SNW1

Summary

SNW1 (SNW domain containing 1, HGNC:16696) is a protein-coding gene on chromosome 14q24.3, encoding SNW domain-containing protein 1 (Q13573). Involved in pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 99.9% of cancer cell lines).

This gene, a member of the SNW gene family, encodes a coactivator that enhances transcription from some Pol II promoters. This coactivator can bind to the ligand-binding domain of the vitamin D receptor and to retinoid receptors to enhance vitamin D-, retinoic acid-, estrogen-, and glucocorticoid-mediated gene expression. It can also function as a splicing factor by interacting with poly(A)-binding protein 2 to directly control the expression of muscle-specific genes at the transcriptional level. Finally, the protein may be involved in oncogenesis since it interacts with a region of SKI oncoproteins that is required for transforming activity. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 22938 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 59 total — 1 likely-pathogenic
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.9% of screened cell lines (common-essential)
• MANE Select transcript: NM_012245

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:16696
Approved symbol	SNW1
Name	SNW domain containing 1
Location	14q24.3
Locus type	gene with protein product
Status	Approved
Aliases	NCoA-62, SKIP, Prp45, PRPF45, Bx42, SKIP1, FUN20
Ensembl gene	ENSG00000100603
Ensembl biotype	protein_coding
OMIM	603055
Entrez	22938

Gene structure

Transcript identifiers

Ensembl transcripts: 9 — 6 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000261531, ENST00000553565, ENST00000554324, ENST00000554775, ENST00000555761, ENST00000556428, ENST00000557663, ENST00000851821, ENST00000851822

RefSeq mRNA: 2 — MANE Select: NM_012245 NM_001318844, NM_012245

CCDS: CCDS81830, CCDS9867

Canonical transcript exons

ENST00000261531 — 14 exons

Exon	Start	End
ENSE00002465921	77717599	77718286
ENSE00003477252	77720711	77720828
ENSE00003490006	77754967	77755120
ENSE00003522438	77736971	77737075
ENSE00003533298	77732485	77732601
ENSE00003558516	77730988	77731129
ENSE00003562202	77734947	77735012
ENSE00003581447	77738966	77739061
ENSE00003616127	77723181	77723277
ENSE00003619599	77738778	77738884
ENSE00003634976	77751319	77751480
ENSE00003676828	77735937	77736006
ENSE00003678607	77718367	77718530
ENSE00003903439	77761114	77761156

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 98.41.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 37.2810 / max 819.9124, expressed in 1813 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
144247	36.9209	1813
207313	0.3602	137

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	98.41	gold quality
epithelium of nasopharynx	UBERON:0001951	98.04	gold quality
parotid gland	UBERON:0001831	98.03	gold quality
nasopharynx	UBERON:0001728	98.02	gold quality
calcaneal tendon	UBERON:0003701	97.99	gold quality
tendon	UBERON:0000043	97.85	gold quality
amniotic fluid	UBERON:0000173	97.72	gold quality
parietal pleura	UBERON:0002400	97.72	gold quality
tendon of biceps brachii	UBERON:0008188	97.45	gold quality
germinal epithelium of ovary	UBERON:0001304	97.40	gold quality
esophagus squamous epithelium	UBERON:0006920	97.39	gold quality
trabecular bone tissue	UBERON:0002483	97.26	gold quality
squamous epithelium	UBERON:0006914	97.25	gold quality
tibia	UBERON:0000979	97.23	gold quality
pleura	UBERON:0000977	97.20	gold quality
vena cava	UBERON:0004087	97.02	gold quality
visceral pleura	UBERON:0002401	96.95	gold quality
saphenous vein	UBERON:0007318	96.91	gold quality
mammary duct	UBERON:0001765	96.89	gold quality
epithelium of mammary gland	UBERON:0003244	96.89	gold quality
synovial joint	UBERON:0002217	96.74	gold quality
oviduct epithelium	UBERON:0004804	96.74	gold quality
epithelium of esophagus	UBERON:0001976	96.70	gold quality
palpebral conjunctiva	UBERON:0001812	96.62	gold quality
superficial temporal artery	UBERON:0001614	96.60	gold quality
superior surface of tongue	UBERON:0007371	96.53	gold quality
pericardium	UBERON:0002407	96.52	gold quality
ventricular zone	UBERON:0003053	96.49	gold quality
mucosa of paranasal sinus	UBERON:0005030	96.42	gold quality
pharyngeal mucosa	UBERON:0000355	96.40	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-GEOD-124858	no	182.39
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

4 targets.

Target	Regulation
AR	Activation
HES1	Unknown
RARB	Unknown
VDR	Unknown

Upstream regulators (CollecTRI, top): AR, MYOD1, NR0B1, VDR

miRNA regulators (miRDB)

41 targeting SNW1, 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-3925-3P	100.00	69.95	1237
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-548J-3P	99.94	72.61	4881
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-3151-5P	99.86	63.83	1069
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-33A-3P	99.70	70.27	3362
HSA-MIR-29B-2-5P	99.67	68.98	1726
HSA-MIR-3679-3P	99.64	69.88	1599
HSA-MIR-7150	99.62	66.80	1322
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4688	99.48	64.68	828
HSA-MIR-6743-5P	99.48	63.60	721
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-519D-5P	99.41	69.30	2057
HSA-MIR-6853-3P	99.36	70.79	1558
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-3973	99.20	69.19	1990
HSA-MIR-520G-3P	98.91	67.38	1914
HSA-MIR-520H	98.91	67.38	1914

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.9% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 27)

• may couple vitamin D receptor-mediated transcription and RNA splicing (PMID:12840015)
• These results show that the human SKIP gene can functionally substitute for the mRNA splicing gene PRP45 of S. cerevisiae. (PMID:15194481)
• SKIIP plays independent roles in transcription elongation and pre-mRNA splicing. (PMID:15905409)
• SKIP binds with CHES1 in a region within the final 66 hydrophobic residues, and thus defining a new protein-protein interaction domain of SKIP. (PMID:16102918)
• SifA, SKIP, SseJ, and RhoA family GTPases cooperatively promote host membrane tubulation. (PMID:18996344)
• SKIP acts with c-Myc and Menin to promote HIV-1 Tat:P-TEFb transcription at an elongation step that is bypassed under stress. (PMID:19818711)
• SIRT1 associates with SKI-interacting protein (SKIP) and modulates its activity as a coactivator of retinoic acid receptor. (PMID:19934264)
• The large disordered region in SKIP provides an interaction platform. Its disorder-order transition, induced by PPIL1 binding, may adapt the requirement for a large structural rearrangement occurred in the activation of spliceosome (PMID:20007319)
• molecular model for the binding mode of SKIP to PPIL1 which emphasizes the versatility of cyclophilin-type PPIases to engage in additional interactions with other proteins apart from active site contacts despite their limited surface area. (PMID:20368803)
• SKIP is required for epithelial mesenchymal transition and invasiveness induced by TGF-beta1 in transformed cells. (PMID:20965173)
• SKIP is essential for p53 stress-induced expression of the p21 (PMID:21460037)
• This suggests that transcription of stress response genes, unlike, e.g., the SNW1-sensitive mitosis-specific genes, can proceed uncoupled from regulators that normally function under physiological conditions. (PMID:21461980)
• Arl8 and SKIP are required for lysosomes to distribute away from the microtubule-organizing center. We identify two kinesin light chain binding motifs in SKIP that are required for lysosomes to accumulate kinesin-1 and redistribute to the cell periphery. (PMID:22172677)
• SKIP increased 5alpha-dihydrotestosterone (DHT) induced N-terminal/C-terminal AR interaction from 12-fold to almost 300-fold in a two-hybrid assay, and enhanced AR ligand-independent AF-1 transactivation. (PMID:23566155)
• High SKIP expression was detected in clinical HCC samples. (PMID:23696020)
• SKIP overexpression is involved in the pathogenesis of breast cancer. (PMID:24150787)
• A transcriptome-wide analysis revealed that SNW1 or PRPF8 depletion affects the splicing of specific introns in a subset of pre-mRNAs, including pre-mRNAs encoding the cohesion protein sororin and the APC/C subunit APC2. (PMID:25257309)
• Results show that SNW1 directly associates with EFTUD2 and SNRNP200 and that disruption of SNW1 association with these proteins promotes the apoptosis of breast cancer cells. (PMID:25450007)
• Rab1A regulates anterograde melanosome transport by recruiting kinesin-1 to melanosomes through interaction with SKIP (PMID:25649263)
• Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. (PMID:26393790)
• Higher SKIP expression is associated with poor prognosis in malignant pleural mesothelioma (PMID:27543864)
• c-Abl promotes TGF-beta-induced SKIP/Smad3 interaction. (PMID:28666867)
• SNW1 is a unique protein previously shown to be involved in both splicing and transcription, and in this case, its role involves binding to the NF-kappaB-p-TEFb complex to facilitate transcriptional elongation of some NF-kappaB target genes. (PMID:30397075)
• SNW1 interacts with RBPJ to regulate the Notch signaling pathway in neuroblastoma (PMID:30642633)
• These results demonstrate that SNW1 overexpression is an independent prognostic marker in prostate cancer with potential clinical utility. (PMID:31043167)
• Skip is essential for Notch signaling to induce Sox2 in cerebral arteriovenous malformations. (PMID:31927035)
• SNW1 interacts with IKKgamma to positively regulate antiviral innate immune responses against influenza A virus infection. (PMID:32805409)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	snw1	ENSDARG00000091563
mus_musculus	Snw1	ENSMUSG00000021039
rattus_norvegicus	Snw1	ENSRNOG00000037998
drosophila_melanogaster	Bx42	FBGN0004856
caenorhabditis_elegans		WBGENE00004806

Protein

Protein identifiers

SNW domain-containing protein 1 — Q13573 (reviewed: Q13573)

Alternative names: Nuclear protein SkiP, Nuclear receptor coactivator NCoA-62, Ski-interacting protein

All UniProt accessions (5): Q13573, G3V3A4, G3V4E0, G3V4X8, G3V5R3

UniProt curated annotations — full annotation on UniProt →

Function. Involved in pre-mRNA splicing as component of the spliceosome. As a component of the minor spliceosome, involved in the splicing of U12-type introns in pre-mRNAs. Required for the specific splicing of CDKN1A pre-mRNA; the function probably involves the recruitment of U2AF2 to the mRNA. May recruit PPIL1 to the spliceosome. May be involved in cyclin-D1/CCND1 mRNA stability through the SNARP complex which associates with both the 3’end of the CCND1 gene and its mRNA. Involved in transcriptional regulation. Modulates TGF-beta-mediated transcription via association with SMAD proteins, MYOD1-mediated transcription via association with PABPN1, RB1-mediated transcriptional repression, and retinoid-X receptor (RXR)- and vitamin D receptor (VDR)-dependent gene transcription in a cell line-specific manner probably involving coactivators NCOA1 and GRIP1. Is involved in NOTCH1-mediated transcriptional activation. Binds to multimerized forms of Notch intracellular domain (NICD) and is proposed to recruit transcriptional coactivators such as MAML1 to form an intermediate preactivation complex which associates with DNA-bound CBF-1/RBPJ to form a transcriptional activation complex by releasing SNW1 and redundant NOTCH1 NICD. (Microbial infection) Is recruited by HIV-1 Tat to Tat:P-TEFb:TAR RNA complexes and is involved in Tat transcription by recruitment of MYC, MEN1 and TRRAP to the HIV promoter. (Microbial infection) Proposed to be involved in transcriptional activation by EBV EBNA2 of CBF-1/RBPJ-repressed promoters.

Subunit / interactions. Identified in the spliceosome C complex. Associates with U4/U6-U5 tri-small nuclear ribonucleoproteins (U4/U6-U5 tri-snRNPs). Component of the minor spliceosome, which splices U12-type introns. Interacts with SKI, SMAD2,SMAD3, RBPJ, RB1, PABPN1, MAGEA1, SIRT1, FOXN3, U2AF2, DAXX and ATP1B4. Interacts with PPIL1. Interacts with VDR and RXRA; preferentially associates with VDR:RXRA heterodimers. Interacts with NCOR2. Interacts with MAML1. Interacts with NOTCH1 NICD; the interaction involves multimerized NOTCH1 NICD. Forms a complex with NOTCH1 NICD and MAML1; the association is dissociated by RBPJ. Associates with positive transcription elongation factor b (P-TEFb). Component of the SNARP complex which consists at least of SNIP1, SNW1, THRAP3, BCLAF1 and PNN. (Microbial infection) Interacts with human papillomavirus type-16 (HPV16) E7 protein. (Microbial infection) Interacts with EBV EBNA2; EBNA2 competes with NCOR2 for interaction with SNW1.

Subcellular location. Nucleus.

Similarity. Belongs to the SNW family.

RefSeq proteins (2): NP_001305773, NP_036377* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR004015	SKI-int_prot_SKIP_SNW-dom	Domain
IPR017862	SKI-int_prot_SKIP	Family

Pfam: PF02731

UniProt features (70 total): cross-link 18, strand 11, helix 11, modified residue 10, turn 8, region of interest 6, mutagenesis site 2, compositionally biased region 2, initiator methionine 1, chain 1

Structure

Experimental structures (PDB)

34 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8C6J	ELECTRON MICROSCOPY	2.8
6ID1	ELECTRON MICROSCOPY	2.86
7DVQ	ELECTRON MICROSCOPY	2.89
6ID0	ELECTRON MICROSCOPY	2.9
6ICZ	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
9R3D	ELECTRON MICROSCOPY	3.12
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
6FF4	ELECTRON MICROSCOPY	3.4
6ZYM	ELECTRON MICROSCOPY	3.4
8I0P	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
8RO2	ELECTRON MICROSCOPY	3.5
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
7ABF	ELECTRON MICROSCOPY	3.9
5YZG	ELECTRON MICROSCOPY	4.1
7AAV	ELECTRON MICROSCOPY	4.2
8I0S	ELECTRON MICROSCOPY	4.2
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
7A5P	ELECTRON MICROSCOPY	5
5MQF	ELECTRON MICROSCOPY	5.9

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q13573-F1	78.52	0.40

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 (28): 2, 14, 182, 190, 224, 232, 234, 446, 479, 481, 23, 81, 97, 115, 122, 141, 158, 170, 193, 240 …

Mutagenesis-validated functional residues (2):

Position	Phenotype
66	abolishes interaction with ppil1.
76	abolishes interaction with ppil1.

Function

Pathways and Gene Ontology

Reactome pathways

38 pathways

ID	Pathway
R-HSA-1912408	Pre-NOTCH Transcription and Translation
R-HSA-210744	Regulation of gene expression in late stage (branching morphogenesis) pancreatic bud precursor cells
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-72163	mRNA Splicing - Major Pathway
R-HSA-8941856	RUNX3 regulates NOTCH signaling
R-HSA-9013508	NOTCH3 Intracellular Domain Regulates Transcription
R-HSA-9013695	NOTCH4 Intracellular Domain Regulates Transcription
R-HSA-9793380	Formation of paraxial mesoderm
R-HSA-9918481	Dengue Virus-Host Interactions
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-186712	Regulation of beta-cell development
R-HSA-1912422	Pre-NOTCH Expression and Processing
R-HSA-1980143	Signaling by NOTCH1
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer
R-HSA-2644603	Signaling by NOTCH1 in Cancer
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers
R-HSA-72172	mRNA Splicing
R-HSA-72203	Processing of Capped Intron-Containing Pre-mRNA

MSigDB gene sets: 290 (showing top): REACTOME_SIGNALING_BY_NOTCH, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, GOBP_INTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_RESPONSE_TO_DNA_DAMAGE_BY_P53_CLASS_MEDIATOR, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, TGCGCANK_UNKNOWN, GOBP_REGULATION_OF_MRNA_CATABOLIC_PROCESS, GOBP_POSITIVE_REGULATION_OF_RNA_SPLICING, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_POSITIVE_REGULATION_OF_MRNA_PROCESSING, GOBP_HOST_MEDIATED_ACTIVATION_OF_VIRAL_TRANSCRIPTION, MORF_SNRP70, GOBP_MACROMOLECULE_CATABOLIC_PROCESS, GOBP_REGULATION_OF_RETINOIC_ACID_RECEPTOR_SIGNALING_PATHWAY, GOBP_MODULATION_OF_PROCESS_OF_ANOTHER_ORGANISM, GOBP_NEUROGENESIS

GO Biological Process (17): negative regulation of transcription by RNA polymerase II (GO:0000122), mRNA splicing, via spliceosome (GO:0000398), regulation of transcription by RNA polymerase II (GO:0006357), positive regulation of transforming growth factor beta receptor signaling pathway (GO:0030511), intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator (GO:0042771), host-mediated activation of viral transcription (GO:0043923), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of mRNA splicing, via spliceosome (GO:0048026), retinoic acid receptor signaling pathway (GO:0048384), regulation of retinoic acid receptor signaling pathway (GO:0048385), positive regulation of neurogenesis (GO:0050769), regulation of vitamin D receptor signaling pathway (GO:0070562), positive regulation of vitamin D receptor signaling pathway (GO:0070564), cellular response to retinoic acid (GO:0071300), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

