PRPF38A

Summary

PRPF38A (pre-mRNA processing factor 38A, HGNC:25930) is a protein-coding gene on chromosome 1p32.3, encoding Pre-mRNA-splicing factor 38A (Q8NAV1). Involved in pre-mRNA splicing as a component of the spliceosome. It is a common-essential gene (DepMap: required in 100.0% of cancer cell lines).

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nucleoplasm. Part of U2-type precatalytic spliceosome.

Source: NCBI Gene 84950 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 42 total
• Cancer dependency (DepMap): dependent in 100.0% of screened cell lines (common-essential)
• MANE Select transcript: NM_032864

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25930
Approved symbol	PRPF38A
Name	pre-mRNA processing factor 38A
Location	1p32.3
Locus type	gene with protein product
Status	Approved
Aliases	FLJ14936, Prp38
Ensembl gene	ENSG00000134748
Ensembl biotype	protein_coding
OMIM	617031
Entrez	84950

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 6 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000257181, ENST00000474048, ENST00000487160, ENST00000879463, ENST00000879464, ENST00000879465, ENST00000921590, ENST00000956531

RefSeq mRNA: 1 — MANE Select: NM_032864 NM_032864

CCDS: CCDS567

Canonical transcript exons

ENST00000257181 — 10 exons

Exon	Start	End
ENSE00001377312	52416648	52420836
ENSE00001684143	52408569	52408690
ENSE00001705305	52411115	52411200
ENSE00001806530	52404602	52404879
ENSE00003473155	52413879	52413991
ENSE00003480524	52412514	52412624
ENSE00003563744	52414762	52414859
ENSE00003611011	52415338	52415386
ENSE00003660795	52405680	52405839
ENSE00003692089	52414621	52414647

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 93.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 41.7243 / max 644.1420, expressed in 1816 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2874	37.7359	1813
2873	3.9884	1476

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
tendon of biceps brachii	UBERON:0008188	93.94	gold quality
epithelial cell of pancreas	CL:0000083	93.50	gold quality
thymus	UBERON:0002370	92.78	gold quality
ventricular zone	UBERON:0003053	92.71	gold quality
ganglionic eminence	UBERON:0004023	92.66	gold quality
vermiform appendix	UBERON:0001154	91.33	gold quality
bone marrow	UBERON:0002371	91.30	gold quality
medial globus pallidus	UBERON:0002477	90.85	gold quality
bone marrow cell	CL:0002092	90.78	gold quality
tendon	UBERON:0000043	90.66	gold quality
lymph node	UBERON:0000029	90.55	gold quality
rectum	UBERON:0001052	90.50	gold quality
left ovary	UBERON:0002119	90.45	gold quality
monocyte	CL:0000576	90.40	gold quality
leukocyte	CL:0000738	90.40	gold quality
caecum	UBERON:0001153	90.10	gold quality
globus pallidus	UBERON:0001875	89.87	gold quality
ovary	UBERON:0000992	89.74	gold quality
right ovary	UBERON:0002118	89.59	gold quality
mucosa of transverse colon	UBERON:0004991	89.59	gold quality
islet of Langerhans	UBERON:0000006	89.42	gold quality
esophagus mucosa	UBERON:0002469	89.27	gold quality
body of uterus	UBERON:0009853	89.19	gold quality
kidney epithelium	UBERON:0004819	89.16	gold quality
sural nerve	UBERON:0015488	89.05	gold quality
left testis	UBERON:0004533	89.04	gold quality
calcaneal tendon	UBERON:0003701	89.02	gold quality
upper arm skin	UBERON:0004263	88.96	gold quality
ectocervix	UBERON:0012249	88.80	gold quality
right testis	UBERON:0004534	88.66	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

89 targeting PRPF38A, 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-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-4723-5P	99.97	68.70	2034
HSA-MIR-5698	99.97	68.49	2029
HSA-MIR-7111-5P	99.97	68.48	2062
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-22-3P	99.93	68.13	917
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-335-3P	99.93	73.36	4958
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-6809-3P	99.91	71.45	3814
HSA-MIR-4753-3P	99.90	71.03	3786
HSA-MIR-4492	99.87	68.25	3611
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-130B-5P	99.83	68.50	1888

Functional genomics

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

Literature-anchored findings (GeneRIF, showing 2)

• Multiple protein-protein interactions are converging on the Prp38 protein during activation of the human spliceosome. (PMID:26673105)
• Mechanism of protein-guided folding of the active site U2/U6 RNA during spliceosome activation. (PMID:33243851)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	prpf38a	ENSDARG00000039213
mus_musculus	Prpf38a	ENSMUSG00000063800
rattus_norvegicus	Prpf38a	ENSRNOG00000009451
drosophila_melanogaster	Prp38	FBGN0050342
caenorhabditis_elegans		WBGENE00008380

Protein

Protein identifiers

Pre-mRNA-splicing factor 38A — Q8NAV1 (reviewed: Q8NAV1)

All UniProt accessions (1): Q8NAV1

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as a component of the spliceosome.

