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
• Regional missense constraint (gnomAD): 1 of 2 regions constrained (≈6% of expected missense variation)
• GTEx eGene: eQTL in 37 tissues, sQTL in 20 (q < 0.05)
• Cancer dependency (DepMap): dependent in 21.2% of screened cell lines
• Constraint (gnomAD): pLI 0.00 (LoF-tolerant), LOEUF 0.80 (unconstrained)
• MANE Select transcript: NM_017748
• Notable: 83 clinical variants but no curated precision-oncology (CIViC) evidence yet

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: 13 — 6 nonsense_mediated_decay, 5 protein_coding, 1 retained_intron, 1 protein_coding_CDS_not_defined

MANE Select: ENST00000614790

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 1, TSL 2: 4, TSL 3: 1, TSL 5: 1

ENST00000614790, ENST00000611845, ENST00000618122, ENST00000619299, ENST00000619462, ENST00000619818, ENST00000622665, ENST00000905240, ENST00000905241, ENST00000941317, ENST00001030141, ENST00001030142, ENST00001139027

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.

Highest expression (Bgee): sural nerve, bone marrow, granulocyte, testis, skin of leg.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CWC25 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 37 tissues and its splicing (sQTL) in 20 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 57 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Brain Cerebellum	eqtl	1.2e-24	+0.63	17:38791503:G:A
Thyroid	eqtl	4.6e-24	+0.30	17:38811918:T:C
Pituitary	eqtl	9.9e-21	+0.38	17:38809226:A:G
Testis	eqtl	2.8e-17	+0.23	17:38825661:T:G
Brain Cerebellar Hemisphere	eqtl	1.8e-12	+0.39	17:38809226:A:G
Esophagus Muscularis	eqtl	9.2e-12	+0.24	17:38791503:G:A
Nerve Tibial	eqtl	1.8e-11	+0.21	17:38827767:C:T
Colon Transverse	eqtl	6.5e-11	+0.31	17:38791503:G:A
Pancreas	eqtl	8.0e-11	+0.32	17:38807218:A:G
Heart Atrial Appendage	eqtl	1.3e-10	+0.28	17:38800959:A:AT
Prostate	eqtl	1.8e-09	+0.41	17:38809226:A:G
Artery Aorta	eqtl	4.2e-09	+0.27	17:38825661:T:G
Esophagus Gastroesophageal Junction	eqtl	5.2e-09	+0.25	17:38783746:G:C
Spleen	eqtl	2.2e-08	+0.38	17:38783746:G:C
Artery Tibial	eqtl	2.4e-08	+0.17	17:38827767:C:T
Heart Left Ventricle	eqtl	1.1e-07	+0.24	17:38783746:G:C
Adipose Subcutaneous	sqtl	2.3e-07	-0.32	17:38791503:G:A
Esophagus Mucosa	eqtl	4.0e-07	+0.24	17:38795050:A:G
Colon Sigmoid	eqtl	6.5e-07	+0.28	17:38809226:A:G
Nerve Tibial	sqtl	9.1e-07	-0.31	17:38825661:T:G

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

showing 100 of 134 tissues 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
esophagus	UBERON:0001043	88.54	gold quality
duodenum	UBERON:0002114	88.49	gold quality
fundus of stomach	UBERON:0001160	88.43	gold quality
left uterine tube	UBERON:0001303	88.42	gold quality
body of stomach	UBERON:0001161	88.37	gold quality
prostate gland	UBERON:0002367	88.30	gold quality
minor salivary gland	UBERON:0001830	88.28	gold quality
mucosa of stomach	UBERON:0001199	88.25	gold quality
right adrenal gland cortex	UBERON:0035827	88.24	gold quality
ectocervix	UBERON:0012249	88.23	gold quality
vagina	UBERON:0000996	88.22	gold quality
gastrocnemius	UBERON:0001388	88.22	gold quality
saliva-secreting gland	UBERON:0001044	88.15	gold quality
left lobe of thyroid gland	UBERON:0001120	88.15	gold quality
thyroid gland	UBERON:0002046	88.12	gold quality
left ovary	UBERON:0002119	88.12	gold quality
pituitary gland	UBERON:0000007	88.09	gold quality
tibial artery	UBERON:0007610	88.07	gold quality
popliteal artery	UBERON:0002250	88.06	gold quality
colon	UBERON:0001155	88.00	gold quality
urinary bladder	UBERON:0001255	87.99	gold quality
intestine	UBERON:0000160	87.98	gold quality
body of uterus	UBERON:0009853	87.98	gold quality
right lobe of thyroid gland	UBERON:0001119	87.97	gold quality
transverse colon	UBERON:0001157	87.92	gold quality
esophagus mucosa	UBERON:0002469	87.88	gold quality
right ovary	UBERON:0002118	87.76	gold quality
ovary	UBERON:0000992	87.73	gold quality
muscle of leg	UBERON:0001383	87.73	gold quality
adenohypophysis	UBERON:0002196	87.71	gold quality
left adrenal gland cortex	UBERON:0035825	87.70	gold quality
endocervix	UBERON:0000458	87.67	gold quality
uterine cervix	UBERON:0000002	87.65	gold quality
pancreas	UBERON:0001264	87.53	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.51	gold quality
right adrenal gland	UBERON:0001233	87.51	gold quality
myometrium	UBERON:0001296	87.50	gold quality
bone marrow cell	CL:0002092	87.49	gold quality
tonsil	UBERON:0002372	87.47	gold quality
left adrenal gland	UBERON:0001234	87.43	gold quality
lung	UBERON:0002048	87.36	gold quality
calcaneal tendon	UBERON:0003701	87.28	gold quality
liver	UBERON:0002107	87.14	gold quality
stomach	UBERON:0000945	87.10	gold quality
adrenal gland	UBERON:0002369	87.10	gold quality
tibial nerve	UBERON:0001323	87.06	gold quality
thoracic aorta	UBERON:0001515	87.05	gold quality
ascending aorta	UBERON:0001496	87.04	gold quality
multicellular organism	UBERON:0000468	87.02	gold quality
smooth muscle tissue	UBERON:0001135	87.02	gold quality
muscle tissue	UBERON:0002385	86.94	gold quality
left coronary artery	UBERON:0001626	86.91	gold quality
metanephros cortex	UBERON:0010533	86.91	gold quality
skeletal muscle tissue	UBERON:0001134	86.87	gold quality
descending thoracic aorta	UBERON:0002345	86.71	gold quality
apex of heart	UBERON:0002098	86.66	gold quality
rectum	UBERON:0001052	86.64	gold quality
right uterine tube	UBERON:0001302	86.44	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.34	gold quality
right coronary artery	UBERON:0001625	86.26	gold quality
cortex of kidney	UBERON:0001225	86.24	gold quality
fallopian tube	UBERON:0003889	85.76	gold quality
gall bladder	UBERON:0002110	85.58	gold quality
placenta	UBERON:0001987	85.55	gold quality
hindlimb stylopod muscle	UBERON:0004252	85.50	gold quality
mucosa of transverse colon	UBERON:0004991	85.37	gold quality
adult mammalian kidney	UBERON:0000082	85.03	gold quality
heart left ventricle	UBERON:0002084	84.98	gold quality
heart	UBERON:0000948	84.64	gold quality
right atrium auricular region	UBERON:0006631	84.45	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

HPA expression

RNA tissue specificity: Tissue enhanced

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Bone marrow	tissue	58.7	high
Skin 1	tissue	13.5	high
Thymus	tissue	13.2
Corpus callosum	tissue	12.6
Cerebellum	tissue	12.1	medium
Pituitary gland	tissue	11.9
Vagina	tissue	11.9	high
Cerebral cortex	tissue	11.8	high
Occipital cortex	tissue	11.8
Lymph node	tissue	11.7	high
Somatosensory cortex	tissue	11.7
Temporal cortex	tissue	11.5
Prefrontal cortex	tissue	11.2
Hippocampal formation	tissue	11.1
Entorhinal cortex	tissue	11.1
Retrosplenial cortex	tissue	11.0
Pons	tissue	10.9
Motor cortex	tissue	10.7
Retrosplenial and cingulate cortex	tissue	10.7
Midbrain	tissue	10.6
Substantia nigra	tissue	10.6
Medulla oblongata	tissue	10.5
Superior colliculi	tissue	10.5
Spinal cord	tissue	10.5
Putamen	tissue	10.2
Thalamus	tissue	10.2
Ventral forebrain	tissue	10.2
Hypothalamus	tissue	10.1
Insular cortex	tissue	10.1
Olfactory bulb	tissue	10.0
Periaqueductal gray	tissue	9.8
Amygdala	tissue	9.7
Duodenum	tissue	9.7	high
Septum	tissue	9.7
Appendix	tissue	9.4	high
Spleen	tissue	9.3	high
Basal ganglia	tissue	9.0	medium
Tonsil	tissue	8.5	high
Small intestine	tissue	8.4	high
Adipose tissue	tissue	8.3	low
Choroid plexus	tissue	8.3
Frontal cortex	tissue	8.2
Retina	tissue	7.9
Urinary bladder	tissue	7.8	high
Endometrium 1	tissue	7.7	medium
Lung	tissue	7.6	medium
Testis	tissue	7.4	high
Liver	tissue	7.4	not detected
Caudate putamen	tissue	7.4
Adrenal gland	tissue	7.3	high
Salivary gland	tissue	7.1	high
Gallbladder	tissue	7.1	high
Skeletal muscle	tissue	6.9	high
Nucleus accumbens	tissue	6.9
Parathyroid gland	tissue	6.8	high
Kidney	tissue	6.8	high
Stomach 1	tissue	6.7	high
Postcentral gyrus	tissue	6.7
Tongue	tissue	6.6
Breast	tissue	6.5	high

