PRPF4

Summary

PRPF4 (pre-mRNA splicing tri-snRNP complex factor PRPF4, HGNC:17349) is a protein-coding gene on chromosome 9q32, encoding U4/U6 small nuclear ribonucleoprotein Prp4 (O43172). 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 99.7% of cancer cell lines).

The protein encoded by this gene is part of a heteromeric complex that binds U4, U5, and U6 small nuclear RNAs and is involved in pre-mRNA splicing. The encoded protein also is a mitotic checkpoint protein and a regulator of chemoresistance in human ovarian cancer. Several transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 9128 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 70 (Definitive, GenCC) — +2 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 392 total — 1 likely-pathogenic
• Phenotypes (HPO): 37
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_001244926

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17349
Approved symbol	PRPF4
Name	pre-mRNA splicing tri-snRNP complex factor PRPF4
Location	9q32
Locus type	gene with protein product
Status	Approved
Aliases	Prp4p, HPRP4, HPRP4P, PRP4, SNRNP60
Ensembl gene	ENSG00000136875
Ensembl biotype	protein_coding
OMIM	607795
Entrez	9128

Gene structure

Transcript identifiers

Ensembl transcripts: 12 — 11 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000374198, ENST00000374199, ENST00000488937, ENST00000894604, ENST00000894605, ENST00000921172, ENST00000921173, ENST00000921174, ENST00000921175, ENST00000921176, ENST00000921177, ENST00000945708

RefSeq mRNA: 4 — MANE Select: NM_001244926 NM_001244926, NM_001322266, NM_001322267, NM_004697

CCDS: CCDS59142, CCDS6791

Canonical transcript exons

ENST00000374198 — 14 exons

Exon	Start	End
ENSE00000806178	113290898	113291016
ENSE00000806180	113290700	113290807
ENSE00000806182	113290466	113290588
ENSE00000806185	113288175	113288264
ENSE00000806186	113286705	113286828
ENSE00000806188	113286232	113286290
ENSE00000806190	113284295	113284389
ENSE00000806192	113283389	113283482
ENSE00000806194	113283132	113283211
ENSE00000806196	113282646	113282733
ENSE00000806199	113278945	113279131
ENSE00001462766	113276548	113276725
ENSE00001519311	113291467	113292905
ENSE00001519346	113275658	113275770

Expression profiles

Bgee: expression breadth ubiquitous, 287 present calls, max score 93.36.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.6061 / max 398.8763, expressed in 1816 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
98080	22.6061	1816

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
secondary oocyte	CL:0000655	93.36	gold quality
corpus epididymis	UBERON:0004359	93.26	gold quality
cartilage tissue	UBERON:0002418	91.19	gold quality
endothelial cell	CL:0000115	89.99	gold quality
islet of Langerhans	UBERON:0000006	89.47	gold quality
cauda epididymis	UBERON:0004360	89.39	gold quality
adrenal tissue	UBERON:0018303	89.17	gold quality
oocyte	CL:0000023	88.95	gold quality
caput epididymis	UBERON:0004358	88.23	gold quality
embryo	UBERON:0000922	86.89	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	86.67	gold quality
ventricular zone	UBERON:0003053	86.54	gold quality
gastrocnemius	UBERON:0001388	86.14	gold quality
ganglionic eminence	UBERON:0004023	85.92	gold quality
muscle of leg	UBERON:0001383	85.91	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	85.23	gold quality
monocyte	CL:0000576	85.09	gold quality
leukocyte	CL:0000738	85.06	gold quality
tendon of biceps brachii	UBERON:0008188	85.06	silver quality
mononuclear cell	CL:0000842	84.92	gold quality
right uterine tube	UBERON:0001302	84.90	gold quality
vermiform appendix	UBERON:0001154	84.86	gold quality
stromal cell of endometrium	CL:0002255	84.85	gold quality
right adrenal gland cortex	UBERON:0035827	84.78	gold quality
left adrenal gland cortex	UBERON:0035825	84.73	gold quality
pancreas	UBERON:0001264	84.72	gold quality
adrenal gland	UBERON:0002369	84.68	gold quality
tendon	UBERON:0000043	84.65	gold quality
muscle organ	UBERON:0001630	84.56	gold quality
left ovary	UBERON:0002119	84.56	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.94

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

55 targeting PRPF4, 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-12118	100.00	65.88	1270
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-6778-3P	99.96	67.29	2693
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-6755-5P	99.95	65.59	464
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-4778-3P	99.93	70.40	1818
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-374C-5P	99.80	72.06	2910
HSA-MIR-655-3P	99.80	72.19	2909
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-548M	99.70	68.87	1749
HSA-MIR-548BA	99.69	69.14	1514
HSA-MIR-4804-3P	99.65	67.78	866
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-6833-5P	99.50	68.93	1161
HSA-MIR-3915	99.45	68.49	1905
HSA-MIR-330-3P	99.41	69.95	2521
HSA-MIR-3160-5P	99.28	69.07	1938
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-194-5P	99.01	69.65	1465
HSA-MIR-12135	98.99	70.26	1814
HSA-MIR-4716-5P	98.82	68.57	1168
HSA-MIR-4297	98.77	66.95	2013
HSA-MIR-5011-3P	98.63	64.81	638

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 8)

• interaction between Hprp3p and Hprp4p (PMID:11971898)
• PRP4 is a spindle assembly checkpoint protein required for MPS1, MAD1, and MAD2 localization to the kinetochores. (PMID:17998396)
• PRP-4 belongs to the serine/threonine protein kinase family, plays a role in pre-mRNA splicing and cell mitosis, and interacts with CLK1 (PMID:18687998)
• the requirement of enzymatic activity of PRP4 in regulating cancer cell growth and identified an array of potential novel substrates through orthogonal proteomics approaches (PMID:24003220)
• PRPF4 missense mutations is associated with autosomal dominant retinitis pigmentosa. (PMID:24419317)
• The p.R192H variant of PRPF4 represents a functional null allele which compromises the function of the tri-snRNP, reinforcing the notion that this spliceosomal particle is of crucial importance in the physiology of the retina. (PMID:25383878)
• Possible molecular mechanism of PRP4-induced actin cytoskeleton remodeling and epithelial-mesenchymal transition, makes PRP4 an important target in colon cancer. (PMID:29787735)
• Results confirmed that the PRPF4 gene was overexpressed in various breast cancer cell lines. Its knockdown slows down breast cancer progression via suppression of p38 MAPK phosphorylation. In conclusion, the PRPF4 gene plays an important role in the growth of breast cancer cells. (PMID:31445970)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf4	ENSDARG00000067639
mus_musculus	Prpf4	ENSMUSG00000066148
rattus_norvegicus	Prpf4	ENSRNOG00000014777
drosophila_melanogaster	U4-U6-60K	FBGN0036733
caenorhabditis_elegans	prp-4	WBGENE00007972

Protein

Protein identifiers

U4/U6 small nuclear ribonucleoprotein Prp4 — O43172 (reviewed: O43172)

Alternative names: PRP4 homolog, U4/U6 snRNP 60 kDa protein, WD splicing factor Prp4

All UniProt accessions (2): O43172, Q5T1M7

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 PRPF18, PPIH and PRPF3. Part of a heteromeric complex containing PPIH, PRPF3 and PRPF4 that is stable in the absence of RNA. Interacts with ERCC6.

Subcellular location. Nucleus. Nucleus speckle.

Disease relevance. Retinitis pigmentosa 70 (RP70) [MIM:615922] 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?
O43172-1	1	yes
O43172-2	2

RefSeq proteins (4): NP_001231855, NP_001309195, NP_001309196, NP_004688 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR014906	PRP4-like	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036285	PRP4-like_sf	Homologous_superfamily
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily

Pfam: PF00400, PF08799

UniProt features (70 total): strand 29, sequence conflict 11, repeat 7, turn 7, helix 6, mutagenesis site 3, sequence variant 2, chain 1, modified residue 1, splice variant 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

25 structures.

