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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
EXOSC8
exosome component 8
Chromosome 13 Β· 13q13.3
NCBI Gene: 11340Ensembl: ENSG00000120699.15HGNC: HGNC:17035UniProt: Q96B26
109PubMed Papers
21Diseases
0Drugs
2Pathogenic Variants
FUNCTIONAL ROLE
Hub Gene
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mRNA 3'-UTR AU-rich region bindingfibrillar centernucleusnucleoplasmpontocerebellar hypoplasia, type 1Cneurodegenerative diseasepontocerebellar hypoplasia type 1spastic ataxia
✦AI Summary

EXOSC8 encodes a non-catalytic structural component of the RNA exosome complex, a critical multisubunit ribonuclease involved in RNA processing and degradation 1. As part of the exosome core, EXOSC8 participates in the degradation of AU-rich element (ARE)-containing mRNAs and plays essential roles in ribosome biogenesis, particularly in 18S rRNA processing and 40S ribosomal subunit maturation 23. The protein functions both in nuclear RNA surveillance pathways and cytoplasmic mRNA turnover 1. Homozygous mutations in EXOSC8 cause pontocerebellar hypoplasia type 1C (PCH1C), a rare autosomal recessive neurodegenerative disease characterized by cerebellar hypoplasia, spinal muscular atrophy, and abnormal myelination 42. Disease mechanisms involve disrupted mRNA metabolism, specifically affecting myelin protein-encoding transcripts, leading to imbalanced myelin protein supply and subsequent demyelination 2. Clinical presentation includes progressive neurological deterioration with cerebellar atrophy, motor neuron disease, and developmental delays 56. In cancer contexts, EXOSC8 upregulation promotes tumorigenesis through enhanced ribosome biogenesis and translation, suggesting potential therapeutic targeting opportunities 7. The protein's dual roles in RNA surveillance and ribosome maturation make it critical for cellular homeostasis and neurological development.

Sources cited
1
EXOSC8 is a structural component of the RNA exosome complex involved in RNA processing and degradation
PMID: 29093021
2
EXOSC8 mutations cause neurological disease with cerebellar hypoplasia and affect ARE-containing mRNAs encoding myelin proteins
PMID: 24989451
3
EXOSC8 participates in 18S rRNA processing and 40S ribosomal subunit maturation
PMID: 37851577
4
EXOSC8 mutations cause pontocerebellar hypoplasia type 1C (PCH1C)
PMID: 31768969
5
PCH1C is characterized by cerebellar hypoplasia, spinal muscular atrophy and motor neuron involvement
PMID: 40428407
6
Clinical presentation includes cerebellar atrophy, motor symptoms, and developmental delays
PMID: 34210538
7
EXOSC8 upregulation in cancer promotes tumorigenesis through ribosome biogenesis
PMID: 36348012
Disease Associationsβ“˜21
pontocerebellar hypoplasia, type 1COpen Targets
0.64Moderate
neurodegenerative diseaseOpen Targets
0.52Moderate
pontocerebellar hypoplasia type 1Open Targets
0.37Weak
spastic ataxiaOpen Targets
0.34Weak
pontocerebellar hypoplasiaOpen Targets
0.19Weak
distal hereditary motor neuropathyOpen Targets
0.18Weak
insomniaOpen Targets
0.15Weak
lysosomal storage diseaseOpen Targets
0.14Weak
hyperinsulinism due to INSR deficiencyOpen Targets
0.06Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.05Suggestive
leukemiaOpen Targets
0.05Suggestive
hemoglobin D diseaseOpen Targets
0.05Suggestive
delta-beta-thalassemiaOpen Targets
0.05Suggestive
exercise-induced hyperinsulinismOpen Targets
0.05Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.05Suggestive
MODYOpen Targets
0.05Suggestive
dominant beta-thalassemiaOpen Targets
0.05Suggestive
hyperinsulinism due to glucokinase deficiencyOpen Targets
0.05Suggestive
hyperproinsulinemiaOpen Targets
0.05Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.04Suggestive
Pontocerebellar hypoplasia 1CUniProt
Pathogenic Variants2
NM_181503.3(EXOSC8):c.269C>G (p.Ser90Ter)Pathogenic
Spastic ataxia
β˜…β˜†β˜†β˜†2021β†’ Residue 90
NM_181503.3(EXOSC8):c.5C>T (p.Ala2Val)Pathogenic
Pontocerebellar hypoplasia, type 1C
β˜†β˜†β˜†β˜†2014β†’ Residue 2
View on ClinVar β†—
Related Genes
RBM7Protein interaction100%HBS1LProtein interaction100%EXOSC1Protein interaction100%MTREXProtein interaction100%HELZ2Protein interaction100%PNPT1Protein interaction97%
Tissue Expression6 tissues
Bone Marrow
100%
Ovary
89%
Liver
56%
Lung
54%
Heart
47%
Brain
31%
Gene Interaction Network
Click a node to explore
EXOSC8RBM7HBS1LEXOSC1MTREXHELZ2PNPT1
PROTEIN STRUCTURE
Preparing viewer…
PDB9G8M Β· 3.30 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
1.94LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF1.61 [1.04–1.94]
RankingsWhere EXOSC8 stands among ~20K protein-coding genes
  • #4,355of 20,598
    Most Researched109 Β· top quartile
  • #4,302of 5,498
    Most Pathogenic Variants2
  • #17,622of 17,882
    Most Constrained (LOEUF)1.94
Genes detectedEXOSC8
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
A 20-year Clinical and Genetic Neuromuscular Cohort Analysis in Lebanon: An International Effort.
PMID: 34602496
J Neuromuscul Dis Β· 2022
1.00
2
The RNA Exosome and Human Disease.
PMID: 31768969
Methods Mol Biol Β· 2020
0.90
3
Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.
PMID: 40428407
Genes (Basel) Β· 2025
0.80
4
EXOSC8 mutations alter mRNA metabolism and cause hypomyelination with spinal muscular atrophy and cerebellar hypoplasia.
PMID: 24989451
Nat Commun Β· 2014
0.70
5
The RNA exosome and RNA exosome-linked disease.
PMID: 29093021
RNA Β· 2018
0.60