PRPF19

Summary

PRPF19 (pre-mRNA processing factor 19, HGNC:17896) is a protein-coding gene on chromosome 11q12.2, encoding Pre-mRNA-processing factor 19 (Q9UMS4). Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Enables identical protein binding activity and ubiquitin-ubiquitin ligase activity. Involved in several processes, including DNA damage checkpoint signaling; mRNA splicing, via spliceosome; and protein K63-linked ubiquitination. Acts upstream of or within protein polyubiquitination. Located in cytoplasm; nuclear lumen; and site of double-strand break. Part of Prp19 complex and U2-type catalytic step 2 spliceosome.

Source: NCBI Gene 27339 — RefSeq curated summary.

At a glance

• Gene–disease (curated): neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• Clinical variants (ClinVar): 58 total — 1 likely-pathogenic
• Phenotypes (HPO): 1
• Druggable target: yes
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_014502

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17896
Approved symbol	PRPF19
Name	pre-mRNA processing factor 19
Location	11q12.2
Locus type	gene with protein product
Status	Approved
Aliases	UBOX4, NMP200, PSO4, hPSO4, SNEV
Ensembl gene	ENSG00000110107
Ensembl biotype	protein_coding
OMIM	608330
Entrez	27339

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 7 protein_coding, 2 retained_intron

ENST00000227524, ENST00000535326, ENST00000539180, ENST00000539960, ENST00000540473, ENST00000541371, ENST00000546152, ENST00000907533, ENST00000918252

RefSeq mRNA: 1 — MANE Select: NM_014502 NM_014502

CCDS: CCDS7995

Canonical transcript exons

ENST00000227524 — 16 exons

Exon	Start	End
ENSE00000721018	60902583	60902656
ENSE00001108342	60906364	60906585
ENSE00001167683	60897846	60897951
ENSE00001167717	60899149	60899304
ENSE00001167724	60900582	60900691
ENSE00001167731	60900854	60900929
ENSE00001167737	60901295	60901369
ENSE00001167760	60902403	60902465
ENSE00002246652	60890547	60891263
ENSE00003462786	60898862	60898931
ENSE00003510056	60898101	60898271
ENSE00003585619	60902740	60902881
ENSE00003588469	60903712	60903861
ENSE00003654388	60903459	60903535
ENSE00003663184	60898541	60898626
ENSE00003788733	60901499	60901540

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 97.33.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 90.8272 / max 489.8018, expressed in 1823 samples.

FANTOM5 promoters (4 alternative TSS)

Promoter ID	TPM avg	Samples expressed
119919	59.2784	1818
119918	28.6631	1802
119917	2.5248	1204
119916	0.3609	150

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
pons	UBERON:0000988	97.33	gold quality
right frontal lobe	UBERON:0002810	97.18	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.00	gold quality
ventricular zone	UBERON:0003053	96.84	gold quality
ganglionic eminence	UBERON:0004023	96.71	gold quality
prefrontal cortex	UBERON:0000451	96.66	gold quality
cerebellar hemisphere	UBERON:0002245	96.61	gold quality
right hemisphere of cerebellum	UBERON:0014890	96.57	gold quality
cerebellar cortex	UBERON:0002129	96.55	gold quality
adenohypophysis	UBERON:0002196	96.55	gold quality
islet of Langerhans	UBERON:0000006	96.37	gold quality
superior vestibular nucleus	UBERON:0007227	96.27	gold quality
pituitary gland	UBERON:0000007	96.25	gold quality
skin of leg	UBERON:0001511	96.10	gold quality
cerebellum	UBERON:0002037	96.05	gold quality
skin of abdomen	UBERON:0001416	96.04	gold quality
embryo	UBERON:0000922	95.95	gold quality
cingulate cortex	UBERON:0003027	95.90	gold quality
anterior cingulate cortex	UBERON:0009835	95.83	gold quality
hypothalamus	UBERON:0001898	95.81	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	95.58	gold quality
nucleus accumbens	UBERON:0001882	95.50	gold quality
left adrenal gland	UBERON:0001234	95.47	gold quality
right ovary	UBERON:0002118	95.39	gold quality
left adrenal gland cortex	UBERON:0035825	95.39	gold quality
neocortex	UBERON:0001950	95.29	gold quality
cortical plate	UBERON:0005343	95.28	gold quality
esophagus mucosa	UBERON:0002469	95.27	gold quality
frontal cortex	UBERON:0001870	95.22	gold quality
adrenal cortex	UBERON:0001235	95.16	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-3929	yes	151.95
E-ANND-3	yes	3.60
E-CURD-53	no	351.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting PRPF19, 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-4455	100.00	65.48	1587
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4715-3P	99.98	66.03	670
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-1255A	99.74	68.09	744
HSA-MIR-1255B-5P	99.74	68.16	741
HSA-MIR-3158-5P	99.65	67.51	1763
HSA-MIR-488-3P	99.61	68.79	1731
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-7844-5P	99.55	68.56	1428
HSA-MIR-203A-3P	99.49	70.56	2806
HSA-MIR-542-3P	99.34	67.58	1270
HSA-MIR-4292	99.16	65.57	1767
HSA-MIR-6791-5P	99.16	65.92	1844
HSA-MIR-6071	99.16	67.77	1780
HSA-MIR-452-3P	99.01	66.25	1241
HSA-MIR-4738-3P	98.98	67.98	1846
HSA-MIR-1257	98.97	68.02	1133
HSA-MIR-6756-3P	98.94	66.79	1104
HSA-MIR-3127-3P	98.94	67.34	1055
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-1227-5P	98.65	65.32	1549
HSA-MIR-5011-3P	98.63	64.81	638
HSA-MIR-5008-5P	98.42	65.87	1019
HSA-MIR-6804-5P	98.39	65.77	1084
HSA-MIR-4772-3P	98.04	65.60	1203
HSA-MIR-6890-3P	97.50	65.71	997
HSA-MIR-4433A-5P	96.79	65.01	599
HSA-MIR-490-5P	96.75	65.81	661
HSA-MIR-4433B-5P	95.91	66.56	727

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 100.0% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 37)

• concluded that hPso4 plays a major and previously undefined role in mammalian DNA DSB repair[Pso4] (PMID:12960389)
• required prior to catalytic step 1 of splicing, but not for stable integration of U4/U6.U5 tri-snRNPs (PMID:15175653)
• report the identification of two additional factors required in the DNA interstrand cross-links repair process, a previously characterized pre-mRNA splicing complex composed of Pso4/Prp19 and Werner syndrome protein(WRN) (PMID:16223718)
• SNEV, the human orthologue of yeast PRP19, functions in splicing and homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly. (PMID:16332694)
• The high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells. (PMID:16388800)
• ubiquitylated hPrp19 fails to interact with either Cdc5L or Plrg1 indicating that DNA damage can induce profound alterations to hPrp19 core complex. (PMID:17276391)
• hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair (PMID:18263876)
• Blom7alpha is a novel splicing factor of the K homology domain family that might be implicated in alternative splicing by helping to position the CDC5L-SNEV(Prp19-Pso4) complex at the splice sites [Blom7alpha] (PMID:19641227)
• Purified hPrp19/CDC5L complexes exhibit an elongated, asymmetric shape with a maximum dimension of approximately 20 nm. (PMID:20176811)
• hPso4, once it forms a complex with Metnase, negatively regulates Metnase’s TIR binding activity (PMID:20416268)
• U2AF65 binds directly to the phosphorylated C-terminal domain, and that this interaction results in increased recruitment of U2AF65 and PRP19C to the pre-mRNA (PMID:21536736)
• SNEV phosphorylation at S149 is essential for mediating the cytoprotective effect of SNEV upon DNA damage/oxidative stress and partially contributes to the life span extension caused by SNEV overexpression. (PMID:22529335)
• New insights into pre-mRNA processing factor 19 (PMID:22967061)
• PRP19 over-expression is associated with hepatocellular carcinoma recurrence. (PMID:23220010)
• Prp19 complex as the first spliceosome subcomplex that directly contributes to mitosis in vertebrates independently of its function in interphase. (PMID:24069358)
• PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. (PMID:24332808)
• DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells. (PMID:24587161)
• The Prp19-CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. (PMID:24598747)
• involvement of hPso4 in the recombinational repair of DSBs (PMID:24675077)
• These findings suggest that SKAP promotes ultraviolet rays-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19. (PMID:24718257)
• We report that PRP19 expression is elevated in lung carcinoma tissues compared to non-tumor tissues (PMID:24731397)
• role of Pso4 in DNA repair and DNA damage (PMID:26364595)
• This work implies that the gain of Prp19 is a critical event during the progression of hepatocellular carcinoma (PMID:26959880)
• the interactome of influenza A virus NS1 in host cells was comprehensively profiled, and our findings reveal a novel regulatory role for PRP19 in viral replication (PMID:27096427)
• These results demonstrate that SNEV regulates adipogenesis in hASCs and indicate that DDR capacity in general might be a pre-requisite for this process. (PMID:28041875)
• Study demonstrates that the levels of Prp19 and Cdc5L are overexpressed in hepatocellular carcinoma (HCC). Prp19 binds with Cdc5L and its downregulation results in reduction of Cdc5L. Mechanistic insights reveal that silencing Prp19 compromises translation activity of Cdc5L and facilitates lysosome-induced degradation of Cdc5L in HCC cells. (PMID:28387715)
• The results suggest that RPA phosphorylation enhances the recruitment of PRP19 to RPA-ssDNA and stimulates RPA ubiquitylation through a process requiring both PRP19 and RFWD3, thereby triggering a phosphorylation-ubiquitylation circuitry that promotes ATR activation and homologous recombination. (PMID:28666352)
• Crystal structure revealed features of the WD40 domain of human PRPF19. (PMID:28962858)
• Formation of the nineteen complex core by stepwise assembly of SPF27, CDC5L, and PLRG1 onto the Prp19 tetramer enables ubiquitin ligation. (PMID:29547724)
• A fine balance between Prpf19 and Exoc7 in achieving degradation of aggregated protein and suppression of cell death in spinocerebellar ataxia type 3. (PMID:33542212)
• PRPF19 promotes tongue cancer growth and chemoradiotherapy resistance. (PMID:33954334)
• PRPF19 regulates p53-dependent cellular senescence by modulating alternative splicing of MDM4 mRNA. (PMID:34144037)
• A distinct complex of PRP19-related and trypanosomatid-specific proteins is required for pre-mRNA splicing in trypanosomes. (PMID:34850936)
• PRP19 Enhances Esophageal Squamous Cell Carcinoma Progression by Reprogramming SREBF1-Dependent Fatty Acid Metabolism. (PMID:36723974)
• PRPF19 promotes the proliferation, migration, and inhibits autophagy in prostate cancer by suppressing SLC40A1. (PMID:37929350)
• Comprehensive analysis of PRPF19 immune infiltrates, DNA methylation, senescence-associated secretory phenotype and ceRNA network in bladder cancer. (PMID:38022515)
• PRPF19 mRNA Encodes a Small Open Reading Frame That Is Important for Viability of Human Cells. (PMID:38472668)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf19	ENSDARG00000015239
mus_musculus	Prpf19	ENSMUSG00000024735
rattus_norvegicus	Prpf19	ENSRNOG00000020897
drosophila_melanogaster	Prp19	FBGN0261119
caenorhabditis_elegans		WBGENE00020423

Paralogs (1): WDR36 (ENSG00000134987)

Protein

Protein identifiers

Pre-mRNA-processing factor 19 — Q9UMS4 (reviewed: Q9UMS4)

Alternative names: Nuclear matrix protein 200, PRP19/PSO4 homolog, RING-type E3 ubiquitin transferase PRP19, Senescence evasion factor

All UniProt accessions (5): Q9UMS4, F5GY56, F5H2I0, H0YGF3, H0YGZ5

UniProt curated annotations — full annotation on UniProt →

Function. Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates ‘Lys-63’-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex. Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries. The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair. Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. ‘Lys-63’-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response. May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA. As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process. In addition, may also mediate ‘Lys-48’-linked polyubiquitination of substrates and play a role in proteasomal degradation. May play a role in the biogenesis of lipid droplets. May play a role in neural differentiation possibly through its function as part of the spliceosome.

Subunit / interactions. Homotetramer. Component of activated, catalytic and post-catalytic spliceosomes. Component of the Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes described as PRP19-CDC5L splicing complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The Prp19 complex associates with the spliceosome during its assembly and remodeling recruiting additional proteins. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it interacts with the replication protein A complex (RPA). Interacts with SETMAR; required for SETMAR recruitment to site of DNA damage. Interacts with U2AF2; the interaction is direct and recruits the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with PSMC5. Interacts with KNSTRN. Interacts (via N-terminus) with CDC5L. Interacts with KHDC4. Interacts with USB1. Interacts with DDX41.

Subcellular location. Nucleus. Nucleoplasm. Cytoplasm. Cytoskeleton. Spindle. Lipid droplet.

Tissue specificity. Ubiquitous. Weakly expressed in senescent cells of different tissue origins. Highly expressed in tumor cell lines.

Domain organisation. The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex.

Induction. By gamma irradiation and chemical mutagens but not by UV irradiation.

Pathway. Protein modification; protein ubiquitination.

Similarity. Belongs to the WD repeat PRP19 family.

RefSeq proteins (1): NP_055317* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR003613	Ubox_domain	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR013915	Prp19_cc	Domain
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR020472	WD40_PAC1	Repeat
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR038959	Prp19	Family
IPR055340	RING-Ubox_PRP19	Domain

Pfam: PF04564, PF08606, PF24814

UniProt features (67 total): strand 35, turn 10, repeat 7, modified residue 5, helix 5, initiator methionine 1, chain 1, region of interest 1, mutagenesis site 1, domain 1

Structure

Experimental structures (PDB)

23 structures.

PDB	Method	Resolution (Å)
4LG8	X-RAY DIFFRACTION	1.89
8C6J	ELECTRON MICROSCOPY	2.8
6ID1	ELECTRON MICROSCOPY	2.86
6ID0	ELECTRON MICROSCOPY	2.9
6ICZ	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
8I0W	ELECTRON MICROSCOPY	3.4
8RO2	ELECTRON MICROSCOPY	3.5
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
7A5P	ELECTRON MICROSCOPY	5
5Z56	ELECTRON MICROSCOPY	5.1
5MQF	ELECTRON MICROSCOPY	5.9
8CH6	ELECTRON MICROSCOPY	5.9
5Z57	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UMS4-F1	89.35	0.77

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): 2, 122, 179, 244, 261

Mutagenesis-validated functional residues (1):

Position	Phenotype
405	loss of interaction with the rpa complex and loss of recruitment to sites of dna damage.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-6781823	Formation of TC-NER Pre-Incision Complex
R-HSA-6781827	Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135	Dual incision in TC-NER
R-HSA-6782210	Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-9918481	Dengue Virus-Host Interactions

MSigDB gene sets: 240 (showing top): MODULE_52, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, ENK_UV_RESPONSE_KERATINOCYTE_UP, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN, GOBP_CELL_CYCLE_PHASE_TRANSITION, GOBP_GROWTH, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, AACYNNNNTTCCS_UNKNOWN, BROWNE_HCMV_INFECTION_16HR_UP, MODULE_16, PUJANA_CHEK2_PCC_NETWORK, MODULE_66, MODULE_118

GO Biological Process (17): DNA damage checkpoint signaling (GO:0000077), protein polyubiquitination (GO:0000209), spliceosomal tri-snRNP complex assembly (GO:0000244), spliceosomal complex assembly (GO:0000245), mRNA splicing, via spliceosome (GO:0000398), inner cell mass cell proliferation (GO:0001833), double-strand break repair via nonhomologous end joining (GO:0006303), intracellular protein localization (GO:0008104), lipid biosynthetic process (GO:0008610), proteasomal protein catabolic process (GO:0010498), positive regulation of mRNA splicing, via spliceosome (GO:0048026), protein K63-linked ubiquitination (GO:0070534), DNA repair (GO:0006281), mRNA processing (GO:0006397), DNA damage response (GO:0006974), RNA splicing (GO:0008380), protein ubiquitination (GO:0016567)

GO Molecular Function (6): ubiquitin-protein transferase activity (GO:0004842), ubiquitin-ubiquitin ligase activity (GO:0034450), identical protein binding (GO:0042802), ubiquitin protein ligase activity (GO:0061630), protein binding (GO:0005515), transferase activity (GO:0016740)

GO Cellular Component (15): Prp19 complex (GO:0000974), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), lipid droplet (GO:0005811), spindle (GO:0005819), membrane (GO:0016020), nuclear speck (GO:0016607), site of double-strand break (GO:0035861), U2-type catalytic step 1 spliceosome (GO:0071006), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), DNA replication factor A complex (GO:0005662), spliceosomal complex (GO:0005681), cytoskeleton (GO:0005856)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	3
Nucleotide Excision Repair	1
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
intracellular membraneless organelle	3
mRNA splicing, via spliceosome	2
RNA processing	2
U2-type spliceosomal complex	2
U2 snRNP	2
U6 snRNP	2
nuclear protein-containing complex	2
DNA integrity checkpoint signaling	1
signal transduction in response to DNA damage	1
protein ubiquitination	1
spliceosomal snRNP assembly	1
protein-RNA complex assembly	1
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
blastocyst growth	1
cell population proliferation	1
double-strand break repair	1
macromolecule localization	1
lipid metabolic process	1
biosynthetic process	1
protein catabolic process	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
protein polyubiquitination	1
DNA metabolic process	1
DNA damage response	1
mRNA metabolic process	1
cellular response to stress	1
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
ubiquitin protein ligase activity	1
protein binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
binding	1
catalytic activity	1
protein-containing complex	1
intracellular membrane-bounded organelle	1

Protein interactions and networks

STRING

3599 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF19	CDC5L	Q99459	998
PRPF19	BCAS2	O75934	994
PRPF19	PLRG1	O43660	989
PRPF19	SETMAR	Q53H47	987
PRPF19	PTPN11	Q06124	982
PRPF19	CTNNBL1	Q8WYA6	932
PRPF19	ZNF830	Q96NB3	874
PRPF19	PPIE	Q9UNP9	846
PRPF19	XAB2	Q9HCS7	830
PRPF19	ALYREF	Q86V81	819
PRPF19	BANP	Q8N9N5	810
PRPF19	TOP1	P11387	755
PRPF19	AQR	O60306	742
PRPF19	RBMX	P38159	714
PRPF19	PSMB4	P28070	684

IntAct

250 interactions, top by confidence:

A	B	Type	Score
CDC5L	PRPF19	psi-mi:“MI:0915”(physical association)	0.920
PRPF19	CDC5L	psi-mi:“MI:0915”(physical association)	0.920
BCAS2	PRPF19	psi-mi:“MI:0915”(physical association)	0.900
PRPF19	BCAS2	psi-mi:“MI:0915”(physical association)	0.900
MED29	MED19	psi-mi:“MI:0914”(association)	0.890
CDC5L	PLRG1	psi-mi:“MI:0915”(physical association)	0.860
PRPS1	PRPSAP2	psi-mi:“MI:0914”(association)	0.840
PPIE	AQR	psi-mi:“MI:0914”(association)	0.810
BCAS2	PLRG1	psi-mi:“MI:0914”(association)	0.790
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
PLRG1	BCAS2	psi-mi:“MI:0914”(association)	0.790
PLRG1	PRPF19	psi-mi:“MI:0407”(direct interaction)	0.770
PRPF19	PLRG1	psi-mi:“MI:0914”(association)	0.770
SYF2	AQR	psi-mi:“MI:0914”(association)	0.730
SNW1	AQR	psi-mi:“MI:0914”(association)	0.650
GCFC2	SNRNP200	psi-mi:“MI:0914”(association)	0.640
NCBP1	KPNA3	psi-mi:“MI:0914”(association)	0.640
NCBP2	KPNA3	psi-mi:“MI:0914”(association)	0.640
PPP4C	SUPT5H	psi-mi:“MI:0914”(association)	0.640
SF3B1	SAP18	psi-mi:“MI:0914”(association)	0.640
PNN	SAP18	psi-mi:“MI:0914”(association)	0.620

BioGRID (809): PRPF19 (Affinity Capture-MS), USP4 (Affinity Capture-Western), UBE2D3 (Reconstituted Complex), PRPF19 (Affinity Capture-RNA), PRPF19 (Affinity Capture-RNA), PRPF19 (Affinity Capture-RNA), PRPF19 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), PRPF19 (Reconstituted Complex), PRPF19 (Affinity Capture-MS), PRPF19 (Affinity Capture-MS), PRPF19 (Two-hybrid)

ESM2 similar proteins: A1CF18, A1DP19, A2QP30, A8NEG8, A8XZJ9, A9V790, B0W517, B2B766, B3MJV8, B3N534, B4GT01, B4HWV6, B4JPT9, B4MU54, B4P116, B4Q9T6, B6GZD3, B6QC06, B6QC56, B7FNU7, B7PY76, B8M0Q1, B8N9H4, B8P4B0, B8PD53, C0NRC6, C4JPW9, C4JZS6, C6HTE8, C7Z6H2, D1ZEM6, D3BUN1, D5GBI7, O94365, P87177, Q00664, Q0D0X6, Q29KQ0, Q2GT28, Q2UGU1

Diamond homologs: A1CUD6, A2AH22, A7TLU2, A8IZG4, A8X8C6, B0R0D7, B0XAF3, B4GDM7, B4JW81, B4LJT7, E7FAG6, F1LTR1, G0SA60, G0SC29, O13046, O13923, O22468, O75717, O76071, O93377, O94527, P0CS38, P0CS39, P0DPA1, P25382, P25569, P26309, P57737, Q06440, Q08E38, Q09028, Q16576, Q1DZQ0, Q24572, Q28D01, Q28DW0, Q292E8, Q3MHL3, Q3SWX8, Q4KLI9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
PRPF19	“up-regulates activity”	PRPF3	polyubiquitination
PRPF19	“form complex”	PRP19-CDC5L	binding
PRPF19	“up-regulates activity”	RPA2	polyubiquitination
PRPF19	“up-regulates activity”	RPA1	polyubiquitination

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 192 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 Splicing - Major Pathway	39	14.3×	6e-32
mRNA Splicing	19	14.0×	1e-14
Processing of Capped Intron-Containing Pre-mRNA	21	11.6×	1e-14
mRNA Splicing - Minor Pathway	7	10.5×	4e-04
RNA Polymerase II Transcription Termination	7	10.3×	4e-04
SPOP-mediated proteasomal degradation of PD-L1(CD274)	6	9.2×	2e-03
mRNA Polyadenylation	15	8.8×	1e-08
mRNA 3’-end processing	6	7.9×	4e-03

GO biological processes:

GO term	Partners	Fold	FDR
mRNA splicing, via spliceosome	37	19.8×	1e-34
positive regulation of transcription elongation by RNA polymerase II	7	12.3×	4e-04
mRNA export from nucleus	7	12.1×	4e-04
RNA splicing	19	9.8×	5e-11
mRNA processing	13	6.0×	1e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	36
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4144956	NM_014502.5(PRPF19):c.515T>G (p.Ile172Ser)	Likely pathogenic

SpliceAI

2016 predictions. Top by Δscore:

Variant	Effect	Δscore
11:60897840:CTCTA:C	donor_loss	1.0000
11:60897841:TCTA:T	donor_loss	1.0000
11:60897842:CTAC:C	donor_loss	1.0000
11:60897843:TACCT:T	donor_loss	1.0000
11:60897844:AC:A	donor_loss	1.0000
11:60897845:C:G	donor_loss	1.0000
11:60897947:TTTAC:T	acceptor_gain	1.0000
11:60897948:TTAC:T	acceptor_gain	1.0000
11:60897949:TAC:T	acceptor_gain	1.0000
11:60897949:TACC:T	acceptor_loss	1.0000
11:60897950:AC:A	acceptor_gain	1.0000
11:60897951:CC:C	acceptor_gain	1.0000
11:60897951:CCT:C	acceptor_loss	1.0000
11:60897952:C:A	acceptor_loss	1.0000
11:60897952:C:CC	acceptor_gain	1.0000
11:60897956:C:CT	acceptor_gain	1.0000
11:60897956:C:T	acceptor_gain	1.0000
11:60897957:A:T	acceptor_gain	1.0000
11:60898237:G:T	acceptor_gain	1.0000
11:60898244:C:CT	acceptor_gain	1.0000
11:60898539:ACCTT:A	donor_loss	1.0000
11:60898622:GAGAG:G	acceptor_gain	1.0000
11:60898623:AGAG:A	acceptor_gain	1.0000
11:60898624:GAG:G	acceptor_gain	1.0000
11:60898625:AG:A	acceptor_gain	1.0000
11:60898626:GC:G	acceptor_loss	1.0000
11:60898627:C:CC	acceptor_gain	1.0000
11:60898628:T:G	acceptor_loss	1.0000
11:60898629:G:C	acceptor_gain	1.0000
11:60898860:A:AC	donor_gain	1.0000

AlphaMissense

3302 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:60897870:A:G	W465R	1.000
11:60897870:A:T	W465R	1.000
11:60897914:A:G	L450P	1.000
11:60897918:A:C	Y449D	1.000
11:60897923:C:A	G447V	1.000
11:60897923:C:T	G447D	1.000
11:60897924:C:G	G447R	1.000
11:60897932:T:A	D444V	1.000
11:60897934:A:C	F443L	1.000
11:60897934:A:T	F443L	1.000
11:60897935:A:C	F443C	1.000
11:60897935:A:G	F443S	1.000
11:60897936:A:G	F443L	1.000
11:60898141:A:G	L424P	1.000
11:60898141:A:T	L424H	1.000
11:60898145:T:C	K423E	1.000
11:60898147:C:A	R422L	1.000
11:60898147:C:G	R422P	1.000
11:60898147:C:T	R422H	1.000
11:60898148:G:A	R422C	1.000
11:60898148:G:C	R422G	1.000
11:60898148:G:T	R422S	1.000
11:60898150:A:C	L421R	1.000
11:60898150:A:G	L421P	1.000
11:60898150:A:T	L421Q	1.000
11:60898152:A:C	D420E	1.000
11:60898152:A:T	D420E	1.000
11:60898153:T:A	D420V	1.000
11:60898153:T:C	D420G	1.000
11:60898153:T:G	D420A	1.000

