EXOSC10
protein-codingexosome component 10, the group of Exosome complex
Gene summary
Enables 3'-5'-RNA exonuclease activity and telomerase RNA binding activity. Involved in several processes, including RNA catabolic process; negative regulation of telomere maintenance via telomerase; and ribosome biogenesis. Located in cytosol; euchromatin; and nuclear lumen. Part of nuclear exosome (RNase complex) and small-subunit processome. [provided by Alliance of Genome Resources, Jun 2026]
- PMSCL2
MANE transcript
Inheritance
ClinVar variants
Top phenotype
gnomAD constraint
Max pathogenic AF
Genomic locus
External References & Databases
Transcript & Mutation Effects
hg38 • Region Span ~33.3 kbGenCC Phenotypes & Disease Associations
Curated gene-disease validity assertions and inheritance patterns
No GenCC data available for this gene.
ClinVar Associated Diseases & Phenotypes
Reported disease conditions connected to EXOSC10 variants in ClinVar
ClinVar Variants & Pathogenicity by Type
Statistics based on transcript NM_001001998.3. Only rare variants are included.
We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.
Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.
| Effect | PathogenicP | Likely pathogenicLP | VUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 4 | 1 | 5 | |||
| missense | 114 | 3 | 117 | |||
| nonsense | 1 | 1 | ||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| splice donor/acceptor (+/-2bp) | 9 | 9 | ||||
| Total | 0 | 0 | 128 | 3 | 1 | 132 |
Transcript Catalog
Annotated transcript isoforms across RefSeq and Ensembl databases
| Transcript ID | Source | Protein ID | Coding Exons | MANE Status |
|---|---|---|---|---|
| RefSeq | NP_001001998.1 | 25 | MANE Select | |
| Ensembl | ENSP00000366135.4 | 25 | MANE Select | |
| RefSeq | NP_002676.1 | 24 | Standard | |
| Ensembl | ENSP00000307307.7 | 24 | Standard |
Gene Ontology (GO) Annotations & Pathways
Biological processes, molecular functions, cellular components and pathways
Pathways ConsensusPathDB
- RNA degradation - Homo sapiens (human)
Biological Process
- nuclear-transcribed mRNA catabolic process, nonsense-mediated decay
- maturation of 5.8S rRNA
- nuclear-transcribed mRNA catabolic process
- rRNA processing
- dosage compensation by inactivation of X chromosome
Molecular Function
- nucleotide binding
- 3'-5'-exoribonuclease activity
- RNA binding
- exoribonuclease activity
- protein binding
Cellular Component
- nuclear exosome (RNase complex)
- exosome (RNase complex)
- nucleus
- nucleoplasm
- nucleolus
gnomAD Constraint
Source:
- Gene type
- protein_coding
- Transcript type
- protein_coding
- Transcript
- ENST00000376936
- Coding exons
- 25
- Length
- 33264
- Individuals with no LoFs
- 125668
- Homozygous LoFs
- 0
- Heterozygous LoFs
- 80
- Defined
- 125748
- p
- 0.000318
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible | |
|---|---|---|---|---|---|---|
| Missense | 0.870 | 453 | 508 | 0.891 | 0.0000283 | 5840 |
| Missense (PolyPhen) | 129 | 172.88 | 0.74617 | 2029 | ||
| Synonymous | -0.0408 | 194 | 193 | 1.00 | 0.0000114 | 1644 |
| Loss of Function | 3.19 | 32 | 58.3 | 0.549 | 0.00000321 | 619 |
Population LoF Frequency
| Population | CAF | p-value | Status |
|---|---|---|---|
| African | 0.00043 | 0.00043 | rare |
| Latino/Admixed American | 0.00035 | 0.00035 | rare |
| Ashkenazi Jewish | 0.000099 | 0.000099 | rare |
| East Asian | 0.00049 | 0.00049 | rare |
| Finnish | 0.000093 | 0.000092 | rare |
| European (Non-Finnish) | 0.00028 | 0.00028 | rare |
| South Asian | 0.00043 | 0.00042 | rare |
| Other | 0.00065 | 0.00065 | rare |
dbNSFP Gene Annotations
Source:
- Function
- FUNCTION: Putative catalytic component of the RNA exosome complex which has 3'->5' exoribonuclease activity and participates in a multitude of cellular RNA processing and degradation events. In the nucleus, the RNA exosome complex is involved in proper maturation of stable RNA species such as rRNA, snRNA and snoRNA, in the elimination of RNA processing by-products and non-coding 'pervasive' transcripts, such as antisense RNA species and promoter-upstream transcripts (PROMPTs), and of mRNAs with processing defects, thereby limiting or excluding their export to the cytoplasm. The RNA exosome may be involved in Ig class switch recombination (CSR) and/or Ig variable region somatic hypermutation (SHM) by targeting AICDA deamination activity to transcribed dsDNA substrates. In the cytoplasm, the RNA exosome complex is involved in general mRNA turnover and specifically degrades inherently unstable mRNAs containing AU-rich elements (AREs) within their 3' untranslated regions, and in RNA surveillance pathways, preventing translation of aberrant mRNAs. It seems to be involved in degradation of histone mRNA. EXOSC10 has 3'-5' exonuclease activity (By similarity). EXOSC10 is required for nucleolar localization of C1D and probably mediates the association of MTREX, C1D and MPP6 wth the RNA exosome involved in the maturation of 5.8S rRNA. {ECO:0000250, ECO:0000269|PubMed:14527413, ECO:0000269|PubMed:16455498, ECO:0000269|PubMed:17412707, ECO:0000269|PubMed:17545563, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:20368444, ECO:0000269|PubMed:20699273}.;
Recessive Scores
- pRec
- 0.306
Intolerance Scores
- LoFtool
- 0.0801
- RVIS EVS
- -1.24
- RVIS percentile EVS
- 5.49
Essentials
- Essential (CRISPR)
- E
- Essential (CRISPR2)
- E
- Essential (gene trap)
- E
- Indispensability pred.
- E
- Indispensability score
- 0.963
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |