EXOSC3 (exosome component 3)

Gene

• Entrez ID: 51010
• Gene name: Exosome component 3
• Gene symbol: EXOSC3
• Synonyms (NCBI Gene): CGI-102, PCH1B, RRP40, Rrp40p, bA3J10.7, hRrp-40, p10
• Chromosome: 9
• Chromosome location: 9p13.2
• Summary: This gene encodes a non-catalytic component of the human exosome, a complex with 3`-5` exoribonuclease activity that plays a role in numerous RNA processing and degradation activities. Related pseudogenes of this gene are found on chromosome 19 and 21. Al

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs141138948	T>C,G	Pathogenic, pathogenic-likely-pathogenic	Coding sequence variant, missense variant
rs370087266	T>C	Uncertain-significance, pathogenic	Intron variant
rs374550999	C>A,G	Likely-pathogenic	Missense variant, coding sequence variant
rs387907195	C>G	Pathogenic	Missense variant, coding sequence variant
rs387907196	C>G	Pathogenic	Missense variant, coding sequence variant
rs587780333	C>-	Pathogenic	Coding sequence variant, frameshift variant
rs672601331	AGTAAACACC>-	Pathogenic	Coding sequence variant, frameshift variant
rs730882145	C>A,T	Pathogenic	Missense variant, coding sequence variant, intron variant
rs797045567	C>T	Uncertain-significance, likely-pathogenic	Coding sequence variant, missense variant, intron variant
rs886041316	G>-	Pathogenic	Coding sequence variant, frameshift variant
rs1057518124	A>C	Likely-pathogenic	Coding sequence variant, missense variant
rs1160669103	->TTAA	Pathogenic	Coding sequence variant, inframe indel, stop gained, intron variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT973204	hsa-miR-181a	CLIP-seq
MIRT973205	hsa-miR-181b	CLIP-seq
MIRT973206	hsa-miR-181c	CLIP-seq
MIRT973207	hsa-miR-181d	CLIP-seq
MIRT973208	hsa-miR-369-3p	CLIP-seq
MIRT973209	hsa-miR-374c	CLIP-seq
MIRT973210	hsa-miR-4262	CLIP-seq
MIRT973211	hsa-miR-655	CLIP-seq
MIRT973212	hsa-miR-150	CLIP-seq
MIRT973213	hsa-miR-188-3p	CLIP-seq
MIRT973214	hsa-miR-4713-5p	CLIP-seq
MIRT973215	hsa-miR-4719	CLIP-seq
MIRT973216	hsa-miR-4768-5p	CLIP-seq
MIRT973217	hsa-miR-532-3p	CLIP-seq
MIRT973218	hsa-miR-628-5p	CLIP-seq
MIRT973219	hsa-miR-944	CLIP-seq
MIRT1988353	hsa-miR-1275	CLIP-seq
MIRT1988354	hsa-miR-3182	CLIP-seq
MIRT1988355	hsa-miR-4303	CLIP-seq
MIRT1988356	hsa-miR-4525	CLIP-seq
MIRT1988357	hsa-miR-4665-5p	CLIP-seq
MIRT1988358	hsa-miR-4682	CLIP-seq
MIRT1988359	hsa-miR-4694-3p	CLIP-seq
MIRT1988360	hsa-miR-4723-5p	CLIP-seq
MIRT1988361	hsa-miR-496	CLIP-seq
MIRT1988362	hsa-miR-522	CLIP-seq
MIRT1988363	hsa-miR-625	CLIP-seq
MIRT2222815	hsa-miR-1228	CLIP-seq
MIRT973204	hsa-miR-181a	CLIP-seq
MIRT973205	hsa-miR-181b	CLIP-seq
MIRT973206	hsa-miR-181c	CLIP-seq
MIRT973207	hsa-miR-181d	CLIP-seq
MIRT2222816	hsa-miR-3163	CLIP-seq
MIRT2222817	hsa-miR-340	CLIP-seq
MIRT2222818	hsa-miR-3607-3p	CLIP-seq
MIRT2222819	hsa-miR-3661	CLIP-seq
MIRT973208	hsa-miR-369-3p	CLIP-seq
MIRT973209	hsa-miR-374c	CLIP-seq
MIRT2222820	hsa-miR-377	CLIP-seq
MIRT973210	hsa-miR-4262	CLIP-seq
MIRT2222821	hsa-miR-548aa	CLIP-seq
MIRT2222822	hsa-miR-548c-3p	CLIP-seq
MIRT2222823	hsa-miR-631	CLIP-seq
MIRT973211	hsa-miR-655	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0000175	Function	3'-5'-RNA exonuclease activity	NAS	11110791
GO:0000176	Component	Nuclear exosome (RNase complex)	IBA
GO:0000176	Component	Nuclear exosome (RNase complex)	IDA	11110791
GO:0000176	Component	Nuclear exosome (RNase complex)	NAS	20531386
GO:0000177	Component	Cytoplasmic exosome (RNase complex)	IBA
GO:0000177	Component	Cytoplasmic exosome (RNase complex)	IDA	11110791
GO:0000177	Component	Cytoplasmic exosome (RNase complex)	NAS	20531386
GO:0000178	Component	Exosome (RNase complex)	IDA	20531389
GO:0000178	Component	Exosome (RNase complex)	IEA
GO:0000178	Component	Exosome (RNase complex)	NAS	20531386
GO:0000467	Process	Exonucleolytic trimming to generate mature 3'-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	IBA
GO:0000791	Component	Euchromatin	IMP	20699273
GO:0000956	Process	Nuclear-transcribed mRNA catabolic process	IBA
GO:0003723	Function	RNA binding	IBA
GO:0003723	Function	RNA binding	IEA
GO:0004532	Function	RNA exonuclease activity	IDA	17174896
GO:0005515	Function	Protein binding	IPI	11719186, 12419256, 14731398, 15231747, 16396833, 17185417, 17545563, 18334637, 20531386, 20531389, 21255825, 21876179, 23756462, 24981860, 26496610, 28514442, 32296183, 33961781
GO:0005634	Component	Nucleus	IDA	17545563, 20531386
GO:0005634	Component	Nucleus	IEA
GO:0005654	Component	Nucleoplasm	IDA
GO:0005654	Component	Nucleoplasm	TAS
GO:0005730	Component	Nucleolus	IDA	20531386, 20531389
GO:0005730	Component	Nucleolus	IEA
GO:0005737	Component	Cytoplasm	IDA	17545563
GO:0005737	Component	Cytoplasm	IEA
GO:0005829	Component	Cytosol	IDA	20531386
GO:0005829	Component	Cytosol	TAS
GO:0006259	Process	DNA metabolic process	IEA
GO:0006364	Process	RRNA processing	IDA	11110791
GO:0006364	Process	RRNA processing	IEA
GO:0006396	Process	RNA processing	IDA	17174896, 20531386
GO:0006401	Process	RNA catabolic process	IDA	17174896, 20531386
GO:0006402	Process	MRNA catabolic process	IMP	11782436
GO:0010467	Process	Gene expression	IEA
GO:0010468	Process	Regulation of gene expression	IEA
GO:0034475	Process	U4 snRNA 3'-end processing	IBA
GO:0045006	Process	DNA deamination	IDA	21255825
GO:0045190	Process	Isotype switching	IEA
GO:0045190	Process	Isotype switching	ISS
GO:0045830	Process	Positive regulation of isotype switching	IEA
GO:0071034	Process	CUT catabolic process	IBA
GO:0071034	Process	CUT catabolic process	IMP	19056938
GO:0071035	Process	Nuclear polyadenylation-dependent rRNA catabolic process	IBA
GO:0071038	Process	TRAMP-dependent tRNA surveillance pathway	IBA
GO:0071051	Process	Poly(A)-dependent snoRNA 3'-end processing	IBA
GO:0101019	Component	Nucleolar exosome (RNase complex)	NAS	20531386

Other IDs

• MIM: 606489
• HGNC: 17944
• e!Ensembl: ENSG00000107371

Protein

• UniProt ID: Q9NQT5
• Protein name: Exosome complex component RRP40 (Exosome component 3) (Ribosomal RNA-processing protein 40) (p10)
• Protein 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 maturat
• PDB: 2NN6, 6D6Q, 6D6R, 6H25, 9G8M, 9G8N, 9G8O, 9G8P
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF15985	KH_6	197 → 245	KH domain	Domain

• Sequence:

  MAEPASVAAESLAGSRARAARTVLGQVVLPGEELLLPEQEDAEGPGGAVERPLSLNARAC
  SRVRVVCGPGLRRCGDRLLVTKCGRLRHKEPGSGSGGGVYWVDSQQKRYVPVKGDHVIGI
  VTAKSGDIFKVDVGGSEPASLSYLSFEGATKRNRPNVQVGDLIYGQFVVANKDMEPEMVC
  IDSCGRANGMGVIGQDGLLFKVTLGLIRKLLAPDCEIIQEVGKLYPLEIVFGMNGRIWVK
  AKTIQQTLILANILEACEHMTSDQRKQIFSRLAES

• Sequence length: 275

Pathways

KEGG:

RNA degradation

Reactome:

ATF4 activates genes in response to endoplasmic reticulum stress
mRNA decay by 3' to 5' exoribonuclease
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
KSRP (KHSRP) binds and destabilizes mRNA
Major pathway of rRNA processing in the nucleolus and cytosol

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Causal
Phenotype Name	Clinical Significance	dbSNP ID	RCV Accession	Evidence Score
Abnormality of the nervous system	Pathogenic	rs141138948	RCV001836713	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital myopathy	Likely pathogenic; Pathogenic	rs387907196	RCV004586024	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Congenital pontocerebellar hypoplasia type 1	Pathogenic	rs141138948	RCV005364888	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
EXOSC3-related disorder	Pathogenic	rs141138948	RCV004757111	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Hypotonia	Pathogenic	rs141138948	RCV000761614	★★★★☆ ClinVar: Pathogenic / Likely Pathogenic (<5 Variants)
Pontocerebellar hypoplasia type 1B	Pathogenic; Likely pathogenic	rs2118980242, rs1198691735, rs1296865764, rs769374744, rs587780333, rs374550999, rs2118980158, rs2118977758, rs149049356, rs730882145, rs1325914775, rs114878910, rs1395561739, rs2489890955, rs797045567, rs1258608435, rs886041316, rs2489883308, rs2489888242, rs944335096, rs773436764, rs2489891748, rs2489888636, rs2489891724, rs758899003, rs777100034, rs2489890979, rs1398939540, rs141138948, rs672601331, rs387907196, rs672601332, rs1160669103	RCV001783217 RCV003827688 RCV001781059 RCV004720318 RCV000117004 RCV000117005 RCV002032143 RCV002211035 RCV003102289 RCV000161917 RCV002470377 RCV003072623 RCV003530273 RCV002801869 RCV000625808 RCV003225691 RCV000499694 RCV003530937 RCV003531289 RCV003529833 RCV003529892 RCV003646413 RCV003646533 RCV003646646 RCV003646743 RCV003646792 RCV003647073 RCV003647130 RCV003867910 RCV003876594 RCV000024366 RCV000024368 RCV000024369 RCV000024370 RCV002499349 RCV003770230	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Pontoneocerebellar hypoplasia	Likely pathogenic; Pathogenic	rs769374744, rs374550999, rs149049356, rs1395561739, rs886041316, rs1427979807, rs1325914775	RCV001797933 RCV000825519 RCV002308518 RCV002510386 RCV002509341 RCV004018282 RCV003331076	★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
CONGENITAL NEUROLOGIC ANOMALIES	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
LISSENCEPHALY	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PENA-SHOKEIR SYNDROME TYPE I	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA TYPE 1	—	CTD, Orphanet CTD, Orphanet CTD, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1A	—	Disgenet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	—	CTD, Disgenet, HPO CTD, Disgenet, HPO CTD, Disgenet, HPO	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Atypical Hemolytic Uremic Syndrome	Hemolytic uremic syndrome	Pubtator	35522339	Associate	★☆☆☆☆ Found in Text Mining only
CATARACT, MARNER TYPE	Cataract	BEFREE	30319361		★☆☆☆☆ Found in Text Mining only
Central nervous system demyelination	Central Nervous System Demyelination	BEFREE	27193168		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	BEFREE	23975261		★☆☆☆☆ Found in Text Mining only
Cerebellar atrophy	Cerebellar atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Cerebellar Hypoplasia	Cerebellar Hypoplasia	BEFREE	23564332, 31770597		★☆☆☆☆ Found in Text Mining only
Cerebral atrophy	Cerebral Atrophy	HPO_DG			★☆☆☆☆ Found in Text Mining only
Chronic kidney disease stage 5	Kidney Disease	BEFREE	30320415, 30499177		★☆☆☆☆ Found in Text Mining only
Chronic Kidney Diseases	Kidney Disease	BEFREE	30499177		★☆☆☆☆ Found in Text Mining only
Colitis	Colitis	BEFREE	27955827		★☆☆☆☆ Found in Text Mining only
Colorectal Neoplasms	Colorectal neoplasm	Pubtator	34626022	Associate	★☆☆☆☆ Found in Text Mining only
Complicated hereditary spastic paraplegia	Spastic paraplegia	BEFREE	25149867		★☆☆☆☆ Found in Text Mining only
Congenital pontocerebellar hypoplasia	Pontoneocerebellar hypoplasia	BEFREE	22544365, 23564332, 24524299, 27193168, 28053271, 28687512, 28877463, 30025162		★☆☆☆☆ Found in Text Mining only
Congenital pontocerebellar hypoplasia	Pontoneocerebellar hypoplasia	GENOMICS_ENGLAND_DG	23564332, 24524299		★☆☆☆☆ Found in Text Mining only
Contracture	Contracture	Pubtator	23284067	Associate	★☆☆☆☆ Found in Text Mining only
Degenerative polyarthritis	Arthritis	BEFREE	31545916		★☆☆☆☆ Found in Text Mining only
Depression Postpartum	Major depressive disorder	Pubtator	23284067	Associate	★☆☆☆☆ Found in Text Mining only
Epilepsy	Epilepsy	BEFREE	22589250		★☆☆☆☆ Found in Text Mining only
Fatty Liver Disease	Fatty Liver	BEFREE	31585800		★☆☆☆☆ Found in Text Mining only
Glioblastoma	Glioblastoma	BEFREE	11563632, 27436023, 27678152		★☆☆☆☆ Found in Text Mining only
Glioblastoma Multiforme	Glioblastoma	BEFREE	11563632, 27436023, 27678152		★☆☆☆☆ Found in Text Mining only
Global developmental delay	Developmental Delay	HPO_DG			★☆☆☆☆ Found in Text Mining only
Glomerulonephritis	Glomerulonephritis	BEFREE	12970356		★☆☆☆☆ Found in Text Mining only
Hypersomnia	Hypersomnia	BEFREE	29684437		★☆☆☆☆ Found in Text Mining only
Kidney Failure Chronic	Kidney failure	Pubtator	30499177	Associate	★☆☆☆☆ Found in Text Mining only
Kidney Failure, Chronic	Kidney Failure	BEFREE	30320415, 30499177		★☆☆☆☆ Found in Text Mining only
Leukemia, Myelocytic, Acute	Leukemia	BEFREE	29725008		★☆☆☆☆ Found in Text Mining only
Lissencephaly	Lissencephaly	CLINVAR_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Liver Failure, Acute	Liver failure	BEFREE	30538751		★☆☆☆☆ Found in Text Mining only
Lung Neoplasms	Lung neoplasms	Pubtator	39176091	Associate	★☆☆☆☆ Found in Text Mining only
Lupus Erythematosus, Systemic	Lupus Erythematosus	BEFREE	28987592		★☆☆☆☆ Found in Text Mining only
Malabsorption Syndrome	Malabsorption Syndrome	BEFREE	29321312		★☆☆☆☆ Found in Text Mining only
Meningioma	Meningioma	BEFREE	11859969		★☆☆☆☆ Found in Text Mining only
Microcephaly	Microcephaly	BEFREE	22544365		★☆☆☆☆ Found in Text Mining only
Motor neuron atrophy	Motor neuron atrophy	BEFREE	22544365, 28053271		★☆☆☆☆ Found in Text Mining only
Motor Neuron Disease	Motor Neuron Disease	BEFREE	22544365		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	11859969		★☆☆☆☆ Found in Text Mining only
nervous system disorder	Nervous System Disorder	BEFREE	30141626, 30986545		★☆☆☆☆ Found in Text Mining only
Neurodevelopmental Disorders	Neurodevelopmental Disorders	BEFREE	30986545		★☆☆☆☆ Found in Text Mining only
Nystagmus	Nystagmus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculomotor apraxia	Oculomotor apraxia	HPO_DG			★☆☆☆☆ Found in Text Mining only
Oculovestibuloauditory syndrome	Oculovestibuloauditory Syndrome	HPO_DG			★☆☆☆☆ Found in Text Mining only
Pontocerebellar Hypoplasia	Pontocerebellar hypoplasia	Pubtator	24524299, 28053271, 34089229	Associate	★☆☆☆☆ Found in Text Mining only
Pontocerebellar Hypoplasia Type 1	Pontoneocerebellar hypoplasia	BEFREE	22544365, 23284067, 23564332, 23883322, 23975261, 24524299, 25149867, 29656927		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontocerebellar Hypoplasia Type 1	Pontoneocerebellar hypoplasia	CTD_human_DG	22544365		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontocerebellar Hypoplasia Type 1	Pontoneocerebellar hypoplasia	ORPHANET_DG	22544365		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontocerebellar hypoplasia type 1	Pontoneocerebellar hypoplasia	Orphanet			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontocerebellar Hypoplasia Type 1	Pontocerebellar hypoplasia	Pubtator	23284067	Associate	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontocerebellar Hypoplasia Type 1	Pontoneocerebellar hypoplasia	GENOMICS_ENGLAND_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	Pontoneocerebellar hypoplasia	CLINVAR_DG	22544365, 23564332, 23975261, 24524299, 25809939, 29656927		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	Pontoneocerebellar hypoplasia	GENOMICS_ENGLAND_DG	22544365, 23284067, 23564332, 24524299		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	Pontoneocerebellar hypoplasia	UNIPROT_DG	22544365		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	Pontoneocerebellar hypoplasia	BEFREE	27777260, 28687512, 30141626, 31768969, 31770597		★★☆☆☆ Found in Text Mining + Unknown/Other Associations
PONTOCEREBELLAR HYPOPLASIA, TYPE 1B	Pontoneocerebellar hypoplasia	CTD_human_DG			★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Pontoneocerebellar hypoplasia	Pontoneocerebellar hypoplasia	BEFREE	22544365, 23564332, 24524299, 27193168, 28053271, 28687512, 28877463, 30025162		★★★★★ ClinVar: Pathogenic / Likely Pathogenic (≥5 Variants)
Primary central nervous system lymphoma	Central Nervous System Lymphoma	BEFREE	27436023		★☆☆☆☆ Found in Text Mining only
Profound global developmental delay	Developmental Delay	BEFREE	22544365		★☆☆☆☆ Found in Text Mining only
Psychomotor Disorders	Psychiatric disorders	Pubtator	23284067	Associate	★☆☆☆☆ Found in Text Mining only
Respiration Disorders	Respiration Disorders	BEFREE	29321312		★☆☆☆☆ Found in Text Mining only
Spinal Muscular Atrophy	Spinal Muscular Atrophy	BEFREE	29440993, 29656927, 31770597		★☆☆☆☆ Found in Text Mining only
Strabismus	Strabismus	HPO_DG			★☆☆☆☆ Found in Text Mining only
Varicosity	Vulval varices	BEFREE	28638718		★☆☆☆☆ Found in Text Mining only