EXOSC3

exosome component 3, the group of Exosome complex

Basic information

Region (hg38): 9:37759233-37832117

Links

ENSG00000107371 ∙ NCBI:51010 ∙ OMIM:606489 ∙ HGNC:17944 ∙ Uniprot:Q9NQT5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia type 1A (Definitive), mode of inheritance: AR
• pontocerebellar hypoplasia type 1B (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1B (Strong), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia type 1B (Definitive), mode of inheritance: AR
• pontocerebellar hypoplasia type 1B (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia type 1B	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	Neurologic	11020648; 12731647; 22544365; 24524299; 25149867

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC3 gene.

• Pontocerebellar hypoplasia type 1B (144 variants)
• Inborn genetic diseases (39 variants)
• not provided (37 variants)
• not specified (18 variants)
• Pontoneocerebellar hypoplasia (7 variants)
• Abnormality of the nervous system (1 variants)
• Hypotonia (1 variants)
• 7 conditions (1 variants)
• See cases (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC3 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				37	2	39
missense	1	7	57	2	1	68
nonsense	2	2				4
start loss	1	2				3
frameshift	8	2	2			12
inframe indel			3			3
splice donor/acceptor (+/-2bp)		1				1
splice region			1	3		4
non coding			33	13	9	55
Total	12	14	95	52	12

Highest pathogenic variant AF is 0.000480

Variants in EXOSC3

This is a list of pathogenic ClinVar variants found in the EXOSC3 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-37761968-G-A		not specified	Uncertain significance (Apr 04, 2023)
9-37761975-C-T		not specified	Uncertain significance (May 23, 2023)
9-37762069-G-C		not specified	Uncertain significance (Aug 30, 2021)
9-37762586-C-G		not specified	Uncertain significance (Jul 05, 2022)
9-37762614-T-C		not specified	Uncertain significance (Feb 15, 2023)
9-37762634-A-G		not specified	Uncertain significance (Jun 22, 2021)
9-37762667-A-C		not specified	Uncertain significance (Aug 17, 2021)
9-37763635-G-A		not specified	Uncertain significance (May 16, 2023)
9-37763715-T-C		not specified	Uncertain significance (Feb 27, 2023)
9-37769942-T-C		not specified	Uncertain significance (Apr 26, 2023)
9-37769999-T-C		not specified	Uncertain significance (May 09, 2022)
9-37770710-G-A		not specified	Uncertain significance (Aug 22, 2023)
9-37770723-A-T		not specified	Uncertain significance (Feb 22, 2023)
9-37770724-T-G		not specified	Uncertain significance (Feb 22, 2023)
9-37776373-A-C		not specified	Uncertain significance (Nov 14, 2023)
9-37777616-C-G		not specified	Uncertain significance (Jan 23, 2024)
9-37777622-A-T			Likely benign (Jan 01, 2023)
9-37777623-C-A			Likely benign (Jan 01, 2023)
9-37777666-T-C		not specified	Uncertain significance (Jan 10, 2022)
9-37777687-C-T		not specified	Uncertain significance (Nov 03, 2023)
9-37777691-G-A		not specified	Likely benign (Feb 06, 2023)
9-37779725-C-T		Pontocerebellar hypoplasia type 1B	Uncertain significance (Jan 13, 2018)
9-37779798-T-C		Pontocerebellar hypoplasia type 1B	Likely benign (Jan 13, 2018)
9-37779832-A-T		Pontocerebellar hypoplasia type 1B	Uncertain significance (Jan 13, 2018)
9-37779867-A-C		Pontocerebellar hypoplasia type 1B	Uncertain significance (Jan 13, 2018)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC3	protein_coding	protein_coding	ENST00000327304	4	34460

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.000243	0.777	125695	0	53	125748	0.000211

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.224	162	154	1.05	0.00000685	1745
Missense in Polyphen		59	56.303	1.0479		681
Synonymous	-2.84	87	59.2	1.47	0.00000273	575
Loss of Function	1.08	7	10.8	0.646	5.54e-7	131

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000710	0.000681
Ashkenazi Jewish	0.00	0.00
East Asian	0.000928	0.000925
Finnish	0.00	0.00
European (Non-Finnish)	0.000112	0.000105
Middle Eastern	0.000928	0.000925
South Asian	0.000132	0.000131
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. EXOSC3 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC9 and EXOSC5. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:17545563, ECO:0000269|PubMed:19056938, ECO:0000269|PubMed:21255825}.
• Disease: DISEASE: Pontocerebellar hypoplasia 1B (PCH1B) [MIM:614678]: A severe autosomal recessive neurologic disorder characterized by a combination of cerebellar and spinal motor neuron degeneration beginning at birth. There is diffuse muscle weakness, progressive microcephaly, global developmental delay, and brainstem involvement. {ECO:0000269|PubMed:22544365}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• 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: 0.320
• rvis_EVS: 0.62
• rvis_percentile_EVS: 83.25

Haploinsufficiency Scores

• pHI: 0.0805
• hipred: Y
• hipred_score: 0.748
• ghis: 0.575

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.924

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exosc3
• 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); normal phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: exosc3
• 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;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;isotype switching;positive regulation of isotype switching;CUT catabolic process;nuclear polyadenylation-dependent rRNA catabolic process;nuclear polyadenylation-dependent tRNA catabolic process;nuclear retention of pre-mRNA with aberrant 3'-ends at the site of transcription;polyadenylation-dependent snoRNA 3'-end processing
• 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