EXOSC1

exosome component 1, the group of Exosome complex

Basic information

Region (hg38): 10:97435909-97446017

Links

ENSG00000171311

∙ NCBI:51013 ∙ OMIM:606493 ∙ HGNC:17286 ∙ Uniprot:Q9Y3B2 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

pontocerebellar hypoplasia, type 1F (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 1F	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	Craniofacial; Neurologic; Ophthalmologic	33463720

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC1 gene.

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC1 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						0
missense			7 clinvar			7
nonsense						0
start loss						0
frameshift						0
inframe indel						0
splice donor/acceptor (+/-2bp)						0
splice region						0
non coding						0
Total	0	0	7	0	0

Variants in EXOSC1

This is a list of pathogenic ClinVar variants found in the EXOSC1 region.

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

Position	Phenotype	Significance	ClinVar
10-97436485-C-T	not specified	Uncertain significance (May 09, 2023)	2545790
10-97437202-T-G	not specified	Uncertain significance (Aug 28, 2023)	2591977
10-97437734-C-T	not specified	Uncertain significance (Dec 06, 2022)	2227281
10-97437740-T-C	not specified	Uncertain significance (Jun 02, 2023)	2556308
10-97441172-G-A	not specified	Uncertain significance (May 05, 2023)	2511040
10-97441201-G-A	not specified	Uncertain significance (Jan 27, 2022)	2381681
10-97445775-G-A	Pontocerebellar hypoplasia, type 1F	Pathogenic (May 06, 2021)	1068761
10-97445970-T-C	not specified	Uncertain significance (Oct 26, 2022)	2362532

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC1	protein_coding	protein_coding	ENST00000370902	8	9876

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
7.35e-9	0.150	125677	0	71	125748	0.000282

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.290	108	117	0.925	0.00000615	1254
Missense in Polyphen		40	45.234	0.88429		470
Synonymous	0.494	38	42.1	0.903	0.00000221	372
Loss of Function	0.217	13	13.9	0.937	7.38e-7	152

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000803	0.000803
Ashkenazi Jewish	0.00198	0.00199
East Asian	0.000163	0.000163
Finnish	0.0000462	0.0000462
European (Non-Finnish)	0.000114	0.000114
Middle Eastern	0.000163	0.000163
South Asian	0.000315	0.000294
Other	0.000163	0.000163

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. EXOSC1 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC6 and EXOSC8.;
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: 0.156

Intolerance Scores

loftool: 0.424
rvis_EVS: -0.36
rvis_percentile_EVS: 28.63

Haploinsufficiency Scores

pHI: 0.162
hipred: Y
hipred_score: 0.614
ghis: 0.693

Essentials

essential_gene_CRISPR: E
essential_gene_CRISPR2: E
essential_gene_gene_trap: E
gene_indispensability_pred: E
gene_indispensability_score: 0.973

Gene Damage Prediction

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

Mouse Genome Informatics

Gene name: Exosc1
Phenotype

Gene ontology

Biological process: rRNA processing;regulation of mRNA stability;exonucleolytic nuclear-transcribed mRNA catabolic process involved in deadenylation-dependent decay;RNA phosphodiester bond hydrolysis, exonucleolytic
Cellular component: nuclear exosome (RNase complex);exosome (RNase complex);nucleoplasm;nucleolus;cytoplasm;cytosol
Molecular function: RNA binding;exoribonuclease activity;protein binding