PRPF3

Summary

PRPF3 (pre-mRNA processing factor 3, HGNC:17348) is a protein-coding gene on chromosome 1q21.2, encoding U4/U6 small nuclear ribonucleoprotein Prp3 (O43395). Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex). It is a common-essential gene (DepMap: required in 97.6% of cancer cell lines).

The removal of introns from nuclear pre-mRNAs occurs on complexes called spliceosomes, which are made up of 4 small nuclear ribonucleoprotein (snRNP) particles and an undefined number of transiently associated splicing factors. This gene product is one of several proteins that associate with U4 and U6 snRNPs. Mutations in this gene are associated with retinitis pigmentosa-18.

Source: NCBI Gene 9129 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 18 (Definitive, ClinGen) — +1 more curated relationship
• GWAS associations: 20
• Clinical variants (ClinVar): 447 total — 7 pathogenic, 4 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 97.6% of screened cell lines (common-essential)
• MANE Select transcript: NM_004698

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17348
Approved symbol	PRPF3
Name	pre-mRNA processing factor 3
Location	1q21.2
Locus type	gene with protein product
Status	Approved
Aliases	Prp3, hPrp3, SNRNP90
Ensembl gene	ENSG00000117360
Ensembl biotype	protein_coding
OMIM	607301
Entrez	9129

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 10 protein_coding, 6 protein_coding_CDS_not_defined

ENST00000324862, ENST00000467329, ENST00000467514, ENST00000470824, ENST00000476970, ENST00000493553, ENST00000496202, ENST00000907625, ENST00000907626, ENST00000907627, ENST00000907628, ENST00000907629, ENST00000927114, ENST00000927115, ENST00000957677, ENST00000957678

RefSeq mRNA: 2 — MANE Select: NM_004698 NM_001350529, NM_004698

CCDS: CCDS951

Canonical transcript exons

ENST00000324862 — 16 exons

Exon	Start	End
ENSE00001820718	150321533	150321592
ENSE00003467046	150346408	150346491
ENSE00003476865	150328320	150328466
ENSE00003480922	150334935	150335241
ENSE00003509876	150343309	150343452
ENSE00003517533	150344434	150344547
ENSE00003540686	150332979	150333199
ENSE00003548538	150344162	150344261
ENSE00003555875	150346018	150346136
ENSE00003556831	150325751	150325881
ENSE00003566361	150324895	150325087
ENSE00003577347	150352833	150353233
ENSE00003591399	150332684	150332767
ENSE00003614956	150338160	150338326
ENSE00003658310	150340398	150340477
ENSE00003677592	150349157	150349218

Expression profiles

Bgee: expression breadth ubiquitous, 290 present calls, max score 97.39.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 39.9001 / max 354.6034, expressed in 1826 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
5093	37.9673	1824
5091	0.9824	578
5094	0.6050	335
5092	0.3453	156

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	97.39	gold quality
right uterine tube	UBERON:0001302	97.18	gold quality
left ovary	UBERON:0002119	96.97	gold quality
right ovary	UBERON:0002118	96.76	gold quality
left lobe of thyroid gland	UBERON:0001120	96.72	gold quality
right lobe of thyroid gland	UBERON:0001119	96.65	gold quality
adenohypophysis	UBERON:0002196	96.45	gold quality
tibial nerve	UBERON:0001323	96.28	gold quality
thyroid gland	UBERON:0002046	96.25	gold quality
cerebellar hemisphere	UBERON:0002245	96.19	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.11	gold quality
cerebellar cortex	UBERON:0002129	96.06	gold quality
body of uterus	UBERON:0009853	96.04	gold quality
endocervix	UBERON:0000458	95.97	gold quality
calcaneal tendon	UBERON:0003701	95.77	gold quality
pituitary gland	UBERON:0000007	95.72	gold quality
granulocyte	CL:0000094	95.71	gold quality
body of pancreas	UBERON:0001150	95.61	gold quality
ectocervix	UBERON:0012249	95.59	gold quality
metanephros cortex	UBERON:0010533	95.36	gold quality
spleen	UBERON:0002106	95.29	gold quality
small intestine Peyer’s patch	UBERON:0003454	95.21	gold quality
mucosa of stomach	UBERON:0001199	95.16	gold quality
right lung	UBERON:0002167	95.15	gold quality
left uterine tube	UBERON:0001303	95.14	gold quality
skin of abdomen	UBERON:0001416	95.12	gold quality
minor salivary gland	UBERON:0001830	94.98	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.96	gold quality
right lobe of liver	UBERON:0001114	94.92	gold quality
skin of leg	UBERON:0001511	94.72	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.13

