EXOSC2

Chr 9AR

exosome component 2

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

The EXOSC2 protein is a non-catalytic component of the RNA exosome complex that processes and degrades various RNA species in both the nucleus and cytoplasm. Biallelic mutations cause an autosomal recessive syndrome characterized by short stature, hearing loss, retinitis pigmentosa, and distinctive facial features. The gene is highly constrained against loss-of-function variants (pLI near 1), indicating that complete loss of function is poorly tolerated.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.101 OMIM phenotype
Clinical SummaryEXOSC2
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.10LOEUF
pLI 0.000
Z-score 1.28
OE 0.66 (0.421.10)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.39Z-score
OE missense 0.92 (0.801.05)
153 obs / 167.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.66 (0.421.10)
00.351.4
Missense OE0.92 (0.801.05)
00.61.4
Synonymous OE0.90
01.21.6
LoF obs/exp: 11 / 16.6Missense obs/exp: 153 / 167.2Syn Z: 0.60
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
limitedEXOSC2-related short stature, hearing loss, retinitis pigmentosa, and distinctive facies syndromeOTHERAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.6842th %ile
GOF
0.4283th %ile
LOF
0.48top 25%

The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.

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

ClinVar Variant Classifications

0 submitted variants 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.

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC