EXOSC8

exosome component 8, the group of Exosome complex

Basic information

Region (hg38): 13:36998815-37025881

Links

ENSG00000120699 ∙ NCBI:11340 ∙ OMIM:606019 ∙ HGNC:17035 ∙ Uniprot:Q96B26 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, type 1C (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia, type 1C (Limited), mode of inheritance: Unknown

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 1C	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Audiologic/Otolaryngologic; Neurologic; Ophthalmologic	24989451

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC8 gene.

• Spastic ataxia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC8 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				13	1	14
missense			37		2	39
nonsense	1		1			2
start loss			1			1
frameshift			1			1
inframe indel			2			2
splice donor/acceptor (+/-2bp)			1			1
splice region			4	4	1	9
non coding			12	14	4	30
Total	1	0	55	27	7

Variants in EXOSC8

This is a list of pathogenic ClinVar variants found in the EXOSC8 region.

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

Position	Type	Phenotype	Significance	ClinVar
13-36999247-T-G		ALG5-related disorder	Benign (Dec 13, 2023)
13-36999265-G-A		ALG5-related disorder	Benign (Nov 16, 2023)
13-36999270-G-C		ALG5-related disorder	Likely benign (Apr 17, 2023)
13-36999279-G-C		not specified	Uncertain significance (May 29, 2024)
13-37000341-T-C			Benign (May 12, 2021)
13-37000344-CA-C			Benign (Jun 03, 2021)
13-37000344-CAA-C			Benign (May 20, 2021)
13-37000544-C-T			Benign (May 11, 2021)
13-37000571-G-A			Benign (May 11, 2021)
13-37000577-C-T			Benign (May 11, 2021)
13-37000807-T-G			Uncertain significance (Mar 19, 2021)
13-37000810-C-T		Pontocerebellar hypoplasia, type 1C	Pathogenic (Jul 03, 2014)
13-37000812-G-T		not specified	Uncertain significance (Nov 19, 2022)
13-37000814-T-G			Likely benign (Aug 31, 2023)
13-37000816-G-C			Uncertain significance (Jun 01, 2021)
13-37000818-T-C		Pontocerebellar hypoplasia, type 1C • not specified	Conflicting classifications of pathogenicity (Aug 22, 2022)
13-37000820-C-G		not specified	Uncertain significance (Apr 15, 2024)
13-37000823-G-T		Pontocerebellar hypoplasia, type 1C	Uncertain significance (Dec 03, 2018)
13-37000826-AG-A		Pontocerebellar hypoplasia, type 1C	Uncertain significance (-)
13-37000829-G-A			Likely benign (May 02, 2022)
13-37000830-T-C			Likely benign (Dec 12, 2023)
13-37002283-C-T			Uncertain significance (Sep 18, 2023)
13-37002297-CAGG-C			Uncertain significance (Oct 28, 2022)
13-37002324-T-TATAA			Likely benign (Jun 17, 2022)
13-37002329-A-G			Likely benign (Jul 14, 2023)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC8	protein_coding	protein_coding	ENST00000389704	11	10798

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
6.94e-15	0.00443	125656	0	92	125748	0.000366

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.846	115	144	0.801	0.00000703	1778
Missense in Polyphen		22	40.069	0.54905		464
Synonymous	1.81	34	50.3	0.676	0.00000269	524
Loss of Function	-0.660	20	17.1	1.17	8.02e-7	227

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000934	0.000919
Ashkenazi Jewish	0.00	0.00
East Asian	0.000114	0.000109
Finnish	0.00	0.00
European (Non-Finnish)	0.000560	0.000554
Middle Eastern	0.000114	0.000109
South Asian	0.000316	0.000294
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. EXOSC8 binds to ARE-containing RNAs. {ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563}.
• Disease: DISEASE: Pontocerebellar hypoplasia 1C (PCH1C) [MIM:616081]: A severe autosomal recessive neurodegenerative disease characterized by cerebellar and corpus callosum hypoplasia, abnormal myelination of the central nervous system, and spinal motor neuron disease. Affected individuals manifest failure to thrive, severe muscle weakness, spasticity and psychomotor retardation. Vision and hearing are impaired. {ECO:0000269|PubMed:24989451}. Note=The disease is caused by mutations affecting the gene represented in this entry. EXOSC8 dysfunction causes myelin disruption through an imbalanced supply of myelin proteins due to dysregulation of their ARE-containing mRNAs (PubMed:24989451). {ECO:0000269|PubMed:24989451}.
• 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: 0.137

Intolerance Scores

• loftool: 0.831
• rvis_EVS: 0.1
• rvis_percentile_EVS: 61.49

Haploinsufficiency Scores

• pHI: 0.110
• hipred: Y
• hipred_score: 0.721
• ghis: 0.661

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.930

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exosc8
• Phenotype: mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span)

Zebrafish Information Network

• Gene name: exosc8
• Affected structure: motor neuron
• Phenotype tag: abnormal
• Phenotype quality: branchiness

Gene ontology

• Biological process: exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA);rRNA processing;biological_process;rRNA catabolic process;nuclear-transcribed mRNA catabolic process, exonucleolytic, 3'-5';U1 snRNA 3'-end processing;U4 snRNA 3'-end processing;U5 snRNA 3'-end processing;regulation of mRNA stability;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;nuclear mRNA surveillance;nuclear polyadenylation-dependent rRNA catabolic process;nuclear polyadenylation-dependent tRNA catabolic process;nuclear polyadenylation-dependent mRNA catabolic process
• Cellular component: nuclear exosome (RNase complex);cytoplasmic exosome (RNase complex);exosome (RNase complex);nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol
• Molecular function: exoribonuclease activity;protein binding;AU-rich element binding;identical protein binding