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): HNF4A

miRNA regulators (miRDB)

29 targeting PRPF3, 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-450A-1-3P	100.00	69.33	1837
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-12119	99.87	68.35	1653
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-5007-3P	99.51	68.14	1242
HSA-MIR-4251	99.40	69.19	3363
HSA-MIR-501-3P	99.33	66.12	651
HSA-MIR-502-3P	99.33	66.12	651
HSA-MIR-5589-3P	99.29	68.30	1443
HSA-MIR-6809-5P	99.13	68.45	1223
HSA-MIR-4478	99.07	65.16	2320
HSA-MIR-4646-3P	98.65	66.98	693
HSA-MIR-4733-3P	98.35	65.20	994
HSA-MIR-92A-1-5P	98.28	64.51	631
HSA-MIR-6867-3P	98.12	66.07	1305
HSA-MIR-4303	98.01	68.13	2304
HSA-MIR-6783-5P	97.67	67.21	1528
HSA-MIR-3936	97.64	64.47	732
HSA-MIR-618	97.62	67.46	861
HSA-MIR-6818-5P	97.50	67.10	1167
HSA-MIR-939-5P	97.10	65.80	1579
HSA-MIR-1343-5P	96.48	66.06	1506
HSA-MIR-4740-5P	96.25	67.96	726

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 97.6% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 17)

• Mutations in HPRP3, a third member of pre-mRNA splicing factor genes, implicated in autosomal dominant retinitis pigmentosa. (PMID:11773002)
• The human HPRP3 gene, the orthologue of the yeast pre-mRNA splicing factor (PRP3) (PMID:11773002)
• role in the recruitment of Hprp4p for the U4/U6 snRNP assembly (PMID:11971898)
• Nine mutations, six of which are novel, in the pre-mRNA splicing-factor genes PRPF3, PRPF8, and PRPF31, causing adRP have been identified in the Spanish population. (PMID:12714658)
• Free and complexed cyclophilin H have virtually identical conformations suggesting that the U4/U6-60K binding site is pre-shaped and the peptidyl-prolyl-cis/trans isomerase activity is unaffected by complex formation (PMID:12875835)
• We conclude that the Thr494Met mutation in the HPRP3 gene causes ADRP in Japanese patients. This mutation was found in 1% of patients with ADRP in Japan (PMID:15085354)
• PAP-1 interacted with Prp3p but not Prp31p in human cells and yeast, and the basic region of PAP-1 and the C-terminal region of Prp3p, regions beside spots found in retinitis pigmentosa mutations, were needed for binding (PMID:15541726)
• splicing factor PRPF3 mutations cause retinal degeneration and form detrimental aggregates in photoreceptor cells (PMID:17517693)
• Findings suggest that the loss of Hprp3p phosphorylation at Thr494 is a key step for initiating Thr494Met aberrant interactions within U4/U6 snRNP complex and these are likely linked to the retinitis pigmentosa type 18 phenotype. (PMID:17932117)
• splicing activity is significantly influenced by the CK2-hPrp3p interaction (PMID:18026141)
• U2AF35 and hPrp3 interactions with SPF30 can occur simultaneously, thereby potentially linking 3’ splice site recognition with tri-small nuclear ribonucleoprotein addition (PMID:18211889)
• TASP1, EPS15R, and PRPF3 expression were significantly induced in HCCs of transgenic EGF2B mice as was P2 promoter-driven HNF4alpha (PMID:18395097)
• These data support the notion about individual roles for CK2alpha and CK2alpha’ in the splicing process. (PMID:18553058)
• A mutation in the PRPF3 gene is rare compared to other genes causing autosomal dominant retinitis pigmentosa. (PMID:20309403)
• RP-PRPF defects affect the stoichiometry of spliceosomal small nuclear RNAs. Mutant PRPF3 proteins stably associated with tri-snRNPs. (PMID:21378395)
• Results from whole-exome sequencing identified 2 variants c.1345C > G (p.R449G) and c.1532A > C (p.H511P) in PRPF3 which co-segregate with retinitis pigmentosa in two families respectively. (PMID:27886254)
• SUMO conjugation plays a role during mRNA splicing processes including a role for Prp3 SUMOylation in U4/U6*U5 tri-snRNP formation and/or recruitment. (PMID:28379520)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf3	ENSDARG00000086425
mus_musculus	Prpf3	ENSMUSG00000015748
rattus_norvegicus	Prpf3	ENSRNOG00000025629
drosophila_melanogaster	Prp3	FBGN0036915
caenorhabditis_elegans		WBGENE00010844

Protein

Protein identifiers

U4/U6 small nuclear ribonucleoprotein Prp3 — O43395 (reviewed: O43395)

Alternative names: Pre-mRNA-splicing factor 3, U4/U6 snRNP 90 kDa protein

All UniProt accessions (1): O43395

UniProt curated annotations — full annotation on UniProt →

Function. Plays a role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).

Subunit / interactions. Component of the precatalytic spliceosome (spliceosome B complex). Component of the U4/U6-U5 tri-snRNP complex, a building block of the precatalytic spliceosome (spliceosome B complex). The U4/U6-U5 tri-snRNP complex is composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, SNRPB, SNRPD1, SNRPD2, SNRPD3, SNRPE, SNRPF, SNRPG, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, plus LSM2, LSM3, LSM4, LSM5, LSM6, LSM7 and LSM8. Interacts directly with PRPF4. Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA. Interacts with SART3; the interaction is direct and recruits the deubiquitinase USP4 to PRPF3. Interacts with PRPF19. Interacts (‘Lys-63’-linked polyubiquitinated) with PRPF8 (via the MPN (JAB/Mov34) domain); may stabilize the U4/U6-U5 tri-snRNP complex. Interacts with ERCC6.

Subcellular location. Nucleus. Nucleus speckle.

Tissue specificity. Highly expressed in retina, liver, kidney and blood. Detected at lower levels in heart and brain.

Post-translational modifications. Ubiquitinated. Undergoes ‘Lys-63’-linked polyubiquitination by PRPF19 and deubiquitination by USP4. ‘Lys-63’-linked ubiquitination increases the affinity for PRPF8 and may regulate the assembly of the U4/U6-U5 tri-snRNP complex.

Disease relevance. Retinitis pigmentosa 18 (RP18) [MIM:601414] A retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. The disease is caused by variants affecting the gene represented in this entry.

Isoforms (2)

UniProt ID	Names	Canonical?
O43395-1	1	yes
O43395-3	2

RefSeq proteins (2): NP_001337458, NP_004689* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR002483	PWI_dom	Domain
IPR010541	Prp3_C	Domain
IPR013881	Pre-mRNA_splic_Prp3_dom	Domain
IPR027104	Prp3	Family
IPR036483	PWI_dom_sf	Homologous_superfamily

Pfam: PF01480, PF06544, PF08572

UniProt features (43 total): helix 15, strand 6, cross-link 3, splice variant 3, sequence variant 3, region of interest 3, modified residue 3, sequence conflict 2, turn 2, chain 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

30 structures.

PDB	Method	Resolution (Å)
7N2R	X-RAY DIFFRACTION	2.28
7N2S	X-RAY DIFFRACTION	2.37
7N2N	X-RAY DIFFRACTION	2.6
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
6QW6	ELECTRON MICROSCOPY	2.92
8Q7N	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8Y6O	ELECTRON MICROSCOPY	3.38
8QP8	ELECTRON MICROSCOPY	3.5
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
6AHD	ELECTRON MICROSCOPY	3.8
8QP9	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
6AH0	ELECTRON MICROSCOPY	5.7
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1
8RM5	ELECTRON MICROSCOPY	6.9
3JCR	ELECTRON MICROSCOPY	7
8QXD	ELECTRON MICROSCOPY	9.6
1X4Q	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43395-F1	73.75	0.24

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 (6): 244, 252, 164, 167, 619, 139

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway

MSigDB gene sets: 206 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_DN, GSE18804_SPLEEN_MACROPHAGE_VS_BRAIN_TUMORAL_MACROPHAGE_DN, ENK_UV_RESPONSE_KERATINOCYTE_UP, GAUSSMANN_MLL_AF4_FUSION_TARGETS_A_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, GGAANCGGAANY_UNKNOWN, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, WEST_ADRENOCORTICAL_CARCINOMA_VS_ADENOMA_UP, REACTOME_MRNA_SPLICING, AACTTT_UNKNOWN, BASAKI_YBX1_TARGETS_UP, AGTCAGC_MIR345

GO Biological Process (5): spliceosomal tri-snRNP complex assembly (GO:0000244), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (3): RNA binding (GO:0003723), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytosol (GO:0005829), Cajal body (GO:0015030), nuclear speck (GO:0016607), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
cellular anatomical structure	2
nuclear ribonucleoprotein granule	2
spliceosomal snRNP assembly	1
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
protein binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cytoplasm	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
cellular_component	1

Protein interactions and networks

STRING

2606 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF3	PRPF4	O43172	996
PRPF3	PRPF31	Q8WWY3	993
PRPF3	PRPF8	Q6P2Q9	990
PRPF3	PRPF6	O94906	988
PRPF3	PPIH	O43447	988
PRPF3	SNRNP200	O75643	959
PRPF3	SART1	O43290	912
PRPF3	RP9	Q8TA86	891
PRPF3	SNU13	P55769	871
PRPF3	PPIA	P05092	826
PRPF3	EFTUD2	Q15029	822
PRPF3	FSCN2	O14926	811
PRPF3	SART3	Q15020	802
PRPF3	TOPORS	Q9NS56	796
PRPF3	IMPDH1	P20839	790

IntAct

285 interactions, top by confidence:

A	B	Type	Score
KIFAP3	KIF3B	psi-mi:“MI:0914”(association)	0.900
PRPF3	FAM9B	psi-mi:“MI:0915”(physical association)	0.810
FAM9B	PRPF3	psi-mi:“MI:0915”(physical association)	0.810
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
PRPF3	TRIM39	psi-mi:“MI:0915”(physical association)	0.720
PRPF3	SART1	psi-mi:“MI:0915”(physical association)	0.720
SART1	PRPF3	psi-mi:“MI:0915”(physical association)	0.720
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
PRPF3	TRIM39	psi-mi:“MI:0915”(physical association)	0.670
TRIM39	PRPF3	psi-mi:“MI:0915”(physical association)	0.670
PRPF6	PRPF3	psi-mi:“MI:0915”(physical association)	0.670
PRPF3	PRPF6	psi-mi:“MI:0915”(physical association)	0.670
PRPF8	PRPF4	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
SNRNP40	PRPF4	psi-mi:“MI:0914”(association)	0.640
LSM5	LSM1	psi-mi:“MI:0914”(association)	0.640
PRPF3	MID2	psi-mi:“MI:0915”(physical association)	0.560
PRPF3	PSMD3	psi-mi:“MI:0915”(physical association)	0.560
PRPF3	GPRASP2	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (475): TRIM39 (Two-hybrid), FAM9B (Two-hybrid), BRCA1 (Two-hybrid), PRPF3 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), PRPF3 (Affinity Capture-MS), CCDC85B (Two-hybrid), GTPBP3 (Two-hybrid), PRPF3 (Two-hybrid), DPY30 (Two-hybrid), PRPF3 (Two-hybrid), CD2BP2 (Co-fractionation)

ESM2 similar proteins: A0A5F9D2E6, A1XQU3, O13784, O42387, O43395, O59865, P02377, P12001, P16149, P21533, P35980, P47911, P62847, P62848, P62849, P62850, P69090, P69091, P82915, Q2HJ41, Q2KIA6, Q2YDN6, Q2YGT9, Q3T0U2, Q4R5H5, Q56JU9, Q58DQ3, Q5E973, Q5EAV6, Q5R5F1, Q5RAQ8, Q5REY4, Q5XGS8, Q5ZJ85, Q6Y263, Q8LC83, Q90YQ0, Q90YU3, Q922U1, Q943Z6

Diamond homologs: O43395, Q09856, Q2KIA6, Q5R5F1, Q5ZJ85, Q922U1, Q9C7E7

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
CSNK2A1	up-regulates	PRPF3	phosphorylation
PRPF19	“up-regulates activity”	PRPF3	polyubiquitination
PRPF3	“form complex”	“U4/U6.U5 snRNP complex”	binding
USP4	“down-regulates activity”	PRPF3	deubiquitination
MECP2	“up-regulates activity”	PRPF3	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 134 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
Metabolism of non-coding RNA	6	40.9×	2e-07
mRNA Splicing	22	26.0×	2e-23
mRNA Splicing - Minor Pathway	10	24.1×	5e-10
SARS-CoV-2 modulates host translation machinery	9	21.7×	1e-08
mRNA Splicing - Major Pathway	36	21.1×	2e-36
Processing of Capped Intron-Containing Pre-mRNA	23	20.3×	4e-22
RNA Polymerase II Transcription Termination	7	16.5×	8e-06
mRNA Polyadenylation	17	16.1×	2e-14

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal snRNP assembly	12	58.6×	8e-17
spliceosomal tri-snRNP complex assembly	6	56.6×	4e-08
spliceosomal complex assembly	10	50.6×	4e-13
U2-type prespliceosome assembly	9	47.2×	2e-11
RNA splicing, via transesterification reactions	8	42.0×	9e-10
mRNA splicing, via spliceosome	34	26.2×	1e-36
RNA splicing	22	16.3×	3e-18
mRNA export from nucleus	5	12.4×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	7
Likely pathogenic	4
Uncertain significance	192
Likely benign	162
Benign	41

Top pathogenic / likely-pathogenic (11)

Variant ID	HGVS	Classification
1996039	NM_004698.4(PRPF3):c.1426+1G>A	Pathogenic
2016027	NM_004698.4(PRPF3):c.591dup (p.Asp198Ter)	Pathogenic
3352	NM_004698.4(PRPF3):c.1481C>T (p.Thr494Met)	Pathogenic
3353	NM_004698.4(PRPF3):c.1477C>T (p.Pro493Ser)	Pathogenic
3354	NM_004698.4(PRPF3):c.1466C>A (p.Ala489Asp)	Pathogenic
812123	NM_004698.4(PRPF3):c.1285G>T (p.Asp429Tyr)	Pathogenic
813205	NM_004698.4(PRPF3):c.1496A>C (p.His499Pro)	Pathogenic
2747842	NM_004698.4(PRPF3):c.1283-1G>A	Likely pathogenic
848318	NM_004698.4(PRPF3):c.1427-2A>C	Likely pathogenic
866476	NM_004698.4(PRPF3):c.1532A>C (p.His511Pro)	Likely pathogenic
982384	NM_004698.4(PRPF3):c.1504G>C (p.Ala502Pro)	Likely pathogenic

SpliceAI

2621 predictions. Top by Δscore:

Variant	Effect	Δscore
1:150321588:GTGAG:G	donor_gain	1.0000
1:150321589:TGAG:T	donor_gain	1.0000
1:150321590:GAG:G	donor_gain	1.0000
1:150321590:GAGG:G	donor_gain	1.0000
1:150321592:GGT:G	donor_loss	1.0000
1:150321593:G:GG	donor_gain	1.0000
1:150324890:TTTA:T	acceptor_loss	1.0000
1:150324893:A:AG	acceptor_gain	1.0000
1:150324893:A:C	acceptor_loss	1.0000
1:150324894:G:GT	acceptor_gain	1.0000
1:150324894:GGT:G	acceptor_gain	1.0000
1:150324937:T:TA	acceptor_gain	1.0000
1:150324944:T:TA	acceptor_gain	1.0000
1:150325083:AGCCG:A	donor_gain	1.0000
1:150325084:GCCG:G	donor_gain	1.0000
1:150325084:GCCGG:G	donor_gain	1.0000
1:150325085:CCG:C	donor_gain	1.0000
1:150325086:CG:C	donor_gain	1.0000
1:150325087:GG:G	donor_gain	1.0000
1:150325088:G:GG	donor_gain	1.0000
1:150325088:GTAT:G	donor_loss	1.0000
1:150325750:GATC:G	acceptor_gain	1.0000
1:150325878:AAAGG:A	donor_loss	1.0000
1:150325881:GGTA:G	donor_loss	1.0000
1:150325882:G:T	donor_loss	1.0000
1:150325883:T:A	donor_loss	1.0000
1:150328317:TAG:T	acceptor_loss	1.0000
1:150328318:A:AG	acceptor_gain	1.0000
1:150328318:A:T	acceptor_loss	1.0000
1:150328319:G:GA	acceptor_loss	1.0000

