CWC15

Summary

CWC15 (CWC15 spliceosome associated protein, HGNC:26939) is a protein-coding gene on chromosome 11q21, encoding Spliceosome-associated protein CWC15 homolog (Q9P013). Involved in pre-mRNA splicing as component of the spliceosome. It is a selective cancer dependency (DepMap: 51.4% of cell lines).

Predicted to enable RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in nuclear speck. Part of U2-type catalytic step 2 spliceosome.

Source: NCBI Gene 51503 — automated summary from GO annotations (Alliance of Genome Resources).

At a glance

• GWAS associations: 2
• Clinical variants (ClinVar): 19 total
• Regional missense constraint (gnomAD): 1 of 2 regions constrained (≈8% of expected missense variation)
• GTEx eGene: eQTL in 44 tissues, sQTL in 5 (q < 0.05)
• Cancer dependency (DepMap): dependent in 51.4% of screened cell lines
• Constraint (gnomAD): pLI 0.76 (intermediate), LOEUF 0.66 (unconstrained)
• MANE Select transcript: NM_016403
• Interaction hub: 2,063 STRING partners (top 7% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:26939
Approved symbol	CWC15
Name	CWC15 spliceosome associated protein
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	C11orf5, HSPC148, Cwf15, AD002
Ensembl gene	ENSG00000150316
Ensembl biotype	protein_coding
Entrez	51503

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 16 protein_coding, 5 retained_intron, 3 nonsense_mediated_decay

MANE Select: ENST00000279839

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

ENST00000279839, ENST00000539856, ENST00000542165, ENST00000542907, ENST00000616442, ENST00000621358, ENST00000884093, ENST00000884094, ENST00000884095, ENST00000884096, ENST00000884097, ENST00000884098, ENST00000884099, ENST00000884100, ENST00000928765, ENST00000928766, ENST00000928767, ENST00000928768, ENST00000995869, ENST00001072533, ENST00001072534, ENST00001072538, ENST00001103563, ENST00001136041

RefSeq mRNA: 3 — MANE Select: NM_016403 NM_001363371, NM_001363372, NM_016403

CCDS: CCDS73369

Canonical transcript exons

ENST00000279839 — 7 exons

Exon	Start	End
ENSE00001254719	94962620	94963514
ENSE00001377352	94966295	94966413
ENSE00001434060	94973498	94973556
ENSE00003581041	94971375	94971487
ENSE00003582644	94969989	94970096
ENSE00003602456	94970977	94971065
ENSE00003613033	94972055	94972193

Expression profiles

Bgee: expression breadth ubiquitous, 262 present calls, max score 99.12.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 66.2949 / max 2083.0208, expressed in 1818 samples.

Highest expression (Bgee): kidney epithelium, tibialis anterior, cardiac muscle of right atrium, ventricle myocardium, myocardium.

Genetic regulation across tissues (GTEx eQTL / sQTL)

CWC15 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 44 tissues and its splicing (sQTL) in 5 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 49 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Cells Cultured fibroblasts	eqtl	2.1e-54	-0.32	11:94973294:AGGCGAGCT:A
Muscle Skeletal	eqtl	1.2e-41	-0.28	11:94974645:A:G
Thyroid	eqtl	6.6e-28	-0.29	11:94995735:T:C
Adipose Visceral Omentum	eqtl	5.6e-27	-0.33	11:94973294:AGGCGAGCT:A
Adipose Subcutaneous	eqtl	1.5e-24	-0.30	11:94962057:A:G
Nerve Tibial	eqtl	2.0e-24	-0.26	11:94973294:AGGCGAGCT:A
Heart Atrial Appendage	eqtl	5.3e-23	-0.33	11:94973294:AGGCGAGCT:A
Cells EBV-transformed lymphocytes	eqtl	8.1e-23	-0.40	11:94983834:A:C
Esophagus Mucosa	eqtl	8.2e-23	-0.25	11:94973294:AGGCGAGCT:A
Esophagus Muscularis	eqtl	5.4e-22	-0.36	11:94973294:AGGCGAGCT:A
Esophagus Gastroesophageal Junction	eqtl	3.4e-19	-0.42	11:94962057:A:G
Testis	eqtl	8.6e-19	+0.20	11:94973294:AGGCGAGCT:A
Heart Left Ventricle	eqtl	6.1e-18	-0.23	11:94995735:T:C
Lung	eqtl	5.0e-17	-0.22	11:94973294:AGGCGAGCT:A
Artery Tibial	eqtl	6.8e-17	-0.22	11:94962057:A:G
Colon Sigmoid	eqtl	1.9e-15	-0.30	11:94973294:AGGCGAGCT:A
Colon Transverse	eqtl	3.0e-15	-0.27	11:94962057:A:G
Breast Mammary Tissue	eqtl	3.3e-15	-0.21	11:94991264:A:C
Artery Aorta	eqtl	6.8e-15	-0.28	11:95018107:T:G
Liver	eqtl	5.2e-14	-0.37	11:94973294:AGGCGAGCT:A

FANTOM5 promoters

1 alternative TSS:

Promoter ID	TPM avg	Samples expressed
121854	66.2949	1818

Top tissues by expression

showing 100 of 263 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
kidney epithelium	UBERON:0004819	99.12	gold quality
tibialis anterior	UBERON:0001385	98.95	gold quality
cardiac muscle of right atrium	UBERON:0003379	98.63	gold quality
left ventricle myocardium	UBERON:0006566	98.56	gold quality
myocardium	UBERON:0002349	98.24	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	98.12	gold quality
vastus lateralis	UBERON:0001379	98.11	gold quality
biceps brachii	UBERON:0001507	97.97	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	97.85	gold quality
body of tongue	UBERON:0011876	97.72	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.69	gold quality
skeletal muscle tissue	UBERON:0001134	97.65	gold quality
left testis	UBERON:0004533	97.55	gold quality
calcaneal tendon	UBERON:0003701	97.54	gold quality
right testis	UBERON:0004534	97.54	gold quality
tongue	UBERON:0001723	97.53	gold quality
superior surface of tongue	UBERON:0007371	97.53	gold quality
deltoid	UBERON:0001476	97.52	gold quality
mammary duct	UBERON:0001765	97.47	gold quality
epithelium of mammary gland	UBERON:0003244	97.42	gold quality
lateral globus pallidus	UBERON:0002476	97.29	gold quality
testis	UBERON:0000473	97.28	gold quality
muscle tissue	UBERON:0002385	97.28	gold quality
upper arm skin	UBERON:0004263	97.04	gold quality
pons	UBERON:0000988	96.97	gold quality
ganglionic eminence	UBERON:0004023	96.94	gold quality
embryo	UBERON:0000922	96.93	gold quality
lateral nuclear group of thalamus	UBERON:0002736	96.83	gold quality
pharyngeal mucosa	UBERON:0000355	96.80	gold quality
quadriceps femoris	UBERON:0001377	96.74	gold quality
muscle organ	UBERON:0001630	96.74	gold quality
skeletal muscle organ	UBERON:0014892	96.74	gold quality
muscle of leg	UBERON:0001383	96.60	gold quality
corpus epididymis	UBERON:0004359	96.59	gold quality
superior vestibular nucleus	UBERON:0007227	96.58	gold quality
nasal cavity epithelium	UBERON:0005384	96.56	gold quality
colonic epithelium	UBERON:0000397	96.51	gold quality
superficial temporal artery	UBERON:0001614	96.51	gold quality
caput epididymis	UBERON:0004358	96.49	gold quality
tendon	UBERON:0000043	96.47	gold quality
gastrocnemius	UBERON:0001388	96.47	gold quality
medulla oblongata	UBERON:0001896	96.45	gold quality
substantia nigra pars reticulata	UBERON:0001966	96.45	gold quality
cauda epididymis	UBERON:0004360	96.41	gold quality
nasal cavity mucosa	UBERON:0001826	96.35	gold quality
oral cavity	UBERON:0000167	96.31	gold quality
ventral tegmental area	UBERON:0002691	96.30	gold quality
cardia of stomach	UBERON:0001162	96.27	gold quality
dorsal plus ventral thalamus	UBERON:0001897	96.25	gold quality
inferior vagus X ganglion	UBERON:0005363	96.24	gold quality
ventricular zone	UBERON:0003053	96.22	gold quality
cortical plate	UBERON:0005343	96.22	gold quality
metanephros	UBERON:0000081	96.19	gold quality
hypothalamus	UBERON:0001898	96.18	gold quality
heart right ventricle	UBERON:0002080	96.15	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	96.14	gold quality
body of pancreas	UBERON:0001150	96.13	gold quality
layer of synovial tissue	UBERON:0007616	96.12	gold quality
adrenal tissue	UBERON:0018303	96.11	gold quality
substantia nigra	UBERON:0002038	96.09	gold quality
midbrain	UBERON:0001891	96.08	gold quality
cerebellar hemisphere	UBERON:0002245	96.08	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	96.08	gold quality
trigeminal ganglion	UBERON:0001675	96.04	gold quality
subthalamic nucleus	UBERON:0001906	96.03	gold quality
substantia nigra pars compacta	UBERON:0001965	96.03	gold quality
bone marrow	UBERON:0002371	96.03	gold quality
lower esophagus mucosa	UBERON:0035834	96.02	gold quality
cerebellar cortex	UBERON:0002129	96.01	gold quality
pylorus	UBERON:0001166	96.00	gold quality
pericardium	UBERON:0002407	96.00	gold quality
cortex of kidney	UBERON:0001225	95.99	gold quality
spinal cord	UBERON:0002240	95.96	gold quality
putamen	UBERON:0001874	95.95	gold quality
pancreatic ductal cell	CL:0002079	95.91	silver quality
amygdala	UBERON:0001876	95.89	gold quality
cerebellum	UBERON:0002037	95.87	gold quality
nucleus accumbens	UBERON:0001882	95.84	gold quality
adult organism	UBERON:0007023	95.83	gold quality
mucosa of paranasal sinus	UBERON:0005030	95.82	gold quality
bone marrow cell	CL:0002092	95.80	gold quality
right hemisphere of cerebellum	UBERON:0014890	95.79	gold quality
seminal vesicle	UBERON:0000998	95.77	gold quality
cardiac ventricle	UBERON:0002082	95.77	gold quality
corpus callosum	UBERON:0002336	95.77	gold quality
heart left ventricle	UBERON:0002084	95.74	gold quality
vena cava	UBERON:0004087	95.66	gold quality
tendon of biceps brachii	UBERON:0008188	95.66	gold quality
caudate nucleus	UBERON:0001873	95.62	gold quality
trachea	UBERON:0003126	95.62	gold quality
synovial joint	UBERON:0002217	95.61	gold quality
left ovary	UBERON:0002119	95.57	gold quality
heart	UBERON:0000948	95.55	gold quality
ovary	UBERON:0000992	95.55	gold quality
cardiac atrium	UBERON:0002081	95.53	gold quality
saphenous vein	UBERON:0007318	95.52	gold quality
Brodmann (1909) area 9	UBERON:0013540	95.52	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	95.51	gold quality
adenohypophysis	UBERON:0002196	95.49	gold quality
monocyte	CL:0000576	95.47	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	11.13

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 79 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Caudate putamen	tissue	125.2
Frontal cortex	tissue	110.6
Thalamus	tissue	103.9
Putamen	tissue	99.0
Superior colliculi	tissue	98.3
Pons	tissue	93.9
Midbrain	tissue	93.5
Spinal cord	tissue	91.8
Cerebral cortex	tissue	88.2	medium
Occipital cortex	tissue	88.2
Medulla oblongata	tissue	81.6
Somatosensory cortex	tissue	81.2
Substantia nigra	tissue	78.5
Hippocampal formation	tissue	77.2
Motor cortex	tissue	69.8
Periaqueductal gray	tissue	69.2
Prefrontal cortex	tissue	69.1
Temporal cortex	tissue	66.8
Entorhinal cortex	tissue	66.4
Ventral forebrain	tissue	65.2
Septum	tissue	64.7
Corpus callosum	tissue	64.6
Basal ganglia	tissue	63.4	medium
Retrosplenial and cingulate cortex	tissue	63.3
Cerebellum	tissue	61.7	medium
Skeletal muscle	tissue	61.4	low
Hypothalamus	tissue	59.4
Retrosplenial cortex	tissue	58.4
Amygdala	tissue	56.9
Tongue	tissue	56.1
Insular cortex	tissue	53.1
Olfactory bulb	tissue	53.0
Testis	tissue	37.4	high
Liver	tissue	35.1	low
Heart muscle	tissue	32.6	low
Epididymis	tissue	32.2	medium
Bone marrow	tissue	30.5	not detected
Ovary	tissue	30.0	medium
Kidney	tissue	29.1	medium
Thymus	tissue	28.7
Breast	tissue	28.6	medium
Salivary gland	tissue	25.4	medium
Parathyroid gland	tissue	24.4	medium
Placenta	tissue	24.1	medium
Lymph node	tissue	23.5	low
Thyroid gland	tissue	23.5	high
Retina	tissue	23.4
Tonsil	tissue	22.9	medium
Cervix	tissue	21.2	medium
Pancreas	tissue	21.1	medium
Vagina	tissue	21.0	medium
Stomach 1	tissue	20.5	high
Urinary bladder	tissue	20.5	medium
Fallopian tube	tissue	20.0	medium
Postcentral gyrus	tissue	19.8
Endometrium 1	tissue	19.5	medium
Locus coeruleus	tissue	19.0
Prostate	tissue	18.7	low
Adrenal gland	tissue	18.7	low
Nucleus accumbens	tissue	18.6

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Ventral spinal cord (91.8), Dorsal spinal cord (77.3), Dorsal hippocampus (77.2), White matter (64.6), Ventral hippocampus (62.4).

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

Targeting CWC15 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

showing 30 of 60 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6798-5P	100.00	65.77	699
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-1-3P	99.93	72.35	1914
HSA-MIR-206	99.93	72.50	1893
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-613	99.91	71.50	1710
HSA-MIR-498-3P	99.91	71.27	1114
HSA-MIR-1297	99.91	73.41	3162
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-548AR-3P	99.85	71.26	3889
HSA-MIR-4503	99.85	71.45	1869
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-548AZ-3P	99.82	70.56	3549
HSA-MIR-548BC	99.82	70.61	3524
HSA-MIR-548E-3P	99.82	70.59	3514
HSA-MIR-548F-3P	99.82	70.59	3540
HSA-MIR-4760-5P	99.80	69.88	1619
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-548A-3P	99.76	70.58	3524
HSA-MIR-494-3P	99.70	71.45	2795
HSA-MIR-548AU-3P	99.70	68.22	1373
HSA-MIR-6892-3P	99.68	66.40	1178

Functional genomics

gnomAD constraint: pLI 0.757, LOEUF 0.658, missense Z 1.41 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000279839 splits into 2 regions with different missense tolerance; 1 is missense-constrained (≈8% 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
11:94,963,388–94,972,130	188 / 250.3	0.75	no
11:94,972,131–94,972,185	4 / 21.2	0.19	yes (p 1.9e-04)
DepMap (CRISPR cell-line fitness): dependent in 51.4% of screened cell lines.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): HD-MB03 (-1.163), SW 620 (-0.92), YCUB-2 (-0.901), KP-N-SI9s (-0.814), C3A (-0.81), HCT 116 (-0.792), NCI-H1882 (-0.747), U-CHCF365 (-0.737), CHLA-06-ATRT (-0.721), Ty-82 (-0.71), OVISE (-0.705), ZR-75-1 (-0.69), NRH-OS4 (-0.678), CHLA-136 (-0.659), NRH-OS2 (-0.645).

Literature-anchored findings (GeneRIF, showing 1)

• The results show that CTNNBL1 enhances the association of CWC15 and CDC5L, both core Prp19 complex proteins and identify an overlap in the region of CDC5L that binds either CTNNBL1 or CWC15 suggesting the two proteins might exchange places in the complex. (PMID:26130721)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	cwc15	ENSDARG00000013382
mus_musculus	Cwc15	ENSMUSG00000004096
rattus_norvegicus	Cwc15	ENSRNOG00000008490
rattus_norvegicus	Cwc15-ps3	ENSRNOG00000025157
drosophila_melanogaster	c12.1	FBGN0040235
caenorhabditis_elegans		WBGENE00011687

