EXOSC3

Chr 9AR

exosome component 3

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

The protein is a non-catalytic component of the human exosome complex, which has 3'-5' exoribonuclease activity and functions in RNA processing and degradation. Mutations cause pontocerebellar hypoplasia type 1B, inherited in an autosomal recessive pattern. The pathogenic mechanism involves disruption of essential RNA processing pathways required for normal brain development.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.211 OMIM phenotype
Clinical SummaryEXOSC3
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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GeneReview available — EXOSC3
Authoritative clinical overview · Recommended first read
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
1.21LOEUF
pLI 0.000
Z-score 1.08
OE 0.65 (0.371.21)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
-0.22Z-score
OE missense 1.05 (0.921.20)
162 obs / 154.2 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.65 (0.371.21)
00.351.4
Missense OE1.05 (0.921.20)
00.61.4
Synonymous OE1.47
01.21.6
LoF obs/exp: 7 / 10.8Missense obs/exp: 162 / 154.2Syn Z: -2.84
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveEXOSC3-related pontocerebellar hypoplasiaOTHERAR

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

DN
0.6454th %ile
GOF
0.4677th %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

EXOSC3 · 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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