EXOSC8

Chr 13AR

exosome component 8

Also known as: CIP3, EAP2, OIP2, PCH1C, RRP43, Rrp43p, bA421P11.3, p9

NCBI Gene: 11340ENSG00000120699UniProt: Q96B26

This gene encodes a 3'-5' exoribonuclease that specifically interacts with mRNAs containing AU-rich elements. The encoded protein is part of the exosome complex that is important for the degradation of numerous RNA species. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 1CMIM #616081
AR
0
Active trials
50
Pathogenic / LP
179
ClinVar variants
6
Pubs (1 yr)
0.8
Missense Z
1.69
LOEUF
Clinical Summary— EXOSC8
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
50 Pathogenic / Likely Pathogenic· 69 VUS of 179 total submissions
📖
GeneReview available — EXOSC8
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.69LOEUF
pLI 0.000
Z-score -0.66
OE 1.17 (0.82–1.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.85Z-score
OE missense 0.80 (0.69–0.94)
115 obs / 143.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.17 (0.82–1.69)
0≤0.351.4
Missense OE0.80 (0.69–0.94)
0≤0.61.4
Synonymous OE0.68
0≤1.21.6
LoF obs/exp: 20 / 17.1Missense obs/exp: 115 / 143.5Syn Z: 1.81

ClinVar Variant Classifications

179 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic50
VUS69
Likely Benign40
Benign16
Conflicting4
50
Pathogenic
69
VUS
40
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
1
49
0
50
Likely Pathogenic
0
0
0
0
0
VUS
3
53
13
0
69
Likely Benign
0
0
26
14
40
Benign
0
2
12
2
16
Conflicting
—4
Total35610016179

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

EXOSC8 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Gene2Phenotype Curations

EXOSC8-related pontocerebellar hypoplasia

moderate
ARLoss Of FunctionAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. Disorders
G2P ↗
splice region variantmissense variant

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Landmark / reviewRecent case evidence
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Exploring Pontocerebellar Hypoplasia Type 1C: A Case Study of the 6th Family with The EXOSC8 Gene Mutation
Sharifi S et al.·Ann Indian Acad Neurol
2025
Molecular characterization and prognostic modeling of liquid-liquid phase separation-related genes in osteosarcoma based on single-cell sequencing and weighted gene co-expression network analysis.
Huang X et al.·Transl Cancer Res
2025Functional
The Rat Brain Transcriptome: From Infancy to Aging and Sporadic Alzheimer's Disease-like Pathology
Stefanova NA et al.·Int J Mol Sci
2023
[Molecular and Genetic Analysis of a Rare Primary Culture of Head and Neck Paraganglioma].
Snezhkina AV et al.·Mol Biol (Mosk)
2025
13q Deletion Syndrome Involving RB1: Characterization of a New Minimal Critical Region for Psychomotor Delay
Privitera F et al.·Genes (Basel)
2021
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Top 5 results · since 2015Search PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients