Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.4.24.11 (
CD10
)
9,792
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Perrault syndrome is a genetically and clinically heterogeneous autosomal-recessive condition characterized by sensorineural hearing loss and ovarian failure. By a combination of linkage analysis, homozygosity mapping, and exome sequencing in three families, we identified mutations in
CLPP
as the likely cause of this phenotype. In each family, affected individuals were homozygous for a different pathogenic
CLPP
allele: c.433A>C (p.Thr145Pro), c.440G>C (p.Cys147Ser), or an experimentally demonstrated splice-donor-site mutation, c.270+4A>G.
CLPP
, a component of a mitochondrial ATP-dependent proteolytic complex, is a highly conserved
endopeptidase
encoded by
CLPP
and forms an element of the evolutionarily ancient mitochondrial unfolded-protein response (UPR(mt)) stress signaling pathway. Crystal-structure modeling suggests that both substitutions would alter the structure of the
CLPP
barrel chamber that captures unfolded proteins and exposes them to proteolysis. Together with the previous identification of mutations in HARS2, encoding mitochondrial histidyl-tRNA synthetase, mutations in
CLPP
expose dysfunction of mitochondrial protein homeostasis as a cause of Perrault syndrome.
...
PMID:Perrault syndrome is caused by recessive mutations in CLPP, encoding a mitochondrial ATP-dependent chambered protease. 2354 40
