EXOSC3

Chr 9AR

exosome component 3

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

NCBI Gene: 51010 ENSG00000107371 UniProt: Q9NQT5 OMIM: 606489

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.

GeneReviews OMIM ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a non-catalytic component of the human exosome, a complex with 3'-5' exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jun 2012]

GeneReviews OMIM ResearchGenerating clinical summary…

MultiplemechanismARLOEUF 1.211 OMIM phenotype

Clinical Summary— EXOSC3

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Population Constraint (gnomAD)

Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.

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ClinVar Variants

51 unique Pathogenic / Likely Pathogenic· 110 VUS of 323 total submissions

Explore recent and relevant literature in Research Assistant →

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GeneReview available — EXOSC3

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.21LOEUF

pLI 0.000

Z-score 1.08

OE 0.65 (0.37–1.21)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.22Z-score

OE missense 1.05 (0.92–1.20)

162 obs / 154.2 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?0.65 (0.37–1.21)

0≤0.351.4

Missense OE?1.05 (0.92–1.20)

0≤0.61.4

Synonymous OE?1.47

0≤1.21.6

LoF obs/exp: 7 / 10.8Missense obs/exp: 162 / 154.2Syn Z: -2.84

Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗

definitiveEXOSC3-related pontocerebellar hypoplasiaOTHERAR

This gene — mechanism propensity

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

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. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

323 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic22

Likely Pathogenic29

VUS110

Likely Benign132

Benign13

Conflicting14

Pathogenic

Likely Pathogenic

110

VUS

132

Likely Benign

Benign

Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

Classification	LoF	Missense + Inframe	Non-coding	Synonymous	Total
Pathogenic	16	5	1	0	22
Likely Pathogenic	17	12	0	0	29
VUS	4	91	15	0	110
Likely Benign	1	5	31	95	132
Benign	0	1	9	3	13
Conflicting	—				14
Total	38	114	56	98	320

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

View in ClinVar →

71 pathogenic / likely-pathogenic (of 75) ClinVar copy-number / structural variants overlap EXOSC3 — these span large chromosomal regions, not the gene specifically, and are excluded from the counts above. Explore in CNV tools →