EXOSC2

Summary

EXOSC2 (exosome component 2, HGNC:17097) is a protein-coding gene on chromosome 9q34.12, encoding Exosome complex component RRP4 (Q13868). 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 98.3% of cancer cell lines).

Predicted to enable RNA binding activity. Involved in RNA catabolic process; RNA processing; and positive regulation of cell growth. Located in cytosol; nucleolus; and nucleoplasm. Part of nuclear exosome (RNase complex). Implicated in short stature, hearing loss, retinitis pigmentosa, and distinctive facies.

Source: NCBI Gene 23404 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (Strong, GenCC)
• Clinical variants (ClinVar): 303 total — 2 likely-pathogenic
• Phenotypes (HPO): 43
• Cancer dependency (DepMap): dependent in 98.3% of screened cell lines (common-essential)
• MANE Select transcript: NM_014285

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17097
Approved symbol	EXOSC2
Name	exosome component 2
Location	9q34.12
Locus type	gene with protein product
Status	Approved
Aliases	hRrp4p, Rrp4p, RRP4, p7
Ensembl gene	ENSG00000130713
Ensembl biotype	protein_coding
OMIM	602238
Entrez	23404

Gene structure

Transcript identifiers

Ensembl transcripts: 45 — 17 protein_coding, 13 nonsense_mediated_decay, 11 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000372350, ENST00000372351, ENST00000372352, ENST00000372358, ENST00000430138, ENST00000463488, ENST00000467138, ENST00000490641, ENST00000491115, ENST00000495699, ENST00000546165, ENST00000685137, ENST00000685277, ENST00000686102, ENST00000686106, ENST00000687051, ENST00000687420, ENST00000688258, ENST00000688350, ENST00000688364, ENST00000688967, ENST00000689662, ENST00000689890, ENST00000691104, ENST00000691162, ENST00000691284, ENST00000691425, ENST00000691926, ENST00000691956, ENST00000692554, ENST00000692794, ENST00000693011, ENST00000693435, ENST00000693610, ENST00000851442, ENST00000851443, ENST00000851444, ENST00000851445, ENST00000851446, ENST00000917908, ENST00000917909, ENST00000954431, ENST00000954432, ENST00000954433, ENST00000954434

RefSeq mRNA: 3 — MANE Select: NM_014285 NM_001282708, NM_001282709, NM_014285

CCDS: CCDS65160, CCDS65161, CCDS6935

Canonical transcript exons

ENST00000372358 — 9 exons

Exon	Start	End
ENSE00003458912	130699329	130699394
ENSE00003472459	130695492	130695593
ENSE00003489687	130700867	130700935
ENSE00003520620	130698162	130698251
ENSE00003655953	130697582	130697627
ENSE00003679934	130693780	130693913
ENSE00003690464	130702134	130702310
ENSE00003788968	130703053	130703181
ENSE00003848430	130703694	130704892

Expression profiles

Bgee: expression breadth ubiquitous, 256 present calls, max score 91.28.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.9712 / max 553.9949, expressed in 1805 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
99029	24.9712	1805

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	91.28	gold quality
ventricular zone	UBERON:0003053	90.81	gold quality
cortical plate	UBERON:0005343	88.46	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.31	gold quality
calcaneal tendon	UBERON:0003701	87.92	gold quality
cerebellar hemisphere	UBERON:0002245	87.27	gold quality
cerebellar cortex	UBERON:0002129	87.17	gold quality
left ovary	UBERON:0002119	87.13	gold quality
granulocyte	CL:0000094	87.07	gold quality
right hemisphere of cerebellum	UBERON:0014890	86.94	gold quality
right ovary	UBERON:0002118	86.87	gold quality
endometrium epithelium	UBERON:0004811	86.65	gold quality
rectum	UBERON:0001052	86.63	gold quality
embryo	UBERON:0000922	86.61	gold quality
left uterine tube	UBERON:0001303	86.02	gold quality
sural nerve	UBERON:0015488	85.87	gold quality
body of uterus	UBERON:0009853	85.77	gold quality
cerebellum	UBERON:0002037	85.75	gold quality
colonic epithelium	UBERON:0000397	85.71	gold quality
body of pancreas	UBERON:0001150	85.62	gold quality
monocyte	CL:0000576	85.58	gold quality
islet of Langerhans	UBERON:0000006	85.42	gold quality
muscle of leg	UBERON:0001383	85.22	gold quality
stromal cell of endometrium	CL:0002255	85.21	gold quality
gastrocnemius	UBERON:0001388	85.16	gold quality
mucosa of stomach	UBERON:0001199	85.08	gold quality
ovary	UBERON:0000992	85.06	gold quality
right lobe of liver	UBERON:0001114	85.04	gold quality
body of stomach	UBERON:0001161	85.03	gold quality
skin of abdomen	UBERON:0001416	85.00	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

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting EXOSC2, 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-6778-3P	99.96	67.29	2693
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-136-5P	99.50	67.26	1153
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-6882-5P	99.35	71.13	1206
HSA-MIR-1273H-3P	99.29	67.55	980
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-4742-3P	98.73	69.82	1803
HSA-MIR-4726-3P	98.49	63.89	1385
HSA-MIR-6827-5P	98.46	64.88	1256
HSA-MIR-138-1-3P	98.25	67.89	867
HSA-MIR-3166	98.24	66.63	1223
HSA-MIR-4443	98.02	66.25	1928
HSA-MIR-3144-5P	97.64	65.45	646
HSA-MIR-4639-3P	97.54	67.12	787
HSA-MIR-3200-5P	97.34	65.97	826
HSA-MIR-5187-3P	97.28	67.10	1037
HSA-MIR-4264	96.35	64.76	1480

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.3% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• Protein-protein interactions between human exosome components support the assembly of RNase PH-type subunits into a six-membered PNPase-like ring. (PMID:12419256)
• Knock-down of hRrp41p or hRrp4p but not PM/Scl-100 or PM/Scl-75 leads to codepletion of other subunits. (PMID:17545563)
• The EXOSC2-associated phenotype shows only minimal overlap with the previously reported diseases associated with mutations. (PMID:26843489)
• Genetic and genomic studies of pathogenic EXOSC2 mutations in the newly described disease SHRF implicate the autophagy pathway in disease pathogenesis. (PMID:31628467)
• A budding yeast model for human disease mutations in the EXOSC2 cap subunit of the RNA exosome complex. (PMID:34162742)
• Low expression of EXOSC2 protects against clinical COVID-19 and impedes SARS-CoV-2 replication. (PMID:36241425)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	exosc2	ENSDARG00000028688
mus_musculus	Exosc2	ENSMUSG00000039356
rattus_norvegicus	Exosc2	ENSRNOG00000009245
drosophila_melanogaster	Rrp4	FBGN0034879
caenorhabditis_elegans		WBGENE00022232

Paralogs (1): EXOSC3 (ENSG00000107371)

Protein

Protein identifiers

Exosome complex component RRP4 — Q13868 (reviewed: Q13868)

Alternative names: Exosome component 2, Ribosomal RNA-processing protein 4

All UniProt accessions (9): Q13868, A0A8I5KRS5, A0A8I5KV47, A0A8I5KVY3, A0A8I5KYK9, A0A8I5QL34, A3KFL2, A3KFL5, B4E001

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. EXOSC2 as peripheral part of the Exo-9 complex stabilizes the hexameric ring of RNase PH-domain subunits through contacts with EXOSC4 and EXOSC7.

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 EXOSC4 and EXOSC7. 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 with GTPBP1. Interacts with ZFP36L1 (via N-terminus).

Subcellular location. Cytoplasm. Nucleus. Nucleolus.

Disease relevance. Short stature, hearing loss, retinitis pigmentosa, and distinctive facies (SHRF) [MIM:617763] An autosomal recessive disorder characterized by childhood myopia, early onset retinitis pigmentosa, progressive sensorineural hearing loss, hypothyroidism, short stature, brachydactyly, recognisable facial gestalt, premature ageing and mild intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the RRP4 family.

Isoforms (3)

UniProt ID	Names	Canonical?
Q13868-1	1	yes
Q13868-2	2
Q13868-3	3

RefSeq proteins (3): NP_001269637, NP_001269638, NP_055100* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004088	KH_dom_type_1	Domain
IPR012340	NA-bd_OB-fold	Homologous_superfamily
IPR025721	Exosome_cplx_N_dom	Domain
IPR026699	Exosome_RNA_bind1/RRP40/RRP4	Family
IPR036612	KH_dom_type_1_sf	Homologous_superfamily
IPR048565	S1_RRP4	Domain

Pfam: PF14382, PF15985, PF21266

UniProt features (36 total): strand 16, helix 7, turn 6, splice variant 2, sequence variant 2, chain 1, domain 1, modified residue 1

Structure

Experimental structures (PDB)

8 structures.

