EXOSC5

exosome component 5, the group of Exosome complex

Basic information

Region (hg38): 19:41386371-41397362

Links

ENSG00000077348 ∙ NCBI:56915 ∙ OMIM:606492 ∙ HGNC:24662 ∙ Uniprot:Q9NQT4 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

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

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Cerebellar ataxia, brain abnormalities, and cardiac conduction defects	AR	Cardiovascular	Among 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; Neurologic	30950035; 32504085; 34089229

ClinVar

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

• Inborn_genetic_diseases (38 variants)
• not_provided (16 variants)
• Cerebellar_ataxia,_brain_abnormalities,_and_cardiac_conduction_defects (10 variants)

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. These statistics are base on transcript: NM_000020158.4. Only rare variants are included in the table.

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.

Effect	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				5		5
missense	1	2	46	1		50
nonsense						0
start loss						0
frameshift	2		1			3
splice donor/acceptor (+/-2bp)		1				1
Total	3	3	47	6	0

Highest pathogenic variant AF is 0.000061530576

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC5	protein_coding	protein_coding	ENST00000221233	6	11106

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00401	0.869	125734	0	13	125747	0.0000517

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.484	131	148	0.888	0.00000933	1476
Missense in Polyphen		49	60.181	0.81421		585
Synonymous	0.206	66	68.2	0.968	0.00000453	508
Loss of Function	1.29	5	9.22	0.543	3.92e-7	111

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.0000289	0.0000289
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.000131	0.0000924
European (Non-Finnish)	0.0000626	0.0000615
Middle Eastern	0.00	0.00
South Asian	0.0000980	0.0000980
Other	0.00	0.00

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

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Exosc5

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