dbSNP variants (sampled 300 via entrez): RS1000067992 (11:60902318 A>G), RS1000119971 (11:60901938 G>A), RS1000808810 (11:60895630 A>G), RS1000847172 (11:60907880 G>A), RS1001021040 (11:60900950 A>C), RS1001072871 (11:60900694 G>A), RS1001116732 (11:60904752 T>C), RS1001525970 (11:60894975 G>A), RS1001548107 (11:60905132 A>G), RS1001582295 (11:60901397 G>A), RS1001857452 (11:60908352 T>G), RS1001858018 (11:60892222 C>A), RS1002461817 (11:60906819 C>A), RS1002535885 (11:60900327 T>C,G), RS1002576463 (11:60893784 G>A)

Disease associations

OMIM: gene MIM:608330 | disease phenotypes: MIM:236750, MIM:209850

GenCC curated gene-disease

Disease	Classification	Inheritance
neurodevelopmental disorder	Strong	Autosomal dominant
PRPF19-related neurodevelopmental disorder	Moderate	Autosomal dominant

Mondo (4): non-immune hydrops fetalis (MONDO:0009369), autism (MONDO:0005260), neurodevelopmental disorder (MONDO:0700092), PRPF19-related neurodevelopmental disorder (MONDO:1040005)

Orphanet (1): Non-immune hydrops fetalis (Orphanet:363999)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0000717	Autism

GWAS associations

0 associations (top):

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D001321	Autistic Disorder	F03.625.164.113.500
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725167 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects expression, decreases expression, affects cotreatment, increases abundance	3
bisphenol A	decreases expression, increases expression	2
Benzo(a)pyrene	increases methylation, increases mutagenesis	2
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
decabromobiphenyl ether	decreases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
cobaltous chloride	decreases expression	1
manganese chloride	affects cotreatment, decreases expression, increases abundance	1
di-n-butylphosphoric acid	affects expression	1
yessotoxin	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
bisphenol S	increases expression	1
LDN 193189	affects cotreatment, increases expression	1
bisphenol AF	increases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	affects cotreatment, decreases expression, increases abundance	1
Atrazine	decreases expression	1
Cannabidiol	increases expression, affects cotreatment	1
Cuprizone	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Dimethyl Sulfoxide	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5652132	Binding	Binding affinity to human PRPF19 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

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT00211796	PHASE4	COMPLETED	Divalproex Sodium ER in Adult Autism
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT00409747	PHASE4	COMPLETED	Minocycline to Treat Childhood Regressive Autism
NCT00576732	PHASE4	COMPLETED	A Study of the Effectiveness and Safety of Two Doses of Risperidone in the Treatment of Children and Adolescents With Autistic Disorder
NCT00844753	PHASE4	COMPLETED	Atomoxetine, Placebo and Parent Management Training in Autism
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01098383	PHASE4	UNKNOWN	Treatment With Acetyl-Choline Esterase Inhibitors in Children With Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02069977	PHASE4	UNKNOWN	Study to Evaluate the Efficacy and Safety of Aripiprazole
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02199925	PHASE4	UNKNOWN	An Open-Label Study to Evaluate the Efficacy of High-Dose Gammaplex in Children on the Autism Spectrum
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02255565	PHASE4	COMPLETED	Dose Response Effects of Quillivant XR in Children With ADHD and Autism: A Pilot Study
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00036231	PHASE3	TERMINATED	Synthetic Human Secretin in Children With Autism and Gastrointestinal Dysfunction
NCT00036244	PHASE3	COMPLETED	Synthetic Human Secretin in Children With Autism
NCT00065884	PHASE3	UNKNOWN	Valproate Response in Aggressive Autistic Adolescents
NCT00065962	PHASE3	COMPLETED	Secretin for the Treatment of Autism
NCT00252603	PHASE3	COMPLETED	Galantamine Versus Placebo in Childhood Autism