EXOSC5

Chr 19AR

exosome component 5

Also known as: CABAC, RRP41B, RRP46, Rrp46p, hRrp46p, p12B

EXOSC5 encodes a non-catalytic component of the RNA exosome complex, which degrades and processes various RNA species in both the nucleus and cytoplasm. Biallelic mutations cause autosomal recessive cerebellar ataxia with brain abnormalities and cardiac conduction defects. The gene is not highly constrained against loss-of-function variants in the general population.

OMIMResearchSummary from RefSeq, OMIM, UniProt
DNmechanismARLOEUF 1.141 OMIM phenotype
Clinical SummaryEXOSC5
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
1.14LOEUF
pLI 0.004
Z-score 1.29
OE 0.54 (0.281.14)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint
0.48Z-score
OE missense 0.89 (0.771.03)
131 obs / 147.5 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.54 (0.281.14)
00.351.4
Missense OE0.89 (0.771.03)
00.61.4
Synonymous OE0.97
01.21.6
LoF obs/exp: 5 / 9.2Missense obs/exp: 131 / 147.5Syn Z: 0.21
DN
0.6358th %ile
GOF
0.4283th %ile
LOF
0.4332th %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

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

EXOSC5 · 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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