EXOSC4

exosome component 4, the group of Exosome complex|MicroRNA protein coding host genes

Basic information

Region (hg38): 8:144078648-144080648

Links

ENSG00000178896NCBI:54512OMIM:606491HGNC:18189Uniprot:Q9NPD3AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

No genCC data.

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC4 gene.

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
1
clinvar
1
clinvar
2
missense
11
clinvar
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)3276839
8-144078849-A-G not specified Uncertain significance (Apr 13, 2022)2252980
8-144079971-C-G not specified Uncertain significance (Oct 29, 2021)2258456
8-144079996-A-G Benign (Jun 06, 2017)774253
8-144080037-G-A not specified Uncertain significance (Mar 16, 2022)2278478
8-144080052-G-A not specified Uncertain significance (Sep 23, 2023)3091197
8-144080091-T-C not specified Uncertain significance (Nov 14, 2023)3091198
8-144080339-C-T not specified Uncertain significance (Aug 16, 2021)2404268
8-144080470-G-A not specified Uncertain significance (Apr 27, 2023)2512448
8-144080474-G-A not specified Uncertain significance (Apr 18, 2023)2511763
8-144080481-C-T Likely benign (Jul 01, 2022)2658966
8-144080552-G-A not specified Uncertain significance (Jan 20, 2023)2476941
8-144080573-G-A not specified Uncertain significance (May 10, 2024)3276840
8-144080584-A-G not specified Uncertain significance (Feb 06, 2023)2464840
8-144080596-G-A not specified Uncertain significance (Dec 27, 2022)2339600

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EXOSC4protein_codingprotein_codingENST00000316052 32022
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.06800.877125736061257420.0000239
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.5571281470.8710.000009651524
Missense in Polyphen4351.8870.82872526
Synonymous0.7345663.40.8830.00000379551
Loss of Function1.6237.940.3784.91e-782

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00005790.0000579
Ashkenazi Jewish0.000.00
East Asian0.00005440.0000544
Finnish0.000.00
European (Non-Finnish)0.00001950.0000176
Middle Eastern0.00005440.0000544
South Asian0.00003270.0000327
Other0.000.00

dbNSFP

Source: dbNSFP

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

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

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