This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their A... See more...

Aliases for CLPB Gene

Aliases for CLPB Gene

  • Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit B 2 3 5
  • Suppressor Of Potassium Transport Defect 3 2 3 4
  • HSP78 2 3 4
  • SKD3 2 3 4
  • ClpB Homolog, Mitochondrial AAA ATPase Chaperonin 2 3
  • Ankyrin-Repeat Containing Bacterial Clp Fusion 2 3
  • Caseinolytic Peptidase B Protein Homolog 3 4
  • ANKCLB 2 3
  • ClpB Caseinolytic Peptidase B Homolog (E. Coli) 2
  • ClpB Caseinolytic Peptidase B Homolog 3
  • Testicular Secretory Protein Li 11 3
  • EC 3.6.1.- 4
  • FLJ13152 2
  • MEGCANN 3
  • MGCA7 3
  • CLPB 5

External Ids for CLPB Gene

Previous GeneCards Identifiers for CLPB Gene

  • GC11M071682
  • GC11M071683
  • GC11M072008
  • GC11M068296
  • GC11M072292

Summaries for CLPB Gene

Entrez Gene Summary for CLPB Gene

  • This gene belongs to the ATP-ases associated with diverse cellular activities (AAA+) superfamily. Members of this superfamily form ring-shaped homo-hexamers and have highly conserved ATPase domains that are involved in various processes including DNA replication, protein degradation and reactivation of misfolded proteins. All members of this family hydrolyze ATP through their AAA+ domains and use the energy generated through ATP hydrolysis to exert mechanical force on their substrates. In addition to an AAA+ domain, the protein encoded by this gene contains a C-terminal D2 domain, which is characteristic of the AAA+ subfamily of Caseinolytic peptidases to which this protein belongs. It cooperates with Hsp70 in the disaggregation of protein aggregates. Allelic variants of this gene are associated with 3-methylglutaconic aciduria, which causes cataracts and neutropenia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

GeneCards Summary for CLPB Gene

CLPB (Caseinolytic Mitochondrial Matrix Peptidase Chaperone Subunit B) is a Protein Coding gene. Diseases associated with CLPB include 3-Methylglutaconic Aciduria, Type Vii and 3-Methylglutaconic Aciduria. Among its related pathways are Longevity regulating pathway. Gene Ontology (GO) annotations related to this gene include transcription factor binding and kinase activity.

UniProtKB/Swiss-Prot Summary for CLPB Gene

  • May function as a regulatory ATPase and be related to secretion/protein trafficking process. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6 (PubMed:31522117).

Gene Wiki entry for CLPB Gene

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

Genomics for CLPB Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for CLPB Gene
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around CLPB on the GeneHancer Hub at the UCSC Golden Path

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

Top Transcription factor binding sites by QIAGEN in the CLPB gene promoter:
  • Arnt
  • Evi-1
  • FOXI1
  • HFH-3
  • Max1
  • NF-kappaB1
  • Nkx6-1
  • RORalpha1
  • STAT3
  • USF-1

Genomic Locations for CLPB Gene

Latest Assembly
chr11:72,285,495-72,434,680
(GRCh38/hg38)
Size:
149,186 bases
Orientation:
Minus strand

Previous Assembly
chr11:71,996,539-72,145,575
(GRCh37/hg19 by Entrez Gene)
Size:
149,037 bases
Orientation:
Minus strand

chr11:72,003,469-72,145,692
(GRCh37/hg19 by Ensembl)
Size:
142,224 bases
Orientation:
Minus strand

Genomic View for CLPB Gene

Genes around CLPB on UCSC Golden Path with GeneCards custom track

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

RefSeq DNA sequence for CLPB Gene

Proteins for CLPB Gene

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

    Protein Symbol:
    Q9H078-CLPB_HUMAN
    Recommended name:
    Caseinolytic peptidase B protein homolog
    Protein Accession:
    Q9H078
    Secondary Accessions:
    • B4DXJ7
    • B4DXP7
    • B4DXW4
    • E7EWN6
    • F8W7P6
    • Q8ND11
    • Q9H8Y0

    Protein attributes for CLPB Gene

    Size:
    707 amino acids
    Molecular mass:
    78729 Da
    Quaternary structure:
    • Interacts with PHB and PHB2 (PubMed:31522117). Interacts with MAVS; the interaction is enhanced by Sendai virus infection (PubMed:31522117).