Subunit / interactions. Component of the spliceosome B complex. Interacts (via N-terminal interaction domain) with ZMAT2 and MFAP1.

Subcellular location. Nucleus.

Similarity. Belongs to the PRP38 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q8NAV1-1	1	yes
Q8NAV1-2	2

RefSeq proteins (1): NP_116253* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005037	PRP38	Family
IPR024767	PRP38_C	Domain

Pfam: PF03371, PF12871

UniProt features (35 total): helix 14, modified residue 5, strand 4, compositionally biased region 4, region of interest 2, chain 1, splice variant 1, mutagenesis site 1, sequence conflict 1, turn 1, coiled-coil region 1

Structure

Experimental structures (PDB)

16 structures.

PDB	Method	Resolution (Å)
4RZ9	X-RAY DIFFRACTION	1.28
4RZA	X-RAY DIFFRACTION	1.9
5F5S	X-RAY DIFFRACTION	2.4
8H6K	ELECTRON MICROSCOPY	2.7
8Q7N	ELECTRON MICROSCOPY	3.1
8QPE	ELECTRON MICROSCOPY	3.1
9R3D	ELECTRON MICROSCOPY	3.12
6AHD	ELECTRON MICROSCOPY	3.8
7ABF	ELECTRON MICROSCOPY	3.9
8QZS	ELECTRON MICROSCOPY	4.1
7AAV	ELECTRON MICROSCOPY	4.2
5O9Z	ELECTRON MICROSCOPY	4.5
8QO9	ELECTRON MICROSCOPY	5.29
7ABG	ELECTRON MICROSCOPY	7.8
7ABI	ELECTRON MICROSCOPY	8
9R8V	ELECTRON MICROSCOPY	8.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q8NAV1-F1	70.78	0.31

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): 194, 209, 226, 11, 193

Mutagenesis-validated functional residues (1):

Position	Phenotype
145	loss of interaction with mfap1.

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 157 (showing top): E2F_Q4_01, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, GEORGES_CELL_CYCLE_MIR192_TARGETS, FOXO1_01, MODULE_308, E2F_Q3, FOSTER_TOLERANT_MACROPHAGE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, TATCTGG_MIR488, REACTOME_MRNA_SPLICING, SLEBOS_HEAD_AND_NECK_CANCER_WITH_HPV_UP, BENPORATH_NOS_TARGETS, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, E2F1_Q3

GO Biological Process (3): mRNA splicing, via spliceosome (GO:0000398), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (2): RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (5): nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type precatalytic spliceosome (GO:0071005), precatalytic spliceosome (GO:0071011), spliceosomal complex (GO:0005681)

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
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
U2-type spliceosomal complex	1
U1 snRNP	1
U2 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
spliceosomal complex	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

2288 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
PRPF38A	MFAP1	P55081	870
PRPF38A	ZMAT2	Q96NC0	827
PRPF38A	SMU1	Q2TAY7	761
PRPF38A	SART1	O43290	742
PRPF38A	WBP4	O75554	741
PRPF38A	PRPF6	O94906	698
PRPF38A	LSM5	Q9Y4Y9	640
PRPF38A	UBL5	Q9BZL1	612
PRPF38A	PRPF31	Q8WWY3	597
PRPF38A	PRPF8	Q6P2Q9	588
PRPF38A	SNRNP200	O75643	584
PRPF38A	SF3A3	Q12874	569
PRPF38A	SYF2	O95926	557
PRPF38A	FCF1	Q9Y324	543
PRPF38A	SNW1	Q13573	538

IntAct

153 interactions, top by confidence:

A	B	Type	Score
PRPF38A	SRPK2	psi-mi:“MI:0915”(physical association)	0.890
SRPK2	PRPF38A	psi-mi:“MI:0915”(physical association)	0.890
SRPK2	PRPF38A	psi-mi:“MI:0217”(phosphorylation reaction)	0.890
PRPF38A	SDCBP2	psi-mi:“MI:0915”(physical association)	0.780
DNAAF2	UBE3D	psi-mi:“MI:0914”(association)	0.780
PRPF38A	SRPK1	psi-mi:“MI:0217”(phosphorylation reaction)	0.690
SRPK1	PRPF38A	psi-mi:“MI:0915”(physical association)	0.690
UBL5	SART1	psi-mi:“MI:0914”(association)	0.670
MFAP1	PRPF38A	psi-mi:“MI:0915”(physical association)	0.670
PRPF38A	SRSF3	psi-mi:“MI:0915”(physical association)	0.640
JMJD6	PRPF38A	psi-mi:“MI:0915”(physical association)	0.630
PRPF38A	JMJD6	psi-mi:“MI:0915”(physical association)	0.630
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
SDCBP	PRPF38A	psi-mi:“MI:0915”(physical association)	0.560
CLK2	PRPF38A	psi-mi:“MI:0915”(physical association)	0.560
PRPF38A	SDCBP	psi-mi:“MI:0915”(physical association)	0.560
PRPF38A	CLK2	psi-mi:“MI:0915”(physical association)	0.560
SRSF7	PRPF38A	psi-mi:“MI:0915”(physical association)	0.560
PRPF38A	DVL3	psi-mi:“MI:0915”(physical association)	0.560
PRPF38A	AP2M1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (216): PRPF38A (Two-hybrid), PRPF38A (Two-hybrid), PRPF38A (Two-hybrid), PRPF38A (Two-hybrid), PRPF38A (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), PRPF38A (Affinity Capture-MS), CSNK2B (Co-fractionation), MFAP1 (Co-fractionation), PRPF38A (Co-fractionation), PRPF38A (Affinity Capture-MS), PRPF38A (Biochemical Activity), PRPF38A (Biochemical Activity), PRPF38A (Affinity Capture-MS), PRPF38A (Affinity Capture-MS)

ESM2 similar proteins: A0A1I8M2I8, A8WT19, A8XEG9, B3MJ69, B3N3F7, B4H732, B4J497, B4KLY7, B4LIK8, B4NYV0, G5EBY0, O15042, P0C1I9, P0CM96, P0CM97, P52016, Q08C72, Q0P5I6, Q17336, Q19375, Q28WQ8, Q4FK66, Q4FZQ6, Q4PCY0, Q4WKB9, Q52B63, Q52KN9, Q5BGP1, Q5R7X2, Q5RA93, Q5RDD2, Q5ZKA3, Q61MR2, Q6C8C5, Q6CC11, Q6DHU4, Q6NV83, Q7JVL3, Q7RX84, Q8C5N3

Diamond homologs: Q0P5I6, Q28H87, Q4FK66, Q4FZQ6, Q5RDD2, Q6DHU4, Q7JVL3, Q8HXH6, Q8LB54, Q8NAV1, Q9UUD2

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 157 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	8	27.7×	3e-08
mRNA 3’-end processing	10	17.9×	2e-08
Transport of Mature mRNA derived from an Intron-Containing Transcript	11	15.2×	2e-08
RNA Polymerase II Transcription Termination	7	14.0×	5e-05
mRNA Splicing	13	13.0×	4e-09
mRNA Splicing - Major Pathway	26	12.9×	3e-19
Processing of Capped Intron-Containing Pre-mRNA	15	11.2×	1e-09
mRNA Polyadenylation	13	10.4×	3e-08

GO biological processes:

GO term	Partners	Fold	FDR
negative regulation of mRNA splicing, via spliceosome	7	39.1×	1e-07
regulation of mRNA splicing, via spliceosome	5	32.4×	7e-05
regulation of alternative mRNA splicing, via spliceosome	9	16.0×	1e-06
mRNA transcription by RNA polymerase II	5	12.1×	1e-02
mRNA splicing, via spliceosome	16	10.7×	2e-09
RNA splicing	15	9.7×	2e-08
mRNA processing	9	5.2×	1e-02

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	30
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1280 predictions. Top by Δscore:

Variant	Effect	Δscore
1:52404241:CTCA:C	donor_loss	1.0000
1:52404242:TCACC:T	donor_loss	1.0000
1:52404243:CACC:C	donor_loss	1.0000
1:52404244:AC:A	donor_gain	1.0000
1:52404245:C:CA	donor_loss	1.0000
1:52404245:CC:C	donor_gain	1.0000
1:52404245:CCCGG:C	donor_gain	1.0000
1:52404876:ACAGG:A	donor_loss	1.0000
1:52404877:CAG:C	donor_gain	1.0000
1:52404877:CAGG:C	donor_loss	1.0000
1:52404878:AG:A	donor_gain	1.0000
1:52404878:AGGTA:A	donor_loss	1.0000
1:52404879:GG:G	donor_gain	1.0000
1:52404879:GGTA:G	donor_loss	1.0000
1:52404880:G:GA	donor_loss	1.0000
1:52404880:G:GG	donor_gain	1.0000
1:52405678:A:AG	acceptor_gain	1.0000
1:52405679:G:GG	acceptor_gain	1.0000
1:52405679:GCT:G	acceptor_gain	1.0000
1:52405840:G:GG	donor_gain	1.0000
1:52408563:TCTCA:T	acceptor_loss	1.0000
1:52408564:CTCAG:C	acceptor_loss	1.0000
1:52408565:TCA:T	acceptor_loss	1.0000
1:52408566:CAG:C	acceptor_loss	1.0000
1:52408568:G:GT	acceptor_loss	1.0000
1:52408568:GGT:G	acceptor_gain	1.0000
1:52408568:GGTAT:G	acceptor_gain	1.0000
1:52408686:TGGGG:T	donor_gain	1.0000
1:52408687:GGGG:G	donor_gain	1.0000
1:52408687:GGGGG:G	donor_gain	1.0000

AlphaMissense

2058 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:52404754:C:A	A2D	1.000
1:52404754:C:T	A2V	1.000
1:52404758:C:A	N3K	1.000
1:52404758:C:G	N3K	1.000
1:52404760:G:C	R4P	1.000
1:52404763:C:A	T5K	1.000
1:52404763:C:G	T5R	1.000
1:52404763:C:T	T5I	1.000
1:52404775:C:A	A9E	1.000
1:52404786:C:G	H13D	1.000
1:52404787:A:C	H13P	1.000
1:52404789:G:C	G14R	1.000
1:52404789:G:T	G14C	1.000
1:52404790:G:A	G14D	1.000
1:52404790:G:T	G14V	1.000
1:52404797:C:A	N16K	1.000
1:52404797:C:G	N16K	1.000
1:52404798:C:A	P17T	1.000
1:52404798:C:T	P17S	1.000
1:52404799:C:A	P17H	1.000
1:52404799:C:G	P17R	1.000
1:52404799:C:T	P17L	1.000
1:52404803:A:C	Q18H	1.000
1:52404803:A:T	Q18H	1.000
1:52404808:T:C	L20P	1.000
1:52404811:T:A	V21E	1.000
1:52404813:G:A	E22K	1.000
1:52404814:A:T	E22V	1.000
1:52404820:T:A	I24N	1.000
1:52404820:T:C	I24T	1.000

dbSNP variants (sampled 300 via entrez): RS1000138712 (1:52410033 G>A), RS1000280713 (1:52419811 G>A), RS1000356802 (1:52413496 A>G), RS1000389479 (1:52414244 C>T), RS1000453398 (1:52415134 G>A), RS1000470514 (1:52407023 C>CT), RS1000649768 (1:52420859 T>C), RS1000742463 (1:52408371 A>G), RS1001021772 (1:52421195 T>C), RS1001300913 (1:52417857 AGAGT>A), RS1001397942 (1:52405336 G>A,C), RS1001426927 (1:52412154 C>T), RS1001582262 (1:52405948 A>C,G,T), RS1001912473 (1:52410135 CAT>C), RS1002249892 (1:52416902 T>A)

Disease associations

OMIM: gene MIM:617031 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

23 total (human), top 23 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	affects expression, decreases expression	2
cylindrospermopsin	increases expression	2
FR900359	increases phosphorylation	1
TAK-243	increases sumoylation	1
2,4,6-tribromophenol	decreases expression	1
decabromobiphenyl ether	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
tetrabromobisphenol A	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
PCI 5002	affects cotreatment, increases expression	1
Calcitriol	decreases expression, affects cotreatment	1
Formaldehyde	decreases expression	1
Polycyclic Aromatic Hydrocarbons	affects expression	1
Ribonucleotides	affects binding	1
Testosterone	affects cotreatment, decreases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Zinc	affects cotreatment, increases expression	1
Cyclosporine	decreases expression	1

Clinical trials (associated diseases)

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