EXOSC2

exosome component 2, the group of Exosome complex

Basic information

Region (hg38): 9:130693720-130707288

Links

ENSG00000130713 ∙ NCBI:23404 ∙ OMIM:602238 ∙ HGNC:17097 ∙ Uniprot:Q13868 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (Strong), mode of inheritance: AR
• retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (Supportive), mode of inheritance: AR
• retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (Limited), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Short stature, hearing loss, retinitis pigmentosa, and distinctive facies	AR	Audiologic/Otolaryngologic	Early recognition and treatment of hearing impairment may improve outcomes, including speech and language development	Audiologic/Otolaryngologic; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic	26843489

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC2 gene.

• not provided (231 variants)
• Inborn genetic diseases (10 variants)
• Retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (5 variants)
• not specified (1 variants)
• Neurodevelopmental delay (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC2 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				47	3	50
missense			96	1	2	99
nonsense		1	4			5
start loss						0
frameshift			8			8
inframe indel			1			1
splice donor/acceptor (+/-2bp)			6			6
splice region			10	7	2	19
non coding				42	5	47
Total	0	1	115	90	10

Variants in EXOSC2

This is a list of pathogenic ClinVar variants found in the EXOSC2 region.

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

Position	Type	Phenotype	Significance	ClinVar
9-130693797-G-A			Likely benign (Dec 22, 2022)
9-130693801-G-C			Uncertain significance (Aug 12, 2022)
9-130693804-A-C			Uncertain significance (Jul 05, 2022)
9-130693804-A-G			Uncertain significance (Jan 28, 2022)
9-130693807-A-C			Likely benign (Jul 20, 2018)
9-130693810-C-A			Uncertain significance (Oct 03, 2023)
9-130693812-T-A			Likely benign (Oct 19, 2023)
9-130693812-T-C			Likely benign (Aug 06, 2022)
9-130693812-TC-T			Uncertain significance (Jul 03, 2022)
9-130693813-C-G			Benign (Jan 29, 2024)
9-130693813-C-T			Uncertain significance (Feb 20, 2022)
9-130693814-C-T			Uncertain significance (Jun 03, 2022)
9-130693815-A-G			Likely benign (Jul 30, 2022)
9-130693820-C-T			Uncertain significance (Oct 16, 2023)
9-130693822-C-A			Uncertain significance (Oct 05, 2022)
9-130693822-C-T			Uncertain significance (Dec 21, 2021)
9-130693825-A-G		not specified	Uncertain significance (Dec 02, 2022)
9-130693827-G-A			Likely benign (Dec 30, 2023)
9-130693828-C-T			Uncertain significance (May 31, 2022)
9-130693833-T-G			Likely benign (May 23, 2023)
9-130693849-C-A			Uncertain significance (Jun 13, 2022)
9-130693851-C-A			Likely benign (Jul 10, 2023)
9-130693854-C-T			Likely benign (Nov 20, 2023)
9-130693855-A-C			Uncertain significance (Jul 01, 2022)
9-130693855-A-G			Uncertain significance (Jun 13, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC2	protein_coding	protein_coding	ENST00000372358	9	11141

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.00000289	0.781	125665	0	83	125748	0.000330

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.390	153	167	0.915	0.00000866	1893
Missense in Polyphen		33	51.475	0.64109		524
Synonymous	0.602	57	63.1	0.904	0.00000348	578
Loss of Function	1.28	11	16.6	0.662	8.65e-7	196

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000605	0.000605
Ashkenazi Jewish	0.0000992	0.0000992
East Asian	0.000435	0.000435
Finnish	0.0000927	0.0000924
European (Non-Finnish)	0.000494	0.000492
Middle Eastern	0.000435	0.000435
South Asian	0.0000655	0.0000653
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. EXOSC2 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC4 and EXOSC7. {ECO:0000269|PubMed:17545563}.
• Disease: DISEASE: Short stature, hearing loss, retinitis pigmentosa, and distinctive facies (SHRF) [MIM:617763]: An autosomal recessive disorder characterized by childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. {ECO:0000269|PubMed:26843489}. 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: 0.116

Intolerance Scores

• loftool: 0.391
• rvis_EVS: -0.23
• rvis_percentile_EVS: 37.32

Haploinsufficiency Scores

• pHI: 0.733
• hipred: Y
• hipred_score: 0.676
• ghis: 0.660

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.997

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exosc2

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;positive regulation of cell growth;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;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
• Molecular function: 3'-5'-exoribonuclease activity;RNA binding;exoribonuclease activity;protein binding;7S RNA binding