EXOSC8

Highest pathogenic variant AF is 0.0000074515187

Gene type

protein_coding

Transcript type

protein_coding

Transcript

ENST00000389704

Coding exons

11

Length

10798

Individuals with no LoFs

125656

Homozygous LoFs

0

Heterozygous LoFs

92

Defined

125748

p

0.000366

Function

FUNCTION: Non-catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC8 binds to ARE-containing RNAs. {ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563}.;

Disease

DISEASE: Pontocerebellar hypoplasia 1C (PCH1C) [MIM:616081]: A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired. {ECO:0000269|PubMed:24989451}. Note=The disease is caused by mutations affecting the gene represented in this entry. EXOSC8 dysfunction causes myelin disruption through an imbalanced supply of myelin proteins due to dysregulation of their ARE-containing mRNAs (PubMed:24989451). {ECO:0000269|PubMed:24989451}.;