EXOSC9

Summary

EXOSC9 (exosome component 9, HGNC:9137) is a protein-coding gene on chromosome 4q27, encoding Exosome complex component RRP45 (Q06265). 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. It is a common-essential gene (DepMap: required in 90.5% of cancer cell lines).

This gene encodes a component of the human exosome, a exoribonuclease complex which processes and degrades RNA in the nucleus and cytoplasm. This component may play a role in mRNA degradation and the polymyositis/scleroderma autoantigen complex. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 5393 — RefSeq curated summary.

At a glance

• Gene–disease (curated): pontocerebellar hypoplasia, type 1D (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 337 total — 22 pathogenic, 7 likely-pathogenic (top 10% of genes corpus-wide)
• GTEx eGene: eQTL in 29 tissues, sQTL in 46 (q < 0.05)
• Phenotypes (HPO): 65
• ChEMBL bioactivity: 1 clinical-phase molecule tested; no curated mechanism-of-action drug
• Cancer dependency (DepMap): dependent in 90.5% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 1.12 (unconstrained)
• MANE Select transcript: NM_005033
• Interaction hub: 1,808 STRING partners (top 9% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9137
Approved symbol	EXOSC9
Name	exosome component 9
Location	4q27
Locus type	gene with protein product
Status	Approved
Aliases	PM/Scl-75, Rrp45p, RRP45, p5, p6
Ensembl gene	ENSG00000123737
Ensembl biotype	protein_coding
OMIM	606180
Entrez	5393

Gene structure

Transcript identifiers

Ensembl transcripts: 36 — 16 nonsense_mediated_decay, 15 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron

MANE Select: ENST00000243498

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 4, TSL 2: 3, TSL 3: 3, TSL 5: 2

ENST00000243498, ENST00000379663, ENST00000503139, ENST00000503236, ENST00000506201, ENST00000508212, ENST00000509800, ENST00000509980, ENST00000511132, ENST00000511454, ENST00000512454, ENST00000513654, ENST00000876433, ENST00000940328, ENST00000940329, ENST00000940330, ENST00000940331, ENST00000962073, ENST00000962074, ENST00000993161, ENST00000993162, ENST00001030990, ENST00001030991, ENST00001030992, ENST00001030993, ENST00001087100, ENST00001087101, ENST00001087102, ENST00001087103, ENST00001087104, ENST00001087105, ENST00001087106, ENST00001087108, ENST00001104327, ENST00001123710, ENST00001136313

RefSeq mRNA: 2 — MANE Select: NM_005033 NM_001034194, NM_005033

CCDS: CCDS34057, CCDS3722

Canonical transcript exons

ENST00000243498 — 12 exons

Exon	Start	End
ENSE00003502554	121816369	121816447
ENSE00003512764	121802915	121803017
ENSE00003544472	121811583	121811671
ENSE00003552850	121802674	121802793
ENSE00003568257	121804622	121804759
ENSE00003586315	121801827	121801921
ENSE00003624835	121809967	121810099
ENSE00003637944	121813234	121813380
ENSE00003659995	121807540	121807622
ENSE00003786405	121813866	121814047
ENSE00003904075	121801323	121801490
ENSE00004788512	121816772	121817021

Expression profiles

Bgee: expression breadth ubiquitous, 285 present calls, max score 98.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 26.5335 / max 664.7939, expressed in 1809 samples.

Highest expression (Bgee): secondary oocyte, oocyte, calcaneal tendon, primordial germ cell in gonad, male germ line stem cell (sensu Vertebrata) in testis.

Genetic regulation across tissues (GTEx eQTL / sQTL)

EXOSC9 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 29 tissues and its splicing (sQTL) in 46 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 75 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	sqtl	6.5e-89	+1.02	4:121808146:T:C
Cells EBV-transformed lymphocytes	sqtl	6.3e-61	+1.12	4:121828850:A:G
Muscle Skeletal	sqtl	8.6e-55	+0.79	4:121825170:A:G
Adipose Subcutaneous	sqtl	5.8e-49	+0.81	4:121828850:A:G
Nerve Tibial	sqtl	9.2e-44	+0.92	4:121808146:T:C
Artery Tibial	sqtl	2.0e-41	+0.84	4:121809666:G:C
Lung	sqtl	8.9e-37	+0.81	4:121808146:T:C
Esophagus Muscularis	sqtl	2.1e-35	+0.90	4:121829295:C:T
Cells EBV-transformed lymphocytes	eqtl	2.0e-34	+0.50	4:121797839:T:C
Esophagus Mucosa	sqtl	6.7e-33	+0.87	4:121871719:G:A
Testis	sqtl	9.4e-33	+0.91	4:121874206:G:A
Skin Not Sun Exposed Suprapubic	sqtl	1.4e-31	+0.80	4:121871719:G:A
Skin Sun Exposed Lower leg	sqtl	4.7e-30	+0.71	4:121808146:T:C
Thyroid	sqtl	2.0e-27	+0.75	4:121808146:T:C
Colon Transverse	sqtl	1.0e-25	+0.90	4:121871719:G:A
Breast Mammary Tissue	sqtl	8.9e-25	+0.73	4:121871719:G:A
Adipose Visceral Omentum	sqtl	1.7e-24	+0.76	4:121808146:T:C
Artery Aorta	sqtl	5.4e-23	+0.81	4:121828850:A:G
Spleen	sqtl	2.9e-21	+1.05	4:121874206:G:A
Whole Blood	sqtl	1.0e-20	+0.56	4:121871719:G:A

