EXOSC9

Chr 4AR

exosome component 9

Also known as: PCH1D, PM/Scl-75, PMSCL1, RRP45, Rrp45p, p5, p6

NCBI Gene: 5393ENSG00000123737UniProt: Q06265

This gene encodes a component of the human exosome, a exoribonuclease complex which processes and degrades RNA in the nucleus and cytoplasm. This component may play a role in mRNA degradation and the polymyositis/scleroderma autoantigen complex. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 1DMIM #618065
AR
0
Active trials
52
Pathogenic / LP
359
ClinVar variants
7
Pubs (1 yr)
0.2
Missense Z
1.11
LOEUF
Clinical Summary— EXOSC9
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 Pathogenic / Likely Pathogenic· 159 VUS of 359 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
1.11LOEUF
pLI 0.000
Z-score 1.12
OE 0.76 (0.54–1.11)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.15Z-score
OE missense 0.97 (0.87–1.08)
234 obs / 240.7 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.76 (0.54–1.11)
0≤0.351.4
Missense OE0.97 (0.87–1.08)
0≤0.61.4
Synonymous OE0.98
0≤1.21.6
LoF obs/exp: 20 / 26.2Missense obs/exp: 234 / 240.7Syn Z: 0.17

ClinVar Variant Classifications

359 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic44
Likely Pathogenic8
VUS159
Likely Benign112
Benign34
Conflicting2
44
Pathogenic
8
Likely Pathogenic
159
VUS
112
Likely Benign
34
Benign
2
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
11
2
31
0
44
Likely Pathogenic
5
1
2
0
8
VUS
4
134
20
1
159
Likely Benign
0
2
62
48
112
Benign
0
3
28
3
34
Conflicting
—2
Total2014214352359

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

View in ClinVar →

EXOSC9 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EXOSC9-related cerebellar atrophy with spinal motor neuronopathy

strong
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

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
Mendelian randomization provides a multi-omics perspective on the regulation of genes involved in ribosome biogenesis in relation to cardiac structure and function
Wei S et al.·Clin Epigenetics
2025
Pontocerebellar Hypoplasia Type 1D: A Case Report and Comprehensive Literature Review
Dabaj I et al.·J Clin Med
2022Review
Complex Changes in the Efficiency of the Expression of Many Genes in Monogenic Diseases, Mucopolysaccharidoses, May Arise from Significant Disturbances in the Levels of Factors Involved in the Gene Expression Regulation Processes
Cyske Z et al.·Genes (Basel)
2022
Transcriptome-Wide Association Analysis Identifies Novel Candidate Susceptibility Genes for Prostate-Specific Antigen Levels in Men Without Prostate Cancer
Chen DM et al.·medRxiv
2023
Integrated multi-omics analysis revealed the molecular networks and potential targets of cellular senescence in Alzheimer's disease.
Xu Y et al.·Hum Mol Genet
2024
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