GO Molecular Function (11): transcription coactivator activity (GO:0003713), transcription corepressor activity (GO:0003714), RNA binding (GO:0003723), Notch binding (GO:0005112), nuclear receptor binding (GO:0016922), enzyme binding (GO:0019899), nuclear vitamin D receptor binding (GO:0042809), nuclear retinoic acid receptor binding (GO:0042974), SMAD binding (GO:0046332), nuclear androgen receptor binding (GO:0050681), protein binding (GO:0005515)

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), nuclear matrix (GO:0016363), nuclear body (GO:0016604), nuclear speck (GO:0016607), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013), cyclin/CDK positive transcription elongation factor complex (GO:0008024)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Pre-NOTCH Expression and Processing	1
Regulation of beta-cell development	1
Signaling by NOTCH1	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Generic Transcription Pathway	1
mRNA Splicing	1
Transcriptional regulation by RUNX3	1
Signaling by NOTCH3	1
Signaling by NOTCH4	1
Gastrulation	1
Dengue Virus Infection	1
Differentiation of T cells	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transcription by RNA polymerase II	3
nuclear receptor binding	3
regulation of transcription by RNA polymerase II	2
negative regulation of DNA-templated transcription	2
regulation of DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
regulation of intracellular signal transduction	2
vitamin D receptor signaling pathway	2
RNA processing	2
transcription coregulator activity	2
protein binding	2
nuclear lumen	2
cellular anatomical structure	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
positive regulation of cellular response to transforming growth factor beta stimulus	1
intrinsic apoptotic signaling pathway in response to DNA damage	1
intrinsic apoptotic signaling pathway by p53 class mediator	1
host-mediated perturbation of viral transcription	1
host-mediated activation of viral process	1
DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
mRNA splicing, via spliceosome	1
positive regulation of RNA splicing	1
regulation of mRNA splicing, via spliceosome	1
positive regulation of mRNA processing	1
hormone-mediated signaling pathway	1
nuclear receptor-mediated signaling pathway	1
retinoic acid receptor signaling pathway	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
regulation of response to nutrient levels	1
regulation of vitamin D receptor signaling pathway	1
positive regulation of intracellular signal transduction	1
response to retinoic acid	1

Protein interactions and networks

STRING

3630 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
SNW1	PPIL1	Q9Y3C6	936
SNW1	SNIP1	Q8TAD8	825
SNW1	RBM22	Q9NW64	815
SNW1	FOXN3	O00409	814
SNW1	CDC5L	Q99459	808
SNW1	ECM2	O94769	805
SNW1	CWC15	Q9P013	805
SNW1	PLRG1	O43660	804
SNW1	SLIRP	Q9GZT3	798
SNW1	CRNKL1	Q9BZJ0	791
SNW1	CDC40	O60508	764
SNW1	BUD31	P41223	759
SNW1	SNRNP200	O75643	731
SNW1	CWC22	Q9HCG8	714
SNW1	PABPN1	Q86U42	703

IntAct

577 interactions, top by confidence:

A	B	Type	Score
PPIL1	SNW1	psi-mi:“MI:0915”(physical association)	0.930
SNW1	PPIL1	psi-mi:“MI:0915”(physical association)	0.930
PPIL1	SNW1	psi-mi:“MI:0914”(association)	0.930
SNW1	TFIP11	psi-mi:“MI:0915”(physical association)	0.830
TFIP11	SNW1	psi-mi:“MI:0915”(physical association)	0.830
SNW1	RINT1	psi-mi:“MI:0915”(physical association)	0.780
RINT1	SNW1	psi-mi:“MI:0915”(physical association)	0.780
SNW1	GOLGA2	psi-mi:“MI:0915”(physical association)	0.720
GOLGA2	SNW1	psi-mi:“MI:0915”(physical association)	0.720
PNN	SNW1	psi-mi:“MI:0915”(physical association)	0.670
SNW1	IKBKG	psi-mi:“MI:0915”(physical association)	0.670
SNW1	EXOSC5	psi-mi:“MI:0915”(physical association)	0.660
SNRPA1	HTATSF1	psi-mi:“MI:0914”(association)	0.640
DHX8	AHCYL1	psi-mi:“MI:0914”(association)	0.640
SNW1	CEP55	psi-mi:“MI:0915”(physical association)	0.560
TRAF1	SNW1	psi-mi:“MI:0915”(physical association)	0.560
SNW1	IKZF1	psi-mi:“MI:0915”(physical association)	0.560
MTUS2	SNW1	psi-mi:“MI:0915”(physical association)	0.560

BioGRID (1065): SNW1 (Two-hybrid), SNW1 (Two-hybrid), SNW1 (Two-hybrid), MTUS2 (Two-hybrid), TFIP11 (Two-hybrid), PPIL1 (Two-hybrid), CEP55 (Two-hybrid), TEX11 (Two-hybrid), RINT1 (Two-hybrid), LZTS2 (Two-hybrid), KRT40 (Two-hybrid), SNW1 (Affinity Capture-RNA), SNW1 (Two-hybrid), SNW1 (Two-hybrid), SNW1 (Affinity Capture-Western)

ESM2 similar proteins: A8WXX7, B8BDW1, C5DMI3, O74517, O80653, P06843, P0CR52, P0CR53, P0CR56, P0CR57, P28004, P39736, P54705, Q02775, Q09882, Q13442, Q13573, Q18691, Q1JQE0, Q21278, Q22836, Q299F9, Q3UHX2, Q4PB95, Q4WEH7, Q5AU50, Q5R7R9, Q5RAA7, Q5U317, Q62785, Q69JZ7, Q69QB5, Q6BMK7, Q6BV91, Q6CC77, Q6CK06, Q6CLJ7, Q6FIT9, Q6FSQ0, Q6K8D9

Diamond homologs: O80653, P0CR56, P0CR57, P28004, P39736, P54705, Q09882, Q13573, Q1JQE0, Q22836, Q4PB95, Q4WEH7, Q5AU50, Q5R7R9, Q69QB5, Q6BV91, Q6CC77, Q6CLJ7, Q6K8D9, Q759B6, Q9CSN1, Q5AC37, Q6FIT9

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
SNW1	up-regulates	NOTCH1	binding
NOTCH	up-regulates	SNW1	binding
NCOR2	up-regulates	SNW1	binding
NOTCH1	up-regulates	SNW1	binding
SNW1	down-regulates	NCOR2	binding
SNW1	“up-regulates activity”	NOTCH1	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 104 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	10	16.9×	6e-08
mRNA Splicing - Major Pathway	19	16.0×	1e-15
Processing of Capped Intron-Containing Pre-mRNA	10	12.6×	7e-07
Metabolism of RNA	12	7.7×	4e-06
Dengue Virus-Host Interactions	10	7.0×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
U2-type prespliceosome assembly	5	34.3×	8e-05
spliceosomal snRNP assembly	5	31.9×	8e-05
mRNA splicing, via spliceosome	21	21.1×	1e-19
RNA splicing	8	7.8×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	45
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
4683090	NM_012245.3(SNW1):c.182_187del (p.Gly61_Gly62del)	Likely pathogenic

SpliceAI

1560 predictions. Top by Δscore:

Variant	Effect	Δscore
14:77718282:CAAAT:C	acceptor_gain	1.0000
14:77718287:C:CC	acceptor_gain	1.0000
14:77718527:TACC:T	acceptor_gain	1.0000
14:77718529:CC:C	acceptor_gain	1.0000
14:77718530:CC:C	acceptor_gain	1.0000
14:77720706:TGTA:T	donor_loss	1.0000
14:77720708:TACCT:T	donor_loss	1.0000
14:77720709:A:C	donor_loss	1.0000
14:77720710:C:T	donor_loss	1.0000
14:77720745:A:C	donor_gain	1.0000
14:77720829:C:CC	acceptor_gain	1.0000
14:77720829:CT:C	acceptor_loss	1.0000
14:77720830:T:C	acceptor_loss	1.0000
14:77730982:TCATA:T	donor_loss	1.0000
14:77730983:CATA:C	donor_loss	1.0000
14:77730984:ATAC:A	donor_loss	1.0000
14:77730985:TA:T	donor_loss	1.0000
14:77730986:A:AC	donor_gain	1.0000
14:77730987:C:CC	donor_gain	1.0000
14:77731125:CGAGC:C	acceptor_gain	1.0000
14:77731126:GAGC:G	acceptor_gain	1.0000
14:77731127:AGC:A	acceptor_gain	1.0000
14:77731128:GC:G	acceptor_gain	1.0000
14:77731128:GCCTG:G	acceptor_loss	1.0000
14:77731129:CC:C	acceptor_gain	1.0000
14:77731130:C:CC	acceptor_gain	1.0000
14:77731131:T:A	acceptor_loss	1.0000
14:77732483:A:AT	donor_loss	1.0000
14:77732487:T:TA	donor_gain	1.0000
14:77732597:TAACC:T	acceptor_gain	1.0000

AlphaMissense

3534 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
14:77720781:G:T	A393D	1.000
14:77731030:C:G	A331P	1.000
14:77731038:G:T	A328D	1.000
14:77731039:C:G	A328P	1.000
14:77731050:A:G	L324P	1.000
14:77731084:C:G	A313P	1.000
14:77731105:C:G	A306P	1.000
14:77731108:G:T	R305S	1.000
14:77731120:C:G	A301P	1.000
14:77731125:C:G	R299P	1.000
14:77731126:G:T	R299S	1.000
14:77731128:G:T	A298D	1.000
14:77731129:C:G	A298P	1.000
14:77732489:C:G	R296P	1.000
14:77732495:G:T	A294D	1.000
14:77732496:C:G	A294P	1.000
14:77732504:A:G	L291P	1.000
14:77732504:A:T	L291H	1.000
14:77732508:C:G	A290P	1.000
14:77732514:C:G	A288P	1.000
14:77732516:A:G	L287S	1.000
14:77732522:G:T	A285D	1.000
14:77732524:G:C	F284L	1.000
14:77732524:G:T	F284L	1.000
14:77732526:A:G	F284L	1.000
14:77732537:A:T	I280K	1.000
14:77732557:T:A	R273S	1.000
14:77732557:T:G	R273S	1.000
14:77732558:C:A	R273I	1.000
14:77732558:C:G	R273T	1.000

dbSNP variants (sampled 300 via entrez): RS1000021833 (14:77745881 G>A), RS1000067780 (14:77725085 C>A,T), RS1000082717 (14:77751562 T>C), RS1000275309 (14:77726347 T>G), RS1000323371 (14:77731361 A>G), RS1000371248 (14:77719348 T>G), RS1000375505 (14:77757634 TACA>T), RS1000497842 (14:77740086 A>G), RS1000553307 (14:77745214 A>G), RS1000633718 (14:77739873 G>A,T), RS1000650557 (14:77751451 C>T), RS1000661908 (14:77751172 C>T), RS1000903230 (14:77745510 C>T), RS1000974877 (14:77720381 C>T), RS1001010207 (14:77747252 G>A,C)

Disease associations

OMIM: gene MIM:603055 | 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
GCST001629_5	Response to platinum-based chemotherapy in non-small-cell lung cancer	4.000000e-06

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5725096 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,538 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1232461	MOLIBRESIB	2	1,538

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

ChEMBL bioactivities

1 potent at pChembl≥5 of 1 total, top 1 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
5.98	IC50	1050	nM	MOLIBRESIB

PubChem BioAssay actives

1 with measured affinity, of 6 total; 1 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	2178852: Inhibition of SNW1 (unknown origin) incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	ic50	1.0500	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Air Pollutants	decreases expression, affects expression, increases abundance	2
FR900359	affects phosphorylation	1
dicrotophos	decreases expression	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
deoxynivalenol	increases expression	1
tetrahydropalmatine	decreases expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sodium arsenite	decreases expression	1
2,3,5-(triglutathion-S-yl)hydroquinone	increases ADP-ribosylation	1
K 7174	increases expression	1
ICG 001	decreases expression	1
abrine	decreases expression, increases expression	1
1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone	decreases phosphorylation	1
enzalutamide	affects expression	1
bisphenol S	affects expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Glyphosate	increases expression	1
Atrazine	increases expression	1
Caffeine	affects phosphorylation	1
Cycloheximide	affects cotreatment, increases expression	1
Doxorubicin	decreases expression	1
Enzyme Inhibitors	decreases activity, increases O-linked glycosylation	1
Estradiol	decreases phosphorylation	1
Ivermectin	decreases expression	1
Lead	affects splicing	1
Ozone	affects expression, increases abundance	1
Phenobarbital	affects expression	1
Plant Extracts	affects cotreatment, increases expression	1

ChEMBL screening assays

6 unique, capped per target: 6 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697582	Binding	Inhibition of SNW1 (unknown origin) assessed as fold change at 10 uM incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	Inhibition of BET recruitment to chromatin as an effective treatment for MLL-fusion leukaemia. — Nature

Clinical trials (associated diseases)

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