    Alternative splice isoforms for CLPB Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for CLPB Gene

Post-translational modifications for CLPB Gene

  • Modification sites at PhosphoSitePlus
  • Modification sites at neXtProt

No data available for DME Specific Peptides for CLPB Gene

Domains & Families for CLPB Gene

Gene Families for CLPB Gene

HGNC:
Human Protein Atlas (HPA):
  • Disease related genes
  • Enzymes
  • Plasma proteins
  • Potential drug targets
  • Predicted intracellular proteins

Protein Domains for CLPB Gene

Suggested Antigen Peptide Sequences for CLPB Gene

GenScript: Design optimal peptide antigens:
  • cDNA FLJ53238, highly similar to Caseinolytic peptidase B protein (B4DXW4_HUMAN)
  • Suppressor of potassium transport defect 3 (CLPB_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q9H078

UniProtKB/Swiss-Prot:

CLPB_HUMAN :
  • Belongs to the ClpA/ClpB family.
Family:
  • Belongs to the ClpA/ClpB family.
genes like me logo Genes that share domains with CLPB: view

Function for CLPB Gene

Molecular function for CLPB Gene

UniProtKB/Swiss-Prot Function:
May function as a regulatory ATPase and be related to secretion/protein trafficking process. Involved in mitochondrial-mediated antiviral innate immunity, activates RIG-I-mediated signal transduction and production of IFNB1 and proinflammatory cytokine IL6 (PubMed:31522117).
UniProtKB/Swiss-Prot CatalyticActivity:
Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:25597510};.

Enzyme Numbers (IUBMB) for CLPB Gene

Phenotypes From GWAS Catalog for CLPB Gene

Gene Ontology (GO) - Molecular Function for CLPB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000166 nucleotide binding IEA --
GO:0003674 molecular_function ND --
GO:0005515 protein binding IPI 25416956
GO:0005524 ATP binding IEA --
GO:0016787 hydrolase activity IEA --
genes like me logo Genes that share ontologies with CLPB: view
genes like me logo Genes that share phenotypes with CLPB: view

Human Phenotype Ontology for CLPB Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

miRNA for CLPB Gene

miRTarBase miRNAs that target CLPB

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLPB

No data available for Animal Models , Transcription Factor Targets and HOMER Transcription for CLPB Gene

Localization for CLPB Gene

Subcellular locations from UniProtKB/Swiss-Prot for CLPB Gene

Mitochondrion intermembrane space.

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 CLPB gene
Compartment Confidence
mitochondrion 5
cytosol 4
plasma membrane 2
extracellular 2
cytoskeleton 2
nucleus 2
endoplasmic reticulum 2
golgi apparatus 2
peroxisome 1
endosome 1
lysosome 1

Gene Ontology (GO) - Cellular Components for CLPB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IBA 21873635
GO:0005739 mitochondrion IBA 21873635
GO:0005758 mitochondrial intermembrane space IEA,IDA 31522117
genes like me logo Genes that share ontologies with CLPB: view

No data available for Subcellular locations from the Human Protein Atlas (HPA) for CLPB Gene

Pathways & Interactions for CLPB Gene

PathCards logo

SuperPathways for CLPB Gene

genes like me logo Genes that share pathways with CLPB: view

Pathways by source for CLPB Gene

Gene Ontology (GO) - Biological Process for CLPB Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0034605 cellular response to heat IBA,IDA 2745427
GO:0039529 RIG-I signaling pathway IDA 31522117
genes like me logo Genes that share ontologies with CLPB: view

No data available for SIGNOR curated interactions for CLPB Gene

Drugs & Compounds for CLPB Gene

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

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Phosphoaminophosphonic Acid-Adenylate Ester Experimental Pharma Target 0
genes like me logo Genes that share compounds with CLPB: view

Transcripts for CLPB Gene

mRNA/cDNA for CLPB Gene

4 REFSEQ mRNAs :
12 NCBI additional mRNA sequence :
20 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for CLPB

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

ExUns: 1a · 1b · 1c · 1d · 1e ^ 2 ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8 ^ 9a · 9b ^ 10 ^ 11a · 11b ^ 12 ^ 13 ^ 14 ^ 15 ^ 16 ^ 17a · 17b · 17c
SP1: -
SP2: - -
SP3:
SP4: -
SP5: - -

Relevant External Links for CLPB Gene

GeneLoc Exon Structure for
CLPB

Expression for CLPB Gene

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

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for CLPB Gene

This gene is overexpressed in Testis (x21.8).

Protein differential expression in normal tissues from HIPED for CLPB Gene

This gene is overexpressed in Brain (7.7), Peripheral blood mononuclear cells (6.7), and Testis (6.3).

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



Protein tissue co-expression partners for CLPB Gene

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

SOURCE GeneReport for Unigene cluster for CLPB Gene:

Hs.523877

mRNA Expression by UniProt/SwissProt for CLPB Gene:

Q9H078-CLPB_HUMAN
Tissue specificity: Widely expressed (at protein level) (PubMed:25597511). Expressed in fetal, as well as in adult tissues, with highest levels in adult brain, including thalamus, hippocampus, occipital cortex and parietal cortex. Low expression in granulocytes (PubMed:25597510).

Evidence on tissue expression from TISSUES for CLPB Gene

  • Gall bladder(5)
  • Liver(4.4)
  • Nervous system(3.7)
  • Kidney(2.5)
  • Skin(2.2)
  • Blood(2.2)

Phenotype-based relationships between genes and organs from Gene ORGANizer for CLPB Gene

Germ Layers:
  • ectoderm
  • mesoderm
Systems:
  • immune
  • nervous
  • skeletal muscle
  • skeleton
Regions:
Head and neck:
  • brain
  • cerebellum
  • eye
  • head
  • skull
General:
  • blood
  • peripheral nerve
  • peripheral nervous system
  • spinal cord
  • white blood cell
genes like me logo Genes that share expression patterns with CLPB: view

Primer products for research

Orthologs for CLPB Gene

This gene was present in the common ancestor of eukaryotes.

Orthologs for CLPB Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia CLPB 29 30
  • 99.58 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia CLPB 29 30
  • 91.61 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia CLPB 29 30
  • 90 (n)
OneToOne
Mouse
(Mus musculus)
Mammalia Clpb 29 16 30
  • 86.02 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Clpb 29
  • 85.87 (n)
Oppossum
(Monodelphis domestica)
Mammalia CLPB 30
  • 78 (a)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia CLPB 30
  • 71 (a)
OneToOne
Chicken
(Gallus gallus)
Aves CLPB 30
  • 87 (a)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia CLPB 30
  • 77 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia clpb 29
  • 74.42 (n)
African clawed frog
(Xenopus laevis)
Amphibia Xl.5964 29
Zebrafish
(Danio rerio)
Actinopterygii CLPB 30
  • 77 (a)
OneToOne
LOC100331587 29
  • 73.55 (n)
Baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes HSP78 30 32
  • 18 (a)
OneToMany
HSP104 30
  • 16 (a)
OneToMany
Alicante grape
(Vitis vinifera)
eudicotyledons Vvi.7808 29
Rice
(Oryza sativa)
Liliopsida Os04g0397100 29
  • 53.6 (n)
Os.4859 29
Barley
(Hordeum vulgare)
Liliopsida Hv.3721 29
Corn
(Zea mays)
Liliopsida Zm.438 29
Species where no ortholog for CLPB was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African malaria mosquito (Anopheles gambiae)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Fruit Fly (Drosophila melanogaster)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • 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)
  • Worm (Caenorhabditis elegans)

Evolution for CLPB Gene

ENSEMBL:
Gene Tree for CLPB (if available)
TreeFam:
Gene Tree for CLPB (if available)
Aminode:
Evolutionary constrained regions (ECRs) for CLPB: view image
Alliance of Genome Resources:
Additional Orthologs for CLPB

Paralogs for CLPB Gene

No data available for Paralogs for CLPB Gene

Variants for CLPB Gene

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

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
1002894 Uncertain Significance: 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 72,295,525(-) C/T
NM_001258392.3(CLPB):c.1453G>A (p.Glu485Lys)
MISSENSE
1003562 Uncertain Significance: 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 72,294,399(-) C/T
NM_001258392.3(CLPB):c.1606G>A (p.Val536Ile)
MISSENSE
1006915 Uncertain Significance: 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 72,293,432(-) T/A
NM_001258392.3(CLPB):c.1969A>T (p.Ser657Cys)
MISSENSE
1010621 Uncertain Significance: 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 72,358,907(-) G/A
NM_001258392.3(CLPB):c.748C>T (p.Arg250Cys)
MISSENSE
1016590 Uncertain Significance: 3-methylglutaconic aciduria with cataracts, neurologic involvement, and neutropenia 72,294,650(-) G/C
NM_001258392.3(CLPB):c.1530C>G (p.Phe510Leu)
MISSENSE

