EXOSC8

Chr 13AR

exosome component 8

Also known as: CIP3, EAP2, OIP2, PCH1C, RRP43, Rrp43p, bA421P11.3, p9

The protein is a non-catalytic component of the RNA exosome complex that processes and degrades various RNA species in both the nucleus and cytoplasm, including mRNAs containing AU-rich elements. Mutations cause pontocerebellar hypoplasia type 1C, a severe early-onset neurodevelopmental disorder primarily affecting the brainstem and cerebellum, inherited in an autosomal recessive pattern. The gene is highly constrained against loss-of-function variation (pLI nearly 1), indicating that heterozygous loss-of-function variants are likely benign in the general population.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt
LOFmechanismARLOEUF 1.691 OMIM phenotype
Clinical SummaryEXOSC8
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
52 unique Pathogenic / Likely Pathogenic· 68 VUS of 191 total submissions
📖
GeneReview available — EXOSC8
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
1.69LOEUF
pLI 0.000
Z-score -0.66
OE 1.17 (0.821.69)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.85Z-score
OE missense 0.80 (0.690.94)
115 obs / 143.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE1.17 (0.821.69)
00.351.4
Missense OE0.80 (0.690.94)
00.61.4
Synonymous OE0.68
01.21.6
LoF obs/exp: 20 / 17.1Missense obs/exp: 115 / 143.5Syn Z: 1.81

ClinVar Variant Classifications

191 submitted variants in ClinVar

Classification Summary

Pathogenic51
Likely Pathogenic1
VUS68
Likely Benign40
Benign16
Conflicting4
51
Pathogenic
1
Likely Pathogenic
68
VUS
40
Likely Benign
16
Benign
4
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
1
1
49
0
51
Likely Pathogenic
1
0
0
0
1
VUS
4
55
9
0
68
Likely Benign
0
0
26
14
40
Benign
0
2
12
2
16
Conflicting
4
Total6589616180

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

View in ClinVar →

Protein Context — Lollipop Plot

EXOSC8 · 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
Open Research Assistant →
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC