quality
amniotic fluid	UBERON:0000173	94.43	gold quality
oocyte	CL:0000023	94.26	gold quality
adrenal tissue	UBERON:0018303	93.93	gold quality
colonic epithelium	UBERON:0000397	93.86	gold quality
gastrocnemius	UBERON:0001388	93.55	gold quality
muscle of leg	UBERON:0001383	93.50	gold quality
cervix squamous epithelium	UBERON:0006922	93.44	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.21	gold quality
ventricular zone	UBERON:0003053	92.61	gold quality
right lobe of liver	UBERON:0001114	92.56	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.50	gold quality
esophagus squamous epithelium	UBERON:0006920	92.44	gold quality
liver	UBERON:0002107	92.41	gold quality
monocyte	CL:0000576	92.32	gold quality
mucosa of stomach	UBERON:0001199	92.07	gold quality
mononuclear cell	CL:0000842	92.01	gold quality
skeletal muscle organ	UBERON:0014892	91.95	gold quality
muscle organ	UBERON:0001630	91.94	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.83	gold quality
leukocyte	CL:0000738	91.82	gold quality
biceps brachii	UBERON:0001507	91.81	gold quality
squamous epithelium	UBERON:0006914	91.64	gold quality
esophagus mucosa	UBERON:0002469	91.52	gold quality
tendon	UBERON:0000043	91.35	gold quality
right adrenal gland cortex	UBERON:0035827	91.11	gold quality
oral cavity	UBERON:0000167	90.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.43

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): RELB

miRNA regulators (miRDB)

121 targeting CLPX, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-6759-5P	99.99	66.54	785
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-551B-5P	99.96	71.28	3493
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-651-3P	99.94	73.48	5177
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-141-3P	99.94	72.79	2421
HSA-MIR-200A-3P	99.94	72.68	2420
HSA-MIR-335-3P	99.93	73.36	4958
HSA-MIR-3143	99.93	71.96	3104
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-3671	99.90	73.04	3897

Literature-anchored findings (GeneRIF, showing 11)

• 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)
• Results reveal that the ssrA tag interacts with different loops that form the top, middle, and lower portions of the central channel of the ClpX hexamer. (PMID:18313382)
• Walker B mutation in human CLPX exhibits improved interaction with the model unfolded substrate casein and several putative physiological substrates in vitro. (PMID:22710082)
• human ClpX, a novel mtDNA regulator, maintains mtDNA nucleoid distribution through TFAM function as a chaperone rather than as a protease and its involvement in mtDNA segregation. (PMID:22841477)
• 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)
• results illustrate that ClpX overexpression is a good and simple model to study the underlying mechanisms of the UPRmt in mammalian cells. (PMID:26142927)
• Data suggest that tumors exploit ClpXP-directed proteostasis to maintain mitochondrial bioenergetics, buffer oxidative stress, and enable metastatic competence. (PMID:27389535)
• The mutation in CLPX inactivates its ATPase activity, resulting in coassembly of mutant and WT protomers to form an enzyme with reduced activity. The presence of low-activity CLPX increases the posttranslational stability of ALAS, causing increased ALAS protein and ALA levels, leading to abnormal accumulation of PPIX. (PMID:28874591)
• Experiencing community and domestic violence is associated with epigenetic changes in DNA methylation of BDNF and CLPX in adolescents. (PMID:31059136)
• Heme-dependent recognition of 5-aminolevulinate synthase by the human mitochondrial molecular chaperone ClpX. (PMID:34704252)
• Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA. (PMID:34943861)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	clpxa	ENSDARG00000029063
danio_rerio	clpxb	ENSDARG00000067796
mus_musculus	Clpx	ENSMUSG00000015357
rattus_norvegicus	Clpx	ENSRNOG00000030225
drosophila_melanogaster	ClpX	FBGN0038745
caenorhabditis_elegans	D2030.2	WBGENE00008412

Protein

Protein identifiers

ATP-dependent clpX-like chaperone, mitochondrial — O76031 (reviewed: O76031)

Alternative names: ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial, Caseinolytic mitochondrial matrix peptidase chaperone subunit X

All UniProt accessions (3): O76031, H0YK07, H0YM48

UniProt curated annotations — full annotation on UniProt →

Function. ATP-dependent chaperone that functions as an unfoldase. As part of the ClpXP protease complex, it recognizes specific protein substrates, unfolds them using energy derived from ATP hydrolysis, and then translocates them to the proteolytic subunit (CLPP) of the ClpXP complex for degradation. Thanks to its chaperone activity, it also functions in the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis. This chaperone is also involved in the control of mtDNA nucleoid distribution, by regulating mitochondrial transcription factor A (TFAM) activity.

Subunit / interactions. Homohexamer that forms a ring structure; this hexamerization requires ATP binding. 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. Interacts with TFAM.

Subcellular location. Mitochondrion. Mitochondrion matrix. Mitochondrion nucleoid.

Tissue specificity. Higher expression in skeletal muscle and heart and to a lesser extent in liver, brain, placenta, lung, kidney and pancreas.

Disease relevance. Protoporphyria, erythropoietic, 2 (EPP2) [MIM:618015] An autosomal dominant form of porphyria with onset in infancy. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Erythropoietic protoporphyria is marked by excessive protoporphyrin in erythrocytes, plasma, liver and feces, and by widely varying photosensitive skin changes ranging from a burning or pruritic sensation to erythema, edema and wheals. The disease may be caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the ClpX chaperone family.

RefSeq proteins (1): NP_006651* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003593	AAA+_ATPase	Domain
IPR003959	ATPase_AAA_core	Domain
IPR004487	Clp_protease_ATP-bd_su_ClpX	Family
IPR019489	Clp_ATPase_C	Domain
IPR027417	P-loop_NTPase	Homologous_superfamily
IPR050052	ATP-dep_Clp_protease_ClpX	Family
IPR059067	Znf_ribbon_CLPX-like	Domain
IPR059188	Znf_CLPX-like	Domain

Pfam: PF07724, PF10431, PF26040

Catalyzed reactions (Rhea), 1 shown:

• ATP + H2O = ADP + phosphate + H(+) (RHEA:13065)

UniProt features (20 total): binding site 5, compositionally biased region 4, modified residue 2, sequence variant 2, region of interest 2, transit peptide 1, chain 1, mutagenesis site 1, sequence conflict 1, domain 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
9DVY	ELECTRON MICROSCOPY	3.2
9P9V	ELECTRON MICROSCOPY	4.4
9YKX	ELECTRON MICROSCOPY	4.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O76031-F1	67.22	0.26

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 (5): 108; 127; 130; 294–301; 105

Post-translational modifications (2): 437, 617

Mutagenesis-validated functional residues (1):

Position	Phenotype
359	abolishes atp hydrolysis.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9837999	Mitochondrial protein degradation

MSigDB gene sets: 234 (showing top): AAGCAAT_MIR137, FREAC2_01, MORF_MSH3, MORF_BRCA1, MORF_ATRX, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_ORGANOPHOSPHATE_METABOLIC_PROCESS, BROWNE_HCMV_INFECTION_16HR_UP, MORF_ESR1, GOBP_CARBOHYDRATE_DERIVATIVE_METABOLIC_PROCESS, PUJANA_CHEK2_PCC_NETWORK, GOBP_NUCLEOBASE_CONTAINING_SMALL_MOLECULE_METABOLIC_PROCESS, GOBP_PROTEIN_MATURATION, SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, MORF_PPP5C

GO Biological Process (4): proteolysis (GO:0006508), ATP metabolic process (GO:0046034), obsolete proteolysis involved in protein catabolic process (GO:0051603), protein folding (GO:0006457)

GO Molecular Function (12): ATP binding (GO:0005524), zinc ion binding (GO:0008270), peptidase activator activity (GO:0016504), ATP hydrolysis activity (GO:0016887), protein dimerization activity (GO:0046983), obsolete unfolded protein binding (GO:0051082), ATP-dependent protein folding chaperone (GO:0140662), nucleotide binding (GO:0000166), ATP-dependent peptidase activity (GO:0004176), protein binding (GO:0005515), hydrolase activity (GO:0016787), metal ion binding (GO:0046872)

