CWC22

Summary

CWC22 (CWC22 spliceosome associated protein, HGNC:29322) is a protein-coding gene on chromosome 2q31.3, encoding Pre-mRNA-splicing factor CWC22 homolog (Q9HCG8). Required for pre-mRNA splicing as component of the spliceosome. It is a common-essential gene (DepMap: required in 99.7% of cancer cell lines).

Enables RNA binding activity. Involved in mRNA splicing, via spliceosome. Located in cytosol and nuclear speck. Part of U2-type catalytic step 1 spliceosome; U2-type catalytic step 2 spliceosome; and U2-type precatalytic spliceosome.

Source: NCBI Gene 57703 — RefSeq curated summary.

At a glance

• GWAS associations: 6
• Clinical variants (ClinVar): 153 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 99.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_020943

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29322
Approved symbol	CWC22
Name	CWC22 spliceosome associated protein
Location	2q31.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA1604, EIF4GL, fSAPb, NCM
Ensembl gene	ENSG00000163510
Ensembl biotype	protein_coding
OMIM	615186
Entrez	57703

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 6 protein_coding

ENST00000404136, ENST00000410053, ENST00000910802, ENST00000910803, ENST00000918074, ENST00000962033

RefSeq mRNA: 5 — MANE Select: NM_020943 NM_001376029, NM_001376030, NM_001376032, NM_001376033, NM_020943

CCDS: CCDS46465

Canonical transcript exons

ENST00000410053 — 20 exons

Exon	Start	End
ENSE00001075491	179964547	179964628
ENSE00001075494	179970501	179970563
ENSE00001075498	179986695	179986805
ENSE00001075504	179965878	179965982
ENSE00001075505	179944876	179945715
ENSE00001075506	179954957	179955034
ENSE00001075507	179993315	179993454
ENSE00001075509	179959022	179959082
ENSE00001075511	179952471	179952598
ENSE00001075514	179950512	179950732
ENSE00001075517	179970941	179971076
ENSE00001075520	179950825	179950926
ENSE00001075522	179970650	179970856
ENSE00001075525	179981752	179981997
ENSE00001075529	179954205	179954357
ENSE00001075532	179988577	179988644
ENSE00001075534	179973193	179973246
ENSE00001558768	180006867	180007297
ENSE00001577932	179973634	179973802
ENSE00001578434	179978190	179978318

Expression profiles

Bgee: expression breadth ubiquitous, 251 present calls, max score 95.40.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.0498 / max 1277.4717, expressed in 1789 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
32708	19.7068	1780
32709	2.3430	1113

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
epithelial cell of pancreas	CL:0000083	95.40	gold quality
calcaneal tendon	UBERON:0003701	92.78	gold quality
tendon	UBERON:0000043	91.80	gold quality
layer of synovial tissue	UBERON:0007616	91.49	gold quality
tendon of biceps brachii	UBERON:0008188	89.87	gold quality
amniotic fluid	UBERON:0000173	88.28	gold quality
synovial joint	UBERON:0002217	88.17	gold quality
epithelium of nasopharynx	UBERON:0001951	87.99	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.96	gold quality
ventricular zone	UBERON:0003053	87.86	gold quality
superficial temporal artery	UBERON:0001614	87.79	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	87.19	gold quality
parietal pleura	UBERON:0002400	86.72	gold quality
oral cavity	UBERON:0000167	86.70	gold quality
smooth muscle tissue	UBERON:0001135	86.29	gold quality
endometrium	UBERON:0001295	86.21	gold quality
visceral pleura	UBERON:0002401	86.10	gold quality
biceps brachii	UBERON:0001507	86.02	gold quality
islet of Langerhans	UBERON:0000006	85.85	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.57	gold quality
leukocyte	CL:0000738	85.57	gold quality
monocyte	CL:0000576	85.55	gold quality
kidney epithelium	UBERON:0004819	85.55	silver quality
lymph node	UBERON:0000029	85.39	gold quality
gingival epithelium	UBERON:0001949	85.39	gold quality
seminal vesicle	UBERON:0000998	85.35	gold quality
upper arm skin	UBERON:0004263	85.24	silver quality
gingiva	UBERON:0001828	85.20	gold quality
popliteal artery	UBERON:0002250	85.16	gold quality
tibial artery	UBERON:0007610	85.15	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-MTAB-7303	no	68.52
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

48 targeting CWC22, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3163	100.00	77.23	8605
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-1250-3P	99.96	70.04	4038
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-381-3P	99.93	71.87	2854
HSA-MIR-300	99.92	71.76	2856
HSA-MIR-5195-3P	99.92	70.92	1877
HSA-MIR-145-5P	99.92	71.13	1836
HSA-MIR-1305	99.91	71.43	3443
HSA-MIR-3671	99.90	73.04	3897

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 99.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 6)

• CWC22 connects pre-mRNA splicing and exon junction complex assembly. (PMID:22959432)
• CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly (PMID:22961380)
• The essential splicing factor CWC22 has acquired functions in exon junction complex assembly and nonsense-mediated decay during evolution from single-celled to complex eukaryotes. (PMID:23236153)
• The binding mode of CWC22 to eIF4AIII reveals a facet of how MIF4G domains use their versatile structural frameworks to activate or inhibit DEAD-box proteins. (PMID:24218557)
• Structural and functional insights into CWC27/CWC22 heterodimer linking the exon junction complex to spliceosomes. (PMID:32329775)
• Gene expression network analysis of lymph node involvement in colon cancer identifies AHSA2, CDK10, and CWC22 as possible prognostic markers. (PMID:32345988)

Cross-species orthologs

15 orthologs

Organism	Symbol	Gene ID
danio_rerio	cwc22	ENSDARG00000014008
mus_musculus	Cwc22	ENSMUSG00000027014
mus_musculus	Cwc22rt6	ENSMUSG00000079247
mus_musculus	Cwc22rt1	ENSMUSG00000094125
mus_musculus	Cwc22rt2	ENSMUSG00000094336
mus_musculus	Cwc22rt7	ENSMUSG00000095824
mus_musculus	Cwc22rt5	ENSMUSG00000096337
mus_musculus	Cwc22rt4	ENSMUSG00000096484
mus_musculus	Cwc22rt3	ENSMUSG00000096729
rattus_norvegicus	LOC134479418	ENSRNOG00000012651
rattus_norvegicus		ENSRNOG00000071808
rattus_norvegicus		ENSRNOG00000082394
rattus_norvegicus		ENSRNOG00000085537
drosophila_melanogaster	ncm	FBGN0086707
caenorhabditis_elegans		WBGENE00002957

Paralogs (1): NOM1 (ENSG00000146909)

Protein

Protein identifiers

Pre-mRNA-splicing factor CWC22 homolog — Q9HCG8 (reviewed: Q9HCG8)

Alternative names: Nucampholin homolog, fSAPb

All UniProt accessions (2): B7WP74, Q9HCG8

UniProt curated annotations — full annotation on UniProt →

Function. Required for 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. Promotes exon-junction complex (EJC) assembly. Hinders EIF4A3 from non-specifically binding RNA and escorts it to the splicing machinery to promote EJC assembly on mature mRNAs. Through its role in EJC assembly, required for nonsense-mediated mRNA decay.

Subunit / interactions. Component of the pre-catalytic spliceosome B and the catalytic spliceosome C complexes. Component of the minor spliceosome, which splices U12-type introns. Interacts with EIF4A3 and PRPF19 in an RNA-independent manner. Direct interaction with EIF4A3 is mediated by the MIF4G domain. Full interaction with EIF4A3 occurs only when EIF4A3 is not part of the EJC and prevents EIF4A3 binding to RNA.

Subcellular location. Nucleus. Nucleus speckle.

Similarity. Belongs to the CWC22 family.

RefSeq proteins (5): NP_001362958, NP_001362959, NP_001362961, NP_001362962, NP_065994* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003890	MIF4G-like_typ-3	Domain
IPR003891	Initiation_fac_eIF4g_MI	Domain
IPR016024	ARM-type_fold	Homologous_superfamily
IPR050781	CWC22_splicing_factor	Family

Pfam: PF02847, PF02854

UniProt features (77 total): helix 31, compositionally biased region 11, sequence conflict 7, modified residue 5, mutagenesis site 5, turn 5, strand 4, sequence variant 3, region of interest 3, domain 2, chain 1

Structure

Experimental structures (PDB)

27 structures.

PDB	Method	Resolution (Å)
4C9B	X-RAY DIFFRACTION	2
8C6J	ELECTRON MICROSCOPY	2.8
7DVQ	ELECTRON MICROSCOPY	2.89
6ICZ	ELECTRON MICROSCOPY	3
8I0R	ELECTRON MICROSCOPY	3
8I0T	ELECTRON MICROSCOPY	3
8I0V	ELECTRON MICROSCOPY	3
7QTT	ELECTRON MICROSCOPY	3.1
6YVH	X-RAY DIFFRACTION	3.19
6QDV	ELECTRON MICROSCOPY	3.3
8I0U	ELECTRON MICROSCOPY	3.3
9FMD	ELECTRON MICROSCOPY	3.3
6ZYM	ELECTRON MICROSCOPY	3.4
8I0W	ELECTRON MICROSCOPY	3.4
5XJC	ELECTRON MICROSCOPY	3.6
7W59	ELECTRON MICROSCOPY	3.6
7W5A	ELECTRON MICROSCOPY	3.6
5YZG	ELECTRON MICROSCOPY	4.1
8I0S	ELECTRON MICROSCOPY	4.2
7W5B	ELECTRON MICROSCOPY	4.3
6FF7	ELECTRON MICROSCOPY	4.5
5Z58	ELECTRON MICROSCOPY	4.9
7A5P	ELECTRON MICROSCOPY	5
5Z56	ELECTRON MICROSCOPY	5.1
5MQF	ELECTRON MICROSCOPY	5.9
8CH6	ELECTRON MICROSCOPY	5.9
5Z57	ELECTRON MICROSCOPY	6.5

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9HCG8-F1	65.00	0.32

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): 39, 61, 107, 786, 829

Mutagenesis-validated functional residues (5):

Position	Phenotype
168	no effect on eif4a3 incorporation into ejcs.
171–174	loss of eif4a3-binding.
171–172	loss of eif4a3-binding.
331	decreased eif4a3-binding; when associated with a-334.
334	decreased eif4a3-binding; when associated with a-331.

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 127 (showing top): RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, REACTOME_PROCESSING_OF_CAPPED_INTRON_CONTAINING_PRE_MRNA, GOBP_RNA_SPLICING, REACTOME_MRNA_SPLICING, WANG_TARGETS_OF_MLL_CBP_FUSION_DN, GOBP_REGULATION_OF_MRNA_SPLICING_VIA_SPLICEOSOME, GOBP_REGULATION_OF_RNA_SPLICING, REACTOME_METABOLISM_OF_RNA, GOCC_U2_TYPE_SPLICEOSOMAL_COMPLEX, GOCC_NUCLEAR_SPECK, GOCC_PRECATALYTIC_SPLICEOSOME, GOCC_NUCLEAR_BODY, GOCC_RIBONUCLEOPROTEIN_GRANULE, GOCC_CATALYTIC_STEP_2_SPLICEOSOME, GOCC_SPLICEOSOMAL_COMPLEX

GO Biological Process (4): mRNA splicing, via spliceosome (GO:0000398), regulation of mRNA splicing, via spliceosome (GO:0048024), mRNA processing (GO:0006397), RNA splicing (GO:0008380)

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

GO Cellular Component (9): nucleus (GO:0005634), nucleoplasm (GO:0005654), spliceosomal complex (GO:0005681), cytosol (GO:0005829), nuclear speck (GO:0016607), U2-type precatalytic spliceosome (GO:0071005), U2-type catalytic step 1 spliceosome (GO:0071006), U2-type catalytic step 2 spliceosome (GO:0071007), catalytic step 2 spliceosome (GO:0071013)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
mRNA Splicing	1
Dengue Virus Infection	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
U2-type spliceosomal complex	3
U2 snRNP	3
RNA processing	2
cellular anatomical structure	2
U6 snRNP	2
RNA splicing, via transesterification reactions with bulged adenosine as nucleophile	1
mRNA processing	1
mRNA splicing, via spliceosome	1
regulation of RNA splicing	1
regulation of mRNA processing	1
mRNA metabolic process	1
nucleic acid binding	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
ribonucleoprotein complex	1
cytoplasm	1
nuclear ribonucleoprotein granule	1
U1 snRNP	1
U4/U6 x U5 tri-snRNP complex	1
precatalytic spliceosome	1
catalytic step 1 spliceosome	1
catalytic step 2 spliceosome	1
Prp19 complex	1
spliceosomal complex	1
U5 snRNP	1
catalytic complex	1

Protein interactions and networks

STRING

2101 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
CWC22	EIF4A3	P38919	974
CWC22	CDC5L	Q99459	849
CWC22	YJU2	Q9BW85	836
CWC22	RNF113A	O15541	825
CWC22	SRRM2	Q9UQ35	824
CWC22	CWC27	Q6UX04	818
CWC22	CWC25	Q9NXE8	770
CWC22	BUD31	P41223	743
CWC22	CWC15	Q9P013	727
CWC22	SLU7	O95391	717
CWC22	CRNKL1	Q9BZJ0	715
CWC22	SNW1	Q13573	714
CWC22	PRPF18	Q99633	712
CWC22	XAB2	Q9HCS7	709
CWC22	EFTUD2	Q15029	707

IntAct

147 interactions, top by confidence:

A	B	Type	Score
EIF4A3	CASC3	psi-mi:“MI:0914”(association)	0.980
EIF4A3	CWC22	psi-mi:“MI:0407”(direct interaction)	0.860
EIF4A3	CWC22	psi-mi:“MI:0915”(physical association)	0.860
EIF4A3	CWC22	psi-mi:“MI:2364”(proximity)	0.860
CWC22	EIF4A3	psi-mi:“MI:0915”(physical association)	0.860
PRPF19	AQR	psi-mi:“MI:0914”(association)	0.790
EXOC1	EXOC5	psi-mi:“MI:0914”(association)	0.730
CTBP2	ZNF217	psi-mi:“MI:0914”(association)	0.690
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
NUAK2	PPP1R12A	psi-mi:“MI:0914”(association)	0.640
YWHAH	PLEKHG3	psi-mi:“MI:0914”(association)	0.610
PTPN21	CWC22	psi-mi:“MI:0915”(physical association)	0.560
KLHL2	CWC22	psi-mi:“MI:0915”(physical association)	0.560
PTGER3	PIK3R2	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EPB41L2	AP3B1	psi-mi:“MI:0914”(association)	0.530
FAM9A	AP3B1	psi-mi:“MI:0914”(association)	0.530
ERMAP	AP3B1	psi-mi:“MI:0914”(association)	0.530
GPR183	NRP1	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
SYT1	PGK2	psi-mi:“MI:0914”(association)	0.530
DENND2D	HSPA8	psi-mi:“MI:0914”(association)	0.530
EPB41L1	AP3B1	psi-mi:“MI:0914”(association)	0.530
EDA	AP3B1	psi-mi:“MI:0914”(association)	0.530

BioGRID (169): CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-MS), CWC22 (Affinity Capture-Western), EIF4A3 (Affinity Capture-Western), PRPF19 (Affinity Capture-Western)

ESM2 similar proteins: A0A1I8M2I8, A8WT19, B3MJ69, B3N3F7, B4H732, B4II37, B4J497, B4KLY7, B4LIK8, B4MR46, B4NYV0, B4QCR6, O15042, O94880, P0CM96, P0CM97, P0DP78, P0DP79, P0DP80, P0DP81, Q08C72, Q08DZ2, Q13523, Q17336, Q20448, Q24168, Q28WQ8, Q4PCY0, Q4WKB9, Q52B63, Q52KN9, Q5R7X2, Q5R814, Q5RA93, Q5RKH1, Q5TUF1, Q5ZKA3, Q61136, Q6C8C5, Q6DE96

Diamond homologs: A0A1I8M2I8, A8WT19, P0CM96, P0CM97, P0DP78, P0DP79, P0DP80, P0DP81, P53333, Q08C72, Q17336, Q4PCY0, Q4WKB9, Q52B63, Q52KN9, Q59XY0, Q5BGP1, Q5RA93, Q5ZKA3, Q6BU84, Q6C8C5, Q7RX84, Q8C5N3, Q9HCG8, Q9P6R9, Q9VJ87, Q751P4

SIGNOR signaling

0 interactions.

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 143 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Transport of Mature Transcript to Cytoplasm	5	20.0×	2e-04
mRNA 3’-end processing	9	18.6×	1e-07
Neurexins and neuroligins	7	14.5×	3e-05
mRNA Splicing	12	13.9×	8e-09
RNA Polymerase II Transcription Termination	6	13.9×	2e-04
mRNA Splicing - Major Pathway	24	13.8×	2e-18
Transport of Mature mRNA derived from an Intron-Containing Transcript	8	12.8×	1e-05
Processing of Capped Intron-Containing Pre-mRNA	14	12.1×	2e-09

GO biological processes:

GO term	Partners	Fold	FDR
actomyosin structure organization	5	23.2×	5e-04
mRNA splicing, via spliceosome	22	16.6×	5e-18
RNA splicing	10	7.3×	4e-04
mRNA processing	11	7.2×	2e-04

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	122
Likely benign	8
Benign	4

Top pathogenic / likely-pathogenic (0)

SpliceAI

2756 predictions. Top by Δscore:

Variant	Effect	Δscore
2:179945722:G:C	acceptor_gain	1.0000
2:179945722:G:GC	acceptor_gain	1.0000
2:179950731:CC:C	acceptor_gain	1.0000
2:179950732:CC:C	acceptor_gain	1.0000
2:179950823:A:AC	donor_gain	1.0000
2:179950824:C:CC	donor_gain	1.0000
2:179950927:C:CA	acceptor_loss	1.0000
2:179950927:C:CC	acceptor_gain	1.0000
2:179950928:T:G	acceptor_loss	1.0000
2:179952465:ACTT:A	donor_loss	1.0000
2:179952467:TTAC:T	donor_loss	1.0000
2:179952468:TACTC:T	donor_loss	1.0000
2:179952469:A:AC	donor_gain	1.0000
2:179952469:ACT:A	donor_gain	1.0000
2:179952469:ACTCA:A	donor_loss	1.0000
2:179952470:C:CA	donor_gain	1.0000
2:179952470:C:G	donor_loss	1.0000
2:179952470:CT:C	donor_gain	1.0000
2:179952470:CTC:C	donor_gain	1.0000
2:179952470:CTCA:C	donor_gain	1.0000
2:179952470:CTCAT:C	donor_gain	1.0000
2:179952473:AT:A	donor_gain	1.0000
2:179952473:ATC:A	donor_gain	1.0000
2:179952474:T:C	donor_gain	1.0000
2:179952474:T:TA	donor_gain	1.0000
2:179954199:A:AC	donor_gain	1.0000
2:179954199:ACTT:A	donor_loss	1.0000
2:179954200:C:CC	donor_gain	1.0000
2:179954203:A:AC	donor_gain	1.0000
2:179954203:A:AG	donor_loss	1.0000

AlphaMissense

6045 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:179950712:A:G	L647P	1.000
2:179950721:C:G	R644P	1.000
2:179950724:A:G	L643P	1.000
2:179950834:C:T	G637E	1.000
2:179950835:C:G	G637R	1.000
2:179950835:C:T	G637R	1.000
2:179950837:A:G	L636P	1.000
2:179950854:G:C	F630L	1.000
2:179950854:G:T	F630L	1.000
2:179950856:A:G	F630L	1.000
2:179950857:G:C	N629K	1.000
2:179950857:G:T	N629K	1.000
2:179950859:T:C	N629D	1.000
2:179950861:A:T	I628N	1.000
2:179950862:T:A	I628F	1.000
2:179950864:G:T	A627D	1.000
2:179950866:A:C	F626L	1.000
2:179950866:A:T	F626L	1.000
2:179950867:A:C	F626C	1.000
2:179950867:A:G	F626S	1.000
2:179950868:A:G	F626L	1.000
2:179950868:A:T	F626I	1.000
2:179950870:C:G	R625P	1.000
2:179952492:A:G	L599P	1.000
2:179952519:A:G	L590P	1.000
2:179952536:T:A	K584N	1.000
2:179952536:T:G	K584N	1.000
2:179952537:T:A	K584I	1.000
2:179952538:T:C	K584E	1.000
2:179952546:A:C	I581S	1.000

dbSNP variants (sampled 300 via entrez): RS1000009078 (2:179995176 C>A), RS1000061373 (2:179994991 G>A), RS1000090089 (2:179960808 T>C), RS1000094095 (2:180004059 A>C), RS1000127240 (2:179975115 A>G), RS1000159399 (2:179970285 G>A), RS1000209485 (2:179970659 C>A,T), RS1000229685 (2:180007517 T>C,G), RS1000266015 (2:179966982 C>T), RS1000282071 (2:180007331 G>A), RS1000324990 (2:179963488 G>A,T), RS1000353275 (2:179954697 C>T), RS1000381460 (2:179956977 A>G), RS1000385267 (2:179980422 T>A), RS1000429995 (2:180003834 C>T)

Disease associations

OMIM: gene MIM:615186 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

6 associations (top):

Study	Trait	p-value
GCST004904_150	Body mass index	2.000000e-13
GCST004904_18	Body mass index	5.000000e-08
GCST007201_30	Schizophrenia	1.000000e-06
GCST009391_844	Metabolite levels	5.000000e-06
GCST010396_100	Gut microbiota (bacterial taxa, hurdle binary method)	1.000000e-06
GCST010988_195	Adult body size	3.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0010400	triacylglycerol 46:0 measurement
EFO:0007874	gut microbiome measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL5724778 (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

2 potent at pChembl≥5 of 2 total, top 2 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
7.82	Kd	15	nM	MOLIBRESIB
7.70	IC50	20	nM	MOLIBRESIB

PubChem BioAssay actives

2 with measured affinity, of 7 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	2179153: Binding affinity against CWC22 (unknown origin) assessed as apparent dissociation constant incubated for 1 hr by colloidal coomassie staining based LC-MS/MS analysis	kd	0.0150	uM

CTD chemical–gene interactions

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, decreases methylation	7
sodium arsenite	increases expression, affects methylation, decreases expression, increases abundance	4
trichostatin A	affects cotreatment, decreases expression	3
perfluorooctane sulfonic acid	decreases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
aristolochic acid I	decreases expression	1
FR900359	affects phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	decreases expression	1
arsenite	decreases reaction, affects binding	1
zinc chromate	increases abundance, increases expression	1
coumarin	affects phosphorylation	1
chromium hexavalent ion	increases abundance, increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
ICG 001	decreases expression	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
Arsenic	increases abundance, increases expression	1
Benzo(a)pyrene	decreases methylation	1
Cisplatin	affects cotreatment, decreases expression	1
Copper	increases expression	1
Formaldehyde	decreases expression	1
Ribonucleotides	affects binding	1
Thiram	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Cyclosporine	increases expression	1
Asbestos, Crocidolite	increases expression	1

ChEMBL screening assays

7 unique, capped per target: 7 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5697219	Binding	Inhibition of CWC22 (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.