EXOSC10

Chr 1

exosome component 10

Also known as: PM-Scl, PM/Scl-100, PMSCL, PMSCL2, RRP6, Rrp6p, p2, p3

NCBI Gene: 5394 ENSG00000171824 UniProt: Q01780

The EXOSC10 protein is the catalytic component of the RNA exosome complex, which performs 3' to 5' RNA degradation and is essential for ribosomal RNA processing, mRNA turnover, and RNA surveillance. Mutations cause autosomal recessive pontocerebellar hypoplasia with microcephaly, developmental delay, and progressive neurodegeneration typically manifesting in infancy. This gene shows extreme intolerance to loss-of-function variants, reflecting its essential role in RNA metabolism and cellular function.

ResearchSummary from RefSeq, UniProt

Enables 3'-5'-RNA exonuclease activity and telomerase RNA binding activity. Involved in several processes, including RNA metabolic process; negative regulation of telomere maintenance via telomerase; and regulation of telomerase RNA localization to Cajal body. Located in cytosol; euchromatin; and nuclear lumen. Part of nuclear exosome (RNase complex) and small-subunit processome. [provided by Alliance of Genome Resources, Jul 2025]

ResearchGenerating clinical summary…

DNmechanismLOEUF 0.74

Clinical Summary— EXOSC10

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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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Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

0.74LOEUF

pLI 0.000

Z-score 3.19

OE 0.55 (0.41–0.74)

Tolerant

Typical tolerance to LoF variation

Missense Constraint?

0.87Z-score

OE missense 0.89 (0.82–0.96)

453 obs / 508.2 exp

Tolerant

Mild missense constraint

Observed / Expected Ratios?

LoF OE?0.55 (0.41–0.74)

0≤0.351.4

Missense OE?0.89 (0.82–0.96)

0≤0.61.4

Synonymous OE?1.00

0≤1.21.6

LoF obs/exp: 32 / 58.3Missense obs/exp: 453 / 508.2Syn Z: -0.04

This gene — mechanism propensity

0.74top 25%

GOF

0.4875th %ile

LOF

0.3355th %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.