AlphaMissense

4482 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:150325039:G:C	A33P	1.000
1:150325042:G:C	A34P	1.000
1:150325043:C:A	A34E	1.000
1:150325757:T:C	L51P	1.000
1:150325790:T:C	F62S	1.000
1:150325802:T:C	L66P	1.000
1:150332685:T:C	I142T	1.000
1:150332705:G:C	A149P	1.000
1:150332718:T:A	I153N	1.000
1:150332718:T:C	I153T	1.000
1:150332718:T:G	I153S	1.000
1:150332728:G:C	R156S	1.000
1:150332728:G:T	R156S	1.000
1:150333066:G:C	A199P	1.000
1:150333067:C:A	A199D	1.000
1:150333078:G:C	A203P	1.000
1:150333087:G:C	A206P	1.000
1:150333090:G:C	A207P	1.000
1:150333097:T:C	L209P	1.000
1:150333102:G:C	A211P	1.000
1:150333109:T:A	I213N	1.000
1:150333109:T:C	I213T	1.000
1:150333109:T:G	I213S	1.000
1:150334973:T:A	L256Q	1.000
1:150334973:T:C	L256P	1.000
1:150334976:T:A	I257N	1.000
1:150334979:T:A	L258Q	1.000
1:150334979:T:C	L258P	1.000
1:150334990:G:A	G262R	1.000
1:150334990:G:C	G262R	1.000

dbSNP variants (sampled 300 via entrez): RS1000036711 (1:150335620 C>T), RS1000073723 (1:150329304 C>T), RS1000283208 (1:150321628 C>T), RS1000424954 (1:150328981 C>T), RS1000659475 (1:150352503 G>A), RS1000767465 (1:150346562 C>T), RS1000820278 (1:150346885 G>A), RS1001030340 (1:150326967 A>G,T), RS1001032895 (1:150334139 T>C,G), RS1001473479 (1:150334604 G>A,C), RS1001674264 (1:150347447 A>T), RS1001765835 (1:150334861 G>A,T), RS1001931611 (1:150351641 C>T), RS1002047729 (1:150351879 A>G), RS1002161179 (1:150338984 T>C)

Disease associations

OMIM: gene MIM:607301 | disease phenotypes: MIM:268000, MIM:601414

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 18	Definitive	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
retinitis pigmentosa 18	Definitive	AD

Mondo (3): retinitis pigmentosa (MONDO:0019200), retinitis pigmentosa 18 (MONDO:0011075), inherited retinal dystrophy (MONDO:0019118)

Orphanet (2): Retinitis pigmentosa (Orphanet:791), OBSOLETE: Inherited retinal disorder (Orphanet:71862)

HPO phenotypes

36 total (30 of 36 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000501	Glaucoma
HP:0000505	Visual impairment
HP:0000510	Rod-cone dystrophy
HP:0000512	Abnormal electroretinogram
HP:0000543	Optic disc pallor
HP:0000546	Retinal degeneration
HP:0000551	Color vision defect
HP:0000563	Keratoconus
HP:0000575	Scotoma
HP:0000602	Ophthalmoplegia
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007737	Spicular pigmentation of the retina
HP:0007787	Posterior subcapsular cataract
HP:0007843	Attenuation of retinal blood vessels
HP:0007987	Progressive visual field defects
HP:0007994	Peripheral visual field loss
HP:0008043	Focal retinal arteriolar constriction
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

20 associations (top):

Study	Trait	p-value
GCST003837_3	Chronotype	6.000000e-17
GCST003838_3	Morning vs. evening chronotype	5.000000e-07
GCST004603_167	Platelet count	2.000000e-09
GCST004607_204	Plateletcrit	3.000000e-10
GCST007204_2	Low density lipoprotein cholesterol levels	5.000000e-07
GCST007565_193	Morning person	8.000000e-30
GCST010002_366	Refractive error	3.000000e-15
GCST010696_11	Cortical thickness (min-P)	2.000000e-23
GCST010697_17	Cortical surface area (min-P)	9.000000e-09
GCST010698_23	Subcortical volume (min-P)	2.000000e-08
GCST010699_48	Brain morphology (min-P)	3.000000e-08
GCST010700_28	Cortical thickness (MOSTest)	8.000000e-38
GCST010701_113	Cortical surface area (MOSTest)	9.000000e-12
GCST010702_126	Subcortical volume (MOSTest)	4.000000e-09
GCST010703_244	Brain morphology (MOSTest)	9.000000e-12
GCST011352_16	Alanine aminotransferase levels	2.000000e-08
GCST90002402_490	Platelet count	1.000000e-15
GCST90002407_668	White blood cell count	9.000000e-17
GCST90013420_1	Ambidextrousness	3.000000e-10
GCST90020026_628	Hip index	4.000000e-08

EFO canonical traits (8, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007985	platelet crit
EFO:0004611	low density lipoprotein cholesterol measurement
EFO:0008328	chronotype measurement
EFO:0004346	neuroimaging measurement
EFO:0004840	cortical thickness
EFO:0009902	handedness
EFO:0008039	BMI-adjusted hip circumference

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D058499	Retinal Dystrophies	C11.768.585.658
D012174	Retinitis Pigmentosa	C11.270.684; C11.768.585.658.500; C16.320.290.684
C563320	Retinitis Pigmentosa 18 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725149 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

