PRPF18

Summary

PRPF18 (pre-mRNA processing factor 18, HGNC:17351) is a protein-coding gene on chromosome 10p13, encoding Pre-mRNA-splicing factor 18 (Q99633). Participates in the second step of pre-mRNA splicing. It is a selective cancer dependency (DepMap: 49.4% of cell lines).

Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is found to be essential for the catalytic step II in pre-mRNA splicing process. It is found in the spliceosome, and contains seven WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to the yeast splicing factor Prp18.

Source: NCBI Gene 8559 — RefSeq curated summary.

At a glance

• GWAS associations: 5
• Clinical variants (ClinVar): 39 total
• Cancer dependency (DepMap): dependent in 49.4% of screened cell lines
• MANE Select transcript: NM_003675

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17351
Approved symbol	PRPF18
Name	pre-mRNA processing factor 18
Location	10p13
Locus type	gene with protein product
Status	Approved
Aliases	hPrp18
Ensembl gene	ENSG00000165630
Ensembl biotype	protein_coding
OMIM	604993
Entrez	8559

Gene structure

Transcript identifiers

Ensembl transcripts: 72 — 53 protein_coding_CDS_not_defined, 17 protein_coding, 2 nonsense_mediated_decay

ENST00000320054, ENST00000378572, ENST00000417658, ENST00000419851, ENST00000430721, ENST00000440878, ENST00000593351, ENST00000593358, ENST00000594575, ENST00000595538, ENST00000596044, ENST00000596235, ENST00000596499, ENST00000597920, ENST00000598625, ENST00000599378, ENST00000599639, ENST00000600249, ENST00000600511, ENST00000601075, ENST00000601460, ENST00000601758, ENST00000610395, ENST00000611235, ENST00000612284, ENST00000612296, ENST00000612304, ENST00000612515, ENST00000612602, ENST00000612960, ENST00000613031, ENST00000613191, ENST00000613332, ENST00000613467, ENST00000613937, ENST00000613992, ENST00000614899, ENST00000614991, ENST00000615209, ENST00000615691, ENST00000616092, ENST00000616222, ENST00000616861, ENST00000616949, ENST00000617260, ENST00000617534, ENST00000618536, ENST00000618688, ENST00000619389, ENST00000619884, ENST00000619944, ENST00000620488, ENST00000620600, ENST00000620849, ENST00000621308, ENST00000621394, ENST00000621532, ENST00000622389, ENST00000622799, ENST00000855615, ENST00000855616, ENST00000855617, ENST00000937337, ENST00000937338, ENST00000937339, ENST00000937340, ENST00000937341, ENST00000937342, ENST00000966917, ENST00000966918, ENST00000966919, ENST00000966920

RefSeq mRNA: 14 — MANE Select: NM_003675 NM_001395875, NM_001395876, NM_001395877, NM_001395878, NM_001395879, NM_001395880, NM_001395881, NM_001395882, NM_001395883, NM_001395884, NM_001395885, NM_001395886, NM_001395887, NM_003675

CCDS: CCDS7100

Canonical transcript exons

ENST00000378572 — 10 exons

Exon	Start	End
ENSE00001094826	13610039	13610185
ENSE00001094835	13597458	13597535
ENSE00001094838	13605631	13605744
ENSE00001094840	13600244	13600348
ENSE00001852793	13586965	13587152
ENSE00001883918	13630260	13630859
ENSE00003477542	13611615	13611683
ENSE00003501083	13614015	13614086
ENSE00003570883	13613741	13613881
ENSE00003604889	13616398	13616553

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 94.83.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 33.0337 / max 509.6753, expressed in 1806 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103948	32.2889	1805
103947	0.7448	438

