CWC25

Summary

CWC25 (CWC25 spliceosome associated protein, HGNC:25989) is a protein-coding gene on chromosome 17q12, encoding Pre-mRNA-splicing factor CWC25 homolog (Q9NXE8). Involved in pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 21.2% of cell lines).

This gene encodes a factor that is part of the multi-protein C complex involved in pre-mRNA splicing. Alternatively spliced transcripts have been described for this gene.

Source: NCBI Gene 54883 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 83 total
• Cancer dependency (DepMap): dependent in 21.2% of screened cell lines
• MANE Select transcript: NM_017748

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25989
Approved symbol	CWC25
Name	CWC25 spliceosome associated protein
Location	17q12
Locus type	gene with protein product
Status	Approved
Aliases	FLJ20291
Ensembl gene	ENSG00000273559
Ensembl biotype	protein_coding
Entrez	54883

Gene structure

Transcript identifiers

Ensembl transcripts: 10 — 4 protein_coding, 4 nonsense_mediated_decay, 1 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000611845, ENST00000614790, ENST00000618122, ENST00000619299, ENST00000619462, ENST00000619818, ENST00000622665, ENST00000905240, ENST00000905241, ENST00000941317

RefSeq mRNA: 1 — MANE Select: NM_017748 NM_017748

CCDS: CCDS45663

Canonical transcript exons

ENST00000614790 — 10 exons

Exon	Start	End
ENSE00003716084	38809702	38809765
ENSE00003717991	38812795	38812864
ENSE00003730106	38820901	38821073
ENSE00003737733	38806765	38806976
ENSE00003742033	38802700	38802861
ENSE00003742168	38814861	38815097
ENSE00003747674	38806297	38806395
ENSE00003748658	38810468	38810595
ENSE00003753269	38800441	38802206
ENSE00003754146	38825166	38825321

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 95.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 20.4946 / max 716.2142, expressed in 1808 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
165562	18.1667	1805
165560	1.1793	491
165561	1.1487	595

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	95.65	gold quality
bone marrow	UBERON:0002371	92.11	gold quality
granulocyte	CL:0000094	91.51	gold quality
left testis	UBERON:0004533	91.37	gold quality
skin of leg	UBERON:0001511	90.89	gold quality
zone of skin	UBERON:0000014	90.82	gold quality
skin of abdomen	UBERON:0001416	90.68	gold quality
blood	UBERON:0000178	90.62	gold quality
testis	UBERON:0000473	90.57	gold quality
right testis	UBERON:0004534	90.51	gold quality
monocyte	CL:0000576	89.78	gold quality
spleen	UBERON:0002106	89.78	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	89.67	gold quality
lower esophagus muscularis layer	UBERON:0035833	89.60	gold quality
leukocyte	CL:0000738	89.58	gold quality
lower esophagus	UBERON:0013473	89.58	gold quality
upper lobe of left lung	UBERON:0008952	89.18	gold quality
right lobe of liver	UBERON:0001114	89.14	gold quality
small intestine Peyer’s patch	UBERON:0003454	89.14	gold quality
body of pancreas	UBERON:0001150	89.09	gold quality
muscle layer of sigmoid colon	UBERON:0035805	89.03	gold quality
right lung	UBERON:0002167	89.02	gold quality
lower esophagus mucosa	UBERON:0035834	88.99	gold quality
small intestine	UBERON:0002108	88.92	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.90	gold quality
lymph node	UBERON:0000029	88.84	gold quality
adipose tissue	UBERON:0001013	88.80	gold quality
omental fat pad	UBERON:0010414	88.79	gold quality
vermiform appendix	UBERON:0001154	88.76	gold quality
thoracic mammary gland	UBERON:0005200	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	yes	11.32

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

82 targeting CWC25, 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-340-5P	100.00	72.50	4437
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-34A-5P	99.99	71.21	1784
HSA-MIR-449A	99.99	71.05	1776
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-34C-5P	99.97	70.45	1577
HSA-MIR-449B-5P	99.97	70.26	1580
HSA-MIR-493-5P	99.96	72.47	2382
HSA-MIR-6778-3P	99.96	67.29	2693
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-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-LET-7C-3P	99.95	73.42	2862
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-6124	99.87	69.78	3551
HSA-LET-7A-2-3P	99.87	70.53	1921
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-7978	99.86	66.90	856
HSA-MIR-4503	99.85	71.45	1869
HSA-LET-7G-3P	99.85	70.43	1929
HSA-MIR-664B-3P	99.84	71.65	3590

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 21.2% of screened cell lines.

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	cwc25	ENSDARG00000003382
mus_musculus	Cwc25	ENSMUSG00000018541
rattus_norvegicus	Cwc25	ENSRNOG00000004091
drosophila_melanogaster	Cwc25	FBGN0031452
caenorhabditis_elegans		WBGENE00003391

Protein

Protein identifiers

Pre-mRNA-splicing factor CWC25 homolog — Q9NXE8 (reviewed: Q9NXE8)

Alternative names: Coiled-coil domain-containing protein 49, Spliceosome-associated protein homolog CWC25

All UniProt accessions (3): Q9NXE8, A0A087WVL7, A0A087WY60

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Identified in the spliceosome C complex.

Subcellular location. Nucleus.

Similarity. Belongs to the CWC25 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9NXE8-1	1	yes
Q9NXE8-2	2

RefSeq proteins (1): NP_060218* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR019339	CIR_N_dom	Domain
IPR022209	CWC25	Family
IPR051376	CWC25_splicing_factor	Family

Pfam: PF10197, PF12542

UniProt features (16 total): helix 3, compositionally biased region 3, modified residue 3, coiled-coil region 2, chain 1, region of interest 1, cross-link 1, splice variant 1, strand 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
6ZYM	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5YZG	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NXE8-F1	66.55	0.12

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 (4): 391, 170, 218, 222

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 170 (showing top): MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GARGALOVIC_RESPONSE_TO_OXIDIZED_PHOSPHOLIPIDS_BLUE_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, HTF_01, REACTOME_MRNA_SPLICING, CREB_Q3, NRF2_01, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, RYTGCNWTGGNR_UNKNOWN, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_SPLICEOSOMAL_COMPLEX

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

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

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), U2-type spliceosomal complex (GO:0005684), nuclear speck (GO:0016607), U2-type catalytic step 1 spliceosome (GO:0071006), spliceosomal complex (GO:0005681)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	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
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
spliceosomal complex	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 1 spliceosome	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1

Protein interactions and networks

STRING

1470 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC25	YJU2	Q9BW85	977
CWC25	SLU7	O95391	893
CWC25	DHX38	Q92620	860
CWC25	PRPF18	Q99633	858
CWC25	RNF113A	O15541	843
CWC25	DHX8	Q14562	833
CWC25	DHX15	O43143	804
CWC25	CDC5L	Q99459	789
CWC25	CWC22	Q9HCG8	770
CWC25	DHX16	O60231	762
CWC25	CWC27	Q6UX04	759
CWC25	SNRNP200	O75643	734
CWC25	SRRM2	Q9UQ35	728
CWC25	TFIP11	Q9UBB9	724
CWC25	EFTUD2	Q15029	716

IntAct

68 interactions, top by confidence:

A	B	Type	Score
CSNK2B	NMT2	psi-mi:“MI:0914”(association)	0.660
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
KRT34	CWC25	psi-mi:“MI:0915”(physical association)	0.560
TRIM21	CWC25	psi-mi:“MI:0915”(physical association)	0.560
FMR1	CWC25	psi-mi:“MI:0915”(physical association)	0.560
EZH1	EPOP	psi-mi:“MI:0914”(association)	0.530
CWC25	UBE4A	psi-mi:“MI:0915”(physical association)	0.400
LAMC3	CWC25	psi-mi:“MI:0915”(physical association)	0.370
CCDC85B	CWC25	psi-mi:“MI:0915”(physical association)	0.370
DVL2	NBAS	psi-mi:“MI:0914”(association)	0.350
COPS6	DDX3X	psi-mi:“MI:0914”(association)	0.350
PEBP1	ANXA2P2	psi-mi:“MI:0914”(association)	0.350
SP100	SART1	psi-mi:“MI:0914”(association)	0.350
P		psi-mi:“MI:0914”(association)	0.350
CACNA1C	SNRPGP15	psi-mi:“MI:0914”(association)	0.350
JPH3	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
SAA1	PLEKHG3	psi-mi:“MI:0914”(association)	0.350
TPX2	MAP1LC3B2	psi-mi:“MI:0914”(association)	0.350
CXorf1	RAP1BL	psi-mi:“MI:0914”(association)	0.350
COL8A1	CCDC85C	psi-mi:“MI:0914”(association)	0.350
MALL	GPR89A	psi-mi:“MI:0914”(association)	0.350
LINC02910	MPHOSPH10	psi-mi:“MI:0914”(association)	0.350
ANKRD50	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
GAGE5	PPP1R12A	psi-mi:“MI:0914”(association)	0.350
ANAPC15	U2SURP	psi-mi:“MI:0914”(association)	0.350
H2AJ	WDR46	psi-mi:“MI:0914”(association)	0.350
TMEM14B	WDR46	psi-mi:“MI:0914”(association)	0.350
UQCR11	WDR46	psi-mi:“MI:0914”(association)	0.350
SERF2	WDR46	psi-mi:“MI:0914”(association)	0.350
IFI6	GPAA1	psi-mi:“MI:0914”(association)	0.350