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

pChembl	Type	Value	Unit	Molecule
6.48	IC50	330	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 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
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178541: Inhibition of PRPF3 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.3300	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	decreases expression, affects expression	3
bisphenol A	decreases expression, increases expression	2
Benzo(a)pyrene	increases mutagenesis, affects methylation	2
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
sodium arsenate	decreases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
jinfukang	affects cotreatment, decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Cisplatin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Methotrexate	decreases expression	1
Ribonucleotides	affects binding	1
Smoke	decreases expression	1
Vitamin E	increases expression	1
Cyclosporine	increases expression	1
Aflatoxin B1	increases methylation	1
Lactic Acid	increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697271	Binding	Inhibition of PRPF3 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00717080	PHASE4	COMPLETED	The Role of Capsular Tension Ring (CTR) in Anterior Capsular Contraction
NCT00000114	PHASE3	COMPLETED	Randomized Trial of Vitamin A and Vitamin E Supplementation for Retinitis Pigmentosa
NCT00000116	PHASE3	COMPLETED	Randomized Trial of DHA for Retinitis Pigmentosa Patients Receiving Vitamin A
NCT00346333	PHASE3	COMPLETED	Clinical Trial of Lutein for Patients With Retinitis Pigmentosa Receiving Vitamin A
NCT01786395	PHASE3	TERMINATED	Phase III Efficacy and Safety Clinical Study of UF-021 for Treatment of Retinitis Pigmentosa
NCT04224207	PHASE3	COMPLETED	Management of Retinitis Pigmentosa by Mesenchymal Stem Cells by Wharton’s Jelly Derived Mesenchymal Stem Cells
NCT04636853	PHASE3	COMPLETED	CB-PRP in Retinitis Pigmentosa and Dry Age-related Macular Degeneration
NCT05537220	PHASE3	ACTIVE_NOT_RECRUITING	Oral N-acetylcysteine for Retinitis Pigmentosa
NCT05800301	PHASE3	COMPLETED	Management of Retinitis Pigmentosa Via Combination of Wharton’s Jelly-derived Mesenchymal Stem Cells and Magnovision
NCT05926583	PHASE3	ACTIVE_NOT_RECRUITING	A Study of AAV5-hRKp.RPGR for the Treatment of Japanese Participants With X-linked Retinitis Pigmentosa
NCT06388200	PHASE3	ACTIVE_NOT_RECRUITING	A Phase 3 Study Of OCU400 Gene Therapy for the Treatment Of Retinitis Pigmentosa
NCT07082855	PHASE3	NOT_YET_RECRUITING	A Multicenter, Randomized, Double-Blind, Controlled Clinical Study of Minocycline for the Treatment of Retinitis Pigmentosa
NCT07290530	PHASE3	NOT_YET_RECRUITING	24-Month Trial of NPI-001 for the Preservation of Photoreceptors in Retinitis Pigmentosa Associated With Usher Syndrome
NCT00100230	PHASE2	COMPLETED	DHA and X-Linked Retinitis Pigmentosa
NCT00447980	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Participants With Early Stage Retinitis Pigmentosa
NCT00447993	PHASE2	COMPLETED	A Study of Encapsulated Cell Technology (ECT) Implant for Patients With Late Stage Retinitis Pigmentosa
NCT01233609	PHASE2	COMPLETED	Trial of Oral Valproic Acid for Retinitis Pigmentosa
NCT01399515	PHASE2	COMPLETED	Efficacy and Safety of Oral Valproic Acid for Retinitis Pigmentosa
NCT01530659	PHASE2	COMPLETED	Retinal Imaging in CNTF -Releasing Encapsulated Cell Implant Treated Patients for Early-stage Retinitis Pigmentosa
NCT01560715	PHASE2	COMPLETED	Autologous Bone Marrow-Derived Stem Cells Transplantation For Retinitis Pigmentosa
NCT02609165	PHASE2	COMPLETED	Nerve Growth Factor Eye Drops Treatment in Patients With Retinitis Pigmentosa and Cystoid Macular Edema
NCT02661711	PHASE2	COMPLETED	Aflibercept for Macular Oedema With Underlying Retinitis Pigmentosa (AMOUR) Study
NCT02804360	PHASE2	UNKNOWN	Intravitreal Dexamethasone Implant in Retinitis Pigmentosa-related Macular Edema- a Retrospective Study
NCT02837640	PHASE2	UNKNOWN	Studying a Potential Protective Effect of L-Dopa on Retinitis Pigmentosa
NCT03073733	PHASE2	COMPLETED	Safety and Efficacy of Intravitreal Injection of Human Retinal Progenitor Cells in Adults With Retinitis Pigmentosa
NCT04068207	PHASE2	COMPLETED	Minocycline Treatment in Retinitis Pigmentosa
NCT04356716	PHASE2	COMPLETED	Sildenafil for Treatment of Choroidal Ischemia
NCT04604899	PHASE2	COMPLETED	Safety of Repeat Intravitreal Injection of Human Retinal Progenitor Cells (jCell) in Adult Subjects With Retinitis Pigmentosa
NCT04763369	PHASE2	UNKNOWN	Investigation of Therapeutic Efficacy and Safety of UMSCs for the Management of Retinitis Pigmentosa (RP)
NCT04864496	PHASE2	UNKNOWN	Effects of Treatment With N- Acetylcysteine on Visual Outcomes in Patients With Retinitis Pigmentosa
NCT04945772	PHASE2	COMPLETED	Efficacy and Safety of MCO-010 Optogenetic Therapy in Adults With Retinitis Pigmentosa [RESTORE]
NCT05085964	PHASE2	TERMINATED	An Open-Label Extension Study to Evaluate Safety & Tolerability of QR-421a in Subjects With Retinitis Pigmentosa
NCT05392179	PHASE2	COMPLETED	A Study in Subjects With Retinitis Pigmentosa
NCT06627179	PHASE2	RECRUITING	Study to Evaluate Ultevursen in Subjects With Retinitis Pigmentosa (RP) Due to Mutations in Exon 13 of the USH2A Gene
NCT06628947	PHASE2	RECRUITING	A Phase II Study of Intravitreal KIO-301 in Patients With Late-stage Retinitis Pigmentosa
NCT06912633	PHASE2	RECRUITING	Safety of a Single, Intravitreal Injection of 6.0M jCell (Famzeretcel) in Retinitis Pigmentosa (RP)
NCT03763227	PHASE2	COMPLETED	Intravitreal Ranibizumab (Lucentis®) in the Treatment of Non-leaking Macular Cysts in Retinal Dystrophy
NCT00063765	PHASE1	COMPLETED	Evaluation of Safety of Ciliary Neurotrophic Factor Implants in the Eye
NCT00065455	PHASE1	COMPLETED	Investigating the Effect of Vitamin A Supplementation on Retinitis Pigmentosa
NCT00458575	PHASE1	TERMINATED	A Study to Evaluate the Safety of CNTO 2476 in Patients With Advanced Retinitis Pigmentosa