PDB	Method	Resolution (Å)
9G8M	ELECTRON MICROSCOPY	3.3
2NN6	X-RAY DIFFRACTION	3.35
9G8O	ELECTRON MICROSCOPY	3.4
6D6Q	ELECTRON MICROSCOPY	3.45
6D6R	ELECTRON MICROSCOPY	3.45
9G8N	ELECTRON MICROSCOPY	3.7
6H25	ELECTRON MICROSCOPY	3.8
9G8P	ELECTRON MICROSCOPY	7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13868-F1	81.25	0.31

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 (1): 124

Function

Pathways and Gene Ontology

Reactome pathways

7 pathways

ID	Pathway
R-HSA-380994	ATF4 activates genes in response to endoplasmic reticulum stress
R-HSA-429958	mRNA decay by 3’ to 5’ exoribonuclease
R-HSA-450385	Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA
R-HSA-450513	Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA
R-HSA-450604	KSRP (KHSRP) binds and destabilizes mRNA
R-HSA-6791226	Major pathway of rRNA processing in the nucleolus and cytosol
R-HSA-9930044	Nuclear RNA decay

MSigDB gene sets: 328 (showing top): GOBP_RIBOSOME_BIOGENESIS, REACTOME_UNFOLDED_PROTEIN_RESPONSE_UPR, GOMF_RNA_NUCLEASE_ACTIVITY, GOMF_NUCLEASE_ACTIVITY, GOBP_SNO_S_RNA_METABOLIC_PROCESS, MODULE_45, KAAB_HEART_ATRIUM_VS_VENTRICLE_UP, GOBP_TRNA_METABOLIC_PROCESS, MATTIOLI_MGUS_VS_PCL, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, KENNY_CTNNB1_TARGETS_UP, GRAESSMANN_RESPONSE_TO_MC_AND_DOXORUBICIN_DN, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, MODULE_16

GO Biological Process (11): 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), positive regulation of cell growth (GO:0030307), U4 snRNA 3’-end processing (GO:0034475), CUT catabolic process (GO:0071034), nuclear polyadenylation-dependent rRNA catabolic process (GO:0071035), TRAMP-dependent tRNA surveillance pathway (GO:0071038), poly(A)-dependent snoRNA 3’-end processing (GO:0071051)

GO Molecular Function (5): 3’-5’-RNA exonuclease activity (GO:0000175), RNA binding (GO:0003723), 7S RNA binding (GO:0008312), exonuclease activity (GO:0004527), protein binding (GO:0005515)

GO Cellular Component (9): nuclear exosome (RNase complex) (GO:0000176), cytoplasmic exosome (RNase complex) (GO:0000177), exosome (RNase complex) (GO:0000178), nucleus (GO:0005634), nucleoplasm (GO:0005654), nucleolus (GO:0005730), cytoplasm (GO:0005737), cytosol (GO:0005829), nucleolar exosome (RNase complex) (GO:0101019)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
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
Metabolism of RNA	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
nuclear lumen	3
cellular anatomical structure	3
nuclear RNA surveillance	2
exosome (RNase complex)	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
rRNA metabolic process	1
ribosome biogenesis	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
RNA metabolic process	1
nucleic acid catabolic process	1
regulation of cell growth	1
cell growth	1
positive regulation of growth	1
positive regulation of cellular process	1
snRNA 3’-end processing	1
RNA catabolic process	1
tRNA surveillance	1
sno(s)RNA 3’-end processing	1
3’-5’ exonuclease activity	1
RNA exonuclease activity, producing 5’-phosphomonoesters	1
nucleic acid binding	1
RNA binding	1
nuclease activity	1
hydrolase activity, acting on ester bonds	1
binding	1
nucleus	1
nuclear protein-containing complex	1
exoribonuclease complex	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1
nuclear exosome (RNase complex)	1
nucleolus	1

Protein interactions and networks

STRING

2147 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EXOSC2	EXOSC3	Q9NQT5	996
EXOSC2	EXOSC1	Q9Y3B2	996
EXOSC2	EXOSC7	Q15024	991
EXOSC2	EXOSC6	Q5RKV6	984
EXOSC2	EXOSC4	Q9NPD3	982
EXOSC2	EXOSC8	Q96B26	978
EXOSC2	EXOSC5	Q9NQT4	972
EXOSC2	EXOSC9	Q06265	943
EXOSC2	DIS3	Q9Y2L1	819
EXOSC2	EXOSC10	Q01780	775
EXOSC2	MTREX	P42285	714
EXOSC2	C1D	Q13901	709
EXOSC2	DIS3L	Q8TF46	649
EXOSC2	GRIPAP1	Q4V328	649
EXOSC2	RBM7	Q9Y580	641

IntAct

134 interactions, top by confidence:

A	B	Type	Score
EXOSC4	EXOSC2	psi-mi:“MI:0915”(physical association)	0.910
EXOSC2	EXOSC4	psi-mi:“MI:0915”(physical association)	0.910
EXOSC3	EXOSC2	psi-mi:“MI:0915”(physical association)	0.910
EXOSC7	EXOSC2	psi-mi:“MI:0915”(physical association)	0.890
EXOSC2	EXOSC7	psi-mi:“MI:0915”(physical association)	0.890
EXOSC1	EXOSC2	psi-mi:“MI:0914”(association)	0.850
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
EXOSC3	EXOSC10	psi-mi:“MI:0914”(association)	0.790
EXOSC2	MPHOSPH6	psi-mi:“MI:0915”(physical association)	0.770
DIS3	EXOSC10	psi-mi:“MI:0914”(association)	0.740
COMMD4	VPS26C	psi-mi:“MI:0914”(association)	0.730
C1D	EXOSC10	psi-mi:“MI:0914”(association)	0.730
DIS3L	EXOSC2	psi-mi:“MI:0914”(association)	0.690
MPHOSPH6	MTREX	psi-mi:“MI:0914”(association)	0.690
PTK2	TGFB1I1	psi-mi:“MI:0914”(association)	0.680
rep	MPHOSPH10	psi-mi:“MI:0914”(association)	0.660
C1D	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
EXOSC3	MTREX	psi-mi:“MI:0914”(association)	0.640
EXOSC5	ZFC3H1	psi-mi:“MI:0914”(association)	0.640
EXOSC9	EXOSC10	psi-mi:“MI:0914”(association)	0.640

BioGRID (322): EXOSC2 (Affinity Capture-RNA), EXOSC2 (Affinity Capture-MS), EXOSC2 (Affinity Capture-MS), EXOSC2 (Affinity Capture-MS), EXOSC2 (Affinity Capture-MS), DIS3 (Co-fractionation), EXOSC10 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation), EXOSC2 (Co-fractionation)

ESM2 similar proteins: A0A0U1WZ18, A0A1S4A695, A2VE01, A4FV08, A4IHW6, C7EXK4, D3ZRP6, O88958, P38421, P43246, P43247, P46279, P46926, P61221, P61222, P62318, P62320, P62323, P62487, P62488, P62489, Q13868, Q1W374, Q1W375, Q1W376, Q1W377, Q24208, Q259G4, Q2KID0, Q3MHE4, Q3SYW1, Q4R7R3, Q503E1, Q5E9B8, Q5R8T8, Q5XXB5, Q5ZJL4, Q64422, Q6PA43, Q7XPW5

Diamond homologs: A1RXQ7, A5UJS0, A9A5C8, B1L6N8, D5U396, E0SQX5, E3GZ90, O26780, O29758, O59221, Q13868, Q469M4, Q4JB26, Q5JIR5, Q6L222, Q8PTT9, Q8TPX7, Q8TYC0, Q8U0L8, Q8ZVM8, Q975G7, Q97BZ6, Q9HIP3, Q9UXC4, Q9V120, Q9YC02, P38792, Q09704, Q2KID0, Q8VBV3, Q95XD0, Q9ZVT7, Q12ZB8

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
EXOSC2	“form complex”	Exosome_Complex	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 114 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	8	65.6×	2e-11
Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA	8	58.3×	3e-11
Tristetraprolin (TTP, ZFP36) binds and destabilizes mRNA	8	58.3×	3e-11
KSRP (KHSRP) binds and destabilizes mRNA	8	58.3×	3e-11
Nuclear RNA decay	14	49.7×	2e-18
ATF4 activates genes in response to endoplasmic reticulum stress	8	37.5×	2e-09
rRNA processing in the nucleus and cytosol	8	14.8×	4e-06
Major pathway of rRNA processing in the nucleolus and cytosol	20	14.2×	2e-15

GO biological processes:

GO term	Partners	Fold	FDR
rRNA catabolic process	7	66.7×	7e-10
RNA catabolic process	12	52.5×	2e-15
maturation of 5.8S rRNA	5	50.6×	3e-06
nuclear-transcribed mRNA catabolic process	5	36.8×	1e-05
RNA processing	14	29.5×	1e-14
rRNA processing	14	19.1×	4e-12
ribosomal small subunit biogenesis	7	15.3×	2e-05
negative regulation of translation	7	13.2×	4e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	2
Uncertain significance	148
Likely benign	127
Benign	11

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
2442149	NM_014285.7(EXOSC2):c.611G>A (p.Trp204Ter)	Likely pathogenic
446203	NM_014285.7(EXOSC2):c.593G>A (p.Gly198Asp)	Likely pathogenic

SpliceAI

1312 predictions. Top by Δscore:

Variant	Effect	Δscore
9:130693910:TGCG:T	donor_gain	1.0000
9:130693910:TGCGG:T	donor_loss	1.0000
9:130693911:GCG:G	donor_gain	1.0000
9:130693911:GCGG:G	donor_gain	1.0000
9:130693914:G:C	donor_loss	1.0000
9:130693914:G:GG	donor_gain	1.0000
9:130693915:T:G	donor_loss	1.0000
9:130695475:T:G	acceptor_gain	1.0000
9:130695479:C:CA	acceptor_gain	1.0000
9:130695487:ATCAG:A	acceptor_gain	1.0000
9:130699393:GT:G	donor_gain	1.0000
9:130702211:T:TA	acceptor_gain	1.0000
9:130703040:T:TA	acceptor_gain	1.0000
9:130703049:A:AG	acceptor_gain	1.0000
9:130703050:T:G	acceptor_gain	1.0000
9:130703050:TAGC:T	acceptor_loss	1.0000
9:130703051:A:AG	acceptor_gain	1.0000
9:130703051:AGCCT:A	acceptor_gain	1.0000
9:130703052:G:GG	acceptor_gain	1.0000
9:130703052:GC:G	acceptor_gain	1.0000
9:130703052:GCC:G	acceptor_gain	1.0000
9:130703052:GCCT:G	acceptor_gain	1.0000
9:130703052:GCCTG:G	acceptor_gain	1.0000
9:130703067:T:TA	acceptor_gain	1.0000
9:130703161:G:GT	donor_gain	1.0000
9:130703179:CAGG:C	donor_loss	1.0000
9:130703180:AGG:A	donor_loss	1.0000
9:130703181:GGTAC:G	donor_loss	1.0000
9:130703692:A:AG	acceptor_gain	1.0000
9:130703692:AGA:A	acceptor_loss	1.0000

AlphaMissense

1902 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:130698177:T:A	W96R	1.000
9:130698177:T:C	W96R	1.000
9:130697599:G:A	G81E	0.999
9:130697614:G:A	G86E	0.999
9:130697617:G:C	R87P	0.999
9:130698178:G:C	W96S	0.999
9:130698179:G:C	W96C	0.999
9:130698179:G:T	W96C	0.999
9:130700867:G:C	A143P	0.999
9:130700868:C:A	A143D	0.999
9:130700916:G:T	R159M	0.999
9:130702238:C:A	N200K	0.999
9:130702238:C:G	N200K	0.999
9:130702240:G:A	G201D	0.999
9:130702248:T:A	W204R	0.999
9:130702248:T:C	W204R	0.999
9:130695493:G:C	G42R	0.998
9:130695494:G:A	G42D	0.998
9:130695500:G:A	G44E	0.998
9:130695530:C:A	A54E	0.998
9:130695542:G:A	G58D	0.998
9:130695566:T:C	L66S	0.998
9:130697599:G:T	G81V	0.998
9:130697602:A:T	D82V	0.998
9:130697613:G:A	G86R	0.998
9:130697613:G:C	G86R	0.998
9:130698214:T:C	L108S	0.998
9:130699330:G:C	R121T	0.998
9:130699331:G:C	R121S	0.998
9:130699331:G:T	R121S	0.998

