EXOSC2

Chr 9AR

exosome component 2

Also known as: RRP4, Rrp4p, SHRF, hRrp4p, p7

NCBI Gene: 23404ENSG00000130713UniProt: Q13868

Predicted to enable RNA binding activity. Involved in RNA catabolic process; RNA processing; and positive regulation of cell growth. Located in cytosol; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). Implicated in short stature, hearing loss, retinitis pigmentosa, and distinctive facies. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

Short stature, hearing loss, retinitis pigmentosa, and distinctive faciesMIM #617763
AR
0
Active trials
31
Pathogenic / LP
336
ClinVar variants
2
Pubs (1 yr)
0.4
Missense Z
1.10
LOEUF
Clinical Summary— EXOSC2
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
31 Pathogenic / Likely Pathogenic· 161 VUS of 336 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.
1.10LOEUF
pLI 0.000
Z-score 1.28
OE 0.66 (0.42–1.10)
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.
0.39Z-score
OE missense 0.92 (0.80–1.05)
153 obs / 167.2 exp
Tolerant

Mild missense constraint

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.0.66 (0.42–1.10)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.92 (0.80–1.05)
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.0.90
0≤1.21.6
LoF obs/exp: 11 / 16.6Missense obs/exp: 153 / 167.2Syn Z: 0.60
DN
0.6842th %ile
GOF
0.4283th %ile
LOF
0.48top 25%

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

336 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic27
Likely Pathogenic4
VUS161
Likely Benign129
Benign11
Conflicting4
27
Pathogenic
4
Likely Pathogenic
161
VUS
129
Likely Benign
11
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
27
0
27
Likely Pathogenic
0
1
3
0
4
VUS
13
118
30
0
161
Likely Benign
0
2
67
60
129
Benign
0
1
7
3
11
Conflicting
—4
Total1312213463336

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

View in ClinVar →

Protein Context — Lollipop Plot

EXOSC2 · protein map & ClinVar variants

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

Gene2Phenotype Curations

EXOSC2-related short stature, hearing loss, retinitis pigmentosa, and distinctive facies syndrome

limited
ARUndeterminedAbsent Gene Product, Altered Gene Product Structure, Decreased Gene Product Level
Dev. DisordersEye
G2P ↗
missense variantinframe deletioninframe insertion

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
Top 5 full-text resultsSearch PubTator3 ↗
Key Publications
Landmark & review papers · by relevance
PubMed
Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication.
Moll T et al.·Life Sci Alliance
2022
Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis.
Yang X et al.·Hum Mol Genet
2020
Comparative analyses of disease-linked missense mutations in the RNA exosome modeled in budding yeast reveal distinct functional consequences in translation.
Sterrett MC et al.·RNA
2025Functional
Bi-allelic missense variant, p.Ser35Leu in EXOSC1 is associated with pontocerebellar hypoplasia.
Somashekar PH et al.·Clin Genet
2021Review
In vivo characterization of the critical interaction between the RNA exosome and the essential RNA helicase Mtr4 in Saccharomyces cerevisiae.
Sterrett MC et al.·G3 (Bethesda)
2023
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