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    CLPP caseinolytic mitochondrial matrix peptidase proteolytic subunit [ Homo sapiens (human) ]

    Gene ID: 8192, updated on 6-Jul-2026
    Official Symbol
    CLPPprovided by HGNC
    Official Full Name
    caseinolytic mitochondrial matrix peptidase proteolytic subunitprovided by HGNC
    Primary source
    HGNC:HGNC:2084
    See related
    Ensembl:ENSG00000125656 MIM:601119; AllianceGenome:HGNC:2084
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    DFNB81; PRLTS3
    Summary
    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. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 19.9), fat (RPKM 18.0) and 25 other tissues See more
    Orthologs
    all
    Try the new Gene page
    Try the new Transcripts and proteins table
    See CLPP in Genome Data Viewer
    Location:
    19p13.3
    Exon count:
    5
    Annotation release Status Assembly Chr Location
    RS_2025_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (6361531..6370242)
    RS_2025_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (6350432..6359144)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (6361542..6370253)

    Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6216753-6217667 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6227079-6227744 Neighboring gene MLLT1 super elongation complex subunit Neighboring gene Sharpr-MPRA regulatory region 3427 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6239861-6240362 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6243510-6244224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6263043-6263544 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6263545-6264044 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6273107-6273706 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6276605-6277105 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13823 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9947 Neighboring gene alkaline ceramidase 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9948 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6362217-6363174 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:6372537-6373459 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:6387043-6387543 Neighboring gene alkB homolog 7, RNA demethylase Neighboring gene general transcription factor IIF subunit 1 Neighboring gene persephin Neighboring gene microRNA 6885

    Go to nucleotide: Graphics FASTA GenBank

    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Related articles in PubMed

    1. Barrel-shaped ClpP Proteases Display Attenuated Cleavage Specificities. Gersch M, et al. ACS Chem Biol, 2016 Feb 19. PMID 26606371
    2. Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. Jenkinson EM, et al. Am J Hum Genet, 2013 Apr 4. PMID 23541340, Free PMC Article
    3. Human CLPP reverts the longevity phenotype of a fungal ClpP deletion strain. Fischer F, et al. Nat Commun, 2013. PMID 23360988, Free PMC Article
    4. Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma. Wang P, et al. Cell Chem Biol, 2022 Sep 15. PMID 35905743
    5. Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site-Specific Photocrosslinking Approach. Nguyen TA, et al. Angew Chem Int Ed Engl, 2022 Mar 1. PMID 34847623, Free PMC Article

    See all (81) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells.
      Title: HSPA8-mediated stability of the CLPP protein regulates mitochondrial autophagy in cisplatin-resistant ovarian cancer cells.
    2. Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.
      Title: Selective activator of human ClpP triggers cell cycle arrest to inhibit lung squamous cell carcinoma.
    3. Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma.
      Title: Aberrant human ClpP activation disturbs mitochondrial proteome homeostasis to suppress pancreatic ductal adenocarcinoma.
    4. CLPP deficiency ameliorates neurodegeneration caused by impaired mitochondrial protein synthesis.
      Title: CLPP deficiency ameliorates neurodegeneration caused by impaired mitochondrial protein synthesis.
    5. Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site-Specific Photocrosslinking Approach.
      Title: Substrate Profiling of Mitochondrial Caseinolytic Protease P via a Site-Specific Photocrosslinking Approach.
    6. Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.
      Title: Inactivity of Peptidase ClpP Causes Primary Accumulation of Mitochondrial Disaggregase ClpX with Its Interacting Nucleoid Proteins, and of mtDNA.
    7. Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer.
      Title: Mitochondrial Caseinolytic Protease P: A Possible Novel Prognostic Marker and Therapeutic Target in Cancer.
    8. Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease.
      Title: Loss of mitochondrial ClpP, Lonp1, and Tfam triggers transcriptional induction of Rnf213, a susceptibility factor for moyamoya disease.
    9. 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).
      Title: 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).
    10. 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.
      Title: Alpha-synuclein suppresses mitochondrial protease ClpP to trigger mitochondrial oxidative damage and neurotoxicity.
    Submit: New GeneRIF Correction See all GeneRIFs (25)

    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Associated conditions

    Description Tests
    Perrault syndrome 3
    MedGen: C3808414 OMIM: 614129 GeneReviews: Perrault Syndrome Overview
    		Compare labs

    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP-dependent peptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables ATP-dependent peptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables ATP-dependent peptidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables ATPase binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables identical protein binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables peptidase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables serine-type endopeptidase activity EXP
    Inferred from Experiment
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables serine-type endopeptidase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables serine-type endopeptidase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in membrane protein proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in mitochondrial protein catabolic process TAS
    Traceable Author Statement
    more info
    		  
    involved_in protein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in protein quality control for misfolded or incompletely synthesized proteins IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in proteolysis IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in proteolysis IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    part_of endopeptidase Clp complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    part_of endopeptidase Clp complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    part_of endopeptidase Clp complex IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    located_in mitochondrial matrix EXP
    Inferred from Experiment
    more info
    		 PubMed 
    located_in mitochondrial matrix IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial matrix NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    located_in mitochondrial matrix TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion IEA
    Inferred from Electronic Annotation
    more info
    		  
    Preferred Names
    ATP-dependent Clp protease proteolytic subunit, mitochondrial
    Names
    ATP-dependent protease ClpAP, proteolytic subunit, human
    ClpP caseinolytic peptidase ATP-dependent, proteolytic subunit
    ClpP caseinolytic peptidase, ATP-dependent, proteolytic subunit homolog
    ClpP caseinolytic protease, ATP-dependent, proteolytic subunit homolog
    endopeptidase Clp
    putative ATP-dependent Clp protease proteolytic subunit, mitochondrial
    NP_006003.1
    XP_047295442.1

    NEW Try the new Transcript table

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_033887.1 RefSeqGene

      Range
      5080..13791
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_1402

    mRNA and Protein(s)

    1. NM_006012.4 → NP_006003.1  ATP-dependent Clp protease proteolytic subunit, mitochondrial precursor

      See identical proteins and their annotated locations for NP_006003.1

      Status: REVIEWED

      Source sequence(s)
      AC011491, BC002956
      Consensus CDS
      CCDS12162.1
      UniProtKB/Swiss-Prot
      B2R4W5, Q16740
      UniProtKB/TrEMBL
      A0ACI8TBK0
      Related
      ENSP00000245816.3, ENST00000245816.11
      Conserved Domains (1) summary
      PRK00277
      Location:55 → 249
      clpP; ATP-dependent Clp protease proteolytic subunit; Reviewed

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2025_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

      Range
      6361531..6370242
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047439486.1 → XP_047295442.1  ATP-dependent Clp protease proteolytic subunit, mitochondrial isoform X1

      UniProtKB/TrEMBL
      A0ACI8TBK0
      Related
      ENSP00000596330.1, ENST00000926271.1

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060943.1 Alternate T2T-CHM13v2.0

      Range
      6350432..6359144
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16740.1 GenPept UniProtKB/Swiss-Prot:Q16740

    Gene LinkOut

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