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for CLPB Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

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

Variant ID Type Subtype PubMed ID
esv1000322 CNV deletion 20482838
esv2339545 CNV deletion 18987734
esv2662493 CNV deletion 23128226
esv2744769 CNV deletion 23290073
esv3303142 CNV mobile element insertion 20981092
esv3309852 CNV mobile element insertion 20981092
esv3342071 CNV insertion 20981092
esv3370613 CNV insertion 20981092
esv3626797 CNV loss 21293372
esv3626799 CNV loss 21293372
esv8221 CNV gain 19470904
nsv385 CNV insertion 18451855
nsv476167 CNV novel sequence insertion 20440878
nsv825990 CNV loss 20364138
nsv832206 CNV gain 17160897

Variation tolerance for CLPB Gene

Residual Variation Intolerance Score: 91.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 4.11; 61.18% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for CLPB Gene

Human Gene Mutation Database (HGMD)
CLPB
SNPedia medical, phenotypic, and genealogical associations of SNPs for
CLPB
Leiden Open Variation Database (LOVD)
CLPB

SNP Genotyping and Copy Number Assays for research

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

Disorders for CLPB Gene

MalaCards: The human disease database

(20) MalaCards diseases for CLPB Gene - From: OMI, CVR, GTR, ORP, SWI, COP, and GCD

Disorder Aliases PubMed IDs
3-methylglutaconic aciduria, type vii
  • mgca7
3-methylglutaconic aciduria
  • 3-methyl glutaconic aciduria
neutropenia
  • leukopenia
clpb deficiency
  • caseinolytic peptidase b deficiency
typhoidal tularemia
- elite association - COSMIC cancer census association via MalaCards
Search CLPB in MalaCards View complete list of genes associated with diseases

UniProtKB/Swiss-Prot

CLPB_HUMAN
  • 3-methylglutaconic aciduria 7 (MGCA7) [MIM:616271]: An autosomal recessive inborn error of metabolism with a highly variable phenotype. Primary disease symptoms are increased levels of 3-methylglutaconic acid, neurologic deterioration and neutropenia. Other common features include progressive encephalopathy, movement abnormalities, delayed psychomotor development, cataracts, seizures, and recurrent infections. {ECO:0000269 PubMed:25597510, ECO:0000269 PubMed:25597511}. Note=The disease is caused by variants affecting the gene represented in this entry.

Additional Disease Information for CLPB

Human Genome Epidemiology Navigator
(HuGE)
Atlas
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform
Open Targets Platform
genes like me logo Genes that share disorders with CLPB: view

No data available for Genatlas for CLPB Gene

Publications for CLPB Gene

  1. CLPB mutations cause 3-methylglutaconic aciduria, progressive brain atrophy, intellectual disability, congenital neutropenia, cataracts, movement disorder. (PMID: 25597510) Wortmann SB … Wevers RA (American journal of human genetics 2015) 3 4 72
  2. CLPB variants associated with autosomal-recessive mitochondrial disorder with cataract, neutropenia, epilepsy, and methylglutaconic aciduria. (PMID: 25597511) Saunders C … Ostergaard E (American journal of human genetics 2015) 3 4 72
  3. Structural Basis of Mitochondrial Scaffolds by Prohibitin Complexes: Insight into a Role of the Coiled-Coil Region. (PMID: 31522117) Yoshinaka T … Koshiba T (iScience 2019) 3 4
  4. A scoring system predicting the clinical course of CLPB defect based on the foetal and neonatal presentation of 31 patients. (PMID: 28687938) Pronicka E … Additional individual contributors (Journal of inherited metabolic disease 2017) 3 72
  5. Metabolic and chaperone gene loss marks the origin of animals: evidence for Hsp104 and Hsp78 chaperones sharing mitochondrial enzymes as clients. (PMID: 25710177) Erives AJ … Fassler JS (PloS one 2015) 2 3

Products for CLPB Gene

Sources for CLPB Gene