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1913320) 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
Pongo abelii	Q5RE65	100.0%	Diamond
Bos taurus	Q2KJD3	99.1%	Diamond
Xenopus tropicalis	Q0VFP5	95.2%	Diamond
Xenopus laevis	Q6DKE6	95.2%	Diamond
Debaryomyces hansenii CBS767	Q6BP48	60.0%	Diamond
Schizosaccharomyces pombe 972h-	P78794	50.0%	Diamond
Aspergillus nidulans FGSC A4	Q5B020	46.4%	Diamond
Yarrowia lipolytica CLIB122	Q6C0E6	45.2%	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
KDM4E	protein-coding	390245
KDM4D	protein-coding	55693
LINC02700	ncRNA	105369436
PIWIL4	protein-coding	143689
AMOTL1	protein-coding	154810
FUT4	protein-coding	2526
MRE11	protein-coding	4361
ANKRD49	protein-coding	54851
C11orf97	protein-coding	643037
PIWIL4-AS1	ncRNA	105369438

Protein

Protein identifiers

Spliceosome-associated protein CWC15 homolog — Q9P013 (reviewed: Q9P013)

All UniProt accessions (1): Q9P013

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as component of the spliceosome. Component of the PRP19-CDC5L complex that forms an integral part of the spliceosome and is required for activating pre-mRNA splicing. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs.

Subunit / interactions. Identified in the spliceosome C complex. Component of the PRP19-CDC5L splicing complex composed of a core complex comprising a homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2, and at least three less stably associated proteins CTNNBL1, CWC15 and HSPA8. Interacts directly with CTNNBL1 in the complex. Component of the minor spliceosome, which splices U12-type introns.

Subcellular location. Nucleus.

Similarity. Belongs to the CWC15 family.

RefSeq proteins (3): NP_001350300, NP_001350301, NP_057487* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006973	Cwf_Cwc_15	Family

Pfam: PF04889

UniProt features (27 total): helix 10, modified residue 5, compositionally biased region 3, strand 2, turn 2, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1, coiled-coil region 1

Structure

Experimental structures (PDB)

showing 30 of 38 structures by resolution:

PDB	Title	Method	Resolution (Å)
9S2E	Human intron-lariat spliceosome-Aquarius (ILSaqr)	ELECTRON MICROSCOPY	2.4
8C6J	Human spliceosomal PM5 C* complex	ELECTRON MICROSCOPY	2.8
6ID1	Cryo-EM structure of a human intron lariat spliceosome after Prp43 loaded (ILS2 complex) …	ELECTRON MICROSCOPY	2.86
7DVQ	Cryo-EM Structure of the Activated Human Minor Spliceosome (minor Bact Complex)	ELECTRON MICROSCOPY	2.89
6ID0	Cryo-EM structure of a human intron lariat spliceosome prior to Prp43 loaded (ILS1 …	ELECTRON MICROSCOPY	2.9
9XTT	Human minor spliceosome branching-completed C complex (after step-I)	ELECTRON MICROSCOPY	2.92
6ICZ	Cryo-EM structure of a human post-catalytic spliceosome (P complex) at 3.0 angstrom	ELECTRON MICROSCOPY	3
8I0R	The cryo-EM structure of human Bact-I complex	ELECTRON MICROSCOPY	3
8I0T	The cryo-EM structure of human Bact-III complex	ELECTRON MICROSCOPY	3
8I0V	The cryo-EM structure of human post-Bact complex	ELECTRON MICROSCOPY	3
9XU3	Human minor spliceosome exon-ligation-ready C* complex (prior to step-II)	ELECTRON MICROSCOPY	3
7QTT	Structural organization of a late activated human spliceosome (Baqr, core region)	ELECTRON MICROSCOPY	3.1
9S2F	Human debranched intron spliceosome (DIS)	ELECTRON MICROSCOPY	3.14
6QDV	Human post-catalytic P complex spliceosome	ELECTRON MICROSCOPY	3.3
8I0U	The cryo-EM structure of human Bact-IV complex	ELECTRON MICROSCOPY	3.3
9FMD	Integrative model of the human post-catalytic spliceosome (P-complex)	ELECTRON MICROSCOPY	3.3
6FF4	human Bact spliceosome core structure	ELECTRON MICROSCOPY	3.4
6ZYM	Human C Complex Spliceosome - High-resolution CORE	ELECTRON MICROSCOPY	3.4
8I0P	The cryo-EM structure of human pre-Bact complex	ELECTRON MICROSCOPY	3.4
8I0W	The cryo-EM structure of human C complex	ELECTRON MICROSCOPY	3.4
8RO2	Integrative Structure of the human intron lariat Spliceosome (ILS’')	ELECTRON MICROSCOPY	3.5
5XJC	Cryo-EM structure of the human spliceosome just prior to exon ligation at 3.6 angstrom	ELECTRON MICROSCOPY	3.6
7W59	The cryo-EM structure of human pre-C*-I complex	ELECTRON MICROSCOPY	3.6
7W5A	The cryo-EM structure of human pre-C*-II complex	ELECTRON MICROSCOPY	3.6
7ABF	Human pre-Bact-1 spliceosome core structure	ELECTRON MICROSCOPY	3.9
5YZG	The Cryo-EM Structure of Human Catalytic Step I Spliceosome (C complex) at 4.1 angstrom …	ELECTRON MICROSCOPY	4.1
7AAV	Human pre-Bact-2 spliceosome core structure	ELECTRON MICROSCOPY	4.2
8I0S	The cryo-EM structure of human Bact-II complex	ELECTRON MICROSCOPY	4.2
7W5B	The cryo-EM structure of human C* complex	ELECTRON MICROSCOPY	4.3
6FF7	human Bact spliceosome core structure	ELECTRON MICROSCOPY	4.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P013-F1	75.72	0.30

Human Protein Atlas

Protein class: Predicted intracellular proteins, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nuclear speckles; mitochondria

Antibody reliability (HPA): IH supported · IF supported

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)

Type	Positions
Phosphothreonine	110, 47
Phosphoserine	121
N-acetylthreonine	2
N6-acetyllysine	18

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: 131 (showing top): SHETH_LIVER_CANCER_VS_TXNIP_LOSS_PAM4, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, NKX22_01, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_MRNA_CIS_SPLICING_VIA_SPLICEOSOME, HOXA4_Q2, NKX3A_01, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_CATALYTIC_STEP_2_SPLICEOSOME

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), mRNA cis splicing, via spliceosome (GO:0045292), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

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

GO Cellular Component (6): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nuclear speck (GO:0016607), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013)

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

21 GO namespaces:

Category	Terms
RNA processing	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
cellular anatomical structure	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
nuclear ribonucleoprotein granule	1
U2-type spliceosomal complex	1
U2 snRNP	1
U6 snRNP	1
catalytic step 2 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 6 of 12 annotations. The rest are phylogenetic / computational / electronic (IEA).

6 experimentally-supported GO terms:

GO term	NS	Evidence
mRNA splicing, via spliceosome	BP	direct assay
U2-type catalytic step 2 spliceosome	CC	direct assay
catalytic step 2 spliceosome	CC	direct assay
nuclear speck	CC	direct assay
nucleus	CC	direct assay
spliceosomal complex	CC	direct assay

Protein interactions and networks

STRING

showing 15 of 2,063 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC15	CTTNBP2	Q8WZ74	918
CWC15	ASZ1	Q8WWH4	910
CWC15	GP5	P40197	777
CWC15	FAM3B	P58499	750
CWC15	BCAS2	O75934	641
CWC15	PLRG1	O43660	636
CWC15	CDC5L	Q99459	626
CWC15	SH2D3A	Q9BRG2	623
CWC15	GP2	P55259	606
CWC15	SH2D3C	Q8N5H7	593
CWC15	GOLPH3	Q9H4A6	570
CWC15	YJU2	Q9BW85	562
CWC15	CWC25	Q9NXE8	555
CWC15	IRF3	Q14653	539
CWC15	MPLKIP	Q8TAP9	537

IntAct

Human interaction partners of CWC15 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

12 partners by confidence:

Partner	Interaction type	MIscore	Records
CTNNBL1	direct interaction	0.850	7
ENG	direct interaction	0.440	1
LRRK1	direct interaction	0.440	1
LRRK2	direct interaction	0.440	1
RBM17	physical association	0.370	1
SGCE	physical association	0.370	1
FNTB	association	0.350	1
PLRG1	association	0.350	1
NR3C1	physical association	0.000	1
PHB1	physical association	0.000	1
PRNP	direct interaction	0.000	1
RAC3	physical association	0.000	1