BioGRID (72): CWC25 (Two-hybrid), CWC25 (Affinity Capture-MS), KCTD3 (Affinity Capture-MS), KIF13B (Affinity Capture-MS), CGN (Affinity Capture-MS), ZBTB21 (Affinity Capture-MS), CWC25 (Affinity Capture-MS), GIGYF1 (Affinity Capture-MS), CWC25 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CWC25 (Affinity Capture-MS), CWC25 (Two-hybrid), CWC25 (Two-hybrid), CWC25 (Two-hybrid), CWC25 (Affinity Capture-MS)

ESM2 similar proteins: A0JNI5, A2AJT4, A2AQ19, A4IFB1, B1H1X4, D3ZTQ1, O43290, P35269, Q05519, Q12872, Q13435, Q3THK3, Q3UJB0, Q3UQU0, Q3USH5, Q4V7C9, Q53F19, Q568R1, Q5EA53, Q5HZB6, Q5PQQ2, Q5R539, Q5RAD5, Q5XIW8, Q5ZM19, Q66I22, Q6AY96, Q6DDA4, Q6GLZ8, Q6INH5, Q6ZPZ3, Q8BZR9, Q8CFC7, Q8K194, Q8N2M8, Q8N5F7, Q8TF01, Q8VHI6, Q8WVK2, Q923D5

Diamond homologs: P0CM98, P0CM99, P53854, Q4IRI9, Q4P6I3, Q4X1D7, Q5B0I1, Q6BNE1, Q6C1V6, Q6FP02, Q7SI59, Q9DBF7, Q9NXE8, Q9Y805, Q59LQ5, Q6CUQ5, Q75AR4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 92 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 - Minor Pathway	5	18.1×	9e-04
mRNA Splicing	7	12.4×	3e-04
mRNA Splicing - Major Pathway	11	9.7×	6e-06
Processing of Capped Intron-Containing Pre-mRNA	7	9.3×	9e-04
mRNA Polyadenylation	6	8.5×	5e-03
Dengue Virus-Host Interactions	9	6.6×	9e-04
Metabolism of RNA	8	5.4×	7e-03

GO biological processes:

GO term	Partners	Fold	FDR
regulation of alternative mRNA splicing, via spliceosome	5	15.5×	5e-03
mRNA splicing, via spliceosome	7	8.1×	5e-03
RNA splicing	7	7.8×	5e-03
mRNA processing	7	7.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	64
Likely benign	4
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1601 predictions. Top by Δscore:

Variant	Effect	Δscore
17:38802202:TGCGG:T	acceptor_gain	1.0000
17:38802203:GCGG:G	acceptor_gain	1.0000
17:38802204:CGG:C	acceptor_gain	1.0000
17:38802204:CGGC:C	acceptor_gain	1.0000
17:38802205:GG:G	acceptor_gain	1.0000
17:38802205:GGCT:G	acceptor_loss	1.0000
17:38802206:GC:G	acceptor_loss	1.0000
17:38802207:C:CC	acceptor_gain	1.0000
17:38802208:T:G	acceptor_loss	1.0000
17:38802693:CACT:C	donor_loss	1.0000
17:38802695:CTCA:C	donor_gain	1.0000
17:38802696:TCA:T	donor_loss	1.0000
17:38802697:CACT:C	donor_loss	1.0000
17:38802698:A:AC	donor_gain	1.0000
17:38802699:C:CC	donor_gain	1.0000
17:38802699:CT:C	donor_gain	1.0000
17:38802699:CTG:C	donor_gain	1.0000
17:38802699:CTGG:C	donor_gain	1.0000
17:38802699:CTGGA:C	donor_gain	1.0000
17:38802710:T:TA	donor_gain	1.0000
17:38802711:C:A	donor_gain	1.0000
17:38802756:AT:A	donor_gain	1.0000
17:38802857:GTTTT:G	acceptor_gain	1.0000
17:38802858:TTTT:T	acceptor_gain	1.0000
17:38802859:TTT:T	acceptor_gain	1.0000
17:38802860:TT:T	acceptor_gain	1.0000
17:38802861:TC:T	acceptor_loss	1.0000
17:38802862:C:A	acceptor_loss	1.0000
17:38802862:C:CC	acceptor_gain	1.0000
17:38806760:CTCA:C	donor_loss	1.0000

AlphaMissense

2808 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
17:38814879:T:C	D137G	1.000
17:38815071:A:G	M73T	1.000
17:38815073:C:A	W72C	1.000
17:38815073:C:G	W72C	1.000
17:38815075:A:G	W72R	1.000
17:38815075:A:T	W72R	1.000
17:38820961:A:G	L44P	1.000
17:38820973:A:G	L40P	1.000
17:38821009:T:G	Q28P	1.000
17:38821016:C:G	A26P	1.000
17:38821020:C:A	W24C	1.000
17:38821020:C:G	W24C	1.000
17:38821035:A:C	N19K	1.000
17:38821035:A:T	N19K	1.000
17:38821037:T:C	N19D	1.000
17:38821053:G:C	H13Q	1.000
17:38821053:G:T	H13Q	1.000
17:38821054:T:C	H13R	1.000
17:38821055:G:C	H13D	1.000
17:38821056:C:A	W12C	1.000
17:38821056:C:G	W12C	1.000
17:38821058:A:G	W12R	1.000
17:38821058:A:T	W12R	1.000
17:38821062:C:A	K10N	1.000
17:38821062:C:G	K10N	1.000
17:38821065:C:A	K9N	1.000
17:38821065:C:G	K9N	1.000
17:38821067:T:C	K9E	1.000
17:38825167:A:G	L6P	1.000
17:38814873:A:G	L139P	0.999

dbSNP variants (sampled 300 via entrez): RS1000024146 (17:38821781 C>G,T), RS1000075967 (17:38806647 C>G,T), RS1000233873 (17:38803318 A>AAT), RS1000267166 (17:38823031 G>A), RS1000370195 (17:38810649 G>C), RS1000476565 (17:38820563 G>A,C), RS1000476940 (17:38817019 G>A), RS1000673563 (17:38814104 G>A), RS1000833942 (17:38804905 G>A), RS1000858653 (17:38801666 C>G), RS1001026392 (17:38809315 C>G), RS1001077073 (17:38809593 G>A,C), RS1001201881 (17:38818147 G>A), RS1001250317 (17:38824596 G>A,C), RS1001709988 (17:38815321 C>T)

Disease associations

OMIM: gene `` | 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
GCST005580_171	Intraocular pressure	1.000000e-08

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	decreases expression, increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
FR900359	affects phosphorylation	1
bisphenol F	affects cotreatment, decreases expression	1
triphenyl phosphate	affects expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
epigallocatechin gallate	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
abrine	increases expression	1
(4-amino-1,4-dihydro-3-(2-pyridyl)-5-thioxo-1,2,4-triazole)copper(II)	decreases expression	1
Resveratrol	affects cotreatment, increases expression	1
Acetaminophen	increases expression	1
Air Pollutants	affects expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	decreases expression	1
Copper	affects binding, decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Disulfiram	affects binding, decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Methotrexate	decreases expression	1
Ozone	affects expression, increases abundance	1
Plant Extracts	affects cotreatment, increases expression	1
Ribonucleotides	affects binding	1
Silver	increases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Cyclosporine	increases expression	1

Cellosaurus cell lines

1 cell lines: 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1661	ZR-75-30	Cancer cell line	Female

Clinical trials (associated diseases)

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