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
calcaneal tendon	UBERON:0003701	94.83	gold quality
corpus callosum	UBERON:0002336	92.55	gold quality
sural nerve	UBERON:0015488	91.98	gold quality
islet of Langerhans	UBERON:0000006	91.53	gold quality
monocyte	CL:0000576	90.84	gold quality
leukocyte	CL:0000738	90.71	gold quality
bone marrow	UBERON:0002371	90.43	gold quality
bone marrow cell	CL:0002092	89.33	gold quality
tonsil	UBERON:0002372	88.38	gold quality
rectum	UBERON:0001052	88.18	gold quality
gastrocnemius	UBERON:0001388	88.15	gold quality
granulocyte	CL:0000094	88.07	gold quality
muscle of leg	UBERON:0001383	88.05	gold quality
ganglionic eminence	UBERON:0004023	87.90	gold quality
colonic epithelium	UBERON:0000397	87.77	gold quality
placenta	UBERON:0001987	87.73	gold quality
skeletal muscle tissue	UBERON:0001134	87.57	gold quality
ventricular zone	UBERON:0003053	87.13	gold quality
smooth muscle tissue	UBERON:0001135	87.08	gold quality
muscle tissue	UBERON:0002385	86.94	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	86.79	gold quality
gall bladder	UBERON:0002110	86.70	gold quality
pancreas	UBERON:0001264	86.63	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	86.53	gold quality
duodenum	UBERON:0002114	86.50	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.37	gold quality
lymph node	UBERON:0000029	86.30	gold quality
adrenal tissue	UBERON:0018303	85.96	gold quality
endometrium	UBERON:0001295	85.89	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.61	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.36

Regulation

Is transcription factor: no

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 49.4% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 3)

• Presented is solution structure of the splicing factor motif of hPrp18, which forms a compact fold with two a helices interacting head-to-tail and a fixed linker loop. (PMID:22213562)
• We identified the pre-mRNA processing factor Prp18 as a stimulatory factor for influenza virus RNA synthesis. Prp18 facilitates the elongation reaction of viral polymerases by preventing the deleterious annealing of newly synthesized RNA to the template. Prp18 functions as a chaperone for NP to stimulate the formation of NP-RNA complexes. (PMID:27852861)
• These results validated the association of two previously known skin pigmentation genes, SLC24A5 (minimum p = 2.62 x 10(-14), rs1426654) and SLC45A2 (minimum p = 9.71 x 10(-10), rs16891982), and revealed the intergenic region of BEND7 and PRPF18 as a novel locus associated with this trait (minimum p = 4.58 x 10(-9), rs6602666). (PMID:28300201)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf18	ENSDARG00000058306
mus_musculus	Prpf18	ENSMUSG00000039449
rattus_norvegicus	Prpf18	ENSRNOG00000018396
drosophila_melanogaster	Prp18	FBGN0027784
caenorhabditis_elegans		WBGENE00009320

Protein

Protein identifiers

Pre-mRNA-splicing factor 18 — Q99633 (reviewed: Q99633)

Alternative names: PRP18 homolog

All UniProt accessions (6): Q99633, M0QXG2, M0QXX3, M0R3G1, Q5T9P7, Q5T9P8

UniProt curated annotations — full annotation on UniProt →

Function. Participates in the second step of pre-mRNA splicing.

Subunit / interactions. Heterodimer with PPIH. Interacts with PRPF4 and with the spliceosome. Part of a complex containing U4/U6 snRNPs.

Subcellular location. Nucleus speckle.

Similarity. Belongs to the PRP18 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q99633-1	1	yes
Q99633-2	2

RefSeq proteins (14): NP_001382804, NP_001382805, NP_001382806, NP_001382807, NP_001382808, NP_001382809, NP_001382810, NP_001382811, NP_001382812, NP_001382813, NP_001382814, NP_001382815, NP_001382816, NP_003666* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004098	Prp18	Domain
IPR014906	PRP4-like	Domain
IPR036285	PRP4-like_sf	Homologous_superfamily
IPR039979	PRPF18	Family

Pfam: PF02840, PF08799

UniProt features (8 total): splice variant 2, strand 2, helix 2, chain 1, modified residue 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2DK4	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q99633-F1	77.38	0.26

Functional residue map

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

Post-translational modifications (1): 1

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 115 (showing top): IVANOVA_HEMATOPOIESIS_MATURE_CELL, chr10p13, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_PROTEIN_RNA_COMPLEX_ORGANIZATION, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, SCHLOSSER_SERUM_RESPONSE_DN, FREAC7_01, SOX5_01, ACEVEDO_LIVER_CANCER_UP, GOBP_RIBONUCLEOPROTEIN_COMPLEX_BIOGENESIS, SPIELMAN_LYMPHOBLAST_EUROPEAN_VS_ASIAN_DN, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK

GO Biological Process (3): generation of catalytic spliceosome for second transesterification step (GO:0000350), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (7): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), U5 snRNP (GO:0005682), nuclear speck (GO:0016607), U4/U6 x U5 tri-snRNP complex (GO:0046540), U2-type post-spliceosomal complex (GO:0071021)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
mRNA Splicing	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
RNA processing	2
spliceosomal conformational changes to generate catalytic conformation	1
protein-RNA complex assembly	1
mRNA metabolic process	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
spliceosomal snRNP complex	1
nuclear ribonucleoprotein granule	1
U5 snRNP	1
U4/U6 snRNP	1
spliceosomal tri-snRNP complex	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
post-spliceosomal complex	1

Protein interactions and networks

STRING

954 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF18	SLU7	O95391	995
PRPF18	DHX38	Q92620	990
PRPF18	CDC40	O60508	984
PRPF18	DHX8	Q14562	958
PRPF18	YJU2	Q9BW85	879
PRPF18	CWC25	Q9NXE8	858
PRPF18	PPIH	O43447	745
PRPF18	CWC22	Q9HCG8	712
PRPF18	DHX15	O43143	711
PRPF18	SNRNP200	O75643	709
PRPF18	XAB2	Q9HCS7	658
PRPF18	PRPF3	O43395	657
PRPF18	DDX23	Q9BUQ8	648
PRPF18	RNF113A	O15541	641
PRPF18	DHX16	O60231	641

IntAct

281 interactions, top by confidence:

A	B	Type	Score
PRPF18	IKZF3	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	FXR1	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	GMCL1	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	SERTAD1	psi-mi:“MI:0915”(physical association)	0.560
GMCL1	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	TXNDC11	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	FANCG	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	AGR2	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	TTC23	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	DDIT4L	psi-mi:“MI:0915”(physical association)	0.560
TRAF2	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
FXR1	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
PRPF18	BLZF1	psi-mi:“MI:0915”(physical association)	0.560
KANK2	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
CDR2	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
TXNDC11	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
FANCG	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
AGR2	PRPF18	psi-mi:“MI:0915”(physical association)	0.560
TTC23	PRPF18	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (105): PRPF18 (Co-fractionation), PRPF18 (Affinity Capture-MS), PRPF18 (Affinity Capture-MS), PRPF18 (Affinity Capture-MS), PRPF18 (Reconstituted Complex), PRPF18 (Negative Genetic), PRPF18 (Positive Genetic), PRPF18 (Negative Genetic), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid), PRPF18 (Two-hybrid)

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

Diamond homologs: O94406, P33411, Q2HJ41, Q5EAV6, Q5RE03, Q6GMH0, Q8BM39, Q99633, Q9JKB8

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 90 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.

GO biological processes:

GO term	Partners	Fold	FDR
morphogenesis of an epithelium	5	22.3×	1e-03
intermediate filament organization	5	15.6×	4e-03
epithelial cell differentiation	5	11.4×	9e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	25
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

4123 predictions. Top by Δscore:

Variant	Effect	Δscore
10:13587150:GTG:G	donor_gain	1.0000
10:13597452:TAATA:T	acceptor_loss	1.0000
10:13597455:TAGG:T	acceptor_loss	1.0000
10:13597456:A:AG	acceptor_gain	1.0000
10:13597456:AG:A	acceptor_gain	1.0000
10:13597456:AGGA:A	acceptor_loss	1.0000
10:13597457:G:GA	acceptor_gain	1.0000
10:13597457:GG:G	acceptor_gain	1.0000
10:13597457:GGA:G	acceptor_gain	1.0000
10:13597457:GGAA:G	acceptor_gain	1.0000
10:13597457:GGAAA:G	acceptor_gain	1.0000
10:13597531:ACAAG:A	donor_loss	1.0000
10:13597532:CAAGG:C	donor_loss	1.0000
10:13597533:AAGG:A	donor_loss	1.0000
10:13597534:AGGTA:A	donor_loss	1.0000
10:13597535:GGTA:G	donor_loss	1.0000
10:13597536:GTATG:G	donor_loss	1.0000
10:13597537:T:A	donor_loss	1.0000
10:13600229:T:TA	acceptor_gain	1.0000
10:13600230:G:A	acceptor_gain	1.0000
10:13600234:A:AG	acceptor_gain	1.0000
10:13600235:T:G	acceptor_gain	1.0000
10:13600237:A:AG	acceptor_gain	1.0000
10:13600238:A:G	acceptor_gain	1.0000
10:13600239:T:G	acceptor_gain	1.0000
10:13600240:A:AG	acceptor_gain	1.0000
10:13600241:T:G	acceptor_gain	1.0000
10:13600242:A:AG	acceptor_gain	1.0000
10:13600243:G:GG	acceptor_gain	1.0000
10:13600243:GA:G	acceptor_gain	1.0000

AlphaMissense

2257 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
10:13613835:A:C	Q225P	1.000
10:13613850:T:C	L230P	1.000
10:13616407:G:C	A268P	1.000
10:13616410:T:C	Y269H	1.000
10:13616410:T:G	Y269D	1.000
10:13616414:T:A	L270H	1.000
10:13616414:T:C	L270P	1.000
10:13616420:T:A	M272K	1.000
10:13616420:T:G	M272R	1.000
10:13616422:G:C	A273P	1.000
10:13616423:C:A	A273D	1.000
10:13616425:A:T	I274F	1.000
10:13616426:T:A	I274N	1.000
10:13616426:T:G	I274S	1.000
10:13616428:G:A	G275R	1.000
10:13616428:G:C	G275R	1.000
10:13616429:G:A	G275E	1.000
10:13616429:G:C	G275A	1.000
10:13616429:G:T	G275V	1.000
10:13616434:G:C	A277P	1.000
10:13616438:C:A	P278H	1.000
10:13616440:T:A	W279R	1.000
10:13616440:T:C	W279R	1.000
10:13616440:T:G	W279G	1.000
10:13616441:G:C	W279S	1.000
10:13616442:G:C	W279C	1.000
10:13616442:G:T	W279C	1.000
10:13616443:C:A	P280T	1.000
10:13616443:C:T	P280S	1.000
10:13616444:C:A	P280H	1.000

dbSNP variants (sampled 300 via entrez): RS1000023371 (10:13627125 C>T), RS1000098672 (10:13647490 G>A,C), RS1000109769 (10:13616161 C>T), RS1000111411 (10:13592358 T>A), RS1000247509 (10:13592625 G>A), RS1000267791 (10:13632080 G>A,T), RS1000353069 (10:13642519 C>T), RS1000368813 (10:13604348 T>A,G), RS1000369714 (10:13637286 C>A,G,T), RS1000389640 (10:13606199 A>G), RS1000395331 (10:13642734 T>C), RS1000436149 (10:13598362 C>G), RS1000487685 (10:13609678 C>T), RS1000500215 (10:13648515 C>CA), RS1000521870 (10:13633140 C>T)

Disease associations

OMIM: gene MIM:604993 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST002176_3	Adverse response to chemotherapy in breast cancer (alopecia) (cyclophosphamide+epirubicin+/-5FU)	7.000000e-06
GCST002479_11	Lupus nephritis in systemic lupus erythematosus	5.000000e-06
GCST003264_944	Post bronchodilator FEV1/FVC ratio	5.000000e-06
GCST004219_3	Skin pigmentation	5.000000e-09
GCST004412_9	Craniofacial microsomia	2.000000e-07

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004713	FEV/FVC ratio

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	4
bisphenol A	affects cotreatment, affects methylation, increases expression	2
sodium arsenite	increases abundance, increases expression	2
Tretinoin	affects cotreatment, increases expression	2
dicrotophos	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
cupric oxide	increases expression	1
di-n-butylphosphoric acid	affects expression	1
monomethylarsonous acid	increases expression	1
K 7174	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	increases expression	1
bisphenol S	increases methylation	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	affects cotreatment, increases expression	1
Fulvestrant	affects cotreatment, affects methylation	1
Air Pollutants	affects expression, increases abundance	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	increases methylation	1
Caffeine	decreases phosphorylation	1
Dimethyl Sulfoxide	increases expression	1
Fluorouracil	decreases expression	1
Hydralazine	affects cotreatment, increases expression	1
Methyl Methanesulfonate	increases expression	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Phenylmercuric Acetate	affects cotreatment, increases expression	1
Piroxicam	decreases expression	1

Clinical trials (associated diseases)

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