PDB	Method	Resolution (Å)
1MZW	X-RAY DIFFRACTION	2
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
8QPA	ELECTRON MICROSCOPY	3.7
8QPB	ELECTRON MICROSCOPY	3.7
6AHD	ELECTRON MICROSCOPY	3.8
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

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O43172-F1	82.33	0.44

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): 27

Mutagenesis-validated functional residues (3):

Position	Phenotype
192	decreases prpf3 binding.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 219 (showing top): DACOSTA_UV_RESPONSE_VIA_ERCC3_UP, BROWNE_HCMV_INFECTION_16HR_UP, MONNIER_POSTRADIATION_TUMOR_ESCAPE_UP, LINDGREN_BLADDER_CANCER_CLUSTER_2A_DN, PUJANA_CHEK2_PCC_NETWORK, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, BACOLOD_RESISTANCE_TO_ALKYLATING_AGENTS_DN, FOSTER_TOLERANT_MACROPHAGE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, WTGAAAT_UNKNOWN, GNF2_XRCC5, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, TATA_C

GO Biological Process (5): RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), RNA processing (GO:0006396), RNA splicing (GO:0008380), mRNA processing (GO:0006397)

GO Molecular Function (3): U6 snRNA binding (GO:0017070), U4 snRNA binding (GO:0030621), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), Cajal body (GO:0015030), nuclear speck (GO:0016607), U4/U6 x U5 tri-snRNP complex (GO:0046540), U4/U6 snRNP (GO:0071001), U2-type precatalytic spliceosome (GO:0071005), spliceosomal snRNP complex (GO:0097525)

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
snRNA binding	2
nuclear ribonucleoprotein granule	2
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U4 snRNP	1
U6 snRNP	1
spliceosomal 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
small nuclear ribonucleoprotein complex	1

Protein interactions and networks

STRING

2359 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF4	PRPF3	O43395	996
PRPF4	PRPF31	Q8WWY3	947
PRPF4	PRPF8	Q6P2Q9	926
PRPF4	PRPF6	O94906	899
PRPF4	PPIH	O43447	889
PRPF4	SNRNP200	O75643	888
PRPF4	EFTUD2	Q15029	764
PRPF4	RP9	Q8TA86	697
PRPF4	DHX38	Q92620	626
PRPF4	SART1	O43290	580
PRPF4	U2AF1	Q01081	571
PRPF4	SART3	Q15020	557
PRPF4	LSM7	Q9UK45	553
PRPF4	DDX23	Q9BUQ8	533
PRPF4	PAXX	Q9BUH6	507

IntAct

141 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
PRPF4	PPIH	psi-mi:“MI:2364”(proximity)	0.910
PPIH	PRPF4	psi-mi:“MI:0915”(physical association)	0.910
PRPF4	PPIH	psi-mi:“MI:0915”(physical association)	0.910
PRPF4	PPIH	psi-mi:“MI:0914”(association)	0.910
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
PPIH	PRPF4	psi-mi:“MI:0407”(direct interaction)	0.910
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
SART3	PRPF4	psi-mi:“MI:0914”(association)	0.730
PRPF3	PRPF4	psi-mi:“MI:0914”(association)	0.730
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
SNRPD2	GEMIN2	psi-mi:“MI:0914”(association)	0.710
SNRPB	PRMT5	psi-mi:“MI:0914”(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
DDX23	PRPF4	psi-mi:“MI:0914”(association)	0.640
PRPF31	PRPF4	psi-mi:“MI:0914”(association)	0.640
PRP4K	PRPF4	psi-mi:“MI:0914”(association)	0.640

BioGRID (433): PRPF4 (Affinity Capture-MS), DDX23 (Co-fractionation), DHX37 (Co-fractionation), LTA4H (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation), PRPF4 (Co-fractionation)

ESM2 similar proteins: A4QNE6, B0BNA7, B5FZ19, O43172, O74184, Q13347, Q29RH4, Q29RZ9, Q38884, Q3KPT3, Q3MHE2, Q3UGF1, Q4R571, Q53HC9, Q561Y0, Q5E959, Q5E966, Q5M7F6, Q5M8I4, Q5MNZ6, Q5NVD0, Q5PPK9, Q5R7W0, Q5XIG8, Q5XJP1, Q5ZL16, Q5ZL33, Q640T2, Q66J51, Q68F45, Q6DUZ9, Q6H8D5, Q6H8D6, Q7ZUW6, Q8BGF3, Q8K0G5, Q8NEZ3, Q8VE80, Q91VM3, Q96J01

Diamond homologs: O22212, O43172, O48847, P41318, Q10282, Q3MHE2, Q5I0B9, Q5NVD0, Q676U5, Q8C0J2, Q9DAW6, Q9FUY2, Q9UTC7, A4RDD7, B0R0D7, O80990, P25382, Q1DPU4, Q5RF51, Q9JJ66

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRPF4	“form complex”	“U4/U6.U5 snRNP complex”	binding
CDK11B	“up-regulates activity”	PRPF4	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 128 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 5’ to 3’ exoribonuclease	7	53.3×	1e-09
Metabolism of non-coding RNA	6	38.1×	3e-07
mRNA Splicing - Minor Pathway	12	26.9×	9e-13
mRNA Splicing	21	23.1×	3e-21
mRNA Splicing - Major Pathway	41	22.4×	4e-43
SARS-CoV-2 modulates host translation machinery	9	20.1×	3e-08
Processing of Capped Intron-Containing Pre-mRNA	23	18.9×	3e-21
mRNA Polyadenylation	18	15.8×	4e-15

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal tri-snRNP complex assembly	7	67.2×	5e-10
spliceosomal snRNP assembly	11	54.6×	8e-15
spliceosomal complex assembly	10	51.4×	4e-13
RNA splicing, via transesterification reactions	8	42.7×	8e-10
U2-type prespliceosome assembly	8	42.7×	8e-10
negative regulation of mRNA splicing, via spliceosome	6	39.3×	5e-07
regulation of mRNA splicing, via spliceosome	5	37.9×	1e-05
mRNA splicing, via spliceosome	39	30.5×	3e-45

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	203
Likely benign	151
Benign	18

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
143057	NM_001244926.2(PRPF4):c.941C>T (p.Pro314Leu)	Likely pathogenic

SpliceAI

1830 predictions. Top by Δscore:

Variant	Effect	Δscore
9:113275699:G:GT	donor_gain	1.0000
9:113275805:G:GT	donor_gain	1.0000
9:113276655:A:T	donor_gain	1.0000
9:113278940:A:AG	acceptor_gain	1.0000
9:113278940:AATAG:A	acceptor_gain	1.0000
9:113278941:A:G	acceptor_gain	1.0000
9:113278943:A:AG	acceptor_gain	1.0000
9:113278944:G:GG	acceptor_gain	1.0000
9:113278944:GGA:G	acceptor_gain	1.0000
9:113279015:G:GT	donor_gain	1.0000
9:113279055:G:GT	donor_gain	1.0000
9:113279122:G:GT	donor_gain	1.0000
9:113282641:A:AG	acceptor_gain	1.0000
9:113282641:AACAG:A	acceptor_gain	1.0000
9:113282643:CAG:C	acceptor_loss	1.0000
9:113282644:A:AG	acceptor_gain	1.0000
9:113282644:A:T	acceptor_loss	1.0000
9:113282644:AG:A	acceptor_gain	1.0000
9:113282645:G:A	acceptor_loss	1.0000
9:113282645:G:GT	acceptor_gain	1.0000
9:113282645:GG:G	acceptor_gain	1.0000
9:113282645:GGT:G	acceptor_gain	1.0000
9:113282645:GGTT:G	acceptor_gain	1.0000
9:113282645:GGTTA:G	acceptor_gain	1.0000
9:113282701:G:GT	donor_gain	1.0000
9:113282722:TCCA:T	donor_gain	1.0000
9:113282729:AAGAG:A	donor_loss	1.0000
9:113282731:G:GT	donor_gain	1.0000
9:113282731:GAG:G	donor_gain	1.0000
9:113282732:AGG:A	donor_loss	1.0000

AlphaMissense

3417 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:113279026:G:C	R97P	1.000
9:113279038:T:A	V101D	1.000
9:113279059:T:A	V108D	1.000
9:113279071:T:A	L112H	1.000
9:113279071:T:C	L112P	1.000
9:113279100:T:C	F122L	1.000
9:113279102:T:A	F122L	1.000
9:113279102:T:G	F122L	1.000
9:113279104:G:A	G123E	1.000
9:113279122:G:C	R129T	1.000
9:113279123:A:C	R129S	1.000
9:113279123:A:T	R129S	1.000
9:113279125:G:C	R130T	1.000
9:113279125:G:T	R130I	1.000
9:113279126:A:C	R130S	1.000
9:113279126:A:T	R130S	1.000
9:113279131:G:C	R132T	1.000
9:113279131:G:T	R132M	1.000
9:113282646:G:C	R132S	1.000
9:113282646:G:T	R132S	1.000
9:113282648:T:C	L133S	1.000
9:113282652:A:C	R134S	1.000
9:113282652:A:T	R134S	1.000
9:113282660:T:C	L137P	1.000
9:113286815:T:A	W308R	1.000
9:113286815:T:C	W308R	1.000
9:113290479:T:A	W347R	1.000
9:113290479:T:C	W347R	1.000
9:113290483:G:C	R348P	1.000
9:113290725:T:A	W392R	1.000

dbSNP variants (sampled 300 via entrez): RS1000033229 (9:113292775 A>G,T), RS1000147463 (9:113276459 T>C), RS1000480157 (9:113276111 C>T), RS1000600816 (9:113288523 G>A), RS1000777457 (9:113282578 A>G,T), RS1000842150 (9:113275549 T>C), RS1001030876 (9:113281084 C>T), RS1001211854 (9:113285594 G>A), RS1001261078 (9:113292354 G>A), RS1001399155 (9:113275666 C>G,T), RS1001730509 (9:113276006 T>G), RS1001806473 (9:113275354 C>G,T), RS1001845953 (9:113291937 G>T), RS1002036630 (9:113281204 A>C,G), RS1002076519 (9:113276236 C>G,T)

Disease associations

OMIM: gene MIM:607795 | disease phenotypes: MIM:615922

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 70	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
inherited retinal dystrophy	Moderate	AD

Mondo (3): retinitis pigmentosa 70 (MONDO:0014400), inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa (MONDO:0019200)

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

HPO phenotypes

37 total (30 of 37 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:0000602	Ophthalmoplegia
HP:0000608	Macular degeneration
HP:0000613	Photophobia
HP:0000618	Blindness
HP:0000639	Nystagmus
HP:0000648	Optic atrophy
HP:0000662	Nyctalopia
HP:0000842	Hyperinsulinemia
HP:0001105	Retinal atrophy
HP:0001133	Constriction of peripheral visual field
HP:0003621	Juvenile onset
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:0007994	Peripheral visual field loss
HP:0008046	Abnormal retinal vascular morphology

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST006221_4	White matter growth	6.000000e-06

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0009335	white matter growth measurement

MeSH disease descriptors (2)

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

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1163119 (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
6.66	IC50	220	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 8 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	2178951: Inhibition of PRPF4 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	0.2200	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, affects expression, decreases expression	3
Cadmium Chloride	decreases expression, increases expression	3
Resveratrol	affects cotreatment, increases expression	2
Estradiol	affects expression, increases expression	2
Aflatoxin B1	increases expression	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
triphenyl phosphate	affects expression	1
deoxynivalenol	increases expression	1
decabromobiphenyl ether	decreases expression	1
tetrahydropalmatine	decreases expression	1
cobaltous chloride	decreases expression	1
tetrabromobisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
triacsin C	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
CGP 52608	affects binding, increases reaction	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
eprenetapopt	affects expression, affects reaction	1
bisphenol S	affects expression	1
PP242	decreases expression	1
Sunitinib	decreases expression	1
Vehicle Emissions	increases expression	1
Benzene	increases expression	1
Coumestrol	affects cotreatment, increases expression	1

ChEMBL screening assays

8 unique, capped per target: 8 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5649398	Binding	Inhibition of PRP4 (unknown origin) assessed as remaining activity at 1 uM by KINOMEscan analysis relative to control	The E3 ligase Cbl-b and TAM receptors regulate cancer metastasis via natural killer cells. — 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