WWOX

Summary

WWOX (WW domain containing oxidoreductase, HGNC:12799) is a protein-coding gene on chromosome 16q23.1-q23.2, encoding WW domain-containing oxidoreductase (Q9NZC7). Putative oxidoreductase.

This gene encodes a member of the short-chain dehydrogenases/reductases (SDR) protein family. This gene spans the FRA16D common chromosomal fragile site and appears to function as a tumor suppressor gene. Expression of the encoded protein is able to induce apoptosis, while defects in this gene are associated with multiple types of cancer. Disruption of this gene is also associated with autosomal recessive spinocerebellar ataxia 12. Disruption of a similar gene in mouse results in impaired steroidogenesis, additionally suggesting a metabolic function for the protein. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 51741 — RefSeq curated summary.

At a glance

• Gene–disease (curated): genetic developmental and epileptic encephalopathy (Definitive, ClinGen) — +4 more curated relationships
• GWAS associations: 72
• Clinical variants (ClinVar): 998 total — 94 pathogenic, 33 likely-pathogenic
• Phenotypes (HPO): 118
• Dosage sensitivity (ClinGen): haploinsufficiency autosomal recessive, triplosensitivity no evidence
• MANE Select transcript: NM_016373

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12799
Approved symbol	WWOX
Name	WW domain containing oxidoreductase
Location	16q23.1-q23.2
Locus type	gene with protein product
Status	Approved
Aliases	FOR, WOX1, SDR41C1
Ensembl gene	ENSG00000186153
Ensembl biotype	protein_coding
OMIM	605131
Entrez	51741

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 11 protein_coding_CDS_not_defined, 8 protein_coding, 3 nonsense_mediated_decay, 2 retained_intron

ENST00000355860, ENST00000402655, ENST00000406884, ENST00000408984, ENST00000539474, ENST00000561846, ENST00000562214, ENST00000562639, ENST00000563358, ENST00000565562, ENST00000565791, ENST00000566103, ENST00000566662, ENST00000566780, ENST00000569332, ENST00000569818, ENST00000627394, ENST00000682609, ENST00000683286, ENST00000683929, ENST00000684070, ENST00000684381, ENST00000684452, ENST00000684632

RefSeq mRNA: 3 — MANE Select: NM_016373 NM_001291997, NM_016373, NM_130791

CCDS: CCDS42196, CCDS42197

Canonical transcript exons

ENST00000566780 — 9 exons

Exon	Start	End
ENSE00001531617	78099654	78099885
ENSE00003494890	78424870	78425055
ENSE00003497093	78386860	78386948
ENSE00003581910	78164183	78164289
ENSE00003603275	78114976	78115154
ENSE00003630116	79211608	79212667
ENSE00003647388	78109778	78109835
ENSE00003679971	78432488	78432752
ENSE00003680693	78108423	78108487

Expression profiles

Bgee: expression breadth ubiquitous, 286 present calls, max score 96.44.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.0221 / max 357.2825, expressed in 1778 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
155081	15.1560	1771
155080	0.8661	452

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
parotid gland	UBERON:0001831	96.44	gold quality
cervix squamous epithelium	UBERON:0006922	95.21	gold quality
cranial nerve II	UBERON:0000941	94.99	gold quality
renal glomerulus	UBERON:0000074	94.29	gold quality
sural nerve	UBERON:0015488	94.20	gold quality
metanephric glomerulus	UBERON:0004736	94.07	gold quality
choroid plexus epithelium	UBERON:0003911	93.76	gold quality
substantia nigra pars reticulata	UBERON:0001966	93.65	gold quality
endothelial cell	CL:0000115	93.09	gold quality
nephron tubule	UBERON:0001231	92.72	gold quality
substantia nigra pars compacta	UBERON:0001965	92.71	gold quality
tongue squamous epithelium	UBERON:0006919	92.36	gold quality
lateral nuclear group of thalamus	UBERON:0002736	92.30	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	91.95	gold quality
lateral globus pallidus	UBERON:0002476	91.80	gold quality
inferior olivary complex	UBERON:0002127	91.75	gold quality
ventral tegmental area	UBERON:0002691	91.37	gold quality
pons	UBERON:0000988	91.22	gold quality
kidney epithelium	UBERON:0004819	91.21	gold quality
subthalamic nucleus	UBERON:0001906	91.14	gold quality
amniotic fluid	UBERON:0000173	91.07	gold quality
medulla oblongata	UBERON:0001896	90.89	gold quality
endometrium epithelium	UBERON:0004811	90.55	gold quality
renal medulla	UBERON:0000362	90.26	gold quality
gingival epithelium	UBERON:0001949	90.17	gold quality
dorsal plus ventral thalamus	UBERON:0001897	90.15	gold quality
superior vestibular nucleus	UBERON:0007227	90.00	gold quality
hair follicle	UBERON:0002073	89.69	gold quality
corpus callosum	UBERON:0002336	89.33	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	89.26	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	25.18
E-HCAD-25	yes	19.94
E-CURD-119	yes	18.20
E-ANND-3	yes	6.44

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): COQ7, E2F1, F2RL1, NFKB, TFAP2C

miRNA regulators (miRDB)

47 targeting WWOX, 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-4455	100.00	65.48	1587
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-9983-3P	99.94	71.48	3631
HSA-MIR-129-5P	99.88	70.26	3273
HSA-MIR-6875-3P	99.82	70.26	2983
HSA-MIR-498-5P	99.76	69.64	1807
HSA-MIR-3680-3P	99.75	72.51	3095
HSA-MIR-132-3P	99.73	70.56	1424
HSA-MIR-212-3P	99.73	70.65	1424
HSA-MIR-4677-5P	99.70	70.09	1940
HSA-MIR-545-5P	99.66	70.18	2308
HSA-MIR-1249-5P	99.61	66.55	2049
HSA-MIR-6797-5P	99.61	66.55	2084
HSA-MIR-516A-3P	99.46	67.96	1378
HSA-MIR-516B-3P	99.46	67.96	1378
HSA-MIR-7162-5P	99.46	68.08	1368
HSA-MIR-520F-5P	99.34	70.40	1632
HSA-MIR-2116-5P	99.32	69.34	1273
HSA-MIR-4505	99.27	67.81	2678
HSA-MIR-223-5P	99.24	68.82	1206
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-3675-3P	99.09	67.70	968
HSA-MIR-4744	99.01	69.91	1581
HSA-MIR-3619-5P	99.00	68.87	2308
HSA-MIR-153-3P	98.96	72.51	1644
HSA-MIR-4477A	98.83	69.75	2952
HSA-MIR-6794-3P	98.76	66.99	894
HSA-MIR-214-3P	98.71	68.12	2128
HSA-MIR-761	98.71	68.07	2051
HSA-MIR-2115-5P	98.66	68.07	1191

Functional genomics

ClinGen dosage: haploinsufficiency 30 (autosomal recessive), triplosensitivity 0 (no evidence). ClinGen Gene Dosage Map

Literature-anchored findings (GeneRIF, showing 40)

• WWOX, the FRA16D gene, behaves as a suppressor of tumor growth. (PMID:11719429)
• Alteration and inactivation of the WWOX gene may play a role in esophageal squamous cell carcinogenesis. (PMID:11956080)
• phosphorylation of JNK1 and WOX1 is necessary for their physical interaction and functional antagonism (PMID:12514174)
• Identification of WWOX as the target of FRA16D and ectopic WWOX expression inhibits tumor growth. (PMID:14526170)
• A model is supported in which FRA16D common fragile sites are sequences that may initiate replication in early-mid S phase but are slow to complete replication, and the chromosomal breaks and gaps observed in metaphase cells result from unreplicated DNA. (PMID:14603443)
• Expression and distribution of WOX1 in developing and adult murine nervous system. Potential role of WOX1 in the neuronal differentiation. (PMID:15026124)
• The data suggest that E2F-1 overexpression plays a role in suppression of tumor, at least in part trough transcriptional regulation of FHIT and relevant activation of WWOX. (PMID:15044096)
• These studies demonstrate that WWOX contains a Group I WW domain that binds known cellular proteins containing the specific ligand PPXY. (PMID:15064722)
• Wwox expression triggers redistribution of nuclear p73 to the cytoplasm and, hence, suppresses its transcriptional activity. (PMID:15070730)
• the WWOX gene may play an important role in pancreatic tumor development (PMID:15073125)
• Wwox has an important and complex association with steroid hormone expression and breast carcinogenesis (PMID:15073846)
• WW domain-containing oxidoreductase downregulation induces Tau phosphorylation in vitro (PMID:15126504)
• Results indicate that alterations of the WWOX gene may be involved quite frequently in gastric tumorigenesis and could be used in future studies to develop diagnostic and targeted therapy of stomach cancer. (PMID:15131042)
• WWOX gene is frequently altered in hepatocelluarl carcinoma; this gene may be implicated in hepatocarcinogenesis (PMID:15266310)
• Wwox expression triggers redistribution of nuclear AP-2gamma to the cytoplasm, hence suppressing its transactivating function (PMID:15548692)
• sex steroid hormone-induced activation of WOX1 and WOX2 is independent of estrogen receptor and androgen receptor (PMID:15580310)
• WWOX hypermethylation analys9s could enrich a panel of DNA methylation markers in breast, lung and bladder cancer. (PMID:15674328)
• UV-induced alterations of the FHIT and WWOX fragile site gene expression are involved at least partially in the checkpoint function of DNA damage (PMID:15798093)
• WWOX protein expression is highly variable among ovarian carcinoma histotypes and may have a role in disease progression (PMID:15982416)
• Reduced Wwox expression in invasive ductal carcinoma in-situ (DCIS) breast cancer was associated, which may contribute to the high-grade DCIS-invasive tumor pathway. (PMID:15998374)
• WWOX antagonizes the function of YAP by competing for interaction with ErbB-4 and other targets and thus affect its transcriptional activity. (PMID:16061658)
• WOX1 (also named WWOX) is essential for UVB-induced apoptosis and likely to be involved in the terminal differentiation of normal keratinocytes. (PMID:16115915)
• WWOX gene is frequently altered in oral squamous cell carcinomas and may contribute to the carcinogenesis processes in oral cancer (PMID:16152610)
• WOX1 plays a critical role in conferring cellular sensitivity to apoptotic stress and Tyr33 phosphorylation in WOX1 is essential for binding and stabilizing Ser46-phosphorylated p53 (PMID:16219768)
• Activated tyrosine kinase Ack1 promotes prostate tumorigenesis by tyrosine phosphorylation of tumor suppressor Wwox at Tyr-287. It leads to polyubiquitination and degradation. (PMID:16288044)
• WWOX may be involved in steroid (estrogens) metabolism and signaling pathways. WWOX can be considered as a new target for gene therapy development due to the association of high WWOX expression with improved disease free survival. (PMID:16360296)
• PKA-mediated phosphorylation of ezrin is essential and sufficient for the apical localization of WWOX protein as disruption of ezrin-WWOX interaction eliminated the apical localization of WWOX (PMID:16438931)
• WWOX overexpression in prostate cancer cells suppressed colony growth and induced apoptosis. Data are consistent with a role for WWOX as a prostate cancer tumor suppressor. (PMID:16818616)
• comprehensive analysis of WWOX protein expression in normal tissues was performed by means of immunohistochemistry (PMID:16941225)
• This gene encodes a protein that contains two WW domains responsible of protein-protein interactions and a short-chain dehydrogenase (SDR) domain likely involved in sex steroid metabolism (PMID:17163164)
• Novel functional cross-talk between c-Jun transcription factor and WWOX tumor suppressor protein (PMID:17178850)
• overexpression of exogenous Wwox inhibits breast cancer cell growth in vitro and in vivo (PMID:17200365)
• loss of WWOX expression plays different roles in tumorigenesis of distinct histotypes and subtypes of NSCLC and is related to high aggressiveness (G3; high proliferating activity) of tumors (PMID:17289881)
• Gene mapping and expression analysis of 16q loss of heterozygosity identifies WWOX and CYLD as being important in determining clinical outcome in multiple myeloma. (PMID:17609426)
• Wwox reduces ErbB2 protein expression in vitro and expression of Wwox protein inversely correlates with expression of ErbB2 protein in prostate cancer tissues. (PMID:17704139)
• Expression of Wwox is associated with ErbB4 expression and that their coexpression has prognostic significance in breast cancer. (PMID:17909041)
• Wwox and Ap2gamma emerge are tumor biomarkers that may be superior to PR and Her2 in predicting tamoxifen response (PMID:17947476)
• WWOX underexpression is an important step that might increase the vulnerability to the carcinogenesis process in papillary thyroid carcinomas. (PMID:18047428)
• results show that the WWOX gene alteration is an early genetic alteration and may contribute to oral carcinogenesis. (PMID:18061530)
• homozygous deletions can be markers of complex rearrangements that have targets outside the homozygous deletion itself and that the target of deletions in the FRA16D region is indeed WWOX, the common outcome being the removal of particular WWOX exons (PMID:18273838)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	wwox	ENSDARG00000007614
mus_musculus	Wwox	ENSMUSG00000004637
rattus_norvegicus	AABR07043897.1	ENSRNOG00000012030
drosophila_melanogaster	Wwox	FBGN0031972

Paralogs (25): HSD17B6 (ENSG00000025423), RDH11 (ENSG00000072042), HSD17B10 (ENSG00000072506), DHRS9 (ENSG00000073737), HSD17B2 (ENSG00000086696), HSD17B14 (ENSG00000087076), DHRS12 (ENSG00000102796), HSDL1 (ENSG00000103160), HSD17B1 (ENSG00000108786), RDH10 (ENSG00000121039), HSD17B3 (ENSG00000130948), HSD17B7 (ENSG00000132196), HSD17B4 (ENSG00000133835), RDH5 (ENSG00000135437), RDH16 (ENSG00000139547), RDH12 (ENSG00000139988), HSD17B12 (ENSG00000149084), BDH1 (ENSG00000161267), DHRS3 (ENSG00000162496), SDR9C7 (ENSG00000170426), HSD17B13 (ENSG00000170509), SDR16C5 (ENSG00000170786), HSD11B2 (ENSG00000176387), HSD17B11 (ENSG00000198189), HSD17B8 (ENSG00000204228)

Protein

Protein identifiers

WW domain-containing oxidoreductase — Q9NZC7 (reviewed: Q9NZC7)

Alternative names: Fragile site FRA16D oxidoreductase, Short chain dehydrogenase/reductase family 41C member 1

All UniProt accessions (6): A0A0D9SER1, A0A411HBC7, A0A804HJX9, Q9NZC7, F5H3R5, H3BMD1

UniProt curated annotations — full annotation on UniProt →

Function. Putative oxidoreductase. Acts as a tumor suppressor and plays a role in apoptosis. Required for normal bone development. May function synergistically with p53/TP53 to control genotoxic stress-induced cell death. Plays a role in TGFB1 signaling and TGFB1-mediated cell death. May also play a role in tumor necrosis factor (TNF)-mediated cell death. Inhibits Wnt signaling, probably by sequestering DVL2 in the cytoplasm.

Subunit / interactions. Interacts with TP53, p73/TP73 and MAPK8. Interacts with MAPT/TAU, RUNX2 and HYAL2. Forms a ternary complex with TP53 and MDM2. Interacts with ERBB4, LITAF and WBP1. Interacts with DVL1, DVL2 and DVL3. May interact with FAM189B and SCOTIN. Interacts with TNK2. Interacts with TMEM207. Interacts (via WW domain) with VOPP1.

Subcellular location. Cytoplasm. Nucleus. Mitochondrion. Golgi apparatus. Lysosome.

Tissue specificity. Widely expressed. Strongly expressed in testis, prostate, and ovary. Overexpressed in cancer cell lines. Isoform 5 and isoform 6 may only be expressed in tumor cell lines.

Post-translational modifications. Phosphorylated upon genotoxic stress. Phosphorylation of Tyr-33 regulates interaction with TP53, TP73 and MAPK8. May also regulate proapoptotic activity. Phosphorylation by TNK2 is associated with polyubiquitination and degradation. Ubiquitinated when phosphorylated by TNK2, leading to its degradation.

Disease relevance. Defects in WWOX may be involved in several cancer types. The gene spans the second most common chromosomal fragile site (FRA16D) which is frequently altered in cancers. Alteration of the expression and expression of some isoforms is associated with cancers. However, it is still unclear if alteration of WWOX is directly implicated in cancerogenesis or if it corresponds to a secondary effect. Esophageal cancer (ESCR) [MIM:133239] A malignancy of the esophagus. The most common types are esophageal squamous cell carcinoma and adenocarcinoma. Cancer of the esophagus remains a devastating disease because it is usually not detected until it has progressed to an advanced incurable stage. The disease may be caused by variants affecting the gene represented in this entry. Spinocerebellar ataxia, autosomal recessive, 12 (SCAR12) [MIM:614322] A form of spinocerebellar ataxia, a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to degeneration of the cerebellum with variable involvement of the brainstem and spinal cord. SCAR12 is additionally characterized by onset of generalized seizures in infancy, and delayed psychomotor development with intellectual disability. Some patients may also show spasticity. The disease is caused by variants affecting the gene represented in this entry. Developmental and epileptic encephalopathy 28 (DEE28) [MIM:616211] A form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WW 1 domain mediates interaction with TP53, and probably TP73, TFAP2C, LITAF and WBP1.

Similarity. Belongs to the short-chain dehydrogenases/reductases (SDR) family.

Isoforms (7)

UniProt ID	Names	Canonical?
Q9NZC7-1	1, FOR II, FOR2, WWOXv1, WWOX v8	yes
Q9NZC7-2	2, FOR I, FOR1, WOX2, WWOXv2
Q9NZC7-3	3, FOR III, FOR3, WOX3
Q9NZC7-4	4, FOR IV
Q9NZC7-5	5, WWOXdelta6-8, WWOXv4
Q9NZC7-6	6, WWOXdelta5-8, WWOXv3
Q9NZC7-7	7

RefSeq proteins (3): NP_001278926, NP_057457, NP_570607 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001202	WW_dom	Domain
IPR002347	SDR_fam	Family
IPR036020	WW_dom_sf	Homologous_superfamily
IPR036291	NAD(P)-bd_dom_sf	Homologous_superfamily
IPR042732	WWOX_SDR_c-like	Domain

Pfam: PF00106, PF00397

UniProt features (48 total): sequence variant 13, splice variant 10, mutagenesis site 8, modified residue 4, region of interest 3, strand 3, domain 2, binding site 2, chain 1, short sequence motif 1, active site 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
1WMV	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9NZC7-F1	85.43	0.56

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Catalytic / active sites (1): 293 (proton acceptor)

Ligand- & substrate-binding residues (2): 131–137; 260

Post-translational modifications (4): 12, 14, 33, 287

Mutagenesis-validated functional residues (8):

Position	Phenotype
28	no effect on interaction with tp53. abolishes interaction with mapk8; when associated with v-29.
29	no effect on interaction with tp53. abolishes interaction with mapk8; when associated with t-28.
33	loss of phosphorylation.
33	abolishes interaction with tp53, tp73, mapk8 and erbb4. partial loss of interaction with tfap2c. loss of phosphorylation
44–47	abolishes interaction with litaf.
61	no effect on interaction with tp73.
85–88	no effect on interaction with litaf.
287	loss of phosphorylation by tnk2.

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-1251985	Nuclear signaling by ERBB4
R-HSA-8866904	Negative regulation of activity of TFAP2 (AP-2) family transcription factors
R-HSA-8866907	Activation of the TFAP2 (AP-2) family of transcription factors

MSigDB gene sets: 455 (showing top): MORF_RAGE, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, GOBP_OSTEOBLAST_DIFFERENTIATION, GOBP_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY, TAKADA_GASTRIC_CANCER_COPY_NUMBER_DN, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, GOBP_ANIMAL_ORGAN_MORPHOGENESIS, GOBP_APOPTOTIC_SIGNALING_PATHWAY, GOBP_RESPONSE_TO_TRANSFORMING_GROWTH_FACTOR_BETA, BLALOCK_ALZHEIMERS_DISEASE_UP, MORF_FANCG, PID_ERBB4_PATHWAY, GOBP_POSITIVE_REGULATION_OF_EXTRINSIC_APOPTOTIC_SIGNALING_PATHWAY_IN_ABSENCE_OF_LIGAND

GO Biological Process (12): osteoblast differentiation (GO:0001649), Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), positive regulation of transcription by RNA polymerase II (GO:0045944), skeletal system morphogenesis (GO:0048705), cellular response to transforming growth factor beta stimulus (GO:0071560), intrinsic apoptotic signaling pathway by p53 class mediator (GO:0072332), extrinsic apoptotic signaling pathway (GO:0097191), positive regulation of extrinsic apoptotic signaling pathway (GO:2001238), positive regulation of extrinsic apoptotic signaling pathway in absence of ligand (GO:2001241), apoptotic process (GO:0006915), regulation of signal transduction (GO:0009966)

GO Molecular Function (5): transcription coactivator activity (GO:0003713), oxidoreductase activity (GO:0016491), enzyme binding (GO:0019899), identical protein binding (GO:0042802), protein binding (GO:0005515)

GO Cellular Component (10): nucleus (GO:0005634), cytoplasm (GO:0005737), mitochondrion (GO:0005739), lysosome (GO:0005764), Golgi apparatus (GO:0005794), cytosol (GO:0005829), RNA polymerase II transcription regulator complex (GO:0090575), plasma membrane (GO:0005886), microvillus (GO:0005902), bicellular tight junction (GO:0005923)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Transcriptional regulation by the AP-2 (TFAP2) family of transcription factors	2
Signaling by ERBB4	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
intracellular membrane-bounded organelle	3
cytoplasm	3
cell surface receptor signaling pathway	2
positive regulation of DNA-templated transcription	2
apoptotic signaling pathway	2
protein binding	2
cellular anatomical structure	2
ossification	1
cell differentiation	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
skeletal system development	1
animal organ morphogenesis	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
signal transduction by p53 class mediator	1
intrinsic apoptotic signaling pathway	1
extrinsic apoptotic signaling pathway	1
positive regulation of apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway	1
extrinsic apoptotic signaling pathway in absence of ligand	1
positive regulation of extrinsic apoptotic signaling pathway	1
regulation of extrinsic apoptotic signaling pathway in absence of ligand	1
programmed cell death	1
execution phase of apoptosis	1
signal transduction	1
regulation of cell communication	1
regulation of signaling	1
regulation of response to stimulus	1
transcription coregulator activity	1
catalytic activity	1
binding	1
intracellular anatomical structure	1
lytic vacuole	1
endomembrane system	1
transcription regulator complex	1
nuclear protein-containing complex	1

Protein interactions and networks

STRING

4993 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WWOX	FHIT	P49789	937
WWOX	ERBB4	Q15303	913
WWOX	JUN	P05412	877
WWOX	TFAP2C	Q92754	869
WWOX	TMEM207	Q6UWW9	759
WWOX	EZR	P15311	750
WWOX	TFAP2A	P05549	744
WWOX	RUNX2	Q13950	709
WWOX	WBP2	Q969T9	696
WWOX	TNK2	Q07912	688
WWOX	MAPK8	P45983	680
WWOX	TP53	P04637	676
WWOX	DVL2	O14641	667
WWOX	HYAL2	Q12891	658
WWOX	ATM	Q13315	622

IntAct

133 interactions, top by confidence:

A	B	Type	Score
ENTREP1	WWP2	psi-mi:“MI:0914”(association)	0.850
ARRDC3	WWP2	psi-mi:“MI:0914”(association)	0.770
WWOX	ENTREP3	psi-mi:“MI:0914”(association)	0.720
ENTREP3	WWOX	psi-mi:“MI:0915”(physical association)	0.720
WWOX	ENTREP3	psi-mi:“MI:0915”(physical association)	0.720
CFTR	ESYT2	psi-mi:“MI:2364”(proximity)	0.710
WWOX	VOPP1	psi-mi:“MI:0915”(physical association)	0.690
WWOX	VOPP1	psi-mi:“MI:0403”(colocalization)	0.690
WWOX	WBP1	psi-mi:“MI:0915”(physical association)	0.690
WBP1	WWOX	psi-mi:“MI:0915”(physical association)	0.690
WWOX	TP73	psi-mi:“MI:0914”(association)	0.640
WWOX	TP73	psi-mi:“MI:0915”(physical association)	0.640
TP73	WWOX	psi-mi:“MI:0915”(physical association)	0.640
RAB9A	CHM	psi-mi:“MI:2364”(proximity)	0.610
WWOX	LITAF	psi-mi:“MI:0915”(physical association)	0.610
LITAF	WWOX	psi-mi:“MI:0915”(physical association)	0.610
LITAF	WWOX	psi-mi:“MI:0403”(colocalization)	0.610
WWOX	TP73	psi-mi:“MI:0915”(physical association)	0.610
TP73	WWOX	psi-mi:“MI:0915”(physical association)	0.610

BioGRID (766): WWOX (Affinity Capture-MS), ATM (Affinity Capture-Western), TRIM28 (Affinity Capture-Western), ITCH (Affinity Capture-Western), WWOX (Affinity Capture-Western), WWOX (Affinity Capture-Western), WWOX (Protein-peptide), WWOX (Affinity Capture-MS), WWOX (Affinity Capture-MS), WWOX (Affinity Capture-MS), WWOX (Affinity Capture-MS), WWOX (Affinity Capture-MS), WWOX (Affinity Capture-MS), WWOX (Two-hybrid), WWOX (Proximity Label-MS)

ESM2 similar proteins: A0A078IS66, A0A078ISJ6, A0A0B6VQ48, A0A1V0QS34, A0A2H3CZZ2, A0AAW1NHX6, A2RVM0, A4UHT7, A5PJJ7, B2X050, B8A5W4, G9N4A9, O17795, O74959, P16232, P40579, P40580, P59837, P70385, Q05A13, Q071N0, Q08651, Q17703, Q17704, Q4JK73, Q5F389, Q5NVG2, Q5R9W5, Q5ZJG8, Q6AYS8, Q6P3L6, Q6QA32, Q6RVV4, Q7SHI2, Q7TQA3, Q7Z5P4, Q8BYK4, Q8CEE7, Q8N3Y7, Q8NBN7

Diamond homologs: A0A017SEY2, A0A023I4F1, A0A078IS66, A0A078ISJ6, A0A0U1LQE2, A0A0U5CNP2, A0A1B7YCL6, A0A1V0QS34, A0A1V6PAN1, A0A223HDI5, A0A2H3CNT9, A0A2H3D905, A0A443HJZ3, A0A482ND39, A0A823A767, A0PJE2, A2RVM0, A6QP05, B2X050, B6H062, B8A5W4, C8VI80, D7UTD0, G1XTZ5, I1RL15, O32291, O74959, P0DXW2, P16152, P19871, P21218, P35320, P40747, P47727, P50163, P51657, P59837, Q01289, Q03326, Q08651

