PRPF6

Summary

PRPF6 (pre-mRNA processing factor 6, HGNC:15860) is a protein-coding gene on chromosome 20q13.33, encoding Pre-mRNA-processing factor 6 (O94906). Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

The protein encoded by this gene appears to be involved in pre-mRNA splicing, possibly acting as a bridging factor between U5 and U4/U6 snRNPs in formation of the spliceosome. The encoded protein also can bind androgen receptor, providing a link between transcriptional activation and splicing.

Source: NCBI Gene 24148 — RefSeq curated summary.

At a glance

• Gene–disease (curated): retinitis pigmentosa 60 (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 4
• Clinical variants (ClinVar): 688 total — 1 likely-pathogenic
• Phenotypes (HPO): 36
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_012469

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:15860
Approved symbol	PRPF6
Name	pre-mRNA processing factor 6
Location	20q13.33
Locus type	gene with protein product
Status	Approved
Aliases	TOM, bB152O15.1, ANT-1, U5-102K, Prp6, hPrp6, SNRNP102, RP60
Ensembl gene	ENSG00000101161
Ensembl biotype	protein_coding
OMIM	613979
Entrez	24148

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 19 protein_coding

ENST00000266079, ENST00000855537, ENST00000855538, ENST00000855539, ENST00000855540, ENST00000855541, ENST00000855542, ENST00000855543, ENST00000855544, ENST00000855545, ENST00000936329, ENST00000936330, ENST00000936331, ENST00000936332, ENST00000936333, ENST00000961100, ENST00000961101, ENST00000961102, ENST00000961103

RefSeq mRNA: 1 — MANE Select: NM_012469 NM_012469

CCDS: CCDS13550

Canonical transcript exons

ENST00000266079 — 21 exons

Exon	Start	End
ENSE00000409281	64011285	64011503
ENSE00000663632	63983047	63983215
ENSE00000663633	63984907	63985025
ENSE00000663634	63993407	63993485
ENSE00000663635	63994916	63995092
ENSE00000663636	63995327	63995482
ENSE00000663637	63999045	63999139
ENSE00000663638	63999603	63999759
ENSE00000663639	64001077	64001239
ENSE00000663640	64010200	64010318
ENSE00000663641	64016723	64016845
ENSE00000663642	64022757	64022878
ENSE00000663643	64024555	64024693
ENSE00000663644	64025939	64026058
ENSE00000663645	64026982	64027158
ENSE00000663646	64027603	64027736
ENSE00000663647	64028478	64028569
ENSE00000663648	64029377	64029491
ENSE00000663649	64031918	64032044
ENSE00000856670	63981132	63981316
ENSE00000856671	64032841	64033100

Expression profiles

Bgee: expression breadth ubiquitous, 289 present calls, max score 96.77.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 94.9598 / max 618.1733, expressed in 1825 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
185897	67.7548	1822
185900	15.6009	1780
185898	6.3079	1739
185896	3.4059	1581
185899	1.8903	1196

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	96.77	gold quality
cortical plate	UBERON:0005343	96.41	gold quality
paraflocculus	UBERON:0005351	95.81	gold quality
cerebellar hemisphere	UBERON:0002245	95.47	gold quality
cerebellar cortex	UBERON:0002129	95.46	gold quality
type B pancreatic cell	CL:0000169	95.37	silver quality
right hemisphere of cerebellum	UBERON:0014890	95.20	gold quality
endometrium epithelium	UBERON:0004811	95.04	gold quality
cerebellum	UBERON:0002037	95.00	gold quality
ganglionic eminence	UBERON:0004023	94.97	gold quality
right uterine tube	UBERON:0001302	94.87	gold quality
ventricular zone	UBERON:0003053	94.78	gold quality
tendon	UBERON:0000043	94.76	gold quality
skin of leg	UBERON:0001511	94.40	gold quality
calcaneal tendon	UBERON:0003701	94.32	gold quality
popliteal artery	UBERON:0002250	93.85	gold quality
tibial artery	UBERON:0007610	93.84	gold quality
skin of abdomen	UBERON:0001416	93.68	gold quality
sural nerve	UBERON:0015488	93.59	gold quality
granulocyte	CL:0000094	93.53	gold quality
muscle of leg	UBERON:0001383	93.53	gold quality
gastrocnemius	UBERON:0001388	93.51	gold quality
apex of heart	UBERON:0002098	93.41	gold quality
mucosa of stomach	UBERON:0001199	93.37	gold quality
nipple	UBERON:0002030	93.34	gold quality
cerebellar vermis	UBERON:0004720	93.33	gold quality
triceps brachii	UBERON:0001509	93.32	silver quality
aorta	UBERON:0000947	93.28	gold quality
left ovary	UBERON:0002119	93.26	gold quality
hindlimb stylopod muscle	UBERON:0004252	93.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.50

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

10 targeting PRPF6, 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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-7154-3P	97.65	65.02	985
HSA-MIR-6730-3P	97.03	67.54	889

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 10)

• identification as a coactivator for the androgen receptor [p102 U5 small nuclear ribonucleoprotein particle-binding protein] (PMID:12039962)
• The interaction of CD2BP2 with a tri-snRNP bridging protein (Prp6), coupled with CD2BP2’s absence from the tri-snRNP, suggests it might function in tri-snRNP assembly (PMID:15840814)
• C20orf14 may have a role in progression of lymphoma (PMID:18278469)
• The authors provide evidence that PRP6 and PRP31 are directly phosphorylated by human PRP4 kinase (PRP4K) concomitant with their incorporation into B complexes. (PMID:20118938)
• Our results identify PRPF6 as the sixth gene involved in pre-mRNA splicing and dominant RP, corroborating the hypothesis that deficiencies in the spliceosome play an important role in the molecular pathology of this disease. (PMID:21549338)
• an essential role for PRPF6 in cancer via splicing of distinct growth-related gene products. (PMID:24788092)
• Splicing factor PRPF6 upregulates oncogenic androgen receptor signaling pathway in hepatocellular carcinoma. (PMID:32745318)
• PRPF6 promotes androgen receptor/androgen receptor-variant 7 actions in castration-resistant prostate cancer cells. (PMID:33390843)
• PRPF6 promotes metastasis and paclitaxel resistance of ovarian cancer via SNHG16/CEBPB/GATA3 axis. (PMID:37303939)
• Pathogenic Variants in USH1G/SANS Alter Protein Interaction with Pre-RNA Processing Factors PRPF6 and PRPF31 of the Spliceosome. (PMID:38139438)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf6	ENSDARG00000091367
mus_musculus	Prpf6	ENSMUSG00000002455
rattus_norvegicus	Linc00176	ENSRNOG00000051498
drosophila_melanogaster	Prp6	FBGN0036828
caenorhabditis_elegans		WBGENE00013343
caenorhabditis_elegans	syf-1	WBGENE00016837

Paralogs (2): XAB2 (ENSG00000076924), CRNKL1 (ENSG00000101343)

Protein

Protein identifiers

Pre-mRNA-processing factor 6 — O94906 (reviewed: O94906)

Alternative names: Androgen receptor N-terminal domain-transactivating protein 1, PRP6 homolog, U5 snRNP-associated 102 kDa protein

All UniProt accessions (1): O94906

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex, one of the building blocks of the spliceosome. Enhances dihydrotestosterone-induced transactivation activity of AR, as well as dexamethasone-induced transactivation activity of NR3C1, but does not affect estrogen-induced transactivation.

Subunit / interactions. Identified in the spliceosome B complex. Identified in the spliceosome C complex. Associates with the U5 snRNP particle. Component of the U4/U6-U5 tri-snRNP complex composed of the U4, U6 and U5 snRNAs and at least PRPF3, PRPF4, PRPF6, PRPF8, PRPF31, SNRNP200, TXNL4A, SNRNP40, DDX23, CD2BP2, PPIH, SNU13, EFTUD2, SART1 and USP39, LSm proteins LSm2-8 and Sm proteins. Interacts with ARAF. Interacts with AR and NR3C1, but not ESR1, independently of the presence of hormones. Interacts with USH1G.

Subcellular location. Nucleus. Nucleoplasm. Nucleus speckle.

Tissue specificity. Widely expressed.

Post-translational modifications. Phosphorylated by PRP4K during spliceosome assembly.

Disease relevance. Retinitis pigmentosa 60 (RP60) [MIM:613983] 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 may be caused by variants affecting the gene represented in this entry. Cells from RP60 patients show intron retention for pre-mRNA bearing specific splicing signals.

Isoforms (2)

UniProt ID	Names	Canonical?
O94906-1	1	yes
O94906-2	2

RefSeq proteins (1): NP_036601* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003107	HAT	Repeat
IPR010491	PRP1_N	Domain
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR045075	Syf1-like	Family

Pfam: PF06424, PF13432, PF14559

UniProt features (95 total): helix 51, strand 14, repeat 9, modified residue 5, turn 5, sequence conflict 4, compositionally biased region 2, sequence variant 2, chain 1, region of interest 1, splice variant 1

Structure

Experimental structures (PDB)

33 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8H6L	ELECTRON MICROSCOPY	2.6
8H6K	ELECTRON MICROSCOPY	2.7
6QW6	ELECTRON MICROSCOPY	2.92
8Q7N	ELECTRON MICROSCOPY	3.1
8Q91	ELECTRON MICROSCOPY	3.1
8QOZ	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
8H6E	ELECTRON MICROSCOPY	3.2
8Q7Q	ELECTRON MICROSCOPY	3.2
8RC0	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
8Q7V	ELECTRON MICROSCOPY	3.8
8Q7W	ELECTRON MICROSCOPY	3.9
8QP9	ELECTRON MICROSCOPY	4.1
8QZS	ELECTRON MICROSCOPY	4.1
8QPK	ELECTRON MICROSCOPY	4.2
8R09	ELECTRON MICROSCOPY	4.3
8R0B	ELECTRON MICROSCOPY	4.4
5O9Z	ELECTRON MICROSCOPY	4.5
8Q7X	ELECTRON MICROSCOPY	4.6
8QO9	ELECTRON MICROSCOPY	5.29
6AH0	ELECTRON MICROSCOPY	5.7
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94906-F1	80.07	0.25

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 (5): 143, 180, 266, 275, 279

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-72165	mRNA Splicing - Minor Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 209 (showing top): RNGTGGGC_UNKNOWN, PATIL_LIVER_CANCER, MODULE_66, GOBP_SPLICEOSOMAL_TRI_SNRNP_COMPLEX_ASSEMBLY, BLALOCK_ALZHEIMERS_DISEASE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, SENESE_HDAC1_TARGETS_UP, MODULE_11, GOBP_RNA_LOCALIZATION, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, LEE_CALORIE_RESTRICTION_NEOCORTEX_DN, GOBP_SPLICEOSOMAL_SNRNP_ASSEMBLY

GO Biological Process (9): spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal complex assembly (GO:0000245), RNA splicing, via transesterification reactions (GO:0000375), mRNA splicing, via spliceosome (GO:0000398), RNA localization (GO:0006403), RNA splicing (GO:0008380), positive regulation of transcription by RNA polymerase II (GO:0045944), RNA processing (GO:0006396), mRNA processing (GO:0006397)

GO Molecular Function (5): RNA binding (GO:0003723), protein-macromolecule adaptor activity (GO:0030674), identical protein binding (GO:0042802), ribonucleoprotein complex binding (GO:0043021), protein binding (GO:0005515)

GO Cellular Component (12): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), centrosome (GO:0005813), cytosol (GO:0005829), membrane (GO:0016020), nuclear speck (GO:0016607), ciliary basal body (GO:0036064), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type precatalytic spliceosome (GO:0071005), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	2
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
RNA processing	2
protein binding	2
microtubule organizing center	2
U5 snRNP	2
spliceosomal snRNP assembly	1
mRNA splicing, via spliceosome	1
protein-RNA complex assembly	1
RNA splicing	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
macromolecule localization	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
gene expression	1
RNA biosynthetic process	1
primary metabolic process	1
mRNA metabolic process	1
nucleic acid binding	1
molecular adaptor activity	1
protein-containing complex binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
centriole	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
cilium	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
Prp19 complex	1

Protein interactions and networks

STRING

2318 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF6	PRPF31	Q8WWY3	996
PRPF6	PRPF3	O43395	988
PRPF6	SNRNP200	O75643	968
PRPF6	PRPF8	Q6P2Q9	931
PRPF6	DDX23	Q9BUQ8	904
PRPF6	PRPF4	O43172	899
PRPF6	SNU13	P55769	855
PRPF6	EFTUD2	Q15029	847
PRPF6	SART1	O43290	834
PRPF6	RP9	Q8TA86	737
PRPF6	PRP4K	Q13523	710
PRPF6	PRPF38A	Q8NAV1	698
PRPF6	USP39	Q53GS9	654
PRPF6	SNRNP40	Q96DI7	645
PRPF6	DHX38	Q92620	644

IntAct

294 interactions, top by confidence:

A	B	Type	Score
LSM3	LSM1	psi-mi:“MI:0914”(association)	0.950
PRPF4	PPIH	psi-mi:“MI:0914”(association)	0.910
EFTUD2	PRPF6	psi-mi:“MI:0915”(physical association)	0.880
PRPF8	PRPF6	psi-mi:“MI:0915”(physical association)	0.830
PRPF6	PRPF8	psi-mi:“MI:0915”(physical association)	0.830
PRPF31	PRPF6	psi-mi:“MI:0915”(physical association)	0.810
PRPF6	PRPF31	psi-mi:“MI:0915”(physical association)	0.810
PRPF6	TXNL4A	psi-mi:“MI:0915”(physical association)	0.790
TXNL4A	PRPF6	psi-mi:“MI:0915”(physical association)	0.790
PRPF6	SNRNP200	psi-mi:“MI:0914”(association)	0.770
SNRNP200	PRPF6	psi-mi:“MI:0915”(physical association)	0.770
PRPF6	SNRNP200	psi-mi:“MI:0915”(physical association)	0.770
PRPF6	SART1	psi-mi:“MI:0915”(physical association)	0.750
SART1	PRPF6	psi-mi:“MI:0915”(physical association)	0.750
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
SNRPG	GEMIN2	psi-mi:“MI:0914”(association)	0.710
PRPF6	PRPF3	psi-mi:“MI:0915”(physical association)	0.670
PRPF3	PRPF6	psi-mi:“MI:0915”(physical association)	0.670
SNRPB	PRMT5	psi-mi:“MI:0914”(association)	0.670

BioGRID (576): PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), PRPF6 (Affinity Capture-MS), CD2BP2 (Co-fractionation), EFTUD2 (Co-fractionation), LUC7L2 (Co-fractionation), PRPF19 (Co-fractionation), PRPF3 (Co-fractionation), PRPF31 (Co-fractionation)

ESM2 similar proteins: A1A5S1, A1Z9G2, A7SK48, B3DJT0, B5X0I6, O36033, O42668, O74970, O76094, O94906, P0CO10, P0CO11, P19735, P33731, P41889, P87312, Q03560, Q12309, Q12381, Q13099, Q20255, Q23049, Q24314, Q2KJJ0, Q4KLU2, Q4PB37, Q4WVF4, Q527H0, Q52DF3, Q5B3U7, Q5BH69, Q5DM57, Q5RCC2, Q5RHH4, Q61371, Q6BSP7, Q6C186, Q6CAR6, Q6INC1, Q7SAK5

Diamond homologs: A1A5S1, O94906, Q12381, Q2KJJ0, Q5RCC2, Q91YR7, Q9ZT71

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
PRPF6	“form complex”	“U4/U6.U5 snRNP complex”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 172 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	8	40.9×	5e-10
mRNA decay by 5’ to 3’ exoribonuclease	5	30.7×	2e-05
mRNA Splicing - Minor Pathway	14	25.3×	1e-14
mRNA Splicing	28	24.8×	1e-29
mRNA Splicing - Major Pathway	48	21.1×	2e-49
Processing of Capped Intron-Containing Pre-mRNA	29	19.2×	2e-27
RNA Polymerase II Transcription Termination	9	15.9×	2e-07
snRNP Assembly	9	15.3×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
spliceosomal complex assembly	15	60.2×	1e-21
spliceosomal tri-snRNP complex assembly	7	52.4×	3e-09
spliceosomal snRNP assembly	12	46.5×	2e-15
RNA splicing, via transesterification reactions	10	41.6×	4e-12
mRNA cis splicing, via spliceosome	6	39.6×	5e-07
U2-type prespliceosome assembly	9	37.5×	2e-10
mRNA splicing, via spliceosome	45	27.5×	3e-50
negative regulation of mRNA splicing, via spliceosome	5	25.5×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	286
Likely benign	298
Benign	49

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
143142	NM_012469.4(PRPF6):c.550G>C (p.Asp184His)	Likely pathogenic

SpliceAI

3711 predictions. Top by Δscore:

Variant	Effect	Δscore
20:63981254:G:GT	donor_gain	1.0000
20:63981257:G:GT	donor_gain	1.0000
20:63981275:G:GT	donor_gain	1.0000
20:63981275:G:T	donor_gain	1.0000
20:63983214:AGG:A	donor_loss	1.0000
20:63983216:GTG:G	donor_loss	1.0000
20:63984901:TCTCA:T	acceptor_loss	1.0000
20:63984902:CTCAG:C	acceptor_loss	1.0000
20:63984903:TCAG:T	acceptor_loss	1.0000
20:63984905:A:AG	acceptor_gain	1.0000
20:63984906:G:GC	acceptor_gain	1.0000
20:63984906:GT:G	acceptor_gain	1.0000
20:63984906:GTT:G	acceptor_gain	1.0000
20:63984906:GTTT:G	acceptor_gain	1.0000
20:63984906:GTTTA:G	acceptor_gain	1.0000
20:63984999:G:GT	donor_gain	1.0000
20:63985022:GACG:G	donor_gain	1.0000
20:63993398:A:AG	acceptor_gain	1.0000
20:63993399:T:G	acceptor_gain	1.0000
20:63993403:CTA:C	acceptor_loss	1.0000
20:63993404:TA:T	acceptor_loss	1.0000
20:63993404:TAGGG:T	acceptor_gain	1.0000
20:63993405:A:AG	acceptor_gain	1.0000
20:63993405:AG:A	acceptor_gain	1.0000
20:63993405:AGG:A	acceptor_gain	1.0000
20:63993405:AGGGA:A	acceptor_gain	1.0000
20:63993406:G:GT	acceptor_gain	1.0000
20:63993406:GG:G	acceptor_gain	1.0000
20:63993406:GGG:G	acceptor_gain	1.0000
20:63993406:GGGA:G	acceptor_gain	1.0000

AlphaMissense

6187 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
20:63981291:G:C	G16R	1.000
20:63981294:T:C	Y17H	1.000
20:63981294:T:G	Y17D	1.000
20:63981303:G:A	G20R	1.000
20:63981303:G:C	G20R	1.000
20:63981303:G:T	G20W	1.000
20:63981304:G:A	G20E	1.000
20:63981304:G:T	G20V	1.000
20:63981309:G:C	G22R	1.000
20:63981309:G:T	G22C	1.000
20:63981310:G:A	G22D	1.000
20:63981310:G:T	G22V	1.000
20:63981313:G:C	R23P	1.000
20:63981315:G:C	G24R	1.000
20:63981315:G:T	G24C	1.000
20:63981316:G:A	G24D	1.000
20:63981316:G:T	G24V	1.000
20:63983049:C:A	A25D	1.000
20:63983054:G:C	G27R	1.000
20:63983055:G:A	G27D	1.000
20:63983057:T:A	F28I	1.000
20:63983057:T:C	F28L	1.000
20:63983057:T:G	F28V	1.000
20:63983058:T:C	F28S	1.000
20:63983058:T:G	F28C	1.000
20:63983059:C:A	F28L	1.000
20:63983059:C:G	F28L	1.000
20:63983064:C:A	T30K	1.000
20:63983064:C:G	T30R	1.000
20:63983064:C:T	T30M	1.000