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
49520	26.2947	1808
49521	0.2389	127

Top tissues by expression

showing 100 of 297 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	98.70	gold quality
oocyte	CL:0000023	97.95	gold quality
calcaneal tendon	UBERON:0003701	94.67	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	94.56	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	94.40	gold quality
buccal mucosa cell	CL:0002336	94.01	gold quality
testis	UBERON:0000473	93.71	gold quality
left testis	UBERON:0004533	93.56	gold quality
right testis	UBERON:0004534	93.34	gold quality
ventricular zone	UBERON:0003053	92.77	gold quality
ganglionic eminence	UBERON:0004023	91.94	gold quality
tendon	UBERON:0000043	90.72	gold quality
embryo	UBERON:0000922	90.62	gold quality
lymph node	UBERON:0000029	90.06	gold quality
sperm	CL:0000019	89.70	gold quality
granulocyte	CL:0000094	89.60	gold quality
monocyte	CL:0000576	89.58	gold quality
mononuclear cell	CL:0000842	89.53	gold quality
leukocyte	CL:0000738	89.50	gold quality
tibial nerve	UBERON:0001323	89.22	gold quality
cerebellar hemisphere	UBERON:0002245	89.18	gold quality
cerebellar cortex	UBERON:0002129	88.99	gold quality
islet of Langerhans	UBERON:0000006	88.79	gold quality
bone marrow	UBERON:0002371	88.67	gold quality
rectum	UBERON:0001052	88.48	gold quality
right hemisphere of cerebellum	UBERON:0014890	88.47	gold quality
male germ cell	CL:0000015	88.31	gold quality
cortical plate	UBERON:0005343	88.30	gold quality
tonsil	UBERON:0002372	88.21	gold quality
body of uterus	UBERON:0009853	88.19	gold quality
vermiform appendix	UBERON:0001154	88.05	gold quality
ovary	UBERON:0000992	88.00	gold quality
bone marrow cell	CL:0002092	87.97	gold quality
muscle of leg	UBERON:0001383	87.72	gold quality
gastrocnemius	UBERON:0001388	87.70	gold quality
left ovary	UBERON:0002119	87.64	gold quality
caecum	UBERON:0001153	87.61	gold quality
hindlimb stylopod muscle	UBERON:0004252	87.57	gold quality
right ovary	UBERON:0002118	87.50	gold quality
cerebellum	UBERON:0002037	87.45	gold quality
spleen	UBERON:0002106	87.45	gold quality
adrenal tissue	UBERON:0018303	87.40	gold quality
left uterine tube	UBERON:0001303	87.20	gold quality
sural nerve	UBERON:0015488	87.12	gold quality
bone element	UBERON:0001474	86.95	gold quality
pancreas	UBERON:0001264	86.76	gold quality
popliteal artery	UBERON:0002250	86.75	gold quality
descending thoracic aorta	UBERON:0002345	86.75	gold quality
tibial artery	UBERON:0007610	86.75	gold quality
body of pancreas	UBERON:0001150	86.70	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	86.59	gold quality
omental fat pad	UBERON:0010414	86.59	gold quality
peritoneum	UBERON:0002358	86.58	gold quality
left coronary artery	UBERON:0001626	86.52	gold quality
ectocervix	UBERON:0012249	86.50	gold quality
muscle layer of sigmoid colon	UBERON:0035805	86.46	gold quality
left adrenal gland	UBERON:0001234	86.42	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	86.42	gold quality
skin of abdomen	UBERON:0001416	86.41	gold quality
aorta	UBERON:0000947	86.36	gold quality
lower esophagus muscularis layer	UBERON:0035833	86.36	gold quality
right lung	UBERON:0002167	86.35	gold quality
upper lobe of left lung	UBERON:0008952	86.34	gold quality
lower esophagus	UBERON:0013473	86.34	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.33	gold quality
coronary artery	UBERON:0001621	86.28	gold quality
right adrenal gland	UBERON:0001233	86.27	gold quality
adipose tissue of abdominal region	UBERON:0007808	86.25	gold quality
right uterine tube	UBERON:0001302	86.23	gold quality
left adrenal gland cortex	UBERON:0035825	86.22	gold quality
adrenal gland	UBERON:0002369	86.20	gold quality
endocervix	UBERON:0000458	86.18	gold quality
heart left ventricle	UBERON:0002084	86.17	gold quality
metanephros cortex	UBERON:0010533	86.04	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	86.02	gold quality
vagina	UBERON:0000996	86.01	gold quality
cardiac ventricle	UBERON:0002082	85.98	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.97	gold quality
thoracic aorta	UBERON:0001515	85.96	gold quality
skin of leg	UBERON:0001511	85.95	gold quality
esophagus	UBERON:0001043	85.94	gold quality
muscle organ	UBERON:0001630	85.94	gold quality
skeletal muscle organ	UBERON:0014892	85.94	gold quality
vena cava	UBERON:0004087	85.93	gold quality
right atrium auricular region	UBERON:0006631	85.93	gold quality
adrenal cortex	UBERON:0001235	85.89	gold quality
right adrenal gland cortex	UBERON:0035827	85.89	gold quality
smooth muscle tissue	UBERON:0001135	85.86	gold quality
ascending aorta	UBERON:0001496	85.85	gold quality
body of stomach	UBERON:0001161	85.80	gold quality
mucosa of stomach	UBERON:0001199	85.79	gold quality
adenohypophysis	UBERON:0002196	85.77	gold quality
upper lobe of lung	UBERON:0008948	85.76	gold quality
mucosa of transverse colon	UBERON:0004991	85.74	gold quality
blood	UBERON:0000178	85.72	gold quality
colonic epithelium	UBERON:0000397	85.72	gold quality
heart	UBERON:0000948	85.71	gold quality
minor salivary gland	UBERON:0001830	85.65	gold quality
esophagus mucosa	UBERON:0002469	85.62	gold quality
female reproductive system	UBERON:0000474	85.54	gold quality

Single-cell (SCXA)

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

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

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Testis	tissue	40.6	high
Frontal cortex	tissue	39.4
Bone marrow	tissue	35.8	medium
Caudate putamen	tissue	33.9
Thymus	tissue	30.5
Lymph node	tissue	24.2	medium
Tonsil	tissue	19.7	medium
Tongue	tissue	17.3
Skeletal muscle	tissue	16.5	medium
Prefrontal cortex	tissue	16.3
Cerebral cortex	tissue	16.3	medium
Retrosplenial and cingulate cortex	tissue	16.1
Appendix	tissue	15.8	medium
Hippocampal formation	tissue	15.7
Entorhinal cortex	tissue	15.7
Occipital cortex	tissue	15.7
Motor cortex	tissue	15.2
Insular cortex	tissue	15.2
Liver	tissue	15.0	medium
Retrosplenial cortex	tissue	15.0
Spleen	tissue	14.9	medium
Cerebellum	tissue	14.8	medium
Heart muscle	tissue	14.7	medium
Temporal cortex	tissue	14.7
Urinary bladder	tissue	13.9	medium
Parathyroid gland	tissue	13.8	not detected
Ovary	tissue	13.7	medium
Epididymis	tissue	13.6	medium
Somatosensory cortex	tissue	13.6
Adrenal gland	tissue	13.5	medium
Breast	tissue	13.3	medium
Corpus callosum	tissue	13.3
Placenta	tissue	13.2	medium
Lung	tissue	12.8	medium
Pons	tissue	12.1
Amygdala	tissue	12.1
Thalamus	tissue	11.9
Spinal cord	tissue	11.9
Olfactory bulb	tissue	11.9
Rectum	tissue	11.8	medium
Midbrain	tissue	11.6
Substantia nigra	tissue	11.6
Septum	tissue	11.5
Putamen	tissue	11.4
Superior colliculi	tissue	11.4
Hypothalamus	tissue	11.3
Medulla oblongata	tissue	11.1
Ventral forebrain	tissue	11.1
Kidney	tissue	11.0	high
Periaqueductal gray	tissue	10.9
Vagina	tissue	10.8	high
Colon	tissue	10.8	medium
Adipose tissue	tissue	10.5	low
Stomach 1	tissue	10.3	medium
Pituitary gland	tissue	10.1
Basal ganglia	tissue	10.0	medium
Endometrium 1	tissue	9.9	medium
Postcentral gyrus	tissue	9.8
Prostate	tissue	9.7	medium
Smooth muscle	tissue	9.5	medium

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (13.7), White matter (13.3), Subiculum (13.0), Ventral spinal cord (11.9), Dorsal hippocampus (11.3).

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F4

miRNA regulators (miRDB)

Targeting EXOSC9 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

24 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-6764-5P	99.75	67.89	2304
HSA-MIR-6832-3P	99.52	70.44	1726
HSA-MIR-1246	98.54	66.21	959
HSA-MIR-758-3P	98.42	68.60	1122
HSA-MIR-633	98.35	69.45	1167
HSA-MIR-188-5P	97.89	67.01	756
HSA-MIR-6866-3P	97.38	66.94	748
HSA-MIR-597-3P	96.46	68.03	1035

Functional genomics

gnomAD constraint: pLI 1.16e-07, LOEUF 1.12, missense Z -0.0593 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD RMC): no regional variation along ENST00000243498 — one region, missense o/e 1.05. DepMap (CRISPR cell-line fitness): dependent in 90.5% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): LOU-NH91 (-1.928), NCI-H226 (-1.449), SNU-626 (-1.436), KMS-20 (-1.322), LS1034 (-1.319), KLE (-1.318), DB (-1.286), OAW28 (-1.218), SCC-9 (-1.218), KNS-81 (-1.196), KMRC-3 (-1.177), SK-ES-1 (-1.158), LUDLU-1 (-1.145), NOMO-1 (-1.12), SK-N-FI (-1.117).

Literature-anchored findings (GeneRIF, showing 10)

• The mammalian exosome mediates the efficient degradation of mRNAs that contain AU-rich elements, possibly by direct binding of PM/Scl-75 to these RNA regions. (PMID:11782436)
• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. (PMID:12419256)
• The association of the human PM/Scl-75 autoantigen with the exosome is dependent on a newly identified N terminus. (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)
• variants in EXOSC9 result in a neurological syndrome combining cerebellar atrophy and spinal motoneuronopathy, thus expanding the list of human exosomopathies. (PMID:29727687)
• Expanded PCH1D phenotype linked to EXOSC9 mutation. (PMID:30690203)
• EXOSC9 depletion attenuates P-body formation, stress resistance, and tumorigenicity of cancer cells. (PMID:32518284)
• Novel EXOSC9 variants cause pontocerebellar hypoplasia type 1D with spinal motor neuronopathy and cerebellar atrophy. (PMID:33040083)
• Exosc9 Initiates SUMO-Dependent lncRNA TERRA Degradation to Impact Telomeric Integrity in Endocrine Therapy Insensitive Hormone Receptor-Positive Breast Cancer. (PMID:37887339)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exosc9	ENSDARG00000006392
mus_musculus	Exosc9	ENSMUSG00000027714
rattus_norvegicus	Exosc9	ENSRNOG00000014674
drosophila_melanogaster	Rrp45	FBGN0030789
caenorhabditis_elegans		WBGENE00018154

Paralogs (2): EXOSC7 (ENSG00000075914), EXOSC8 (ENSG00000120699)

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Saccharolobus islandicus L.S.2.15	C3MQ47	100.0%	Diamond
Saccharolobus islandicus M.14.25	C3MVG5	100.0%	Diamond
Saccharolobus islandicus M.16.27	C3N5R4	100.0%	Diamond
Saccharolobus islandicus Y.G.57.14	C3NED0	100.0%	Diamond
Saccharolobus islandicus M.16.4	C4KHE3	100.0%	Diamond
Saccharolobus islandicus Y.N.15.51	C3NHC2	99.6%	Diamond
Bos taurus	Q3SWZ4	95.1%	Diamond
Methanosarcina mazei Go1	Q8PTT7	95.1%	Diamond
Methanosarcina acetivorans C2A	Q8TGX5	95.1%	Diamond
Saccharolobus solfataricus P2	Q9UXC0	94.9%	Diamond
Thermoplasma volcanium GSS1	Q97BZ4	93.1%	Diamond
Thermoplasma acidophilum DSM 1728	Q9HIP1	93.1%	Diamond
Pyrococcus horikoshii OT3	O59224	91.9%	Diamond
Arabidopsis thaliana	Q9LDM2	91.9%	Diamond
Pyrococcus abyssi GE5	Q9V118	91.9%	Diamond
Pyrococcus furiosus DSM 3638	Q8U0M0	89.7%	Diamond
Thermococcus onnurineus NA1	B6YSE7	80.4%	Diamond
Thermococcus kodakarensis KOD1	Q5JIR7	80.4%	Diamond
Thermococcus gammatolerans EJ3	C5A2B8	79.0%	Diamond
Sulfurisphaera tokodaii str. 7	Q975G9	71.3%	Diamond
Methanocella arvoryzae MRE50	Q0W2Y7	58.8%	Diamond
Archaeoglobus fulgidus DSM 4304	O29756	56.8%	Diamond
Methanopyrus kandleri AV19	Q8TYC2	54.6%	Diamond
Methanothermobacter thermautotrophicus str. Delta H	O26778	52.5%	Diamond
Aeropyrum pernix K1	Q9YC05	50.8%	Diamond
Schizosaccharomyces pombe 972h-	O74918	49.5%	Diamond
Saccharomyces cerevisiae S288C	Q05636	49.5%	Diamond
Pyrobaculum aerophilum str. IM2	Q8ZVN0	46.7%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SMIM43	protein-coding	132332
ANXA5	protein-coding	308
BBS7	protein-coding	55212
CCNA2	protein-coding	890
TRPC3-AS1	ncRNA	102724158
TRPC3	protein-coding	7222
PP12613	ncRNA	100192379
BBS7-DT	ncRNA	119545622

Protein

Protein identifiers

Exosome complex component RRP45 — Q06265 (reviewed: Q06265)

Alternative names: Autoantigen PM/Scl 1, Exosome component 9, P75 polymyositis-scleroderma overlap syndrome-associated autoantigen, Polymyositis/scleroderma autoantigen 1, Polymyositis/scleroderma autoantigen 75 kDa

All UniProt accessions (6): D6R905, D6RA17, D6RAP4, D6RIY6, H0Y9L5, Q06265

UniProt curated annotations — full annotation on UniProt →

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.

Subunit / interactions. Component of the RNA exosome core complex (Exo-9), composed of EXOSC1, EXOSC2, EXOSC3, EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8 and EXOSC9; within the complex interacts with EXOSC3, EXOSC4, EXOSC5 and DIS3. The catalytically inactive RNA exosome core complex (Exo-9) associates with the catalytic subunit EXOSC10/RRP6. Exo-9 may associate with DIS3 to form the nucleolar exosome complex, or DIS3L to form the cytoplasmic exosome complex. Exo-9 is formed by a hexameric base ring consisting of the heterodimers EXOSC4-EXOSC9, EXOSC5-EXOSC8 and EXOSC6-EXOSC7, and a cap ring consisting of EXOSC1, EXOSC2 and EXOSC3. The RNA exosome complex associates with cofactors C1D/RRP47, MPHOSPH6/MPP6 and MTREX/MTR4. Interacts (via C-terminus region) with SETX (via N-terminus domain); the interaction enhances SETX sumoylation. Interacts with DIS3; the interaction is direct.

Subcellular location. Cytoplasm. Nucleus. Nucleolus. Nucleoplasm Nucleus. Nucleolus Nucleus.

Disease relevance. Pontocerebellar hypoplasia 1D (PCH1D) [MIM:618065] An autosomal recessive neurologic disorder with onset at birth or in infancy, and characterized by progressive axonal motor neuronopathy, severe generalized hypotonia, respiratory insufficiency, and cerebellar atrophy. Death in childhood may occur. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RNase PH family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q06265-1	1, PM/SCL-75c-alpha	yes
Q06265-2	2, PM/SCL-75c-beta
Q06265-3	3, PM/SCL-75a-alpha
Q06265-4	4, PM/SCL-75a-beta

RefSeq proteins (2): NP_001029366, NP_005024* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001247	ExoRNase_PH_dom1	Domain
IPR015847	ExoRNase_PH_dom2	Domain
IPR020568	Ribosomal_Su5_D2-typ_SF	Homologous_superfamily
IPR027408	PNPase/RNase_PH_dom_sf	Homologous_superfamily
IPR033100	Rrp45	Family
IPR036345	ExoRNase_PH_dom2_sf	Homologous_superfamily
IPR050590	Exosome_comp_Rrp42_subfam	Family

Pfam: PF01138, PF03725

UniProt features (65 total): strand 19, modified residue 10, helix 9, turn 7, mutagenesis site 5, sequence variant 4, region of interest 3, cross-link 3, splice variant 2, compositionally biased region 2, chain 1

Structure

Experimental structures (PDB)

8 structures by resolution:

PDB	Title	Method	Resolution (Å)
9G8M	human 80S ribosome bound by a SKI2-exosome complex	ELECTRON MICROSCOPY	3.3
2NN6	Structure of the human RNA exosome composed of Rrp41, Rrp45, Rrp46, Rrp43, Mtr3, Rrp42 …	X-RAY DIFFRACTION	3.35
9G8O	human 40S ribosome bound by a SKI238-exosome complex	ELECTRON MICROSCOPY	3.4
6D6Q	Human nuclear exosome-MTR4 RNA complex - overall reconstruction	ELECTRON MICROSCOPY	3.45
6D6R	Human nuclear exosome-MTR4 RNA complex - composite map after focused reconstruction	ELECTRON MICROSCOPY	3.45
9G8N	80S-bound human Ski2-exosome complex	ELECTRON MICROSCOPY	3.7
6H25	Human nuclear RNA exosome EXO-10-MPP6 complex	ELECTRON MICROSCOPY	3.8
9G8P	40S-bound human SKI2-exosome complex	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q06265-F1	77.44	0.57

Human Protein Atlas

Protein class: Predicted intracellular proteins, Disease related genes, Human disease related genes, Congenital malformations, Congenital malformations of the nervous system, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoli; nucleoplasm

Antibody reliability (HPA): IH approved · IF enhanced

Functional residue map

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

Post-translational modifications (13)

Type	Positions
Phosphoserine	392, 394, 65, 409, 411, 325, 327, 306, 346
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo1)	297
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	297, 419
N6-acetyllysine	297

Mutagenesis-validated functional residues (5)

Position	Phenotype
388–391	abolishes interaction with setx.
390–391	abolishes interaction with setx.
395–398	abolishes interaction with setx.

Function

Pathways and Gene Ontology

Reactome pathways

7 curated (TAS) of 17; 0 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

17 pathways:

ID	Pathway	Evidence
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress	curated
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	curated
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA	curated
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol	curated
R-HSA-9930044	Nuclear RNA decay	curated
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	curated
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease	curated
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-429914	Deadenylation-dependent mRNA decay	—
R-HSA-8953854	Metabolism of RNA	—
R-HSA-381042	PERK regulates gene expression	—
R-HSA-450531	Regulation of mRNA stability by proteins that bind AU-rich elements	—
R-HSA-9938024	Somatic hypermutation of immunoglobulin genes	electronic
R-HSA-381119	Unfolded Protein Response (UPR)	—
R-HSA-72312	rRNA processing	—
R-HSA-8868773	rRNA processing in the nucleus and cytosol	—

MSigDB gene sets: 327 (showing top): GSE45365_NK_CELL_VS_CD8A_DC_MCMV_INFECTION_UP, GOBP_RIBOSOME_BIOGENESIS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, GOMF_NUCLEASE_ACTIVITY, GOBP_TRNA_METABOLIC_PROCESS, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, WEI_MYCN_TARGETS_WITH_E_BOX, MUELLER_PLURINET, GOBP_RNA_SURVEILLANCE, MILI_PSEUDOPODIA_HAPTOTAXIS_UP, GOBP_MATURATION_OF_5_8S_RRNA_FROM_TRICISTRONIC_RRNA_TRANSCRIPT_SSU_RRNA_5_8S_RRNA_LSU_RRNA

GO Biological Process (16): 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), rRNA processing (GO:0006364), RNA processing (GO:0006396), RNA catabolic process (GO:0006401), mRNA catabolic process (GO:0006402), immune response (GO:0006955), rRNA catabolic process (GO:0016075), positive regulation of cell growth (GO:0030307), U1 snRNA 3’-end processing (GO:0034473), U4 snRNA 3’-end processing (GO:0034475), U5 snRNA 3’-end processing (GO:0034476), positive regulation of transcription by RNA polymerase II (GO:0045944), nuclear mRNA surveillance (GO:0071028), nuclear polyadenylation-dependent rRNA catabolic process (GO:0071035), TRAMP-dependent tRNA surveillance pathway (GO:0071038)

GO Molecular Function (5): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), mRNA 3’-UTR AU-rich region binding (GO:0035925), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), protein binding (GO:0005515)

GO Cellular Component (11): nuclear exosome (RNase complex) (GO:0000176), cytoplasmic exosome (RNase complex) (GO:0000177), exosome (RNase complex) (GO:0000178), nuclear chromosome (GO:0000228), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), extracellular exosome (GO:0070062), exoribonuclease complex (GO:1905354)

Reactome top-level categories

10 top-level categories:

Category	Pathways
Metabolism of RNA	4
Regulation of mRNA stability by proteins that bind AU-rich elements	3
PERK regulates gene expression	1
Deadenylation-dependent mRNA decay	1
rRNA processing in the nucleus and cytosol	1
Affinity selection of immunoglobulins	1
Cellular responses to stimuli	1
Unfolded Protein Response (UPR)	1
Cellular responses to stress	1
rRNA processing	1

GO top-level categories

46 GO namespaces:

Category	Terms
nuclear lumen	4
snRNA 3’-end processing	3
nuclear RNA surveillance	3
cellular anatomical structure	3
rRNA metabolic process	2
RNA catabolic process	2
exosome (RNase complex)	2
nucleus	2
cytoplasm	2
intracellular anatomical structure	2
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
RNA processing	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
negative regulation of gene expression	1
mRNA metabolic process	1
immune system process	1
response to stimulus	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
nuclear-transcribed mRNA catabolic process	1
tRNA surveillance	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
mRNA 3’-UTR binding	1
DNA-binding transcription factor binding	1
binding	1
nuclear protein-containing complex	1
exoribonuclease complex	1
chromosome	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
extracellular vesicle	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 18 of 32 annotations. The rest are phylogenetic / computational / electronic (IEA).

18 experimentally-supported GO terms:

GO term	NS	Evidence
RNA catabolic process	BP	direct assay
RNA processing	BP	direct assay
mRNA catabolic process	BP	mutant phenotype
nuclear mRNA surveillance	BP	mutant phenotype
nuclear polyadenylation-dependent rRNA catabolic process	BP	mutant phenotype
nuclear-transcribed mRNA catabolic process	BP	mutant phenotype
positive regulation of cell growth	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
exosome (RNase complex)	CC	direct assay
extracellular exosome	CC	high-throughput assay
nuclear chromosome	CC	direct assay
nuclear exosome (RNase complex)	CC	direct assay
nucleolus	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
RNA binding	MF	high-throughput assay
mRNA 3’-UTR AU-rich region binding	MF	direct assay

Protein interactions and networks

STRING

showing 15 of 1,808 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOSC9	EXOSC10	Q01780	994
EXOSC9	EXOSC6	Q5RKV6	963
EXOSC9	EXOSC5	Q9NQT4	962
EXOSC9	EXOSC3	Q9NQT5	962
EXOSC9	EXOSC1	Q9Y3B2	962
EXOSC9	EXOSC4	Q9NPD3	938
EXOSC9	EXOSC7	Q15024	846
EXOSC9	EXOSC2	Q13868	840
EXOSC9	EXOSC8	Q96B26	840
EXOSC9	DIS3	Q9Y2L1	808
EXOSC9	DIS3L	Q8TF46	783
EXOSC9	MTREX	P42285	746
EXOSC9	C1D	Q13901	735
EXOSC9	ZCCHC7	Q8N3Z6	635
EXOSC9	RBM7	Q9Y580	626

IntAct

Human interaction partners of EXOSC9 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

18 partners by confidence:

Partner	Interaction type	MIscore	Records
EXOSC4	physical association	0.900	3
EXOSC10	association	0.640	2
DIS3L	association	0.600	1
UBE2I	physical association	0.550	2
CHMP4B	physical association	0.370	2
SETX	physical association	0.370	2
CHMP1A	physical association	0.370	1
CHMP5	physical association	0.370	1
ZDHHC17	physical association	0.370	1
MPHOSPH6	association	0.350	1
DDX39B	physical association	0.000	1
ERG	physical association	0.000	1
EXOSC2	physical association	0.000	1
EXOSC7	physical association	0.000	1
LRRC47	physical association	0.000	1
LUM	physical association	0.000	1
RSRC1	physical association	0.000	1
SLIT2	physical association	0.000	1

BioGRID (259 interactions; top human partners by supporting records): EXOSC4 (Co-fractionation; 15 records), EXOSC3 (Affinity Capture-MS; 9 records), EXOSC2 (Co-fractionation; 8 records), EXOSC7 (Affinity Capture-MS; 8 records), EXOSC1 (Co-fractionation; 7 records), EXOSC5 (Co-fractionation; 7 records), MPHOSPH6 (Co-fractionation; 7 records), EXOSC10 (Co-fractionation; 6 records), EXOSC8 (Affinity Capture-MS; 6 records), DIS3L (Affinity Capture-MS; 4 records), C1D (Affinity Capture-MS; 3 records), EXOSC6 (Co-fractionation; 3 records), HBS1L (Affinity Capture-MS; 3 records), ANLN (Affinity Capture-MS; 2 records), APEX1 (Affinity Capture-RNA; 2 records)

SIGNOR signaling

showing 2 of 3 signaling interactions:

A	Effect	B	Mechanism
CSNK2A1	up-regulates	EXOSC9	phosphorylation
EXOSC9	“form complex”	Exosome_Complex	binding

Protein complexes (CORUM) (3)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

3 complexes by size:

Complex	Subunits	Members
Exosome	12	EXOSC3, EXOSC6, EXOSC7, EXOSC8, EXOSC1, EXOSC10, EXOSC4, EXOSC5, EXOSC9, MPHOSPH6, DIS3L, EXOSC2
Exosome	11	EXOSC1, EXOSC2, EXOSC6, EXOSC7, EXOSC9, DIS3, EXOSC10, EXOSC3, EXOSC4, EXOSC5, EXOSC8
Exosome	10	EXOSC9, DIS3, EXOSC2, EXOSC3, EXOSC4, EXOSC5, EXOSC6, EXOSC7, EXOSC8, EXOSC1

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 18 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
Nuclear RNA decay	5	128.6×	2e-08
Major pathway of rRNA processing in the nucleolus and cytosol	5	25.7×	1e-05

GO biological processes:

GO term	Partners	Fold	FDR
RNA catabolic process	5	126.5×	3e-08
RNA processing	6	73.0×	2e-08

Disease & clinical

Genetic variants

Variant evidence for EXOSC9: 337 ClinVar records (29 pathogenic / likely pathogenic); 4 GWAS associations. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	22
Likely pathogenic	7
Uncertain significance	144
Likely benign	112
Benign	31

Top pathogenic / likely-pathogenic (15)

Showing the 15 best-reviewed of 29 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
2143770	NM_005033.3(EXOSC9):c.634C>T (p.Arg212Ter)	Pathogenic	criteria provided, multiple submitters, no conflicts	2
1388577	NM_005033.3(EXOSC9):c.1058_1059del (p.Asp352_Ser353insTer)	Pathogenic	criteria provided, single submitter	1
1407196	NM_005033.3(EXOSC9):c.1157-176del	Pathogenic	criteria provided, single submitter	1
1433763	NM_005033.3(EXOSC9):c.881_905dup (p.Pro302_Ile303insSerIleTer)	Pathogenic	criteria provided, single submitter	1
1468857	NM_005033.3(EXOSC9):c.1062del (p.Lys355fs)	Pathogenic	criteria provided, single submitter	1
1899880	NM_005033.3(EXOSC9):c.1034del (p.Asn345fs)	Pathogenic	criteria provided, single submitter	1
1964976	NM_005033.3(EXOSC9):c.129del (p.Asp42_Tyr43insTer)	Pathogenic	criteria provided, single submitter	1
2075346	NM_005033.3(EXOSC9):c.968C>G (p.Ser323Ter)	Pathogenic	criteria provided, single submitter	1
2112278	NM_005033.3(EXOSC9):c.1174_1175del (p.Ser392fs)	Pathogenic	criteria provided, single submitter	1
2123806	NM_005033.3(EXOSC9):c.1157-182del	Pathogenic	criteria provided, single submitter	1
2778095	NM_005033.3(EXOSC9):c.283C>T (p.Gln95Ter)	Pathogenic	criteria provided, single submitter	1
2812511	NM_005033.3(EXOSC9):c.347_348del (p.Ile116fs)	Pathogenic	criteria provided, single submitter	1
2878488	NM_005033.3(EXOSC9):c.1098del (p.Ile367fs)	Pathogenic	criteria provided, single submitter	1
2968175	NM_005033.3(EXOSC9):c.310C>T (p.Arg104Ter)	Pathogenic	criteria provided, single submitter	1
2993571	NM_005033.3(EXOSC9):c.772_781del (p.Val258fs)	Pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore EXOSC9’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 32 predictions of 1,244):

Position(s)	Effect	Δscore	Sites
4:121801491–121801492	donor_loss	1.0000	3
4:121801825–121801826	acceptor_loss	1.0000	2
4:121801922–121801923	donor_loss	1.0000	5
4:121802672–121802673	acceptor_loss	1.0000	5
4:121804609	acceptor_gain	1.0000
4:121804760–121804761	donor_loss	1.0000	5
4:121811581–121811582	acceptor_loss	1.0000	3
4:121811672–121811673	donor_loss	1.0000	4
4:121813864	acceptor_gain	1.0000
4:121814048–121814049	donor_loss	1.0000	3

AlphaMissense

869 missense substitutions predicted likely pathogenic (of 2,892 scored), across 232 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
D208	8	0.981	0.993
D117	8	0.969	0.989
D147	8	0.966	0.991
H189	8	0.963	0.993
N226	8	0.954	0.997
D25	8	0.953	0.988
F13	8	0.928	0.995
H159	8	0.927	0.985
D31	8	0.913	0.966
F196	8	0.903	0.987
D135	8	0.895	0.947
F198	8	0.881	0.985
D272	8	0.819	0.893
W130	7	0.987	0.998
E213	7	0.982	0.989
R33	7	0.978	0.998
F199	7	0.966	0.988
E119	7	0.960	0.984
F160	7	0.933	0.989
E230	7	0.931	0.982

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.000481
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	0.000549
Head and Neck Squamous Cell Carcinoma (TCGA)	unfavorable	0.000941

