EXOSC4

Chr 8

exosome component 4

Also known as: RRP41, RRP41A, Rrp41p, SKI6, Ski6p, hRrp41p, p12A

NCBI Gene: 54512ENSG00000178896UniProt: Q9NPD3

The EXOSC4 protein is a non-catalytic component of the RNA exosome complex that processes and degrades various cellular RNAs, including rRNA maturation, mRNA turnover, and elimination of aberrant transcripts. Mutations in EXOSC4 cause autosomal recessive short stature, hearing loss, retinitis pigmentosa, and distinctive facies (SHRF) syndrome, affecting growth, sensory organs, and development. This gene shows relatively low constraint to loss-of-function variation, suggesting the recessive inheritance pattern aligns with its tolerance profile.

Summary from RefSeq, UniProt
Research Assistant →
0
Active trials
6
Pubs (1 yr)
62
P/LP submissions
0%
P/LP missense
0.98
LOEUF
DN
Mechanism· predicted
Clinical Summary— EXOSC4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.07) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
61 unique Pathogenic / Likely Pathogenic· 42 VUS of 107 total submissions
Explore recent and relevant literature in Research Assistant →

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint
0.98LOEUF
pLI 0.068
Z-score 1.62
OE 0.38 (0.17–0.98)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.56Z-score
OE missense 0.87 (0.75–1.01)
128 obs / 147.0 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.38 (0.17–0.98)
0≤0.351.4
Missense OE0.87 (0.75–1.01)
0≤0.61.4
Synonymous OE0.88
0≤1.21.6
LoF obs/exp: 3 / 7.9Missense obs/exp: 128 / 147.0Syn Z: 0.73
DN
0.6551th %ile
GOF
0.4875th %ile
LOF
0.3744th %ile

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

107 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic56
Likely Pathogenic5
VUS42
Likely Benign2
Benign1
56
Pathogenic
5
Likely Pathogenic
42
VUS
2
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
56
0
56
Likely Pathogenic
0
0
5
0
5
VUS
0
31
11
0
42
Likely Benign
0
0
0
2
2
Benign
0
0
0
1
1
Total031723106

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

View in ClinVar →

Protein Context — Lollipop Plot

EXOSC4 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
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
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