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 ... See more...

Aliases for CLPX Gene

Aliases for CLPX Gene

  • Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit X 2 3
  • ATP-Dependent Clp Protease ATP-Binding Subunit ClpX-Like, Mitochondrial 3 4
  • Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit 5
  • ClpX (Caseinolytic Protease X, E. Coli) Homolog 2
  • ClpX Caseinolytic Protease X Homolog (E. Coli) 2
  • Energy-Dependent Regulator Of Proteolysis 3
  • ClpX Caseinolytic Peptidase X Homolog 3
  • ClpX Caseinolytic Protease X Homolog 3
  • EPP2 3

External Ids for CLPX Gene

Previous GeneCards Identifiers for CLPX Gene

  • GC15M061220
  • GC15M058542
  • GC15M063019
  • GC15M063158
  • GC15M063229
  • GC15M065440
  • GC15M042267

Summaries for CLPX Gene

Entrez Gene Summary for CLPX Gene

  • 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. [provided by RefSeq, Nov 2015]

GeneCards Summary for CLPX Gene

CLPX (Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit X) is a Protein Coding gene. Diseases associated with CLPX include Protoporphyria, Erythropoietic, 2 and Porphyria. Gene Ontology (GO) annotations related to this gene include transcription factor binding and unfolded protein binding.

UniProtKB/Swiss-Prot Summary for CLPX Gene

  • ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP (PubMed:28874591). Targets specific substrates for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:22841477). ATP-dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis (PubMed:28874591). Important for efficient erythropoiesis through upregulation of heme biosynthesis (PubMed:25957689, PubMed:28874591).

Additional gene information for CLPX Gene

No data available for CIViC Summary , Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for CLPX Gene

Genomics for CLPX Gene

GeneHancer (GH) Regulatory Elements for CLPX Gene

Promoters and enhancers for CLPX Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH15J065183 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas 500.7 +0.9 903 3.8 RXRA EP300 FOXK2 HNRNPK ZBTB40 ZNF217 SIN3A NRF1 MYC TCF12 CLPX PARP16 INTS14 TRIP4 SNORA24B RNU5A-1 CILP RNU5B-1 RBPMS2 UBAP1L
GH15J065303 Promoter/Enhancer 2.4 FANTOM5 Ensembl ENCODE CraniofacialAtlas dbSUPER 11.3 -119.0 -119028 2.3 RXRA ZBTB40 ZNF217 EP300 CTCF ZSCAN5C TCF12 POLR2G SP1 BCLAF1 AB330788-002 RNU5B-1 lnc-PARP16-3 ZNF609 PARP16 CSNK1G1 INTS14 TRIP4 SLC24A1 PDCD7
GH15J065132 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 11.6 +52.1 52104 3.4 EP300 ZBTB40 ZNF217 ZSCAN5C SIN3A TCF12 POLR2G SP1 GTF2E2 PHF8 PDCD7 lnc-KBTBD13-4 RNU6-686P CLPX CILP lnc-UBAP1L-2
GH15J065110 Enhancer 1.1 FANTOM5 Ensembl ENCODE 10.7 +74.7 74662 0.9 FOS ZIC2 CTBP1 NR2F2 NCOR1 ZBTB17 GABPA CEBPG SKIL NR2F1 MTFMT CLPX RBPMS2 ANKDD1A PDCD7 UBAP1L piR-61945-160
GH15J065274 Enhancer 1 Ensembl ENCODE 11.3 -90.9 -90897 6.2 ZNF217 FOS AFF1 KLF4 CTBP1 JUN CREB1 FOXA2 ZNF316 TRIM24 PARP16 IGDCC3 RNU5B-1 RNU6-686P CILP CLPX SNORA24B lnc-PARP16-2 lnc-CILP-1
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLPX on UCSC Golden Path with GeneCards custom track

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for CLPX

Top Transcription factor binding sites by QIAGEN in the CLPX gene promoter:
  • C/EBPalpha
  • FOXO1
  • FOXO1a
  • HOXA9
  • HOXA9B
  • IRF-2
  • Meis-1b
  • MyoD
  • PPAR-alpha
  • STAT5A

Genomic Locations for CLPX Gene

Genomic Locations for CLPX Gene
chr15:65,148,219-65,185,404
(GRCh38/hg38)
Size:
37,186 bases
Orientation:
Minus strand
chr15:65,440,557-65,477,680
(GRCh37/hg19)
Size:
37,124 bases
Orientation:
Minus strand

Genomic View for CLPX Gene

Genes around CLPX on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
CLPX Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for CLPX Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for CLPX Gene

Proteins for CLPX Gene

  • Protein details for CLPX Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O76031-CLPX_HUMAN
    Recommended name:
    ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial
    Protein Accession:
    O76031
    Secondary Accessions:
    • A1L428
    • A8K8F1
    • B9EGI8
    • Q9H4D9

    Protein attributes for CLPX Gene

    Size:
    633 amino acids
    Molecular mass:
    69224 Da
    Quaternary structure:
    • Homohexamer that forms a ring structure; this hexamerization requires ATP binding. Component of the Clp 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.

neXtProt entry for CLPX Gene

Post-translational modifications for CLPX Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

Other Protein References for CLPX Gene

No data available for DME Specific Peptides for CLPX Gene

Domains & Families for CLPX Gene

Gene Families for CLPX Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for CLPX Gene

Suggested Antigen Peptide Sequences for CLPX Gene

GenScript: Design optimal peptide antigens:
  • ATP-dependent Clp protease ATP-binding subunit clpX-like, mitochondrial (CLPX_HUMAN)

Graphical View of Domain Structure for InterPro Entry

O76031

UniProtKB/Swiss-Prot:

CLPX_HUMAN :
  • Belongs to the ClpX chaperone family.
Family:
  • Belongs to the ClpX chaperone family.
genes like me logo Genes that share domains with CLPX: view

Function for CLPX Gene

Molecular function for CLPX Gene

UniProtKB/Swiss-Prot Function:
ATP-dependent specificity component of the Clp protease complex. Hydrolyzes ATP (PubMed:28874591). Targets specific substrates for degradation by the Clp complex (PubMed:11923310, PubMed:22710082). Can perform chaperone functions in the absence of CLPP. Enhances the DNA-binding activity of TFAM and is required for maintaining a normal mitochondrial nucleoid structure (PubMed:22841477). ATP-dependent unfoldase that stimulates the incorporation of the pyridoxal phosphate cofactor into 5-aminolevulinate synthase, thereby activating 5-aminolevulinate (ALA) synthesis, the first step in heme biosynthesis (PubMed:28874591). Important for efficient erythropoiesis through upregulation of heme biosynthesis (PubMed:25957689, PubMed:28874591).

Gene Ontology (GO) - Molecular Function for CLPX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004176 contributes_to ATP-dependent peptidase activity IBA,IDA 16115876
GO:0005515 protein binding IPI 11923310
GO:0005524 ATP binding IEA,ISS --
GO:0016504 peptidase activator activity IDA 11923310
GO:0016887 ATPase activity ISS --
genes like me logo Genes that share ontologies with CLPX: view
genes like me logo Genes that share phenotypes with CLPX: view

Human Phenotype Ontology for CLPX Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for CLPX Gene

MGI Knock Outs for CLPX:
  • Clpx Clpx<tm1.1(KOMP)Vlcg>

Animal Model Products

CRISPR Products

Clone Products

No data available for Enzyme Numbers (IUBMB) , Phenotypes From GWAS Catalog , Transcription Factor Targets and HOMER Transcription for CLPX Gene

Localization for CLPX Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLPX Gene

Mitochondrion. Mitochondrion matrix, mitochondrion nucleoid.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for CLPX gene
Compartment Confidence
mitochondrion 5
nucleus 5
cytosol 5
extracellular 2
cytoskeleton 2
plasma membrane 1
peroxisome 1
endoplasmic reticulum 1
endosome 1
lysosome 1
golgi apparatus 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Mitochondria (3)
  • Cytosol (2)
  • Nucleoplasm (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for CLPX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005654 nucleoplasm IDA --
GO:0005739 mitochondrion IDA 11003706
GO:0005743 mitochondrial inner membrane ISS --
GO:0005759 mitochondrial matrix IBA,IDA 10525407
GO:0005829 cytosol IDA --
genes like me logo Genes that share ontologies with CLPX: view

