EXOSC9

exosome component 9, the group of Exosome complex

Basic information

Region (hg38): 4:121801318-121817021

Previous symbols: [ "PMSCL1" ]

Links

ENSG00000123737 ∙ NCBI:5393 ∙ OMIM:606180 ∙ HGNC:9137 ∙ Uniprot:Q06265 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• pontocerebellar hypoplasia, type 1D (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia, type 1D (Moderate), mode of inheritance: AR
• pontocerebellar hypoplasia type 1 (Supportive), mode of inheritance: AR
• pontocerebellar hypoplasia, type 1D (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Pontocerebellar hypoplasia, type 1D	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; Musculoskeletal; Neurologic	29727687; 30690203

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the EXOSC9 gene.

• not provided (19 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the EXOSC9 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			2	34	3	39
missense		1	107	4	2	114
nonsense	7	1				8
start loss						0
frameshift	12		2			14
inframe indel			3			3
splice donor/acceptor (+/-2bp)		5				5
splice region			4	10	1	15
non coding			5	42	26	73
Total	19	7	119	80	31

Highest pathogenic variant AF is 0.0000657

Variants in EXOSC9

This is a list of pathogenic ClinVar variants found in the EXOSC9 region.

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

Position	Type	Phenotype	Significance	ClinVar
4-121801378-G-A			Benign (May 21, 2021)
4-121801444-C-G			Pathogenic (Mar 01, 2023)
4-121801447-A-C		Inborn genetic diseases	Uncertain significance (Dec 10, 2024)
4-121801451-C-T			Likely benign (Sep 19, 2022)
4-121801460-C-G			Likely benign (Jan 02, 2024)
4-121801462-T-C			Uncertain significance (Jun 08, 2021)
4-121801465-T-C		Pontocerebellar hypoplasia, type 1D • Cerebral atrophy • Pontoneocerebellar hypoplasia	Pathogenic/Likely pathogenic (Nov 22, 2024)
4-121801466-A-G			Likely benign (Sep 08, 2023)
4-121801484-G-C			Uncertain significance (May 30, 2022)
4-121801496-G-A			Uncertain significance (Sep 09, 2021)
4-121801505-C-T			Benign (Jan 13, 2024)
4-121801508-C-A			Likely benign (Jun 02, 2022)
4-121801538-C-G			Benign (May 11, 2021)
4-121801541-A-C			Benign (May 21, 2021)
4-121801823-A-T			Likely benign (Apr 05, 2022)
4-121801849-A-G			Uncertain significance (Sep 01, 2021)
4-121801853-T-G		Inborn genetic diseases	Uncertain significance (Feb 22, 2023)
4-121801862-C-T			Likely benign (Mar 08, 2022)
4-121801881-A-G		Inborn genetic diseases	Uncertain significance (Jul 25, 2024)
4-121801882-C-G			Uncertain significance (Aug 03, 2022)
4-121801887-T-G			Uncertain significance (Aug 20, 2022)
4-121801888-AC-A			Pathogenic (Dec 06, 2023)
4-121801892-A-T			Likely benign (May 14, 2023)
4-121801894-G-C			Uncertain significance (Mar 25, 2022)
4-121801899-A-G			Uncertain significance (Aug 17, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
EXOSC9	protein_coding	protein_coding	ENST00000379663	13	15705

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
1.79e-11	0.375	125600	0	148	125748	0.000589

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.153	234	241	0.972	0.0000119	2987
Missense in Polyphen		47	55.795	0.84236		694
Synonymous	0.167	78	79.9	0.976	0.00000405	854
Loss of Function	1.12	20	26.2	0.764	0.00000142	313

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.00104	0.00102
Ashkenazi Jewish	0.0000997	0.0000992
East Asian	0.000217	0.000217
Finnish	0.00134	0.00134
European (Non-Finnish)	0.000657	0.000651
Middle Eastern	0.000217	0.000217
South Asian	0.000504	0.000490
Other	0.000347	0.000326

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. EXOSC9 binds to ARE-containing RNAs. {ECO:0000269|PubMed:11782436, ECO:0000269|PubMed:16455498, ECO:0000269|PubMed:16912217, ECO:0000269|PubMed:17545563}.
• 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: 0.123

Intolerance Scores

• loftool: 0.978
• rvis_EVS: -0.25
• rvis_percentile_EVS: 35.99

Haploinsufficiency Scores

• pHI: 0.219
• hipred: Y
• hipred_score: 0.533
• ghis: 0.651

Essentials

• essential_gene_CRISPR: E
• essential_gene_CRISPR2: E
• essential_gene_gene_trap: E
• gene_indispensability_pred: E
• gene_indispensability_score: 0.750

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Exosc9
• 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)

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);nuclear-transcribed mRNA catabolic process;rRNA processing;immune response;rRNA catabolic process;positive regulation of cell growth;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;positive regulation of transcription by RNA polymerase II;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);nuclear chromosome;nucleus;nucleoplasm;nucleolus;cytoplasm;cytosol;extracellular exosome
• Molecular function: 3'-5'-exoribonuclease activity;RNA polymerase II activating transcription factor binding;RNA binding;exoribonuclease activity;protein binding;AU-rich element binding