EXOSC3

Chr 9AR

exosome component 3

Also known as: CGI-102, PCH1B, RRP40, Rrp40p, bA3J10.7, hRrp-40, p10

NCBI Gene: 51010ENSG00000107371UniProt: Q9NQT5

This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

Primary Disease Associations & Inheritance

Pontocerebellar hypoplasia, type 1BMIM #614678
AR
393
ClinVar variants
120
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— EXOSC3
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
120 Pathogenic / Likely Pathogenic· 114 VUS of 393 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.21LOEUF
pLI 0.000
Z-score 1.08
OE 0.65 (0.37–1.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
-0.22Z-score
OE missense 1.05 (0.92–1.20)
162 obs / 154.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.65 (0.37–1.21)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.05 (0.92–1.20)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.47
0≤1.21.6
LoF obs/exp: 7 / 10.8Missense obs/exp: 162 / 154.2Syn Z: -2.84

ClinVar Variant Classifications

393 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic83
Likely Pathogenic37
VUS114
Likely Benign132
Benign13
Conflicting14
83
Pathogenic
37
Likely Pathogenic
114
VUS
132
Likely Benign
13
Benign
14
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
13
5
65
0
83
Likely Pathogenic
13
12
12
0
37
VUS
4
88
22
0
114
Likely Benign
0
5
32
95
132
Benign
0
1
9
3
13
Conflicting
—14
Total3011114098393

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

View in ClinVar →

Protein Context — Lollipop Plot

EXOSC3 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EXOSC3-related pontocerebellar hypoplasia

definitive
ARUndeterminedAbsent Gene Product
Dev. Disorders
G2P ↗
missense variantinframe deletioninframe insertion

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

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Pontocerebellar hypoplasia, type 1B

MIM #614678

Molecular basis of disorder known

Autosomal recessive
📖
GeneReview available — EXOSC3
Authoritative clinical overview · NCBI Bookshelf · Recommended first read
Open GeneReview ↗
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study.
Brocklebank V et al.·Blood
2023Cohort
EXOSC3 mutations in pontocerebellar hypoplasia type 1: novel mutations and genotype-phenotype correlations.
Eggens VR et al.·Orphanet J Rare Dis
2014
A Chemical Biology Approach to Model Pontocerebellar Hypoplasia Type 1B (PCH1B).
François-Moutal L et al.·ACS Chem Biol
2018Functional
Novel EXOSC3 pathogenic variant results in a mild course of neurologic disease with cerebellum involvement.
Le Duc D et al.·Eur J Med Genet
2020Case report
Pontocerebellar Hypoplasia Type 1 and Associated Neuronopathies.
Škarica M et al.·Genes (Basel)
2025Review
Pontocerebellar hypoplasia type 1: clinical spectrum and relevance of EXOSC3 mutations.
Rudnik-Schöneborn S et al.·Neurology
2013
EXOSC3 mutations in isolated cerebellar hypoplasia and spinal anterior horn involvement.
Biancheri R et al.·J Neurol
2013
Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia.
Somashekar PH et al.·Clin Genet
2021Review
Sarcomeric disorganization and nemaline bodies in muscle biopsies of patients with EXOSC3-related type 1 pontocerebellar hypoplasia.
Pinto MM et al.·Muscle Nerve
2019Case report
Pontocerebellar hypoplasia type 1 for the neuropediatrician: Genotype-phenotype correlations and diagnostic guidelines based on new cases and overview of the literature.
Ivanov I et al.·Eur J Paediatr Neurol
2018Review
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
EXOSC3 knockdown induces G1/S phase arrest to suppress hepatocellular carcinoma cell proliferation.
Chen YM et al.·Sci Rep
2025🔓 Open Access
Potentially functional variants of INPP5D and EXOSC3 in immunity B cell-related genes are associated with non-small cell lung cancer survival.
Lu G et al.·Front Immunol
2024🔓 Open AccessFunctional
Elucidating the EXOSC3-IRE1α interaction: a convergent study incorporating computational, in vitro and in vivo studies.
Ashraf A et al.·J Biomol Struct Dyn
2025
Homozygous EXOSC3 c.395A>C Variants in Pontocerebellar Hypoplasia Type 1B: A Sibling Pair With Childhood Lethal Presentation and Literature Review.
Szeto CH et al.·Cureus
2023🔓 Open AccessReview
Generation of an iPSC line from a Pontocerebellar Hypoplasia 1B patient harboring a homozygous c.395 A > C mutation in EXOSC3 along with a family matched control.
Stansfield BN et al.·Stem Cell Res
2022🔓 Open Access
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools