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EXOSC3

exosome component 3

The EXOSC3 gene provides instructions for a protein that is a crucial component of the RNA exosome, playing a vital role in processing and degrading RNA molecules essential for cellular function and neurological development. EXOSC3 encodes a subunit of the RNA exosome complex, which is fundamental for RNA metabolism within cells.

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, also known as exosome component 3, is responsible for producing a protein that forms part of the RNA exosome complex. This complex is indispensable for the proper processing and degradation of various RNA types within cells. These functions are critical for maintaining cellular health and ensuring normal development, particularly within the nervous system.

What the gene does

The protein encoded by the EXOSC3 gene functions as a subunit of the RNA exosome, a large multi-protein complex. Within this complex, the EXOSC3 protein helps to process RNA molecules by cleaving them at specific points and also participates in breaking down RNA molecules that are no longer needed. The accurate processing and timely degradation of RNA are fundamental for cellular operations [PMID:31505374]. Research indicates that the activity of the EXOSC3 protein is necessary for the typical development and growth of certain brain areas, specifically 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 are essential for muscle movement [PMID:24606775].

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Chromosome location

The EXOSC3 gene is located on chromosome 9 at position 9p13.2. This region specifies the exact chromosomal band where the gene can be found within the human genome.

Protein structure

Domain architecture has not been experimentally characterised in detail for this protein.

Key variants

Variations within the EXOSC3 gene can alter the protein's structure or function, potentially affecting its role in RNA processing and neurological development. At least 16 pathogenic variants in the EXOSC3 gene have been identified in individuals with pontocerebellar hypoplasia [PMID:22080344].

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 ★★☆☆ Pontocerebellar hypoplasia type 1B
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

Research suggests variants in the EXOSC3 gene are associated with pontocerebellar hypoplasia, a severe neurological disorder characterised by impaired brain development. This condition often leads to symptoms such as overall developmental delay, an unusually small head size (microcephaly), and intellectual disability.

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

UK clinical status

The EXOSC3 gene is included in several NHS England Genomic Medicine Service national test panels. These include panels for Arthrogryposis, Ataxia and cerebellar anomalies - childhood onset, Cerebellar hypoplasia, Early onset or syndromic epilepsy, Foetal anomalies, Hereditary ataxia, Hereditary ataxia, adult onset, Hereditary neuropathy or pain disorder, Intellectual disability, 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 function of the EXOSC3 gene?

The EXOSC3 gene provides instructions for a protein that is part of the RNA exosome complex. This complex is vital for processing and degrading RNA molecules, which is essential for normal cell function and neurological development.

What health conditions are associated with the EXOSC3 gene?

Variants in the EXOSC3 gene are primarily associated with pontocerebellar hypoplasia, a disorder affecting brain development. This condition can lead to developmental delay, microcephaly, and intellectual disability.

Where is the EXOSC3 gene located?

The EXOSC3 gene is situated on chromosome 9, specifically at the band position 9p13.2.

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 4 October 2026. Content compiled from HGNC · MedlinePlus Genetics · ClinGen · Genomics England PanelApp · NHS National Genomic Test Directory · ClinVar · UniProt · AlphaFold .