Pathways & Interactions for CLPX Gene

PathCards logo

SuperPathways for CLPX Gene

No Data Available

Gene Ontology (GO) - Biological Process for CLPX Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006457 protein folding IEA --
GO:0010952 positive regulation of peptidase activity IEA --
GO:0030163 protein catabolic process IBA 21873635
GO:0046034 ATP metabolic process IDA 22710082
GO:0051603 proteolysis involved in cellular protein catabolic process IDA 16115876
genes like me logo Genes that share ontologies with CLPX: view

No data available for Pathways by source and SIGNOR curated interactions for CLPX Gene

Drugs & Compounds for CLPX Gene

(2) Drugs for CLPX Gene - From: DrugBank and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Bismuth subcitrate potassium Approved, Investigational Pharma Target, antagonist 0
genes like me logo Genes that share compounds with CLPX: view

Transcripts for CLPX Gene

mRNA/cDNA for CLPX Gene

1 REFSEQ mRNAs :
10 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for CLPX Gene

No ASD Table

Relevant External Links for CLPX Gene

GeneLoc Exon Structure for
CLPX

Expression for CLPX Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for CLPX Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for CLPX Gene

This gene is overexpressed in Adrenal (7.1), Liver (7.0), and Bone (6.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for CLPX Gene



Protein tissue co-expression partners for CLPX Gene

- Elite partner

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for CLPX

SOURCE GeneReport for Unigene cluster for CLPX Gene:

Hs.113823

mRNA Expression by UniProt/SwissProt for CLPX Gene:

O76031-CLPX_HUMAN
Tissue specificity: Higher expression in skeletal muscle and heart and to a lesser extent in liver, brain, placenta, lung, kidney and pancreas.

Evidence on tissue expression from TISSUES for CLPX Gene

  • Liver(4.4)
  • Muscle(4.3)
  • Nervous system(4.3)
genes like me logo Genes that share expression patterns with CLPX: view

No data available for mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for CLPX Gene

Orthologs for CLPX Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CLPX Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia CLPX 31 30
  • 99.79 (n)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia CLPX 31
  • 96 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia CLPX 31
  • 96 (a)
OneToOne
dog
(Canis familiaris)
Mammalia CLPX 31 30
  • 95.16 (n)
OneToOne
cow
(Bos Taurus)
Mammalia CLPX 31 30
  • 95 (n)
OneToOne
rat
(Rattus norvegicus)
Mammalia Clpx 30
  • 91.15 (n)
mouse
(Mus musculus)
Mammalia Clpx 17 31 30
  • 90.42 (n)
chicken
(Gallus gallus)
Aves CLPX 31 30
  • 82.83 (n)
OneToOne
lizard
(Anolis carolinensis)
Reptilia CLPX 31
  • 91 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia Xl.33234 30
tropical clawed frog
(Silurana tropicalis)
Amphibia Str.6113 30
zebrafish
(Danio rerio)
Actinopterygii clpxb 31
  • 80 (a)
OneToMany
clpxa 31 30
  • 71 (n)
OneToMany
CLPX (3 of 3) 31
  • 71 (a)
OneToMany
wufb93b07 30
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.1425 30
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP002996 30
  • 60.55 (n)
fruit fly
(Drosophila melanogaster)
Insecta CG4538 31 32 30
  • 59.21 (n)
OneToOne
worm
(Caenorhabditis elegans)
Secernentea D2030.2 31 32 30
  • 53.37 (n)
OneToMany
K07A3.3 31 32
  • 39 (a)
OneToMany
K. lactis yeast
(Kluyveromyces lactis)
Saccharomycetes KLLA0F09691g 30
  • 51.93 (n)
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes MCX1 33 31 30
  • 51.8 (n)
barley
(Hordeum vulgare)
Liliopsida Hv.10842 30
rice
(Oryza sativa)
Liliopsida Os.21406 30
sea squirt
(Ciona savignyi)
Ascidiacea CSA.10327 31
  • 48 (a)
OneToOne
Cin.5402 30
bread mold
(Neurospora crassa)
Ascomycetes NCU05427 30
  • 47.18 (n)
sea squirt
(Ciona intestinalis)
Ascidiacea Cin.5402 30
Species where no ortholog for CLPX was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • beta proteobacteria (Neisseria meningitidis)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for CLPX Gene