GO Cellular Component (9): nucleoplasm (GO:0005654), mitochondrion (GO:0005739), mitochondrial inner membrane (GO:0005743), mitochondrial matrix (GO:0005759), cytosol (GO:0005829), endopeptidase Clp complex (GO:0009368), mitochondrial endopeptidase Clp complex (GO:0009841), perinuclear theca (GO:0033011), mitochondrial nucleoid (GO:0042645)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Metabolism of proteins	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
ATP-dependent activity	3
mitochondrion	3
peptidase activity	2
cellular anatomical structure	2
cytoplasm	2
mitochondrial matrix	2
protein metabolic process	1
purine ribonucleotide metabolic process	1
purine ribonucleoside triphosphate metabolic process	1
cellular process	1
protein maturation	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
transition metal ion binding	1
enzyme activator activity	1
peptidase regulator activity	1
ribonucleoside triphosphate phosphatase activity	1
protein binding	1
protein folding chaperone	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
binding	1
catalytic activity	1
cation binding	1
nuclear lumen	1
intracellular membrane-bounded organelle	1
organelle inner membrane	1
mitochondrial membrane	1
intracellular organelle lumen	1
catalytic complex	1
endopeptidase Clp complex	1
mitochondrial protein-containing complex	1
cytoskeleton	1
perinuclear region of cytoplasm	1
nucleoid	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CLPX	CLPP	Q16740	998
CLPX	CLPB	Q9H078	965
CLPX	TBX22	Q9Y458	961
CLPX	YME1L1	Q96TA2	905
CLPX	GRPEL1	Q9HAV7	846
CLPX	HSPD1	P10809	783
CLPX	SPX	Q9BT56	774
CLPX	HSPE1	P61604	770
CLPX	LONP1	P36776	770
CLPX	SP100	P23497	723
CLPX	VCP	P55072	690
CLPX	AFG3L2	Q9Y4W6	665
CLPX	RAD51	Q06609	649
CLPX	LONP2	Q86WA8	641
CLPX	SPG7	Q9UQ90	618

IntAct

181 interactions, top by confidence:

A	B	Type	Score
FBL	NOP56	psi-mi:“MI:0914”(association)	0.800
NDUFS3	NDUFS8	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
COQ8A	COQ9	psi-mi:“MI:0914”(association)	0.670
CHCHD10	CLPX	psi-mi:“MI:0914”(association)	0.640
COQ5	COQ9	psi-mi:“MI:0914”(association)	0.590
CLPP	CLPX	psi-mi:“MI:0407”(direct interaction)	0.560
THTPA	RTL8C	psi-mi:“MI:0914”(association)	0.530
ATPAF2	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
GNS	CLPX	psi-mi:“MI:0914”(association)	0.530
GPT2	CLPX	psi-mi:“MI:0914”(association)	0.530
NDEL1	OFD1	psi-mi:“MI:0914”(association)	0.530
LPAR1	TMEM223	psi-mi:“MI:0914”(association)	0.530
UQCRFS1	NDUFAB1	psi-mi:“MI:0914”(association)	0.530
EBNA-LP	HAX1	psi-mi:“MI:0914”(association)	0.530
DDX21	MED19	psi-mi:“MI:2364”(proximity)	0.480
sseJ	AGPS	psi-mi:“MI:0914”(association)	0.460
CLPX		psi-mi:“MI:0570”(protein cleavage)	0.440
AIFM1	HAX1	psi-mi:“MI:0914”(association)	0.420
AIFM1	HAX1	psi-mi:“MI:2364”(proximity)	0.420

BioGRID (252): CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Affinity Capture-MS), CLPX (Co-fractionation), HSPE1 (Co-fractionation)

ESM2 similar proteins: A0A7C9FSB8, A2TLM1, A6H7H7, B8BKI7, B9N1F9, B9SQI7, D2XV59, E0CSI1, F1N9S8, O00178, O08582, O35586, O35760, O48964, O48965, O76031, O81770, P11029, P11497, P58044, P69341, Q0J035, Q13085, Q13907, Q14165, Q1LZ95, Q1LZ96, Q28559, Q2R483, Q38929, Q39471, Q39472, Q39664, Q3UMR5, Q42553, Q4R4W5, Q5NVE1, Q5R8R6, Q5SWU9, Q5U2U0

Diamond homologs: A1B1H7, A1U1Q2, A1USA8, A1V4X0, A2SBG4, A3MKJ7, A3NAI4, A3NWA5, A4XHW1, A4XTZ6, A4YVM3, A5EKA7, A5FX05, A5V3U4, A5VQN3, A5W634, A6U7U8, A6X117, A7HY53, A7ILC7, A8HYF4, A8LJA7, A9HRV3, A9W5F6, B0CGR0, B0KJG7, B0SZ62, B0TFI7, B0UD19, B1J693, B1LW29, B1Z9C8, B2IGP2, B2S5W0, B3PVY5, B3Q7P4, B4RCN8, B5ZY09, B6ISY6, B6JGU8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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.

Reactome pathways:

Pathway	Partners	Fold	FDR
Mitochondrial protein import	7	9.2×	2e-03
Mitochondrial protein degradation	9	8.0×	5e-04

GO biological processes:

GO term	Partners	Fold	FDR
mitochondrial large ribosomal subunit assembly	5	29.3×	4e-04
ubiquinone biosynthetic process	5	27.7×	4e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	89
Likely benign	49
Benign	10

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
545573	NM_006660.5(CLPX):c.893G>A (p.Gly298Asp)	Likely pathogenic

SpliceAI

1903 predictions. Top by Δscore:

Variant	Effect	Δscore
15:65150912:CC:C	acceptor_gain	1.0000
15:65150913:CC:C	acceptor_gain	1.0000
15:65152388:T:C	donor_gain	1.0000
15:65152424:CTTTA:C	donor_loss	1.0000
15:65152425:TTTA:T	donor_loss	1.0000
15:65152428:A:AC	donor_gain	1.0000
15:65152428:A:G	donor_loss	1.0000
15:65152429:C:A	donor_loss	1.0000
15:65152429:C:CC	donor_gain	1.0000
15:65152535:TCCTA:T	acceptor_loss	1.0000
15:65152536:CCTAA:C	acceptor_loss	1.0000
15:65152537:C:CC	acceptor_gain	1.0000
15:65152537:CTAA:C	acceptor_loss	1.0000
15:65152538:T:A	acceptor_loss	1.0000
15:65153541:ACT:A	donor_loss	1.0000
15:65153542:CTCA:C	donor_loss	1.0000
15:65153543:TCACC:T	donor_loss	1.0000
15:65153544:CAC:C	donor_loss	1.0000
15:65153545:A:AC	donor_gain	1.0000
15:65153545:A:AT	donor_loss	1.0000
15:65153546:C:CC	donor_gain	1.0000
15:65153636:CACA:C	acceptor_gain	1.0000
15:65153638:CA:C	acceptor_gain	1.0000
15:65153640:C:CC	acceptor_gain	1.0000
15:65154776:TCTAA:T	donor_loss	1.0000
15:65154777:CTAA:C	donor_loss	1.0000
15:65154778:TAA:T	donor_loss	1.0000
15:65154780:A:AT	donor_loss	1.0000
15:65154781:C:CA	donor_loss	1.0000
15:65154785:AT:A	donor_gain	1.0000

