EXOSC10

Summary

EXOSC10 (exosome component 10, HGNC:9138) is a protein-coding gene on chromosome 1p36.22, encoding Exosome complex component 10 (Q01780). 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. It is a selective cancer dependency (DepMap: 78.8% of cell lines).

Enables 3’-5’-RNA exonuclease activity and telomerase RNA binding activity. Involved in several processes, including RNA metabolic process; negative regulation of telomere maintenance via telomerase; and regulation of telomerase RNA localization to Cajal body. Located in cytosol; euchromatin; and nuclear lumen. Part of nuclear exosome (RNase complex) and small-subunit processome.

Source: NCBI Gene 5394 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 156 total
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 78.8% of screened cell lines
• MANE Select transcript: NM_001001998

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9138
Approved symbol	EXOSC10
Name	exosome component 10
Location	1p36.22
Locus type	gene with protein product
Status	Approved
Aliases	PM-Scl, PM/Scl-100, Rrp6p, RRP6, p2, p3, p4
Ensembl gene	ENSG00000171824
Ensembl biotype	protein_coding
OMIM	605960
Entrez	5394

Gene structure

Transcript identifiers

Ensembl transcripts: 25 — 16 protein_coding, 6 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000304457, ENST00000376936, ENST00000460196, ENST00000469634, ENST00000470611, ENST00000472078, ENST00000474216, ENST00000478271, ENST00000485606, ENST00000490565, ENST00000498576, ENST00000869358, ENST00000869359, ENST00000869360, ENST00000921093, ENST00000921094, ENST00000921095, ENST00000921096, ENST00000921097, ENST00000921098, ENST00000921099, ENST00000971056, ENST00000971057, ENST00000971058, ENST00000971059

RefSeq mRNA: 2 — MANE Select: NM_001001998 NM_001001998, NM_002685

CCDS: CCDS126, CCDS30584

Canonical transcript exons

ENST00000376936 — 25 exons

Exon	Start	End
ENSE00001168203	11077365	11077443
ENSE00001168225	11080499	11080549
ENSE00001168251	11082688	11082878
ENSE00001168258	11087448	11087591
ENSE00001168264	11087800	11087910
ENSE00001168272	11088123	11088198
ENSE00001168279	11090554	11090668
ENSE00001168288	11091014	11091179
ENSE00001168299	11091493	11091597
ENSE00001837770	11099721	11099869
ENSE00001918071	11066618	11066748
ENSE00002747043	11098020	11098156
ENSE00002876920	11095758	11095881
ENSE00003461728	11074231	11074326
ENSE00003466087	11077601	11077651
ENSE00003477758	11068645	11068706
ENSE00003494373	11069559	11069730
ENSE00003518198	11080764	11080912
ENSE00003533108	11072087	11072171
ENSE00003549262	11070900	11070973
ENSE00003622861	11068008	11068084
ENSE00003673100	11073934	11074008
ENSE00003675727	11076842	11076948
ENSE00003677408	11081082	11081238
ENSE00003692448	11079711	11079822

Expression profiles

Bgee: expression breadth ubiquitous, 295 present calls, max score 98.03.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 34.3436 / max 340.1525, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
10290	34.3228	1816
10288	0.0208	6

Top tissues by expression

301 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
cerebellar hemisphere	UBERON:0002245	98.03	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.99	gold quality
cerebellar cortex	UBERON:0002129	97.94	gold quality
tibial nerve	UBERON:0001323	97.74	gold quality
sural nerve	UBERON:0015488	97.57	gold quality
cerebellum	UBERON:0002037	96.73	gold quality
calcaneal tendon	UBERON:0003701	96.66	gold quality
right ovary	UBERON:0002118	96.44	gold quality
left ovary	UBERON:0002119	96.44	gold quality
body of uterus	UBERON:0009853	96.12	gold quality
endocervix	UBERON:0000458	96.01	gold quality
right uterine tube	UBERON:0001302	95.94	gold quality
mucosa of stomach	UBERON:0001199	95.93	gold quality
adenohypophysis	UBERON:0002196	95.86	gold quality
skin of leg	UBERON:0001511	95.70	gold quality
skin of abdomen	UBERON:0001416	95.52	gold quality
ectocervix	UBERON:0012249	95.39	gold quality
right frontal lobe	UBERON:0002810	95.35	gold quality
pituitary gland	UBERON:0000007	95.27	gold quality
left uterine tube	UBERON:0001303	95.24	gold quality
tendon	UBERON:0000043	95.19	gold quality
metanephros cortex	UBERON:0010533	95.07	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	94.96	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.66	gold quality
popliteal artery	UBERON:0002250	94.65	gold quality
tibial artery	UBERON:0007610	94.65	gold quality
descending thoracic aorta	UBERON:0002345	94.59	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.57	gold quality
left lobe of thyroid gland	UBERON:0001120	94.46	gold quality
aorta	UBERON:0000947	94.45	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-100618	no	558.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

11 targeting EXOSC10, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-590-3P	99.96	74.34	6478
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-12129	99.72	67.45	1311
HSA-MIR-297	99.40	69.58	1418
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-10522-5P	99.26	68.50	2087
HSA-MIR-873-5P	98.84	66.90	1348
HSA-MIR-299-5P	98.56	71.14	1140
HSA-MIR-338-3P	98.14	67.38	1137
HSA-MIR-1226-3P	97.51	66.32	1063

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 78.8% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 22)

• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. (PMID:12419256)
• cloning of a more complete cDNA for PM/Scl-75 encoded 84 additional amino acids at its N terminus and only this longer polypeptide is able to associate with the exosome complex. (PMID:12788944)
• PM-Scl-75 is the main autoantigen in patients with the polymyositis/scleroderma overlap syndrome. (PMID:14872500)
• Although not required for exosome stability, PM/Scl-100 and PM/Scl-75 are involved in mRNA degradation. (PMID:17545563)
• autoantibodies specific to this antigen also are found in systemic sclerosis (PMID:19103309)
• Anti-PM/Scl antibodies are common in distinct SSc subsets and are associated with several clinical symptoms (PMID:19220911)
• Saccharomyces cerevisiae Rrp6, and determined the X-ray structure of a human construct containing the exoribonuclease and HRDC domains that retains catalytic activity (PMID:21705430)
• Systemic sclerosis patients with anti-PM-Scl antibody are younger and significantly more often have limited cutaneous involvement, skeletal muscle disease, pulmonary fibrosis and calcinosis. (PMID:22261302)
• Microprocessor orchestrates the recruitment of termination factors Setx and Xrn2, and the 3’-5’ exoribonuclease, Rrp6, to initiate RNAPII pausing and premature termination at the HIV-1 promoter through cleavage of the stem-loop RNA, TAR. (PMID:22980978)
• Rrp6: Integrated roles in nuclear RNA metabolism and transcription termination (PMID:26612606)
• Results show that DGCR8 forms an alternative complex with the RRP6-containing form of the exosome, acts as an adaptor to recruit the exosome to target structured RNAs, and the DGCR8/hRRP6 complex controls the stability of human telomerase RNA. (PMID:26687677)
• EXOSC10 can be modified by SUMOylation and identifies a physiological stress where this regulation is prevalent both in vitro and in vivo. (PMID:26857222)
• Processing of 3’ telomerase RNA occurs in two steps with longer forms first being trimmed by RRP6 and shorter forms then being processed by PARN. (PMID:30575725)
• Authors engineered cells in which the 3’–>5’ exoribonucleases of the exosome complex, DIS3 and EXOSC10, can be rapidly eliminated to assess their immediate roles in nuclear RNA biology. These transcripts are unaffected by the rapid loss of EXOSC10, suggesting that they are rarely targeted to it. (PMID:30840897)
• Study shows that the catalytic activity of the exosome subunit EXOSC10 contributes to the homologous recombination (HR) pathway by degrading damage-induced lncRNAs and maintaining RNA homeostasis at double-strand breaks (DSBs). Results identify RNA clearance at DSBs as a step in the HR pathway that is required for the assembly of RPA onto the resected ssDNA, which in turn is a prerequisite for controlled DNA resection. (PMID:31086179)
• Exploration of Salmonella effector mutant strains on MTR4 and RRP6 degradation. (PMID:32350160)
• The clinical phenotype of systemic sclerosis patients with anti-PM/Scl antibodies: results from the EUSTAR cohort. (PMID:33580257)
• RNA-regulatory exosome complex confers cellular survival to promote erythropoiesis. (PMID:34059908)
• MPP6 stimulates both RRP6 and DIS3 to degrade a specified subset of MTR4-sensitive substrates in the human nucleus. (PMID:35902094)
• The ubiquitin-specific protease USP36 SUMOylates EXOSC10 and promotes the nucleolar RNA exosome function in rRNA processing. (PMID:36912080)
• EXOSC10 is a novel hepatocellular carcinoma prognostic biomarker: a comprehensive bioinformatics analysis and experiment verification. (PMID:37701829)
• Hypoxia-driven deSUMOylation of EXOSC10 promotes adaptive changes in the transcriptome profile. (PMID:38279024)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exosc10	ENSDARG00000037708
mus_musculus	Exosc10	ENSMUSG00000017264
rattus_norvegicus	Exosc10	ENSRNOG00000010719
drosophila_melanogaster	Rrp6	FBGN0038269
caenorhabditis_elegans		WBGENE00000796