ENSEMBL:
Gene Tree for CLPX (if available)
TreeFam:
Gene Tree for CLPX (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CLPX: view image

Paralogs for CLPX Gene

(1) SIMAP similar genes for CLPX Gene using alignment to 3 proteins:

  • CLPX_HUMAN
  • H0YK07_HUMAN
  • H0YM48_HUMAN

Pseudogenes.org Pseudogenes for CLPX Gene

genes like me logo Genes that share paralogs with CLPX: view

No data available for Paralogs for CLPX Gene

Variants for CLPX Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for CLPX Gene

SNP ID Clinical significance and condition Chr 15 pos Variation AA Info Type
rs1555412542 Likely Pathogenic: Protoporphyria, erythropoietic, 2 65,157,910(-) C/T MISSENSE_VARIANT,NON_CODING_TRANSCRIPT_VARIANT
VAR_081001 Protoporphyria, erythropoietic, 2 (EPP2) [MIM:618015] p.Gly298Asp
rs35754835 - p.Ile488Thr

Additional dbSNP identifiers (rs#s) for CLPX Gene

Structural Variations from Database of Genomic Variants (DGV) for CLPX Gene

Variant ID Type Subtype PubMed ID
esv2508866 CNV deletion 19546169
esv2670622 CNV deletion 23128226
esv3636750 CNV loss 21293372
nsv474816 CNV novel sequence insertion 20440878
nsv569704 CNV loss 21841781

Variation tolerance for CLPX Gene

Residual Variation Intolerance Score: 24% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.35; 26.72% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLPX Gene

Human Gene Mutation Database (HGMD)
CLPX
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLPX

SNP Genotyping and Copy Number Assay Products

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for CLPX Gene

Disorders for CLPX Gene

MalaCards: The human disease database

(11) MalaCards diseases for CLPX Gene - From: UniProtKB/Swiss-Prot, OMIM, DISEASES, and GeneCards

Disorder Aliases PubMed IDs
protoporphyria, erythropoietic, 2
  • epp2
porphyria
  • disorder of porphyrin and hem metabolism
tick-borne relapsing fever
  • relapsing fever, tick-borne
spinocerebellar ataxia 28
  • sca28
relapsing fever
- elite association - COSMIC cancer census association via MalaCards
Search CLPX in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CLPX_HUMAN
  • 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. {ECO:0000269 PubMed:28874591}. Note=The disease may be caused by mutations affecting the gene represented in this entry.

Additional Disease Information for CLPX

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with CLPX: view

No data available for Genatlas for CLPX Gene

Publications for CLPX Gene

  1. Maintenance of mitochondrial genome distribution by mitochondrial AAA+ protein ClpX. (PMID: 22841477) Kasashima K … Endo H (Experimental cell research 2012) 2 3 4 54
  2. Human and mouse mitochondrial orthologs of bacterial ClpX. (PMID: 11003706) Corydon TJ … Bross P (Mammalian genome : official journal of the International Mammalian Genome Society 2000) 3 4 23 54
  3. Mutation in human CLPX elevates levels of δ-aminolevulinate synthase and protoporphyrin IX to promote erythropoietic protoporphyria. (PMID: 28874591) Yien YY … Paw BH (Proceedings of the National Academy of Sciences of the United States of America 2017) 3 4 54
  4. Substrate recognition and processing by a Walker B mutant of the human mitochondrial AAA+ protein CLPX. (PMID: 22710082) Lowth BR … Dougan DA (Journal of structural biology 2012) 3 4 54
  5. Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression. (PMID: 20877624) Hendrickson SL … O'Brien SJ (PloS one 2010) 3 41 54

Products for CLPX Gene

Sources for CLPX Gene