dbSNP variants (sampled 300 via entrez): RS1000064620 (9:130701488 G>A,T), RS1000082707 (9:130697855 A>G,T), RS1000158856 (9:130691850 C>G), RS1000645967 (9:130695164 T>C), RS1001414509 (9:130703285 C>A,G), RS1001593582 (9:130697143 G>A), RS1001760788 (9:130703512 C>G), RS1002068791 (9:130704410 A>G), RS1002495136 (9:130696295 G>T), RS1002548991 (9:130695964 A>C), RS1002717639 (9:130693032 C>T), RS1002831285 (9:130701791 C>A,T), RS1002998205 (9:130699694 T>G), RS1003500028 (9:130695005 G>A,C), RS1003555993 (9:130694716 G>A,C)

Disease associations

OMIM: gene MIM:602238 | disease phenotypes: MIM:617763

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome	Strong	Autosomal recessive

Mondo (2): retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (MONDO:0044634), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Retinitis pigmentosa-hearing loss-premature aging-short stature-facial dysmorphism syndrome (Orphanet:494439), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

43 total (30 of 43 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000219	Thin upper lip vermilion
HP:0000343	Long philtrum
HP:0000358	Posteriorly rotated ears
HP:0000365	Hearing impairment
HP:0000369	Low-set ears
HP:0000455	Broad nasal tip
HP:0000463	Anteverted nares
HP:0000486	Strabismus
HP:0000490	Deeply set eye
HP:0000501	Glaucoma
HP:0000510	Rod-cone dystrophy
HP:0000545	Myopia
HP:0000582	Upslanted palpebral fissure
HP:0000639	Nystagmus
HP:0000662	Nyctalopia
HP:0000750	Delayed speech and language development
HP:0000821	Hypothyroidism
HP:0000822	Hypertension
HP:0001131	Corneal dystrophy
HP:0001156	Brachydactyly
HP:0001256	Mild intellectual disability
HP:0001263	Global developmental delay
HP:0001270	Motor delay
HP:0001272	Cerebellar atrophy
HP:0001321	Cerebellar hypoplasia
HP:0002120	Cerebral cortical atrophy
HP:0002135	Basal ganglia calcification
HP:0002188	Delayed CNS myelination
HP:0002232	Patchy alopecia

GWAS associations

0 associations (top):