Disease associations

OMIM: gene MIM:606180 | disease phenotypes: MIM:618065, MIM:300867, MIM:607596

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
pontocerebellar hypoplasia, type 1D	Strong	Autosomal recessive	4
pontocerebellar hypoplasia type 1	Supportive	Autosomal recessive

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (5 panels, 5 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

5 panels:

Panel	Rating
Adult-onset neurological disorders	green
DDG2P	green
Fetal anomalies	green
Hereditary ataxia, adult onset	green
Paediatric disorders	green

Mondo (4): pontocerebellar hypoplasia, type 1D (MONDO:0054844), Kabuki syndrome 2 (MONDO:0010465), pontocerebellar hypoplasia (MONDO:0020135), pontocerebellar hypoplasia type 1 (MONDO:0016396)

Orphanet (2): Kabuki syndrome (Orphanet:2322), Non-syndromic pontocerebellar hypoplasia (Orphanet:98523)

HPO phenotypes

showing 60 of 65 phenotypes (HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000218	High palate
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000286	Epicanthus
HP:0000316	Hypertelorism
HP:0000369	Low-set ears
HP:0000470	Short neck
HP:0000486	Strabismus
HP:0000529	Progressive visual loss
HP:0000565	Esotropia
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus
HP:0000648	Optic atrophy
HP:0000666	Horizontal nystagmus
HP:0001181	Adducted thumb
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001257	Spasticity
HP:0001263	Global developmental delay
HP:0001265	Hyporeflexia
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001290	Generalized hypotonia
HP:0001308	Tongue fasciculations
HP:0001324	Muscle weakness
HP:0001347	Hyperreflexia
HP:0001348	Brisk reflexes
HP:0001371	Flexion contracture
HP:0001508	Failure to thrive
HP:0001511	Intrauterine growth retardation
HP:0001558	Decreased fetal movement
HP:0001562	Oligohydramnios
HP:0001612	Weak cry
HP:0001999	Abnormal facial shape
HP:0002059	Cerebral atrophy
HP:0002093	Respiratory insufficiency
HP:0002120	Cerebral cortical atrophy
HP:0002205	Recurrent respiratory infections
HP:0002350	Cerebellar cyst
HP:0002380	Fasciculations
HP:0002398	Degeneration of anterior horn cells
HP:0002421	Poor head control
HP:0002804	Arthrogryposis multiplex congenita
HP:0002828	Multiple joint contractures
HP:0002878	Respiratory failure
HP:0003202	Skeletal muscle atrophy
HP:0003324	Generalized muscle weakness
HP:0003477	Peripheral axonal neuropathy
HP:0003577	Congenital onset
HP:0003676	Progressive
HP:0003700	Generalized amyotrophy
HP:0004886	Congenital laryngeal stridor
HP:0006934	Congenital nystagmus
HP:0007002	Motor axonal neuropathy
HP:0007360	Aplasia/Hypoplasia of the cerebellum
HP:0008936	Axial hypotonia
HP:0011461	Fetal onset
HP:0011968	Feeding difficulties

GWAS associations

4 associations:

Study	Trait	p-value
GCST004602_207	Mean corpuscular volume	9e-21
GCST004630_146	Mean corpuscular hemoglobin	6e-18
GCST90002403_334	Red blood cell count	5e-14
GCST90020028_1432	Hip circumference adjusted for BMI	3e-12

EFO canonical traits (from GWAS)

3 canonical traits:

EFO ID	Trait name
EFO:0004527	mean corpuscular hemoglobin
EFO:0004305	erythrocyte count
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors

2 disease descriptors:

Descriptor	Name	Tree numbers
C580383	Pontocerebellar Hypoplasia *(supp.)*
C548069	Pontocerebellar Hypoplasia Type 1 *(supp.)*

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725197 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,601 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

1 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,601

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (2 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
5.64	Kd	2292	nM	CHEMBL5653589
5.51	ED50	3108	nM	CHEMBL5653589
5.47	IC50	3390	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 8 total; 2 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-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2148354: Binding affinity to human EXOSC9 incubated for 45 mins by Kinobead based pull down assay	kd	2.2917	uM
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178924: Inhibition of EXOSC9 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	3.3900	uM

CTD chemical–gene interactions

37 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression, increases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
beta-methylcholine	affects expression	1
CGP 52608	affects binding, increases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
jinfukang	decreases expression	1
incobotulinumtoxinA	decreases expression	1
LDN 193189	affects cotreatment, decreases expression	1
Sunitinib	decreases expression	1
Benzo(a)pyrene	increases methylation	1
Benztropine	affects cotreatment, decreases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Carbamazepine	affects expression	1
Coumestrol	increases expression, affects reaction, affects cotreatment	1
Cuprizone	decreases expression, affects cotreatment	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Hydrogen Peroxide	affects expression	1
Ivermectin	decreases expression	1
Methyl Methanesulfonate	increases expression	1
Methylcholanthrene	affects binding, increases reaction	1
Mustard Gas	decreases expression	1
Piroxicam	decreases expression	1
Quercetin	decreases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651396	Binding	Binding affinity to human EXOSC9 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)

Via MONDO — disease-level, not drug-specific.

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for EXOSC9 across ~30M SureChEMBL compounds — explore on Sugi Predict.