EXOSC5

exosome component 5, the group of Exosome complex

Basic information

Region (hg38): 19:41386371-41397362

Links

ENSG00000077348NCBI:56915OMIM:606492HGNC:24662Uniprot:Q9NQT4AlphaFoldGenCCjaxSfariGnomADPubmedClinVar

Phenotypes

GenCC

Source: genCC

  • cerebellar ataxia, brain abnormalities, and cardiac conduction defects (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Cerebellar ataxia, brain abnormalities, and cardiac conduction defectsARCardiovascularAmong other findings, the condition can include cardiovascular anomalies, including conduction defects, and awareness may allow early diagnosis and management (eg, with pacemaker)Cardiovascular; Craniofacial; Musculoskeletal; Neurologic30950035; 32504085; 34089229

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC5 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC5 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
clinvar
2
missense
2
clinvar
24
clinvar
1
clinvar
1
clinvar
28
nonsense
0
start loss
0
frameshift
0
inframe indel
0
splice donor/acceptor (+/-2bp)
0
splice region
0
non coding
0
Total 0 2 24 3 1

Variants in EXOSC5

This is a list of pathogenic ClinVar variants found in the EXOSC5 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
19-41386638-T-C Inborn genetic diseases Uncertain significance (Jan 16, 2024)3091205
19-41386651-CCTCTGCAGCGATTCCCGGTAGAAACGGAAGACGTGTTGCGAAGCGGCCTGGGCCGCAGCCAGGCACTGCTGGAGCTGCGGGGGAGAGACTGGTCGGTGCTGGGGGCCGAGCCCTTCATGCACACACGACTTGGCTGACCCAGGAGGTTCTGCTGACCCCACCTGACTCCCTTAACCTCCCATCACTCCCCTGCCCCCAAGTGAGGCAAGTGGTAAGGGATTATTTCCCATTTCATGAACTGTTTCTTAGAGATCAGGAGAAATAAAAAGAGGGAGAAGGACTTCAGGATCAGATTCTGACAGCAACAGGACTCAGACCTATCAGGCATCCTCACACCTTGGAGGAGGCCCCAGCTGTGCAGAGCTATGGAACTGGAGAGTGCACAGAATTGGAGTGGTCTTGGGATTTTACAGCCACAGTCCCCTTCAGCCCAAATAATCTAAGAGCCATGGAATCAAGAGACTCCCAGTCTTCACTGCCATGTATTCCTAGATTCATGAGGTCCAGGTTGGACATGCTTTTGCAGACAGTCATGTCCAAGAGTTTCCAGGCTCTGCCCCTTAGCCTGAGACCTGGAATTCCCATGGCTCACCACTCTGAGCTGGGAGCTGGGGGACCATCACATGCCCTCTTCTGACTTCAAACTGAGCTCATCCTCTTTTTGCCTGTGTTATAAATTGGGCTTCCCTTAAACATTTCCGCAAAGGTTTCTGGGTCCACAAAGTTTGAAAACTCCCTTTTTACAAGAAGAAATTTAAGAGGCTCTCCTGAAGCCTCTCAGAATCCAGGGCAGAGTTGGGACAAGACCGTATGTCAGTGGGAAGGAAGGTTCTGGCTTTTCCCCTCATCCCCATGCTGGTACCTCAGTGTCTGAGTAGAGCCCCTTGGTGCTGGACATCAGCAGCTTCCGTTCCACGCTGTCCAGGGCAAAGGTCAGGACTGCCCGGGCCTCCTAGGGACAAGGGGTAGAAGGCGGTGGGGGACCTAGGACCTTCCCCTCAGATAAAATCTCAGCCAGTCCTTT-C Cerebellar ataxia, brain abnormalities, and cardiac conduction defects Pathogenic (Oct 21, 2021)1300245
19-41386676-C-T Inborn genetic diseases Uncertain significance (Dec 27, 2023)3091204
19-41386677-G-A Uncertain significance (Jan 01, 2023)2498781
19-41386678-G-C Inborn genetic diseases Uncertain significance (Apr 05, 2023)2533539
19-41386691-G-A Uncertain significance (Feb 05, 2024)3368523
19-41386695-C-T Inborn genetic diseases Uncertain significance (Dec 02, 2022)2356497
19-41386724-A-T Cerebellar ataxia, brain abnormalities, and cardiac conduction defects Pathogenic (Oct 21, 2021)1300246
19-41387561-G-A Inborn genetic diseases Uncertain significance (May 28, 2024)3276842
19-41387574-C-G Likely benign (Dec 01, 2023)3026110
19-41387596-C-T Likely benign (Nov 01, 2022)1879440
19-41389769-T-C Uncertain significance (Jun 13, 2023)3252118
19-41389794-C-T Inborn genetic diseases Uncertain significance (Jan 23, 2023)2461873
19-41389806-C-A Inborn genetic diseases Uncertain significance (Jul 15, 2021)2237802
19-41389817-G-A Uncertain significance (May 01, 2024)3239140
19-41389827-C-A Inborn genetic diseases Uncertain significance (Apr 26, 2023)2507585
19-41389845-G-A Inborn genetic diseases Uncertain significance (Mar 20, 2024)3276841
19-41389847-A-G Cerebellar ataxia, brain abnormalities, and cardiac conduction defects Uncertain significance (Apr 19, 2022)1307391
19-41389881-C-T Inborn genetic diseases Uncertain significance (Jun 28, 2023)2222811
19-41391846-C-G Uncertain significance (May 27, 2022)1801077
19-41391872-A-G Inborn genetic diseases Uncertain significance (Mar 27, 2023)2530250
19-41391884-G-A Cerebellar ataxia, brain abnormalities, and cardiac conduction defects Pathogenic/Likely pathogenic (May 04, 2022)1300244
19-41391887-C-T Uncertain significance (May 27, 2022)1800881
19-41391914-G-A Inborn genetic diseases Uncertain significance (Dec 03, 2021)2393919
19-41391918-C-T Inborn genetic diseases Uncertain significance (Apr 06, 2022)2281385

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
EXOSC5protein_codingprotein_codingENST00000221233 611106
pLI Probability
LOF Intolerant
pRec Probability
LOF Recessive
Individuals with
no LOFs
Individuals with
Homozygous LOFs
Individuals with
Heterozygous LOFs
Defined p
0.004010.8691257340131257470.0000517
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense0.4841311480.8880.000009331476
Missense in Polyphen4960.1810.81421585
Synonymous0.2066668.20.9680.00000453508
Loss of Function1.2959.220.5433.92e-7111

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00002890.0000289
Ashkenazi Jewish0.000.00
East Asian0.000.00
Finnish0.0001310.0000924
European (Non-Finnish)0.00006260.0000615
Middle Eastern0.000.00
South Asian0.00009800.0000980
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. {ECO:0000269|PubMed:11782436, 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
0.109

Intolerance Scores

loftool
0.746
rvis_EVS
-0.29
rvis_percentile_EVS
33.2

Haploinsufficiency Scores

pHI
0.406
hipred
Y
hipred_score
0.650
ghis
0.605

Essentials

essential_gene_CRISPR
E
essential_gene_CRISPR2
E
essential_gene_gene_trap
E
gene_indispensability_pred
E
gene_indispensability_score
0.964

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Exosc5
Phenotype

Gene ontology

Biological process
rRNA processing;rRNA catabolic process;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;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
Molecular function
3'-5'-exoribonuclease activity;RNA binding;exoribonuclease activity;protein binding