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects binding, increases reaction, decreases expression, increases activity, affects expression	4
bisphenol A	decreases expression, decreases methylation	2
deoxynivalenol	increases expression	2
Estradiol	increases expression	2
Tretinoin	decreases expression	2
Particulate Matter	decreases reaction, increases expression, affects cotreatment, decreases expression, increases abundance	2
GSK-J4	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
bufotalin	decreases expression	1
methylmercuric chloride	decreases expression	1
bis(tri-n-butyltin)oxide	decreases expression	1
sodium arsenate	decreases expression	1
trichostatin A	affects expression	1
afimoxifene	decreases reaction, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
cobaltous chloride	decreases expression	1
potassium chromate(VI)	increases expression	1
isobutyl alcohol	affects cotreatment, decreases expression, increases abundance	1
cylindrospermopsin	increases expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	decreases expression	1
2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazophenyl)amide	decreases reaction, increases expression	1
NSC 689534	affects binding, decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Temozolomide	increases expression	1
Sunitinib	decreases expression	1
Arsenic Trioxide	decreases expression	1
Troglitazone	decreases expression	1
Air Pollutants	affects expression, increases abundance	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05902962	PHASE1	COMPLETED	SAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects
NCT06319872	PHASE1	RECRUITING	The Effects of Disulfiram (Antabuse®) on Visual Acuity in Patients With Retinal Degeneration
NCT06455826	PHASE1	COMPLETED	MAD of IVT VP-001 in PRPF31 Mutation-Associated Retinal Dystrophy Subjects (Wallaby)
NCT04855045	PHASE2/PHASE3	UNKNOWN	An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene.
NCT03872479	PHASE1/PHASE2	UNKNOWN	Single Ascending Dose Study in Participants With LCA10
NCT04123626	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Study to Evaluate the Safety and Tolerability of QR-1123 in Subjects With Autosomal Dominant Retinitis Pigmentosa Due to the P23H Mutation in the RHO Gene
NCT04545736	PHASE1/PHASE2	RECRUITING	Oral Metformin for Treatment of ABCA4 Retinopathy
NCT06212297	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Fellow-eye Study (FE) of LX101 in Subjects With Inherited Retinal Dystrophy
NCT06852963	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	A Repeat-Dose, Open-Label, Two Arm Safety and Efficacy Study of Two Doses of VP-001 Administered Intravitreally in Participants With Confirmed PRPF31 Mutation-Associated Retinal Dystrophy, Including Participants Previously Treated With VP001
NCT07177196	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Personalized Antisense Oligonucleotide Therapy for a Single Participant With PRPH2 Mutation Associated With Retinal Dystrophy
NCT07063030	EARLY_PHASE1	RECRUITING	A Study of LX107 Gene Therapy in AIPL1-IRD Patients
NCT01546181	Not specified	COMPLETED	Retinal Imaging by Adaptive Optics in Healthy Eyes and During Retinal and General Diseases
NCT01876147	Not specified	COMPLETED	Visual and Functional Assessment in Low Vision Patients
NCT01920867	Not specified	UNKNOWN	Stem Cell Ophthalmology Treatment Study
NCT02014389	Not specified	RECRUITING	Evaluation of Objective Perimetry Using Chromatic Multifocal Pupillometer
NCT02983305	Not specified	COMPLETED	Optical Head-Mounted Display Technology for Low Vision Rehabilitation
NCT03592017	Not specified	COMPLETED	Performance of Long-wavelength Autofluorescence Imaging
NCT03662386	Not specified	TERMINATED	Prospective Analysis of Genotype-phenotype Correlations Observed in a Large Cohort of Patients With Hereditary Retinal Dystrophies - GEPHIRD
NCT03691168	Not specified	UNKNOWN	Multi-center Observation of the Natural Course of Inherited Retinal Dystrophies
NCT03843840	Not specified	COMPLETED	Dual Wavelength OCT
NCT03853252	Not specified	COMPLETED	iPS Cells of Patients for Models of Retinal Dystrophies
NCT05130385	Not specified	UNKNOWN	High Resolution Optical Coherence Tomography
NCT05294978	Not specified	RECRUITING	EyeConic: Qualification for Cone-Optogenetics
NCT05573984	Not specified	ACTIVE_NOT_RECRUITING	Natural History of PRPF31 Mutation-Associated Retinal Dystrophy
NCT05793515	Not specified	COMPLETED	Mechanisms of Inherited Retinal Dystrophies Using Whole Genome Sequencing and in Vitro and in Vivo Models
NCT05820100	Not specified	COMPLETED	Observational Study to Assess the Reliability and Validity of the MLYMT and MLSDT
NCT05976139	Not specified	RECRUITING	Micropulsed Laser in Patients With Macular Oedema in Retinal Dystrophies
NCT06162585	Not specified	ACTIVE_NOT_RECRUITING	Non-Interventional Long Term Follow-up Study of Participants Previously Enrolled in the RESTORE Study
NCT06177977	Not specified	RECRUITING	SS-HH-OCT as a Novel Diagnostic Modality for Early-Onset Retinal Dystrophies (EORDs)
NCT06375239	Not specified	RECRUITING	Observational Study to Assess Endpoint Operational Feasibility & Measurement Properties in Patients with Retinal Degeneration
NCT06908161	Not specified	NOT_YET_RECRUITING	Functional Assessments in Vision Impairment
NCT07085533	Not specified	RECRUITING	Natural History Study of Inherited Retinal Diseases
NCT07502664	Not specified	RECRUITING	Development and Evaluation of Functional Visual Field and Navigation Endpoints in Moderate to Profound Inherited Retinal Disease (DEFINE-IRD)
NCT07529041	Not specified	ENROLLING_BY_INVITATION	Real-time Acoustic Biofeedback for Enhancing Fixation Stability: A Proof-of-concept Study to Improve Ophthalmic Imaging Diagnostic Quality