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — White matter (12.6), Blood vessel (10.9), Dorsal hippocampus (10.5), Ventral spinal cord (10.5), Dorsal spinal cord (10.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CWC25 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 82 miRNAs:

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

gnomAD constraint: pLI 7.57e-05, LOEUF 0.796, missense Z 1.17 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000614790 splits into 2 regions with different missense tolerance; 1 is missense-constrained (≈6% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
17:38,802,095–38,821,013	444 / 499.2	0.89	no
17:38,821,014–38,825,183	9 / 30.1	0.30	yes (p 1.2e-04)
DepMap (CRISPR cell-line fitness): dependent in 21.2% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): UACC-893 (-1.09), PEO4 (-1.046), PE/CA-PJ34 (clone C12) (-1.034), SCC-25 (-1.022), SF268 (-0.998), MYLA (-0.983), BC-1 (-0.919), NCC-ES1-C1 (-0.912), WM793 (-0.872), MDA-MB-361 (-0.861), SNU-5 (-0.826), KP-1N (-0.821), NCCIT (-0.816), KML-1 (-0.815), C3A (-0.807).

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

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1914730) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 1 distinct phenotype terms.

Mouse phenotype (MP)	Records
preweaning lethality, complete penetrance	1

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Cryptococcus deneoformans JEC21	P0CM98	100.0%	Diamond
Cryptococcus deneoformans B-3501A	P0CM99	100.0%	Diamond
Saccharomyces cerevisiae S288C	P53854	74.1%	Diamond
Candida albicans SC5314	Q59LQ5	68.0%	Diamond
Fusarium graminearum PH-1	Q4IRI9	63.4%	Diamond
Aspergillus fumigatus Af293	Q4X1D7	62.9%	Diamond
Neurospora crassa OR74A	Q7SI59	62.7%	Diamond
Aspergillus nidulans FGSC A4	Q5B0I1	61.8%	Diamond
Nakaseomyces glabratus CBS 138	Q6FP02	56.7%	Diamond
Mycosarcoma maydis	Q4P6I3	53.5%	Diamond
Schizosaccharomyces pombe 972h-	Q9Y805	52.8%	Diamond
Yarrowia lipolytica CLIB122	Q6C1V6	40.2%	Diamond
Debaryomyces hansenii CBS767	Q6BNE1	39.4%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
SPMAP1	protein-coding	388381
PIP4K2B	protein-coding	8396
RPL23	protein-coding	9349
TRN-GTT2-5	tRNA	100189176
PSMB3	protein-coding	5691
PCGF2	protein-coding	7703
MIR4727	ncRNA	100616416
SNORA21B	snoRNA	109617002

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)

4 structures by resolution:

PDB	Title	Method	Resolution (Å)
9XTT	Human minor spliceosome branching-completed C complex (after step-I)	ELECTRON MICROSCOPY	2.92
6ZYM	Human C Complex Spliceosome - High-resolution CORE	ELECTRON MICROSCOPY	3.4
8I0W	The cryo-EM structure of human C complex	ELECTRON MICROSCOPY	3.4
5YZG	The Cryo-EM Structure of Human Catalytic Step I Spliceosome (C complex) at 4.1 angstrom …	ELECTRON MICROSCOPY	4.1

Predicted structure (AlphaFold)

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

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles

Antibody reliability (HPA): IH supported · IF enhanced

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)

Type	Positions
Glycyl lysine isopeptide (lys-gly) (interchain with g-cter in sumo2)	391
Phosphoserine	170, 218, 222

Function

Pathways and Gene Ontology

Reactome pathways

2 curated (TAS) of 5; 1 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

5 pathways:

ID	Pathway	Evidence
R-HSA-9918481	Dengue Virus-Host Interactions ⚕	curated
R-HSA-72163	mRNA Splicing - Major Pathway	curated
R-HSA-8953854	Metabolism of RNA	—
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA	—
R-HSA-72172	mRNA Splicing	—

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

4 top-level categories:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1
Processing of Capped Intron-Containing Pre-mRNA	1
Metabolism of RNA	1

GO top-level categories

16 GO namespaces:

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

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 4 of 10 annotations. The rest are phylogenetic / computational / electronic (IEA).

4 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA splicing, via spliceosome	BP	direct assay
U2-type catalytic step 1 spliceosome	CC	direct assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 1,134 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC25	YJU2	Q9BW85	920
CWC25	DHX38	Q92620	849
CWC25	SLU7	O95391	823
CWC25	PRPF18	Q99633	823
CWC25	RNF113A	O15541	769
CWC25	DHX8	Q14562	766
CWC25	CWC22	Q9HCG8	747
CWC25	DHX16	O60231	744
CWC25	CWC27	Q6UX04	737
CWC25	CDC40	O60508	688
CWC25	SNRNP200	O75643	685
CWC25	EFTUD2	Q15029	667
CWC25	XAB2	Q9HCS7	664
CWC25	DHX15	O43143	663
CWC25	CDC5L	Q99459	643

IntAct

Human interaction partners of CWC25 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

16 partners by confidence:

Partner	Interaction type	MIscore	Records
FMR1	physical association	0.560	3
KRT34	physical association	0.560	3
TRIM21	physical association	0.560	3
UBE4A	physical association	0.400	1
CCDC85B	physical association	0.370	1
LAMC3	physical association	0.370	1
CBY1	physical association	0.000	1
CGN	physical association	0.000	1
GIGYF1	physical association	0.000	1
INPP5E	physical association	0.000	1
KCTD3	physical association	0.000	1
KIF13B	physical association	0.000	1
KSR1	physical association	0.000	1
LPIN3	physical association	0.000	1
MDM2	physical association	0.000	1
ZBTB21	physical association	0.000	1

BioGRID (72 interactions; top human partners by supporting records): GATAD2B (Cross-Linking-MS (XL-MS); 2 records), ANAPC15 (Affinity Capture-MS), ANKRD50 (Affinity Capture-MS), BAG2 (Affinity Capture-MS), C20orf197 (Affinity Capture-MS), CBY1 (Affinity Capture-MS), CCDC85B (Two-hybrid), CDC5L (Proximity Label-MS), CGN (Affinity Capture-MS), COL8A1 (Affinity Capture-MS), COPS6 (Affinity Capture-MS), CYCS (Affinity Capture-MS), CYTH4 (Affinity Capture-MS), DDX23 (Proximity Label-MS), DHX40 (Proximity Label-MS)

Protein complexes (CORUM) (1)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

1 complexes by size:

Complex	Subunits	Members
Spliceosome, C complex	39	MAGOH, PPWD1, RBM8A, SNRPF, SNRPG, SYF2, PPIE, SNRPB2, SNRPA1, BCAS2, BUD31, CWC25, SNRPD2, SNRPD3, CASC3, EIF4A3, PRPF19, SNRPD1, SNRPE, YJU2, SRRM2, XAB2, CWC22, RBM22, SNRNP200, AQR, CWC15, EFTUD2, ISY1, PPIG, CDC40, CDC5L, DHX38, PLRG1, PPIL1, PRPF8, SNRPB, SNW1, CRNKL1

Disease & clinical

Genetic variants

Variant evidence for CWC25: 83 ClinVar records (0 pathogenic / likely pathogenic); 1 GWAS association.

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

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 29 predictions of 803):

Position(s)	Effect	Δscore	Sites
17:38802207–38802208	acceptor_loss	1.0000	6
17:38802698–38802699	donor_loss	1.0000	3
17:38802711	donor_gain	1.0000
17:38802862–38802863	acceptor_loss	1.0000	6
17:38806763–38806764	donor_loss	1.0000	3
17:38806835	donor_gain	1.0000
17:38810470	donor_gain	1.0000
17:38810603	acceptor_gain	1.0000
17:38810607–38810608	acceptor_gain	1.0000	2
17:38812793–38812794	donor_loss	1.0000	5

AlphaMissense

891 missense substitutions predicted likely pathogenic (of 2,808 scored), across 205 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M73	9	0.948	1.000
M348	9	0.944	0.994
M160	9	0.925	0.998
D137	8	0.998	1.000
H13	8	0.997	1.000
D5	8	0.994	0.998
N19	8	0.994	1.000
N7	8	0.988	0.999
D129	8	0.984	0.993
S11	8	0.979	0.999
D93	8	0.957	0.987
F119	8	0.953	0.994
N156	8	0.942	0.997
W12	7	1.000	1.000
W72	7	0.999	1.000
W24	7	0.998	1.000
K10	7	0.994	1.000
E21	7	0.982	0.998
K9	7	0.981	1.000
E33	7	0.978	0.993

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

1 associations:

Study	Trait	p-value
GCST005580_246	Intraocular pressure	1e-8

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004695	intraocular pressure measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (CPIC guideline: no)

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
Air Pollutants	affects expression, increases abundance, increases expression	2
Ozone	increases expression, affects expression, increases abundance	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	decreases expression, affects cotreatment	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	increases expression, affects cotreatment	1
Acetaminophen	increases expression	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
Plant Extracts	increases expression, affects cotreatment	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)

Via MONDO — disease-level, not drug-specific.