BioGRID (183 interactions; top human partners by supporting records): CTNNBL1 (Affinity Capture-MS; 11 records), CDC5L (Affinity Capture-MS; 6 records), SNW1 (Affinity Capture-MS; 5 records), PRPF19 (Affinity Capture-MS; 4 records), BCAS2 (Affinity Capture-MS; 3 records), DNAJC17 (Affinity Capture-MS; 3 records), PLRG1 (Co-fractionation; 3 records), SIRT1 (Affinity Capture-MS; 3 records), SIRT5 (Affinity Capture-MS; 3 records), HSPA8 (Co-fractionation; 2 records), RBM17 (Two-hybrid; 2 records), SF3A1 (Affinity Capture-MS; 2 records), SF3A2 (Co-fractionation; 2 records), SF3B1 (Affinity Capture-MS; 2 records), SF3B4 (Co-fractionation; 2 records)

SIGNOR signaling

1 signaling interactions:

A	Effect	B	Mechanism
CWC15	“form complex”	PRP19-CDC5L	binding

Protein complexes (CORUM) (5)

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

5 complexes by size:

Complex	Subunits	Members
Spliceosome, A complex	112	RBM39, SAP30BP, CDK11A, CHERP, HNRNPA1, HNRNPK, HNRNPR, HNRNPU, RBM25, SF3A1, DDX46, HNRNPA3, RNPS1, SART1, SF1, SF3A2, SF3B4, SNRPB, ACIN1, CCAR2, DHX9, ELAVL1, ILF2, SF3B3, SRSF5, HNRNPA2B1, CD2BP2, DDX5, PUF60, RBM17, SNRPA1, TCERG1, ZC3H18, SNRPD1, SRSF2, SYNCRIP, ZNF207, CTNNBL1, HSPA8, NCBP2, SF3B2, TRA2B, YBX1, RBM10, SF3A3, SRRM1, SRSF6, SRSF7, SUGP1, DDX42, DNAJC8, EFTUD2, PRCC, SF3B5, SMNDC1, SNRNP200, WBP11, CDC5L, PPP1R8, PRPF6, BCAS2, NCBP1, PRPF19, PRPF3, SNRPD3, SRSF4, U2AF2, HNRNPUL1, NRIP2, PHF5A, RBM5, RBMX, SNRPA, SRRM2, U2AF1, CCAR1, CFAP20, CIRBP, DDX23, SF3B1, SF3B6, SNRPB2, SNRPE, BUB3, DHX15, PCBP1, PPP1CA, PQBP1, SNRNP70, SRSF1, U2SURP, DDX17, SNRPC, SNRPD2, SNRPF, SNRPG, SRRT, SRSF3, SRSF9, AGGF1, FUS, HNRNPC, HTATSF1, ILF3, PLRG1, SEC31B, TRIR, CWC15, HNRNPAB, PNN, PRPF40A, PRPF8
C complex spliceosome	80	RBM8A, ZCCHC8, EFTUD2, HNRNPK, PNN, SRSF1, CDC40, DHX35, HNRNPA2B1, HNRNPC, SF3B3, SYNCRIP, U2AF1, PLRG1, RBM22, SNRNP40, SNRPB2, EIF4A3, FRG1, GPATCH1, HNRNPA3, PPIL1, SF3B1, DHX38, HNRNPR, LSM2, LSM3, SNRPE, DDX23, HNRNPU, MTREX, SLU7, AQR, CWC15, CWC22, DDX41, PABPC1, SF3B2, SNRPD1, SNRPD2, DHX8, CWC27, HNRNPA1, HNRNPH1, MAGOH, SF3A1, PPIE, PPIL3, PRP4K, PRPF6, RALY, SNRPA1, SYF2, TFIP11, CACTIN, CRNKL1, DDX5, SF3A3, SNRNP200, SNRPD3, SNRPF, SRRM1, ALYREF, PPWD1, PRPF19, RBMX, SF3A2, SRRM2, WDR83, XAB2, CDC5L, HNRNPF, SART1, SNRPG, ESS2, ISY1, SNRPB, SNW1, HNRNPM, PRPF8
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
★ CDC5L complex	30	SRRM1, SF3B1, SRSF1, CDC5L, DYNC1H1, GCN1, HSPA8, PPP1CA, SF3B2, SCAF8, SNRPA, SRSF2, BZW1, RBMX, SFPQ, SNRPA1, SNRPD3, TCF4, PLRG1, SNRPD2, TOP2A, ILF2, SF3B4, SNRPD1, SFI1, BCAS2, CWC15, PPM1D, PRKDC, PRPF19
CDC5L-PRP19 complex	7	CWC15, HSPA8, PLRG1, PRPF19, BCAS2, CDC5L, CTNNBL1

Disease & clinical

Genetic variants

Variant evidence for CWC15: 19 ClinVar records (0 pathogenic / likely pathogenic); 2 GWAS associations.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	8
Likely benign	0
Benign	0

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 26 predictions of 536):

Position(s)	Effect	Δscore	Sites
11:94963515	acceptor_loss	1.0000
11:94966293–94966294	donor_loss	1.0000	5
11:94966297	donor_gain	1.0000
11:94966414–94966415	acceptor_loss	1.0000	5
11:94966419	acceptor_gain	1.0000
11:94966423	acceptor_gain	1.0000
11:94969987–94969988	donor_loss	1.0000	5
11:94969991	donor_gain	1.0000
11:94970097–94970098	acceptor_loss	1.0000	4
11:94970975–94970976	donor_loss	1.0000	2

AlphaMissense

1,007 missense substitutions predicted likely pathogenic (of 1,523 scored), across 198 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
M224	9	0.925	0.999
D213	8	1.000	1.000
F194	8	0.999	1.000
H220	8	0.999	1.000
D104	8	0.998	0.999
D34	8	0.997	0.999
N167	8	0.997	1.000
F223	8	0.997	1.000
D106	8	0.995	0.999
D189	8	0.995	1.000
D191	8	0.995	0.999
N196	8	0.994	1.000
N212	8	0.993	1.000
F219	8	0.985	1.000
F9	8	0.974	1.000
D58	8	0.971	0.996
D22	8	0.967	0.993
H38	8	0.967	1.000
F210	8	0.965	1.000
D107	8	0.958	0.994

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

2 prognostic cancer types:

Cancer	Prognostic	p-value
Pancreatic Adenocarcinoma (validation)	unfavorable	4.46e-06
Breast Invasive Carcinoma (TCGA)	unfavorable	0.000678

Disease associations

OMIM: gene `` | disease phenotypes:

GWAS associations

2 associations:

Study	Trait	p-value
GCST011741_15	LDL cholesterol levels in HIV infection	1e-6
GCST000253_20	Attention deficit hyperactivity disorder and conduct disorder	2e-6

EFO canonical traits (from GWAS)

1 canonical traits:

EFO ID	Trait name
EFO:0004611	low density lipoprotein cholesterol measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL6066384 (SINGLE PROTEIN)

PharmGKB: 1 entry (CPIC guideline: no)

Binding affinities (BindingDB)

1 measured of 1 human assays (1 total across all organisms); most potent 1 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
CHEMBL5653589	KD	1440 nM

CTD chemical–gene interactions

25 total (human), top 25 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	affects expression, increases abundance, decreases expression	2
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenite	affects cotreatment, increases abundance, increases expression	1
manganese chloride	increases expression, affects cotreatment, increases abundance	1
isobutyl alcohol	decreases expression, increases abundance, affects cotreatment	1
CGP 52608	affects binding, increases reaction	1
abrine	decreases expression	1
3-(2-hydroxy-4-(2-methylnonan-2-yl)phenyl)cyclohexan-1-ol	decreases expression	1
Arsenic	affects cotreatment, increases abundance, increases expression	1
Atrazine	increases expression	1
Doxorubicin	increases expression	1
Gasoline	affects cotreatment, decreases expression, increases abundance	1
Manganese	increases abundance, increases expression, affects cotreatment	1
Ozone	affects expression, increases abundance	1
Polycyclic Aromatic Hydrocarbons	affects cotreatment, decreases expression, increases abundance	1
Smoke	decreases expression, increases abundance	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Valproic Acid	affects expression	1
Aflatoxin B1	decreases methylation	1
Copper Sulfate	decreases expression	1
1-Butanol	increases abundance, affects cotreatment, decreases expression	1
Particulate Matter	affects cotreatment, decreases expression, increases abundance	1

ChEMBL screening assays

1 unique, capped per target: 1 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5651227	Binding	Binding affinity to human CWC15 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)

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

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for CWC15 across ~30M SureChEMBL compounds — explore on Sugi Predict.