AlphaMissense

4092 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
15:65152510:A:C	F577L	1.000
15:65152510:A:T	F577L	1.000
15:65152512:A:G	F577L	1.000
15:65153560:A:G	L564P	1.000
15:65153560:A:T	L564H	1.000
15:65153563:C:T	G563D	1.000
15:65153564:C:G	G563R	1.000
15:65153566:C:G	R562P	1.000
15:65153572:C:T	G560D	1.000
15:65153599:G:T	A551D	1.000
15:65154843:A:T	I517K	1.000
15:65154852:A:G	L514P	1.000
15:65154897:C:G	R499P	1.000
15:65154900:C:T	G498E	1.000
15:65154901:C:G	G498R	1.000
15:65154901:C:T	G498R	1.000
15:65154910:C:T	E495K	1.000
15:65155741:C:T	G421D	1.000
15:65155742:C:G	G421R	1.000
15:65155756:A:G	L416P	1.000
15:65155768:G:T	T412K	1.000
15:65155774:A:T	V410D	1.000
15:65155819:A:T	V395D	1.000
15:65155825:A:T	V393D	1.000
15:65155834:C:A	G390V	1.000
15:65155834:C:T	G390D	1.000
15:65155835:C:G	G390R	1.000
15:65155838:C:T	E389K	1.000
15:65155840:A:G	L388P	1.000
15:65155847:T:C	K386E	1.000

dbSNP variants (sampled 300 via entrez): RS1000032302 (15:65183258 C>G), RS1000049853 (15:65155423 G>T), RS1000061659 (15:65177596 T>C), RS1000115677 (15:65148637 A>G), RS1000130065 (15:65184482 C>G), RS1000246228 (15:65173199 G>A,T), RS1000300767 (15:65148968 T>C), RS1000357230 (15:65153786 C>T), RS1000417655 (15:65178902 GA>G,GAA), RS1000450538 (15:65153369 G>A,C,T), RS1000470197 (15:65178607 G>C), RS1000566701 (15:65180674 G>A), RS1000626444 (15:65184245 G>A), RS1000666640 (15:65167250 T>C), RS1000717454 (15:65172957 G>C)

Disease associations

OMIM: gene MIM:615611 | disease phenotypes: MIM:618015

GenCC curated gene-disease

Disease	Classification	Inheritance
protoporphyria, erythropoietic, 2	Strong	Autosomal dominant

Mondo (1): protoporphyria, erythropoietic, 2 (MONDO:0060729)

Orphanet (0):

HPO phenotypes

5 total (5 of 5 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000992	Cutaneous photosensitivity
HP:0001891	Iron deficiency anemia
HP:0003593	Infantile onset
HP:0012187	Increased erythrocyte protoporphyrin concentration

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL3797014 (SINGLE PROTEIN)

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
5.02	IC50	9500	nM	CHEMBL2047407

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
[(2R)-2-[(1S)-1-[(1S,2R,6S,7R,9R,11S,12S,15R,16S)-6-hydroxy-2,16-dimethyl-3-oxo-8-oxapentacyclo[9.7.0.02,7.07,9.012,16]octadec-4-en-15-yl]ethyl]-4-methyl-6-oxo-2,3-dihydropyran-5-yl]methyl acetate	1558382: Inhibition of ClpX (unknown origin) expressed in Escherichia coli BL21 (DE3) pre-incubated for 10 mins before ATP addition and measured up to 120 mins measured by malachite green assay	ic50	9.5000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Acetaminophen	decreases expression	4
Valproic Acid	affects expression, decreases expression	3
bisphenol A	decreases expression	2
bisphenol F	increases expression	1
titanium dioxide	increases expression	1
trichostatin A	affects expression	1
arsenite	increases reaction, affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
zinc chromate	increases abundance, increases expression	1
chromium hexavalent ion	increases abundance, increases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	increases expression	1
bisphenol B	increases expression	1
jinfukang	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
picoxystrobin	increases expression	1
bisphenol AF	increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Air Pollutants, Occupational	affects expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Quercetin	decreases expression	1
Rotenone	increases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Isotretinoin	decreases expression	1
Josamycin	affects response to substance	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
CHEMBL3802596	Binding	Inhibition of type 1 AAA+ chaperone ClpX (unknown origin) up to 200 uM	Oxaspirol B with p97 Inhibitory Activity and Other Oxaspirols from Lecythophora sp. FL1375 and FL1031, Endolichenic Fungi Inhabiting Parmotrema tinctorum and Cladonia evansii. — J Nat Prod

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B1NM	Abcam HeLa CLPX KO	Cancer cell line	Female
CVCL_XM87	HAP1 CLPX (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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