EXOSC4
exosome component 4, the group of Exosome complex|MicroRNA protein coding host genes
Basic information
Region (hg38): 8:144078648-144080648
Links
Phenotypes
GenCC
Source:
No genCC data.
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC4 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 2 | |||||
| missense | 11 | 11 | ||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 0 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 0 | 11 | 1 | 1 |
Variants in EXOSC4
This is a list of pathogenic ClinVar variants found in the EXOSC4 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 8-144078733-C-T | not specified | Uncertain significance (Apr 15, 2024) | ||
| 8-144078849-A-G | not specified | Uncertain significance (Apr 13, 2022) | ||
| 8-144079971-C-G | not specified | Uncertain significance (Oct 29, 2021) | ||
| 8-144079996-A-G | Benign (Jun 06, 2017) | |||
| 8-144080037-G-A | not specified | Uncertain significance (Mar 16, 2022) | ||
| 8-144080052-G-A | not specified | Uncertain significance (Sep 23, 2023) | ||
| 8-144080091-T-C | not specified | Uncertain significance (Nov 14, 2023) | ||
| 8-144080339-C-T | not specified | Uncertain significance (Aug 16, 2021) | ||
| 8-144080470-G-A | not specified | Uncertain significance (Apr 27, 2023) | ||
| 8-144080474-G-A | not specified | Uncertain significance (Apr 18, 2023) | ||
| 8-144080481-C-T | Likely benign (Jul 01, 2022) | |||
| 8-144080552-G-A | not specified | Uncertain significance (Jan 20, 2023) | ||
| 8-144080573-G-A | not specified | Uncertain significance (May 10, 2024) | ||
| 8-144080584-A-G | not specified | Uncertain significance (Feb 06, 2023) | ||
| 8-144080596-G-A | not specified | Uncertain significance (Dec 27, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| EXOSC4 | protein_coding | protein_coding | ENST00000316052 | 3 | 2022 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0680 | 0.877 | 125736 | 0 | 6 | 125742 | 0.0000239 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 0.557 | 128 | 147 | 0.871 | 0.00000965 | 1524 |
| Missense in Polyphen | 43 | 51.887 | 0.82872 | 526 | ||
| Synonymous | 0.734 | 56 | 63.4 | 0.883 | 0.00000379 | 551 |
| Loss of Function | 1.62 | 3 | 7.94 | 0.378 | 4.91e-7 | 82 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000579 | 0.0000579 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000195 | 0.0000176 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.0000327 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Non-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. The catalytic inactive RNA exosome core complex of 9 subunits (Exo-9) is proposed to play a pivotal role in the binding and presentation of RNA for ribonucleolysis, and to serve as a scaffold for the association with catalytic subunits and accessory proteins or complexes. EXOSC4 binds to ARE-containing RNAs. {ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563, ECO:0000269|PubMed:18172165, ECO:0000269|PubMed:20368444, ECO:0000269|PubMed:21255825}.;
- Pathway
- RNA degradation - Homo sapiens (human);Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA;KSRP (KHSRP) binds and destabilizes mRNA;Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA;Metabolism of RNA;Regulation of mRNA stability by proteins that bind AU-rich elements;mRNA decay by 3, to 5, exoribonuclease;Deadenylation-dependent mRNA decay
(Consensus)
Recessive Scores
- pRec
- 0.118
Intolerance Scores
- loftool
- 0.559
- rvis_EVS
- -0.32
- rvis_percentile_EVS
- 31.69
Haploinsufficiency Scores
- pHI
- 0.442
- hipred
- Y
- hipred_score
- 0.744
- ghis
- 0.524
Essentials
- essential_gene_CRISPR
- E
- essential_gene_CRISPR2
- E
- essential_gene_gene_trap
- H
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.925
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Exosc4
- Phenotype
Zebrafish Information Network
- Gene name
- exosc4
- Affected structure
- head
- Phenotype tag
- abnormal
- Phenotype quality
- decreased size
Gene ontology
- Biological process
- maturation of 5.8S rRNA;nuclear-transcribed mRNA catabolic process;rRNA processing;rRNA catabolic process;positive regulation of cell growth;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';U4 snRNA 3'-end processing;regulation of mRNA stability;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;DNA deamination;defense response to virus;nuclear mRNA surveillance;histone mRNA catabolic process;polyadenylation-dependent snoRNA 3'-end processing;RNA phosphodiester bond hydrolysis, exonucleolytic
- Cellular component
- nuclear exosome (RNase complex);cytoplasmic exosome (RNase complex);exosome (RNase complex);nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;transcriptionally active chromatin;intermediate filament cytoskeleton
- Molecular function
- 3'-5'-exoribonuclease activity;exoribonuclease activity;protein binding;AU-rich element binding