Paralogs (1): EXD1 (ENSG00000178997)

Protein

Protein identifiers

Exosome complex component 10 — Q01780 (reviewed: Q01780)

Alternative names: Autoantigen PM/Scl 2, P100 polymyositis-scleroderma overlap syndrome-associated autoantigen, Polymyositis/scleroderma autoantigen 100 kDa, Polymyositis/scleroderma autoantigen 2

All UniProt accessions (2): Q01780, K7EJ37

UniProt curated annotations — full annotation on UniProt →

Function. 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. Part of the small subunit (SSU) processome, first precursor of the small eukaryotic ribosomal subunit. During the assembly of the SSU processome in the nucleolus, many ribosome biogenesis factors, an RNA chaperone and ribosomal proteins associate with the nascent pre-rRNA and work in concert to generate RNA folding, modifications, rearrangements and cleavage as well as targeted degradation of pre-ribosomal RNA by the RNA exosome. 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. EXOSC10 is required for nucleolar localization of C1D and probably mediates the association of MTREX, C1D and MPHOSPH6 with the RNA exosome involved in the maturation of 5.8S rRNA. Plays a role in the recruitment of replication protein A complex (RPA) and RAD51 to DNA double-strand breaks caused by irradiation, contributing to DNA repair by homologous recombination. Regulates levels of damage-induced RNAs in order to prevent DNA-RNA hybrid formation at DNA double-strand breaks and limit DNA end resection after damage. Plays a role in oocyte development, maturation and survival. Required for normal testis development and mitotic division of spermatogonia. Plays a role in proper embryo development. Required for global protein translation. Required for cell proliferation. Regulates metabolism of C9orf72-derived repeat RNA that can be translated into toxic dipeptide repeat proteins.

Subunit / interactions. Component of the RNA exosome complex. The catalytically inactive RNA exosome core complex (Exo-9) associates with the catalytic subunit EXOSC10/RRP6 (via its N-terminus). Exo-9 may associate with DIS3 to form the nucleolar exosome complex, or DIS3L to form the cytoplasmic exosome complex. The RNA exosome complex interacts with cofactors C1D/RRP47, MPHOSPH6/MPP6 and MTREX/MTR4. Interacts with MTREX; the interaction with MTREX mediates the association of MTREX with nuclear RNA exosomes. Part of the small subunit (SSU) processome, composed of more than 70 proteins and the RNA chaperone small nucleolar RNA (snoRNA) U3. Interacts with ALYREF/THOC4. Interacts with DHX36; this interaction occurs in a RNase-insensitive manner. Interacts with NRDE2. Interacts (via C-terminus) with USP36 (via C-terminus); the interaction is facilitated by the association with RNA and promotes sumoylation of EXOSC10.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm.

Post-translational modifications. Sumoylated by USP36; sumoylation does not significantly affect EXOSC10 nucleolar localization and association with core exosome and USP36, but regulates the nucleolar RNA exosome activity in rRNA processing by promoting binding of EXOSC10 to pre-rRNAs. Effects of sumoylation on EXOSC10 levels vary between different studies. Sumoylation of EXOSC10 is required for the modulation of EXOSC10 effects on cellular protein translation and cell proliferation. Sumoylation is promoted by mild hypothermia.

Activity regulation. Arginine-rich dipeptide repeat proteins expressed from C9orf72-derived repeat RNA interact with EXOSC10 and inhibit its ability to promote degradation of this RNA.

Induction. Down-regulated by mild hypothermia (at protein level).

Similarity. Belongs to the exosome component 10/RRP6 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q01780-1	1	yes
Q01780-2	2

RefSeq proteins (2): NP_001001998, NP_002676 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002121	HRDC_dom	Domain
IPR002562	3’-5’_exonuclease_dom	Domain
IPR010997	HRDC-like_sf	Homologous_superfamily
IPR012337	RNaseH-like_sf	Homologous_superfamily
IPR012588	Exosome-assoc_fac_Rrp6_N	Domain
IPR036397	RNaseH_sf	Homologous_superfamily
IPR044876	HRDC_dom_sf	Homologous_superfamily
IPR045092	Rrp6-like	Family
IPR049559	Rrp6p-like_exo	Domain

Pfam: PF00570, PF01612, PF08066

UniProt features (77 total): helix 24, mutagenesis site 15, strand 12, cross-link 8, binding site 5, compositionally biased region 4, domain 2, turn 2, chain 1, site 1, modified residue 1, splice variant 1, region of interest 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
3SAF	X-RAY DIFFRACTION	2.5
3SAH	X-RAY DIFFRACTION	2.65
3SAG	X-RAY DIFFRACTION	2.7
7MQA	ELECTRON MICROSCOPY	2.7
6D6Q	ELECTRON MICROSCOPY	3.45
6D6R	ELECTRON MICROSCOPY	3.45
2CPR	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q01780-F1	70.44	0.36

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 583 (not ubiquitinated)

Ligand- & substrate-binding residues (5): 315; 371; 440; 313; 313

Post-translational modifications (9): 821, 19, 583, 583, 710, 826, 833, 859, 873

Mutagenesis-validated functional residues (15):

Position	Phenotype
19	no effect on sumoylation by usp36.
168	no effect on sumoylation by usp36. reduces sumoylation levels and increases steady-state expression; when associated wit
201	reduces sumoylation levels and increases steady-state expression; when associated with r-168 and r-583.
313	abolishes exoribonuclease activity.
315	abolishes exoribonuclease activity.
316	slightly reduces exoribonuclease activity.
371	abolishes exoribonuclease activity.
404	increases exoribonuclease activity.
436	significantly reduces exoribonuclease activity.
583	reduces sumoylation by usp36. significantly attenuates binding to pre-rrna across the 5.8s-its2 and 18s-its1 junctions.
710	no effect on sumoylation by usp36.
826	no effect on sumoylation by usp36.
833	no effect on sumoylation by usp36.
859	no effect on sumoylation by usp36.
873	no effect on sumoylation by usp36.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 196 (showing top): GOBP_RNA_TEMPLATED_DNA_BIOSYNTHETIC_PROCESS, GOBP_CHROMOSOME_ORGANIZATION, GOBP_RIBOSOME_BIOGENESIS, GOMF_RNA_NUCLEASE_ACTIVITY, GOBP_NEGATIVE_REGULATION_OF_TELOMERE_MAINTENANCE_VIA_TELOMERASE, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOMF_NUCLEASE_ACTIVITY, GOBP_SNO_S_RNA_METABOLIC_PROCESS, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_TELOMERE_MAINTENANCE_VIA_TELOMERE_LENGTHENING, GOBP_TELOMERE_ORGANIZATION

GO Biological Process (27): nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (GO:0000184), maturation of 5.8S rRNA (GO:0000460), exonucleolytic trimming to generate mature 3’-end of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA) (GO:0000467), nuclear-transcribed mRNA catabolic process (GO:0000956), DNA repair (GO:0006281), rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401), negative regulation of telomere maintenance via telomerase (GO:0032211), ribosomal small subunit biogenesis (GO:0042274), random inactivation of X chromosome (GO:0060816), nuclear mRNA surveillance (GO:0071028), CUT catabolic process (GO:0071034), nuclear polyadenylation-dependent rRNA catabolic process (GO:0071035), nuclear polyadenylation-dependent snoRNA catabolic process (GO:0071036), nuclear polyadenylation-dependent snRNA catabolic process (GO:0071037), TRAMP-dependent tRNA surveillance pathway (GO:0071038), nuclear polyadenylation-dependent CUT catabolic process (GO:0071039), nuclear polyadenylation-dependent antisense transcript catabolic process (GO:0071040), histone mRNA catabolic process (GO:0071044), poly(A)-dependent snoRNA 3’-end processing (GO:0071051), regulation of telomerase RNA localization to Cajal body (GO:1904872), positive regulation of mRNA cis splicing, via spliceosome (GO:1905746), nucleobase-containing compound metabolic process (GO:0006139), DNA damage response (GO:0006974), regulation of gene expression (GO:0010468), regulation of nucleobase-containing compound metabolic process (GO:0019219)

GO Molecular Function (13): nucleotide binding (GO:0000166), 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), single-stranded RNA binding (GO:0003727), RNA exonuclease activity (GO:0004532), metal ion binding (GO:0046872), telomerase RNA binding (GO:0070034), nucleic acid binding (GO:0003676), nuclease activity (GO:0004518), exonuclease activity (GO:0004527), protein binding (GO:0005515), 3’-5’ exonuclease activity (GO:0008408), hydrolase activity (GO:0016787)

GO Cellular Component (12): nuclear exosome (RNase complex) (GO:0000176), cytoplasmic exosome (RNase complex) (GO:0000177), exosome (RNase complex) (GO:0000178), euchromatin (GO:0000791), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), membrane (GO:0016020), small-subunit processome (GO:0032040), nucleolar exosome (RNase complex) (GO:0101019)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
rRNA processing in the nucleus and cytosol	1
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear RNA surveillance	6
cellular anatomical structure	4
nuclear-transcribed mRNA catabolic process	3
nuclear lumen	3
ribosome biogenesis	2
RNA binding	2
exonuclease activity	2
binding	2
exosome (RNase complex)	2
nuclear protein-containing complex	2
cytoplasm	2
intracellular anatomical structure	2
nucleolus	2
rRNA processing	1
maturation of 5.8S rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1
rRNA 3’-end processing	1
mRNA catabolic process	1
DNA metabolic process	1
DNA damage response	1
RNA processing	1
rRNA metabolic process	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
telomere maintenance via telomerase	1
regulation of telomere maintenance via telomerase	1
negative regulation of telomere maintenance via telomere lengthening	1
negative regulation of DNA biosynthetic process	1
ribonucleoprotein complex biogenesis	1
dosage compensation by inactivation of X chromosome	1
RNA catabolic process	1
sno(s)RNA catabolic process	1
poly(A)-dependent snoRNA 3’-end processing	1
snRNA catabolic process	1
tRNA surveillance	1
CUT catabolic process	1
antisense RNA transcript catabolic process	1
histone mRNA metabolic process	1

Protein interactions and networks

STRING

3558 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOSC10	DIS3	Q9Y2L1	999
EXOSC10	EXOSC9	Q06265	998
EXOSC10	C1D	Q13901	997
EXOSC10	MTREX	P42285	982
EXOSC10	EXOSC8	Q96B26	976
EXOSC10	EXOSC4	Q9NPD3	974
EXOSC10	EXOSC3	Q9NQT5	962
EXOSC10	EXOSC5	Q9NQT4	949
EXOSC10	EXOSC1	Q9Y3B2	945
EXOSC10	EXOSC7	Q15024	915
EXOSC10	EXOSC6	Q5RKV6	912
EXOSC10	DIS3L	Q8TF46	885
EXOSC10	ZCCHC7	Q8N3Z6	883
EXOSC10	XRN1	Q8IZH2	839
EXOSC10	SKIC3	Q6PGP7	824

IntAct

206 interactions, top by confidence:

A	B	Type	Score
EXOSC10	EXOSC5	psi-mi:“MI:0915”(physical association)	0.890
EXOSC5	EXOSC10	psi-mi:“MI:0914”(association)	0.890
EXOSC2	EXOSC10	psi-mi:“MI:0914”(association)	0.840
EXOSC4	EXOSC10	psi-mi:“MI:0914”(association)	0.840
EXOSC1	EXOSC10	psi-mi:“MI:0915”(physical association)	0.810
EXOSC1	EXOSC10	psi-mi:“MI:0914”(association)	0.810
MPHOSPH6	EXOSC10	psi-mi:“MI:0407”(direct interaction)	0.810
EXOSC10	MPHOSPH6	psi-mi:“MI:0915”(physical association)	0.810
EXOSC3	EXOSC10	psi-mi:“MI:0914”(association)	0.790
EXOSC10	EXOSC7	psi-mi:“MI:0915”(physical association)	0.750
EXOSC7	EXOSC10	psi-mi:“MI:0914”(association)	0.750
DIS3	EXOSC10	psi-mi:“MI:0914”(association)	0.740
EXOSC10	C1D	psi-mi:“MI:0403”(colocalization)	0.730
C1D	EXOSC10	psi-mi:“MI:0914”(association)	0.730
EXOSC10	C1D	psi-mi:“MI:0407”(direct interaction)	0.730
C1D	EXOSC10	psi-mi:“MI:0915”(physical association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710

BioGRID (357): EXOSC10 (Affinity Capture-RNA), EXOSC10 (Affinity Capture-RNA), EXOSC10 (Affinity Capture-MS), EXOSC10 (Reconstituted Complex), EXOSC10 (Affinity Capture-MS), EXOSC10 (Affinity Capture-MS), EXOSC10 (Affinity Capture-MS), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC10 (Co-fractionation)

ESM2 similar proteins: A2XVF7, A3AVH5, A9LLI7, A9LLI8, B9F4I8, D4A1X2, F4HP88, F4IHJ0, F4JNY0, F4JP52, F4JUQ2, F4JVA6, F4KIA8, F4KIX0, I1HNB2, I3XHK1, M1BJF6, O04539, O48686, O48802, O80792, P56960, P93831, Q01780, Q0WVE8, Q336N8, Q3TLD5, Q60GC1, Q6K7R9, Q6NQ79, Q75LL6, Q8GXC6, Q8L6Z7, Q8RXT5, Q8S4P6, Q8VZ17, Q8W489, Q8W4L5, Q9C5W3, Q9C8S9

Diamond homologs: A9LLI7, A9LLI8, D4A1X2, G5EBX6, P56960, Q01780, Q0WVE8, Q10146, Q12149, Q9VFF3, B8EN54, Q9VGN7, A0KXU5, A5G127, A7HYE5, A9H9B7, D4Z694, F4I6M1, O51498, O52225, O67779, P00582, P19821, P30313, P43741, P52026, P52027, P52028, P59199, P59200, P80194, Q04957, Q0BVP4, Q59156, Q6G329, Q6Z4T3, Q6Z4T5, Q84ND9, Q9F173, Q9HT80

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EXOSC10	“form complex”	Exosome_Complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 169 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
mRNA decay by 3’ to 5’ exoribonuclease	11	65.4×	8e-17
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	10	52.9×	4e-14
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	10	52.9×	4e-14
KSRP (KHSRP) binds and destabilizes mRNA	10	52.9×	4e-14
Nuclear RNA decay	18	46.3×	5e-24
ATF4 activates genes in response to endoplasmic reticulum stress	10	34.0×	7e-12
SARS-CoV-1 modulates host translation machinery	7	18.0×	3e-06
Eukaryotic Translation Initiation	6	15.4×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
rRNA catabolic process	8	53.6×	1e-10
RNA catabolic process	13	40.0×	2e-15
nuclear-transcribed mRNA catabolic process	7	36.2×	6e-08
RNA processing	14	20.7×	1e-12
mRNA catabolic process	6	20.1×	2e-05
rRNA processing	20	19.1×	2e-17
cytoplasmic translation	12	15.0×	3e-09
ribosomal large subunit biogenesis	5	15.0×	7e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

156 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	112
Likely benign	4
Benign	1

Top pathogenic / likely-pathogenic (0)

SpliceAI

2909 predictions. Top by Δscore:

Variant	Effect	Δscore
1:11066745:GCCT:G	acceptor_gain	1.0000
1:11066746:CCTC:C	acceptor_gain	1.0000
1:11066747:CT:C	acceptor_gain	1.0000
1:11066749:C:CC	acceptor_gain	1.0000
1:11068003:CATA:C	donor_loss	1.0000
1:11068004:ATACC:A	donor_loss	1.0000
1:11068005:TA:T	donor_loss	1.0000
1:11068007:C:CT	donor_loss	1.0000
1:11068080:CATTT:C	acceptor_gain	1.0000
1:11068082:TTT:T	acceptor_gain	1.0000
1:11068083:TT:T	acceptor_gain	1.0000
1:11068083:TTCT:T	acceptor_loss	1.0000
1:11068084:TC:T	acceptor_loss	1.0000
1:11068085:C:CC	acceptor_gain	1.0000
1:11068085:C:G	acceptor_loss	1.0000
1:11068086:T:G	acceptor_loss	1.0000
1:11068639:TCTTA:T	donor_loss	1.0000
1:11068640:CTTAC:C	donor_loss	1.0000
1:11068641:TTACC:T	donor_loss	1.0000
1:11068642:TA:T	donor_loss	1.0000
1:11068644:C:G	donor_loss	1.0000
1:11069552:T:TA	donor_gain	1.0000
1:11070895:CATA:C	donor_loss	1.0000
1:11070897:TA:T	donor_loss	1.0000
1:11070898:A:AC	donor_gain	1.0000
1:11070898:A:C	donor_loss	1.0000
1:11070899:C:CC	donor_gain	1.0000
1:11070899:C:CG	donor_loss	1.0000
1:11070969:GGCAG:G	acceptor_gain	1.0000
1:11070970:GCAG:G	acceptor_gain	1.0000

AlphaMissense

5866 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:11082696:C:A	W424C	1.000
1:11082696:C:G	W424C	1.000
1:11082698:A:G	W424R	1.000
1:11082698:A:T	W424R	1.000
1:11087574:G:C	S321R	1.000
1:11087574:G:T	S321R	1.000
1:11087576:T:G	S321R	1.000
1:11080541:A:G	L532P	0.999
1:11080777:C:G	D525H	0.999
1:11080788:G:T	A521D	0.999
1:11081209:G:T	A437D	0.999
1:11082693:T:A	R425S	0.999
1:11082693:T:G	R425S	0.999
1:11082694:C:A	R425I	0.999
1:11082694:C:G	R425T	0.999
1:11082704:C:G	A422P	0.999
1:11082706:A:G	L421P	0.999
1:11082717:C:A	K417N	0.999
1:11082717:C:G	K417N	0.999
1:11082844:A:G	L375P	0.999
1:11082848:A:G	W374R	0.999
1:11082848:A:T	W374R	0.999
1:11087577:C:A	R320S	0.999
1:11087577:C:G	R320S	0.999
1:11087578:C:A	R320M	0.999
1:11087578:C:G	R320T	0.999
1:11079797:A:G	C555R	0.998
1:11080541:A:C	L532R	0.998
1:11080769:A:C	S527R	0.998
1:11080769:A:T	S527R	0.998

dbSNP variants (sampled 300 via entrez): RS1000002776 (1:11098949 T>A), RS1000008241 (1:11077852 G>A), RS1000016951 (1:11084312 T>C), RS1000066567 (1:11099135 G>A), RS1000122249 (1:11071034 C>T), RS1000598019 (1:11088480 T>C,G), RS1000698703 (1:11067586 A>T), RS1000755478 (1:11078629 C>A,T), RS1000921167 (1:11073400 G>C), RS1000923451 (1:11095571 A>G), RS1000949640 (1:11095064 T>C,G), RS1001153464 (1:11100610 C>G), RS1001276856 (1:11089475 A>G), RS1001334501 (1:11083585 A>G,T), RS1001439077 (1:11098296 T>C)

Disease associations

OMIM: gene MIM:605960 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST003475_1	Beard thickness	4.000000e-07
GCST005580_216	Intraocular pressure	2.000000e-21
GCST006979_853	Heel bone mineral density	9.000000e-20

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement
EFO:0009270	heel bone mineral density

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066405 (SINGLE PROTEIN)

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

2 potent at pChembl≥5 of 3 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.43	Kd	3.702	nM	CHEMBL3752910
8.43	ED50	3.702	nM	CHEMBL3752910

PubChem BioAssay actives

1 with measured affinity, of 4 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
4-methyl-3-[(1-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148351: Binding affinity to human EXOSC10 incubated for 45 mins by Kinobead based pull down assay	kd	0.0037	uM

CTD chemical–gene interactions

24 total (human), top 24 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects methylation, affects cotreatment, decreases methylation, decreases expression	3
Valproic Acid	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
manganese chloride	increases abundance, increases expression	1
CGP 52608	affects binding, increases reaction	1
Resveratrol	affects binding, increases reaction	1
Fulvestrant	affects cotreatment, decreases methylation	1
Vorinostat	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Fluorouracil	affects response to substance, increases metabolic processing	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Manganese	increases abundance, increases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Tretinoin	decreases expression	1
Cyclosporine	increases expression	1
Vitamin K 3	affects expression	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651393	Binding	Binding affinity to human EXOSC10 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.