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EXOSC3

exosome component 3

The EXOSC3 gene provides instructions for producing a protein that is a key component of the RNA exosome, a multi-protein complex vital for processing and degrading RNA molecules within cells. The EXOSC3 gene is essential for normal cellular function, as its protein product participates in RNA regulation.

Chromosome 9p13.2 Various HGNC:17944 Tier C
EXOSC3 9p13.2 p arm q arm 9

EXOSC3 is located on the short (p) arm of chromosome 9, at band 9p13.2. Arm ratio per GRCh38 - banding schematic.

Explore chromosome 9 in the library →

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Clinical tests that include this

Carrier Screening panel
EXOSC3 is 1 of 1,008 genes on this panel
Expanded carrier screening for recessive and X-linked conditions

Overview

The EXOSC3 gene encodes exosome component 3, a protein that forms part of the RNA exosome. This large protein complex plays a critical role in cells by processing and degrading various types of RNA molecules. Proper RNA handling is fundamental for all cellular processes.

Research indicates that the EXOSC3 protein is necessary for the normal development and growth of specific brain regions, such as the cerebellum, which coordinates movement. It also appears to be important for the survival of motor neurons, specialised nerve cells in the spinal cord that control muscle movement.

What the gene does

The EXOSC3 gene directs the synthesis of exosome component 3, a subunit of the RNA exosome. This complex is responsible for cleaving RNA molecules at specific points and degrading RNA that is no longer required. The accurate processing and breakdown of RNA are fundamental for healthy cell operation.

Studies suggest that the activity of exosome component 3 is crucial for the normal development and growth of certain areas of the brain, particularly the cerebellum. The cerebellum is the part of the brain responsible for coordinating movement. Additionally, exosome component 3 appears to be vital for the survival of motor neurons, which are specialised nerve cells in the spinal cord that play a key role in muscle movement.

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Chromosome location

The EXOSC3 gene is located on the short arm of chromosome 9 at position 9p13.2. This genomic location specifies where the gene resides within the human genome.

Protein structure

The EXOSC3 gene encodes a protein that is 275 amino acids long. Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Genetic variations, or variants, within the EXOSC3 gene can alter the protein's structure or function. These changes may impact the efficiency of the RNA exosome complex, potentially affecting RNA processing and degradation pathways critical for cellular health and development.

The table below shows the top 10 pathogenic or likely-pathogenic variants currently classified in ClinVar for EXOSC3.
View all on ClinVar →

Sample of pathogenic variants

10 pathogenic / likely-pathogenic variants from ClinVar, ranked by review status (expert-panel-reviewed first). This is a sample; recurrent founder variants in a specific population may not appear here - see the full ClinVar listing via the link above.

Variant (HGVS) Protein change Classification Evidence Associated condition
c.155del
Deletion
 p.Pro52fs Pathogenic ★★☆☆ Pontoneocerebellar hypoplasia
c.167_174del
Deletion
 p.Asn56fs Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B
c.1A>G
single nucleotide variant
 p.Met1Val Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B
c.226dup
Duplication
 p.Asp76fs Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B
c.2T>C
single nucleotide variant
 p.Met1Thr Pathogenic/Likely pathogenic ★★☆☆ Pontoneocerebellar hypoplasia
c.312_313del
Microsatellite
 p.Gln105fs Pathogenic/Likely pathogenic ★★☆☆ Pontoneocerebellar hypoplasia
c.428_431del
Deletion
 p.Tyr143fs Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B
c.556C>T
single nucleotide variant
 p.Arg186Ter Pathogenic/Likely pathogenic ★★☆☆ Pontoneocerebellar hypoplasia
c.619_622dup
Duplication
 p.Arg208delinsAsnTer Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B
c.672_673del
Microsatellite
 p.Tyr225fs Pathogenic/Likely pathogenic ★★☆☆ Pontocerebellar hypoplasia type 1B

Evidence stars indicate ClinVar review status. Individual variant interpretation should always be performed by a qualified clinical laboratory - many variants remain classified as Variants of Uncertain Significance (VUS) pending more research.

Associated conditions

Variants in the EXOSC3 gene have been linked to pontocerebellar hypoplasia, a group of severe neurodevelopmental disorders. These conditions are characterised by impaired brain development, particularly affecting the cerebellum and brainstem, leading to various neurological symptoms.

No disease links recorded for this gene in our reference set.

UK clinical status

The EXOSC3 gene is included on several NHS Genomic Medicine Service national test panels in the UK, indicating its clinical relevance for specific conditions. These include panels for Arthrogryposis (R83), Foetal anomalies (R21), Hereditary neuropathy or pain disorder (R78), Intellectual disability, Hereditary ataxia, and Paediatric motor neuronopathies.

Green-listed
High evidence · clinically actionable in NHS testing
Included in NHS GMS signed-off panels
Arthrogryposis · R83 NHS GMS → Fetal anomalies · R21 NHS GMS → Hereditary neuropathy or pain disorder · R78 NHS GMS → Ataxia and cerebellar anomalies - childhood onset NHS GMS → DDG2P NHS GMS → Early onset or syndromic epilepsy NHS GMS → Hereditary ataxia, adult onset NHS GMS → Intellectual disability NHS GMS →
NHS Genomic Medicine Service Jeen carrier screening

Sources: NHS GMS PanelApp · Genomics England PanelApp · NHS National Genomic Test Directory

Frequently asked questions

What is the EXOSC3 gene?

The EXOSC3 gene provides instructions for making exosome component 3, a protein that is part of the RNA exosome complex. This complex is vital for processing and breaking down RNA molecules within cells.

What does the EXOSC3 protein do?

The EXOSC3 protein helps the RNA exosome complex to process and degrade RNA, which is essential for normal cell function. It is particularly important for the development of the brain's cerebellum and the survival of motor neurons.

What conditions are associated with changes in the EXOSC3 gene?

Changes in the EXOSC3 gene are associated with pontocerebellar hypoplasia, a disorder characterised by impaired brain development, especially affecting the cerebellum.

References

  1. Eggens VR, Barth PG, Niermeijer JM. EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations. Orphanet journal of rare diseases. 2014. PMID: 24524299
  2. Rudnik-Schöneborn S, Senderek J, Jen JC. Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations. Neurology. 2013. PMID: 23284067
  3. Biancheri R, Cassandrini D, Pinto F. EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement. Journal of neurology. 2013. PMID: 23564332
  4. Zanni G, Scotton C, Passarelli C. Exome sequencing in a family with intellectual disability, early onset spasticity, and cerebellar atrophy detects a novel mutation in EXOSC3. Neurogenetics. 2013. PMID: 23975261
  5. Wan J, Yourshaw M, Mamsa H. Mutations in the RNA exosome component gene EXOSC3 cause pontocerebellar hypoplasia and spinal motor neuron degeneration. Nature genetics. 2012. PMID: 22544365
  6. Adam MP, Bick S, Mirzaa GM. EXOSC3 Pontocerebellar Hypoplasia. 1993. PMID: 25144110
Educational content. This page is not medical or genetic advice, is not individually reviewed by a clinician for each reader, and should not replace a consultation with a qualified healthcare professional or genetic counsellor. If you are considering genetic testing or acting on a test result, book a consultation.
Data sources Last updated 13 September 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .