PRP4K

Summary

PRP4K (pre-mRNA processing factor kinase PRP4K, HGNC:17346) is a protein-coding gene on chromosome 6p25.2, encoding Serine/threonine-protein kinase PRP4 homolog (Q13523). Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation. It is a selective cancer dependency (DepMap: 50.0% of cell lines).

Pre-mRNA splicing occurs in two sequential transesterification steps, and the protein encoded by this gene is thought to be involved in pre-mRNA splicing and in signal transduction. This protein belongs to a kinase family that includes serine/arginine-rich protein-specific kinases and cyclin-dependent kinases (CDKs). This protein is regarded as a CDK-like kinase (Clk) with homology to mitogen-activated protein kinases (MAPKs).

Source: NCBI Gene 8899 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 66 total
• Druggable target: yes — 10 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 50.0% of screened cell lines
• MANE Select transcript: NM_003913

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17346
Approved symbol	PRP4K
Name	pre-mRNA processing factor kinase PRP4K
Location	6p25.2
Locus type	gene with protein product
Status	Approved
Aliases	Prp4, PR4H, KIAA0536, Prp4B
Ensembl gene	ENSG00000112739
Ensembl biotype	protein_coding
OMIM	602338
Entrez	8899

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 5 protein_coding, 5 protein_coding_CDS_not_defined, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000337659, ENST00000461612, ENST00000463634, ENST00000466185, ENST00000480058, ENST00000481109, ENST00000490399, ENST00000490653, ENST00000494674, ENST00000935172, ENST00000935173, ENST00000954076, ENST00000954077

RefSeq mRNA: 1 — MANE Select: NM_003913 NM_003913

CCDS: CCDS4488

Canonical transcript exons

ENST00000337659 — 15 exons

Exon	Start	End
ENSE00001484117	4060413	4064983
ENSE00001685620	4021300	4021466
ENSE00001978752	4040772	4040927
ENSE00001990741	4037397	4037570
ENSE00003470080	4058728	4058814
ENSE00003481374	4043813	4044023
ENSE00003495746	4057036	4057187
ENSE00003544751	4047175	4047248
ENSE00003573302	4052720	4052873
ENSE00003581516	4042487	4042568
ENSE00003585409	4051957	4052094
ENSE00003602730	4049732	4049879
ENSE00003649961	4031559	4032755
ENSE00003658214	4049016	4049106
ENSE00003692438	4056321	4056435

Expression profiles

Bgee: expression breadth ubiquitous, 292 present calls, max score 95.70.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 78.0058 / max 1880.3235, expressed in 1820 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65549	53.4312	1799
65548	19.8300	1756
65547	2.8510	958
65550	0.7053	357
65546	0.6403	145
65545	0.3842	100
65555	0.1637	58

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	95.70	gold quality
choroid plexus epithelium	UBERON:0003911	95.43	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.14	gold quality
calcaneal tendon	UBERON:0003701	94.84	gold quality
epithelium of nasopharynx	UBERON:0001951	94.65	gold quality
ventricular zone	UBERON:0003053	94.17	gold quality
left ovary	UBERON:0002119	94.14	gold quality
body of uterus	UBERON:0009853	93.87	gold quality
ovary	UBERON:0000992	93.78	gold quality
right ovary	UBERON:0002118	93.78	gold quality
right uterine tube	UBERON:0001302	93.58	gold quality
mucosa of stomach	UBERON:0001199	93.54	gold quality
mammary duct	UBERON:0001765	93.52	gold quality
epithelium of mammary gland	UBERON:0003244	93.51	gold quality
endometrium	UBERON:0001295	93.47	gold quality
lymph node	UBERON:0000029	93.45	gold quality
tibial nerve	UBERON:0001323	93.43	gold quality
small intestine Peyer’s patch	UBERON:0003454	93.28	gold quality
rectum	UBERON:0001052	93.19	gold quality
bronchial epithelial cell	CL:0002328	93.16	gold quality
body of pancreas	UBERON:0001150	93.16	gold quality
vermiform appendix	UBERON:0001154	93.15	gold quality
adrenal tissue	UBERON:0018303	93.15	gold quality
right lung	UBERON:0002167	93.14	gold quality
ectocervix	UBERON:0012249	93.08	gold quality
muscle layer of sigmoid colon	UBERON:0035805	93.08	gold quality
ganglionic eminence	UBERON:0004023	93.07	gold quality
gastrocnemius	UBERON:0001388	93.04	gold quality
monocyte	CL:0000576	92.99	gold quality
mononuclear cell	CL:0000842	92.97	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.84
E-CURD-135	no	814.36

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

248 targeting PRP4K, 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-3646	100.00	73.56	5283
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4531	99.99	69.70	3181
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-570-3P	99.96	72.41	4910

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 50.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 20)

• Mammalian PRP4 kinase copurifies and interacts with components of both the U5 snRNP and the N-CoR deacetylase complexes. (PMID:12077342)
• interacts specifically with HIV-2 gag (PMID:15452250)
• PRP4, a serine/threonine protein kinase, is identified as a Kruppel-like factor 13 (KLF13)-binding protein; PRP4 phosphorylates KLF13 (PMID:17513757)
• Short-term exercise resulted in a significant increase of mRNA expression of genes encoding proteins involved in the formation of precatalytic splisosome: PRPF4B. (PMID:19902070)
• 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)
• data indicate that miR-371-5p, which is highly expressed in hepatocellular carcinoma, promotes the growth of HCC cells in vitro and in vivo by activating cell cycle progression at the G1/S checkpoint by directly targeting PRPF4B (PMID:23466643)
• expression and activity are closely associated with the survival and regulation of apoptotic events in colon cancer cells (PMID:23686430)
• PRP4K functions as a HER2-regulated modifier of taxane sensitivity and is a prognostic biomarker for better survival in taxane-treated ovarian cancer patients. PRP4K knock-down results in “mitotic slippage” in response to taxanes, and reduced PRP4K expression is associated with both intrinsic and acquired resistance of ovarian and breast cancers to taxanes. (PMID:25602630)
• PRP4K functions as a HER2-regulated modifier of taxane sensitivity that may have prognostic value as a marker of better overall survival in taxane-treated ovarian cancer patients. (PMID:25602630)
• Results from a study on gene expression variability markers in early-stage human embryos shows that PRPF4B is a putative expression variability marker for the 3-day, 8-cell embryo stage. (PMID:26288249)
• PRP4K is novel estrogen regulated kinase, and its levels can be reduced by 4-OHT in ER+ breast cancer cells altering their response to taxanes (PMID:26712520)
• Low PRP4K expression correlates with significantly worse overall survival in high-grade serous ovarian cancer, and its depletion increased metastasis in the mouse ID8 ovarian carcinoma model and promoted both sustained growth factor signalling in detached conditions and anoikis resistance in human cervical, breast and ovarian cancer cells. (PMID:28892043)
• Study identifies a novel role for PRP4K in regulating the endosomal trafficking of EGFR leading to altered anoikis sensitivity in epithelial cancer cells. (PMID:28892043)
• PRP4K inhibits proliferation and invasiveness of cultured breast cancer cells and its high expression correlates with good prognosis in breast cancer patients. (PMID:29695716)
• a SNP in PRPF4B was associated with anhedonia (PMID:30104601)
• PRPF4B is essential for triple-negative breast cancer metastasis formation in vivo, making PRPF4B a candidate for further drug development. (PMID:31278301)
• PRP4 Kinase Domain Loss Nullifies Drug Resistance and Epithelial-Mesenchymal Transition in Human Colorectal Carcinoma Cells. (PMID:32576716)
• Haploinsufficient tumor suppressor PRP4K is negatively regulated during epithelial-to-mesenchymal transition. (PMID:34674320)
• PRP4 Induces Epithelial-Mesenchymal Transition and Drug Resistance in Colon Cancer Cells via Activation of p53. (PMID:35328513)
• PRP4K regulates autophagy by controlling the pre-mRNA splicing of the ESCRT-III gene, CHMP4B. The PRP4K-CHMP4B/vps32 splicing circuit is conserved over at least 600 million years of evolution from the protist Dictyostelium discoideum to humans. (PMID:40531620)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf4ba	ENSDARG00000008784
mus_musculus	Prpf4b	ENSMUSG00000021413
rattus_norvegicus	Prpf4b	ENSRNOG00000016705
drosophila_melanogaster	Prp4k	FBGN0027587
caenorhabditis_elegans	prpf-4	WBGENE00004186

Paralogs (26): CDKL3 (ENSG00000006837), CDKL5 (ENSG00000008086), CDK11A (ENSG00000008128), CDK14 (ENSG00000058091), CDK17 (ENSG00000059758), CDK13 (ENSG00000065883), CDKL1 (ENSG00000100490), CDK16 (ENSG00000102225), CDK6 (ENSG00000105810), CDK18 (ENSG00000117266), CDK2 (ENSG00000123374), CDK8 (ENSG00000132964), CDK7 (ENSG00000134058), CDK4 (ENSG00000135446), CDK9 (ENSG00000136807), CDK15 (ENSG00000138395), CDKL2 (ENSG00000138769), CDK19 (ENSG00000155111), CDK20 (ENSG00000156345), CDK5 (ENSG00000164885), CDK12 (ENSG00000167258), CDK1 (ENSG00000170312), CDK10 (ENSG00000185324), CDKL4 (ENSG00000205111), CDK11B (ENSG00000248333), CDK3 (ENSG00000250506)

Protein

Protein identifiers

Serine/threonine-protein kinase PRP4 homolog — Q13523 (reviewed: Q13523)

Alternative names: PRP4 kinase, PRP4 pre-mRNA-processing factor 4 homolog

All UniProt accessions (2): Q13523, H0YDJ3

UniProt curated annotations — full annotation on UniProt →

Function. Serine/threonine kinase involved in spliceosomal assembly as well as mitosis and signaling regulation. Connects chromatin mediated regulation of transcription and pre-mRNA splicing. During spliceosomal assembly, interacts with and phosphorylates PRPF6 and PRPF31, components of the U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP), to facilitate the formation of the spliceosome B complex. Plays a role in regulating transcription and the spindle assembly checkpoint (SAC). Associates with U5 snRNP and NCOR1 deacetylase complexes which may allow a coordination of pre-mRNA splicing with chromatin remodeling events involved in transcriptional regulation. Associates and probably phosphorylates SMARCA4 and NCOR1. Phosphorylates SRSF1. Associates with kinetochores during mitosis and is necessary for recruitment and maintenance of the checkpoint proteins such as MAD1L1 and MAD12L1 at the kinetochores. Phosphorylates and regulates the activity of the transcription factors such as ELK1 and KLF13. Phosphorylates nuclear YAP1 and WWTR1/TAZ which induces nuclear exclusion and regulates Hippo signaling pathway, involved in tissue growth control.

Subunit / interactions. Interacts with CLK1 C-terminus. Associates with the U5 snRNP and NCOR1 deacetylase complexes. Identified in the spliceosome C complex.

Subcellular location. Nucleus. Chromosome. Centromere. Kinetochore.

Tissue specificity. Ubiquitous.

Post-translational modifications. Phosphorylated by CLK1. Autophosphorylated; phosphorylation inhibits interaction with its targets, such as PRPF6 or SMARCA4.

Similarity. Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family.

RefSeq proteins (1): NP_003904* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000719	Prot_kinase_dom	Domain
IPR008271	Ser/Thr_kinase_AS	Active_site
IPR011009	Kinase-like_dom_sf	Homologous_superfamily
IPR044092	STKc_PRP4	Domain
IPR050494	Ser_Thr_dual-spec_kinase	Family

Pfam: PF00069

Enzyme classification (BRENDA):

• EC 2.7.11.1 — non-specific serine/threonine protein kinase (BRENDA: 71 organisms, 682 substrates, 228 inhibitors, 23 Km, 6 kcat entries)

Substrate kinetics (BRENDA)

8 substrates with measured Km, best-characterized 8. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
ATP	0.0007–0.64	11
KKRAARATSNVFA	0.013–0.045	3
PAH1 PHOSPHATIDATE PHOSPHATASE	0.0002	2
RRRLSSLRA	0.0036–0.0037	2
GTP	0.46	1
KKRAARASSNVFA	0.02	1
LYS-LYS-PHE-ASN-ARG-THR-LEU-SER-VAL-ALA	0.0093	1
MYELIN BASIC PROTEIN	0.145	1

Catalyzed reactions (Rhea), 2 shown:

• L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+) (RHEA:17989)
• L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+) (RHEA:46608)

UniProt features (112 total): modified residue 40, compositionally biased region 16, helix 15, strand 13, cross-link 8, sequence conflict 4, turn 3, region of interest 3, sequence variant 3, binding site 2, initiator methionine 1, chain 1, domain 1, active site 1, mutagenesis site 1

Structure

Experimental structures (PDB)

14 structures.

PDB	Method	Resolution (Å)
4IIR	X-RAY DIFFRACTION	2
6CNH	X-RAY DIFFRACTION	2
6PK6	X-RAY DIFFRACTION	2.1
4IFC	X-RAY DIFFRACTION	2.13
4IJP	X-RAY DIFFRACTION	2.25
6PJJ	X-RAY DIFFRACTION	2.4
4IAN	X-RAY DIFFRACTION	2.44
8H6E	ELECTRON MICROSCOPY	3.2
8H6J	ELECTRON MICROSCOPY	3.25
6QX9	ELECTRON MICROSCOPY	3.28
8Y6O	ELECTRON MICROSCOPY	3.38
8R0A	ELECTRON MICROSCOPY	5.8
8R08	ELECTRON MICROSCOPY	6.1
8QXD	ELECTRON MICROSCOPY	9.6

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13523-F1	60.24	0.29

Functional residue map

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

Catalytic / active sites (1): 815 (proton acceptor)

Ligand- & substrate-binding residues (2): 693–701; 717

Post-translational modifications (48): 2, 8, 20, 23, 32, 87, 93, 99, 131, 140, 142, 144, 166, 239, 241, 257, 277, 283, 292, 294 …

Mutagenesis-validated functional residues (1):

Position	Phenotype
717	loss of kinase activity.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 310 (showing top): GOBP_CHROMOSOME_ORGANIZATION, AGGAAGC_MIR5163P, ELVIDGE_HYPOXIA_DN, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, GGTGTGT_MIR329, E2F4DP1_01, GOBP_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_REGULATION_OF_NUCLEAR_DIVISION, TTTGTAG_MIR520D, GOBP_POSITIVE_REGULATION_OF_INTRACELLULAR_PROTEIN_TRANSPORT, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_POSITIVE_REGULATION_OF_PROTEIN_LOCALIZATION, GAUSSMANN_MLL_AF4_FUSION_TARGETS_C_UP, GOBP_REGULATION_OF_PROTEIN_EXPORT_FROM_NUCLEUS

GO Biological Process (11): spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal snRNP assembly (GO:0000387), mRNA splicing, via spliceosome (GO:0000398), positive regulation of hippo signaling (GO:0035332), mRNA cis splicing, via spliceosome (GO:0045292), positive regulation of protein export from nucleus (GO:0046827), regulation of mitotic cell cycle spindle assembly checkpoint (GO:0090266), mRNA processing (GO:0006397), protein phosphorylation (GO:0006468), RNA splicing (GO:0008380), hippo signaling (GO:0035329)

GO Molecular Function (9): RNA binding (GO:0003723), protein serine/threonine kinase activity (GO:0004674), ATP binding (GO:0005524), protein serine kinase activity (GO:0106310), nucleotide binding (GO:0000166), protein kinase activity (GO:0004672), protein binding (GO:0005515), kinase activity (GO:0016301), transferase activity (GO:0016740)

GO Cellular Component (8): kinetochore (GO:0000776), nucleus (GO:0005634), nucleoplasm (GO:0005654), nuclear speck (GO:0016607), catalytic step 2 spliceosome (GO:0071013), chromosome, centromeric region (GO:0000775), spliceosomal complex (GO:0005681), chromosome (GO:0005694)

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
mRNA splicing, via spliceosome	2
RNA processing	2
protein kinase activity	2
intracellular membraneless organelle	2
spliceosomal snRNP assembly	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
hippo signaling	1
regulation of hippo signaling	1
positive regulation of intracellular signal transduction	1
protein export from nucleus	1
positive regulation of nucleocytoplasmic transport	1
regulation of protein export from nucleus	1
positive regulation of intracellular protein transport	1
regulation of mitotic nuclear division	1
mitotic spindle assembly checkpoint signaling	1
regulation of mitotic sister chromatid separation	1
regulation of mitotic metaphase/anaphase transition	1
regulation of mitotic sister chromatid segregation	1
regulation of mitotic spindle checkpoint	1
mRNA metabolic process	1
phosphorylation	1
protein modification process	1
intracellular signal transduction	1
nucleic acid binding	1
adenyl ribonucleotide binding	1
purine ribonucleoside triphosphate binding	1
nucleoside phosphate binding	1
heterocyclic compound binding	1
kinase activity	1
phosphotransferase activity, alcohol group as acceptor	1
catalytic activity, acting on a protein	1
binding	1
transferase activity, transferring phosphorus-containing groups	1
catalytic activity	1
condensed chromosome, centromeric region	1
supramolecular complex	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

1854 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRP4K	SRSF2	Q01130	772
PRP4K	PRPF6	O94906	710
PRP4K	PRPF31	Q8WWY3	709
PRP4K	SMU1	Q2TAY7	562
PRP4K	SRPK1	Q96SB4	549
PRP4K	PRPF38A	Q8NAV1	535
PRP4K	ZMAT2	Q96NC0	535
PRP4K	KLF13	Q9Y2Y9	523
PRP4K	PRPF39	Q86UA1	520
PRP4K	SFSWAP	Q12872	502
PRP4K	SNRNP200	O75643	494
PRP4K	PRPF4	O43172	489
PRP4K	WBP4	O75554	486
PRP4K	EFTUD2	Q15029	480
PRP4K	PXDC1	Q5TGL8	472

IntAct

208 interactions, top by confidence:

A	B	Type	Score
SNRPF	GEMIN2	psi-mi:“MI:0914”(association)	0.910
CSNK2A1	EIF3J	psi-mi:“MI:0914”(association)	0.810
PNN	PRP4K	psi-mi:“MI:0914”(association)	0.790
SNRPE	GEMIN2	psi-mi:“MI:0914”(association)	0.770
PRP4K	YWHAG	psi-mi:“MI:0915”(physical association)	0.760
PRPF6	SART1	psi-mi:“MI:0914”(association)	0.750
MED19	MED19	psi-mi:“MI:0914”(association)	0.730
PRP4K	KLF13	psi-mi:“MI:0915”(physical association)	0.640
KLF13	PRP4K	psi-mi:“MI:0915”(physical association)	0.640
KLF13	PRP4K	psi-mi:“MI:0217”(phosphorylation reaction)	0.640
PRP4K	KLF13	psi-mi:“MI:0403”(colocalization)	0.640
PNN	CASC3	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
LIN28A	IGF2BP3	psi-mi:“MI:0914”(association)	0.640
SNRPB	SART1	psi-mi:“MI:0914”(association)	0.640
PRP4K	PRPF4	psi-mi:“MI:0914”(association)	0.640
gag	PRP4K	psi-mi:“MI:0915”(physical association)	0.630
NPM1	MPHOSPH10	psi-mi:“MI:0914”(association)	0.610
H1-6	ZNF724	psi-mi:“MI:0914”(association)	0.530
RBM34	NVL	psi-mi:“MI:0914”(association)	0.530
ZNF2	MPHOSPH10	psi-mi:“MI:0914”(association)	0.530
MACROH2A2	PPM1G	psi-mi:“MI:0914”(association)	0.530
ZC3H18	AQR	psi-mi:“MI:0914”(association)	0.530
MAGEB2	POLRMT	psi-mi:“MI:0914”(association)	0.530

BioGRID (417): PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Reconstituted Complex), PRPF4B (Reconstituted Complex), PRPF4B (Proximity Label-MS), PRPF4B (Biochemical Activity), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS), PRPF4B (Affinity Capture-MS)

ESM2 similar proteins: A0A1I8M2I8, A8WT19, B3MJ69, B3N3F7, B4H732, B4II37, B4J497, B4KLY7, B4LIK8, B4MR46, B4NYV0, B4QCR6, O15042, O94880, P0CM96, P0CM97, P0DP78, P0DP79, P0DP80, P0DP81, Q08C72, Q08DZ2, Q13523, Q17336, Q20448, Q24168, Q28WQ8, Q4PCY0, Q4WKB9, Q52B63, Q52KN9, Q5R7X2, Q5R814, Q5RA93, Q5RKH1, Q5TUF1, Q5ZKA3, Q61136, Q6C8C5, Q6DE96

Diamond homologs: A4L9P5, A8WJR8, A8X4H1, A8X5H5, B3WFY8, G5EDB2, O14132, O23145, O43781, O55076, O76039, O88850, O88904, P14680, P18265, P18431, P20911, P22518, P24941, P43288, P43289, P48963, P49657, P49759, P49840, P50613, P51136, P51567, P51568, P51952, P83102, Q00526, Q03147, Q04859, Q07538, Q08DZ2, Q09690, Q09815, Q0IJ08, Q10156

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
PRPF4B	down-regulates	KLF13	phosphorylation
PRPF4B	up-regulates	ELK1	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 197 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
Transport of Mature Transcript to Cytoplasm	11	30.6×	1e-12
RNA Polymerase II Transcription Termination	15	24.1×	3e-15
mRNA 3’-end processing	14	20.1×	3e-13
mRNA Splicing	22	17.6×	3e-19
mRNA Splicing - Minor Pathway	9	14.7×	2e-07
Transport of Mature mRNA derived from an Intron-Containing Transcript	13	14.4×	1e-10
mRNA Splicing - Major Pathway	36	14.4×	2e-29
Processing of Capped Intron-Containing Pre-mRNA	23	13.8×	7e-18

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	8	35.0×	4e-09
regulation of mRNA splicing, via spliceosome	6	30.4×	3e-06
spliceosomal complex assembly	8	27.5×	3e-08
mRNA splice site recognition	5	22.9×	1e-04
RNA splicing, via transesterification reactions	6	21.4×	2e-05
spliceosomal snRNP assembly	6	19.9×	3e-05
U2-type prespliceosome assembly	5	17.8×	5e-04
cytoplasmic translation	16	16.9×	4e-13

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	36
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2848 predictions. Top by Δscore:

Variant	Effect	Δscore
6:4021462:CCAGA:C	donor_gain	1.0000
6:4021463:CAGA:C	donor_gain	1.0000
6:4021464:AGA:A	donor_gain	1.0000
6:4021465:GA:G	donor_gain	1.0000
6:4021465:GAG:G	donor_gain	1.0000
6:4021466:AG:A	donor_loss	1.0000
6:4021467:G:GG	donor_gain	1.0000
6:4021467:GTA:G	donor_loss	1.0000
6:4021468:TAA:T	donor_loss	1.0000
6:4037374:A:AG	acceptor_gain	1.0000
6:4037374:AACTT:A	acceptor_gain	1.0000
6:4037375:A:AG	acceptor_gain	1.0000
6:4037375:ACTT:A	acceptor_gain	1.0000
6:4037378:T:TA	acceptor_gain	1.0000
6:4037381:A:AG	acceptor_gain	1.0000
6:4037381:ATTT:A	acceptor_gain	1.0000
6:4037382:T:G	acceptor_gain	1.0000
6:4037384:T:A	acceptor_gain	1.0000
6:4037393:TAAG:T	acceptor_loss	1.0000
6:4037394:A:AG	acceptor_gain	1.0000
6:4037394:AAGA:A	acceptor_loss	1.0000
6:4037395:A:AC	acceptor_loss	1.0000
6:4037395:A:AG	acceptor_gain	1.0000
6:4037396:G:GG	acceptor_gain	1.0000
6:4037396:GA:G	acceptor_gain	1.0000
6:4037396:GAA:G	acceptor_gain	1.0000
6:4037567:GAAG:G	donor_gain	1.0000
6:4037568:AAGG:A	donor_loss	1.0000
6:4037569:AGG:A	donor_loss	1.0000
6:4037571:G:GA	donor_loss	1.0000

AlphaMissense

6683 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:4047210:T:C	F633L	1.000
6:4047211:T:G	F633C	1.000
6:4047212:T:A	F633L	1.000
6:4047212:T:G	F633L	1.000
6:4049081:C:A	N667K	1.000
6:4049081:C:G	N667K	1.000
6:4049082:T:A	W668R	1.000
6:4049082:T:C	W668R	1.000
6:4049088:G:C	D670H	1.000
6:4049097:G:C	G673R	1.000
6:4049098:G:A	G673D	1.000
6:4049098:G:T	G673V	1.000
6:4049103:T:G	Y675D	1.000
6:4049771:T:A	V689E	1.000
6:4049785:G:A	G694R	1.000
6:4049785:G:C	G694R	1.000
6:4049785:G:T	G694W	1.000
6:4049786:G:A	G694E	1.000
6:4049786:G:T	G694V	1.000
6:4049791:G:A	G696S	1.000
6:4049791:G:C	G696R	1.000
6:4049791:G:T	G696C	1.000
6:4049792:G:A	G696D	1.000
6:4049792:G:T	G696V	1.000
6:4049797:T:A	F698I	1.000
6:4049797:T:C	F698L	1.000
6:4049797:T:G	F698V	1.000
6:4049798:T:C	F698S	1.000
6:4049798:T:G	F698C	1.000
6:4049799:C:A	F698L	1.000

dbSNP variants (sampled 300 via entrez): RS1000057393 (6:4034574 C>T), RS1000105102 (6:4059583 A>C), RS1000116888 (6:4059864 C>G,T), RS1000241080 (6:4023352 T>C), RS1000254813 (6:4046464 C>T), RS1000307813 (6:4052301 C>G), RS1000336721 (6:4053216 G>A), RS1000487465 (6:4034838 A>G), RS1000490093 (6:4046148 G>A), RS1000565044 (6:4029549 C>T), RS1000591286 (6:4029772 T>C,G), RS1000744167 (6:4023331 A>G), RS1000808019 (6:4027551 A>G), RS1000867177 (6:4029104 C>G), RS1000908608 (6:4035161 G>C)

Disease associations

OMIM: gene MIM:602338 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST003542_140	Night sleep phenotypes	9.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1908382 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

10 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 107,382 (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
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL502835	NINTEDANIB	4	8,545
CHEMBL535	SUNITINIB	4	79,020
CHEMBL608533	MIDOSTAURIN	4	7,259
CHEMBL522892	DOVITINIB	3	4,944
CHEMBL603469	LESTAURTINIB	3
CHEMBL91829	RUBOXISTAURIN	3	77
CHEMBL1721885	SU-014813	2	363
CHEMBL572878	TOZASERTIB	2	2,998
CHEMBL1908397	KW-2449	1	622

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

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — PRP4 subfamily

Binding affinities (BindingDB)

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

Ligand	Measure	Value
4-ylmethyl)-carbamoyl]-thiophen-2-yl}-benzo[b]thiophene-2-carboxylic acid amine (Compound A)	IC50	16 nM

ChEMBL bioactivities

19 potent at pChembl≥5 of 19 total, top 16 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.08	Kd	8.4	nM	NINTEDANIB
7.26	Kd	55	nM	MIDOSTAURIN
6.66	Kd	220	nM	STAUROSPORINE
6.57	Kd	270	nM	KW-2449
6.41	Kd	390	nM	SUNITINIB
6.41	Kd	390	nM	FEDRATINIB
6.26	Kd	550	nM	LESTAURTINIB
6.25	Kd	560	nM	DOVITINIB
5.89	Ki	1300	nM	CHEMBL5186861
5.89	Kd	1300	nM	SU-014813
5.80	Kd	1600	nM	RUBOXISTAURIN
5.60	Kd	2500	nM	TOZASERTIB
5.58	Kd	2600	nM	PHA-665752
5.34	Kd	4600	nM	CHEMBL379218
5.12	Kd	7600	nM	TAE-684
5.06	Kd	8700	nM	CHEMBL1908395

PubChem BioAssay actives

20 with measured affinity, of 176 total; 17 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
methyl 2-hydroxy-3-[N-[4-[methyl-[2-(4-methylpiperazin-1-yl)acetyl]amino]phenyl]-C-phenylcarbonimidoyl]-1H-indole-6-carboxylate	624750: Binding constant for PRP4 kinase domain	kd	0.0084	uM
4-[5-[(2-chloro-4-pyridinyl)methylcarbamoyl]thiophen-2-yl]-1-benzothiophene-2-carboxamide	1802402: MS-Based Biochemical Assay from Article 10.1074/jbc.M113.473348: “Evaluation of cancer dependence and druggability of PRP4 kinase using cellular, biochemical, and structural approaches.”	ic50	0.0160	uM
Midostaurin	508054: Binding affinity to PRP4	kd	0.0550	uM
(2S,3R,4R,6R)-3-methoxy-2-methyl-4-(methylamino)-29-oxa-1,7,17-triazaoctacyclo[12.12.2.12,6.07,28.08,13.015,19.020,27.021,26]nonacosa-8,10,12,14,19,21,23,25,27-nonaen-16-one	624750: Binding constant for PRP4 kinase domain	kd	0.2200	uM
[4-[(E)-2-(1H-indazol-3-yl)ethenyl]phenyl]-piperazin-1-ylmethanone	624750: Binding constant for PRP4 kinase domain	kd	0.2700	uM
Fedratinib	624750: Binding constant for PRP4 kinase domain	kd	0.3900	uM
Sunitinib	508054: Binding affinity to PRP4	kd	0.3900	uM
(15S,16S,18R)-16-hydroxy-16-(hydroxymethyl)-15-methyl-28-oxa-4,14,19-triazaoctacyclo[12.11.2.115,18.02,6.07,27.08,13.019,26.020,25]octacosa-1,6,8,10,12,20,22,24,26-nonaen-3-one	508054: Binding affinity to PRP4	kd	0.5500	uM
4-amino-5-fluoro-3-[6-(4-methylpiperazin-1-yl)-1H-benzimidazol-2-yl]-1H-quinolin-2-one	624750: Binding constant for PRP4 kinase domain	kd	0.5600	uM
5-[(Z)-(5-fluoro-2-oxo-1H-indol-3-ylidene)methyl]-N-[(2S)-2-hydroxy-3-morpholin-4-ylpropyl]-2,4-dimethyl-1H-pyrrole-3-carboxamide	624750: Binding constant for PRP4 kinase domain	kd	1.3000	uM
4-[5-[(2-aminophenyl)methylcarbamoyl]thiophen-2-yl]-1-benzothiophene-2-carboxamide	1892064: Inhibition of DNA-tagged human PRP4 expressed in Escherichia coli incubated for 1.5 hrs by KINOMEscan assay	ki	1.3000	uM
(18S)-18-[(dimethylamino)methyl]-17-oxa-4,14,21-triazahexacyclo[19.6.1.17,14.02,6.08,13.022,27]nonacosa-1(28),2(6),7(29),8,10,12,22,24,26-nonaene-3,5-dione	624750: Binding constant for PRP4 kinase domain	kd	1.6000	uM
N-[4-[4-(4-methylpiperazin-1-yl)-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]sulfanylphenyl]cyclopropanecarboxamide	624750: Binding constant for PRP4 kinase domain	kd	2.5000	uM
(3Z)-5-[(2,6-dichlorophenyl)methylsulfonyl]-3-[[3,5-dimethyl-4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidine-1-carbonyl]-1H-pyrrol-2-yl]methylidene]-1H-indol-2-one	624750: Binding constant for PRP4 kinase domain	kd	2.6000	uM
(2S)-1-[[5-(3-methyl-2H-indazol-5-yl)-3-pyridinyl]oxy]-3-phenylpropan-2-amine	624750: Binding constant for PRP4 kinase domain	kd	4.6000	uM
5-chloro-2-N-[2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]phenyl]-4-N-(2-propan-2-ylsulfonylphenyl)pyrimidine-2,4-diamine	624750: Binding constant for PRP4 kinase domain	kd	7.6000	uM
5-cyano-N-[2-(cyclohexen-1-yl)-4-[1-[2-(dimethylamino)acetyl]piperidin-4-yl]phenyl]-1H-imidazole-2-carboxamide;hydrochloride	624750: Binding constant for PRP4 kinase domain	kd	8.7000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects expression, decreases expression	2
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	2
aristolochic acid I	decreases expression	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
uranyl acetate	affects expression	1
bisphenol A	decreases expression	1
trichostatin A	affects expression	1
arsenite	affects binding, decreases reaction	1
ochratoxin A	decreases expression	1
coumarin	decreases phosphorylation	1
perfluorooctane sulfonic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
ICG 001	decreases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
jinfukang	decreases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Caffeine	affects phosphorylation	1
Diethylstilbestrol	decreases expression	1
Formaldehyde	decreases expression	1
Indomethacin	decreases expression	1
Ivermectin	decreases expression	1
Lipopolysaccharides	affects expression, affects reaction	1
Methyl Methanesulfonate	decreases expression	1
Piroxicam	decreases expression	1
Plant Extracts	affects expression, affects reaction	1
Quercetin	decreases expression	1
Ribonucleotides	affects binding	1

ChEMBL screening assays

120 unique, capped per target: 120 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1166832	Binding	Inhibition of PRP4 at 1 uM	Synthesis and structure-activity relationships of 1,2,3,4-tetrahydropyrido[2,3-b]pyrazines as potent and selective inhibitors of the anaplastic lymphoma kinase. — Bioorg Med Chem

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B3F0	Abcam HEK293T PRPF4B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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