dbSNP variants (sampled 300 via entrez): RS1000004918 (20:63996576 A>G), RS1000139600 (20:63991332 G>A,C), RS1000225483 (20:64030900 A>G), RS1000252535 (20:63987362 T>C), RS1000333537 (20:63996389 A>G), RS1000394121 (20:64016669 A>T), RS1000426349 (20:63982126 A>G), RS1000427485 (20:64023144 C>G,T), RS1000443068 (20:64004235 C>G), RS1000517404 (20:64013701 A>G), RS1000517766 (20:63986442 A>G), RS1000551651 (20:64027541 A>G), RS1000616662 (20:64028895 T>C), RS1000617382 (20:64014270 C>T), RS1000741944 (20:64008498 C>T)

Disease associations

OMIM: gene MIM:613979 | disease phenotypes: MIM:613983, MIM:268000

GenCC curated gene-disease

Disease	Classification	Inheritance
retinitis pigmentosa 60	Strong	Autosomal dominant
retinitis pigmentosa	Supportive	Autosomal dominant

Mondo (3): inherited retinal dystrophy (MONDO:0019118), retinitis pigmentosa 60 (MONDO:0013516), retinitis pigmentosa (MONDO:0019200)

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

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: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:0001133	Constriction of peripheral visual field
HP:0007663	Reduced visual acuity
HP:0007675	Progressive night blindness
HP:0007703	Abnormal retinal pigmentation
HP:0007722	Retinal pigment epithelial atrophy
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
HP:0011462	Young adult onset

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001942_22	Prostate cancer	4.000000e-16
GCST007001_16	Cerebrospinal AB1-42 levels in normal cognition	3.000000e-07
GCST008158_107	Body mass index	2.000000e-06
GCST010002_71	Refractive error	1.000000e-14

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004670	beta-amyloid 1-42 measurement
EFO:0004340	body mass index

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): CHEMBL5725164 (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

4 potent at pChembl≥5 of 5 total, top 4 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.31	Kd	49	nM	MOLIBRESIB
6.82	IC50	150	nM	MOLIBRESIB
5.68	Kd	2107	nM	CHEMBL5653589
5.68	ED50	2107	nM	CHEMBL5653589

PubChem BioAssay actives

3 with measured affinity, of 11 total; 2 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2179162: Binding affinity against PRPF6 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0490	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149092: Binding affinity to human PRPF6 incubated for 45 mins by Kinobead based pull down assay	kd	2.1069	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression	2
FR900359	increases phosphorylation	1
geldanamycin	increases expression	1
bisphenol A	decreases expression	1
tanshinone	decreases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	decreases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	decreases ADP-ribosylation, increases ADP-ribosylation	1
perfluoro-n-nonanoic acid	decreases expression	1
K 7174	decreases expression	1
abrine	increases expression	1
Bortezomib	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Vorinostat	decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Benztropine	affects cotreatment, decreases expression	1
Cadmium	increases abundance, increases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	affects cotreatment, decreases expression	1
Clozapine	decreases expression, affects cotreatment	1
Cuprizone	affects cotreatment, decreases expression	1
Dinitrochlorobenzene	affects binding	1
Estradiol	increases expression	1
Ivermectin	decreases expression	1
Methotrexate	increases expression	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Selenium	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
CHEMBL5652134	Binding	Binding affinity to human PRPF6 incubated for 45 mins by Kinobead based pull down assay	NVP-BHG712: Effects of Regioisomers on the Affinity and Selectivity toward the EPHrin Family. — ChemMedChem

Cellosaurus cell lines

2 cell lines: 2 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_C4SD	CSUASOi004-A-1	Induced pluripotent stem cell	Female
CVCL_YU18	CSUASOi004-A	Induced pluripotent stem cell	Female

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