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
SRC	up-regulates	WWOX	phosphorylation
F2RL1	“up-regulates quantity by expression”	WWOX	“transcriptional regulation”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 115 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
Processing of Intronless Pre-mRNAs	9	68.5×	6e-13
RNA Polymerase II Transcription Termination	9	26.4×	7e-09
mRNA 3’-end processing	9	23.6×	1e-08
Transport of Mature mRNA Derived from an Intronless Transcript	6	21.8×	2e-05
mRNA Polyadenylation	16	18.7×	8e-14
Dengue Virus-Host Interactions	15	9.1×	8e-09
Processing of Capped Intron-Containing Pre-mRNA	8	8.8×	2e-04

GO biological processes:

GO term	Partners	Fold	FDR
mRNA 3’-end processing	6	35.9×	1e-05
protein tetramerization	5	33.2×	1e-04
mRNA processing	9	7.5×	5e-04
transcription by RNA polymerase II	8	6.0×	7e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	94
Likely pathogenic	33
Uncertain significance	380
Likely benign	342
Benign	72

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
100649	NM_016373.4(WWOX):c.139C>A (p.Pro47Thr)	Pathogenic
1013119	GRCh37/hg19 16q23.1(chr16:78420757-78466649)x1	Pathogenic
1068501	NM_016373.4(WWOX):c.127C>T (p.Gln43Ter)	Pathogenic
1072064	NM_016373.4(WWOX):c.321C>G (p.Tyr107Ter)	Pathogenic
1076468	NC_000016.9:g.(?78133671)(78149061_?)del	Pathogenic
1076469	NC_000016.9:g.(?78420747)(78458962_?)del	Pathogenic
1076470	NC_000016.9:g.(?78420747)(78466659_?)del	Pathogenic
120325	NM_016373.4(WWOX):c.160C>T (p.Arg54Ter)	Pathogenic
1338793	NM_016373.4:c.(516+1_517-1)_(605+1_606-1)del	Pathogenic
1339501	NM_016373.4(WWOX):c.409+1G>T	Pathogenic
1452002	NM_016373.4(WWOX):c.333del (p.Thr112fs)	Pathogenic
1456547	NC_000016.9:g.(?78142310)(78142394_?)del	Pathogenic
1459088	NM_016373.4(WWOX):c.517-1G>T	Pathogenic
1676782	NM_016373.4(WWOX):c.172+1G>C	Pathogenic
1686306	NM_016373.4(WWOX):c.1056G>C (p.Met352Ile)	Pathogenic
1712484	NC_000016.9:g.78179358_78219143delins[78185355_78199419inv]	Pathogenic
180247	NM_016373.4(WWOX):c.517-44258_606-268del	Pathogenic
180249	NM_016373.4(WWOX):c.1005G>A (p.Trp335Ter)	Pathogenic
180250	NM_016373.4(WWOX):c.46_49del (p.Asp16fs)	Pathogenic
180251	NM_016373.4(WWOX):c.140C>G (p.Pro47Arg)	Pathogenic
1810421	NM_016373.4:c.517-11252_606-17640del	Pathogenic
183303	NM_016373.4(WWOX):c.606-1G>A	Pathogenic
1898392	NM_016373.4(WWOX):c.2T>C (p.Met1Thr)	Pathogenic
1938931	NM_016373.4(WWOX):c.108_112dup (p.Thr38fs)	Pathogenic
1979930	NM_016373.4(WWOX):c.1A>C (p.Met1Leu)	Pathogenic
2025591	NM_016373.4(WWOX):c.1035del (p.Arg346fs)	Pathogenic
2099038	NM_016373.4(WWOX):c.552dup (p.Ala185fs)	Pathogenic
2114515	NM_016373.4(WWOX):c.173-1G>C	Pathogenic
2137848	NM_016373.4(WWOX):c.173-1G>T	Pathogenic
241104	NM_016373.4(WWOX):c.779C>G (p.Ser260Ter)	Pathogenic

SpliceAI

5526 predictions. Top by Δscore:

Variant	Effect	Δscore
16:78099997:A:T	donor_gain	1.0000
16:78108421:A:AG	acceptor_gain	1.0000
16:78108422:G:GA	acceptor_gain	1.0000
16:78108485:G:GT	donor_gain	1.0000
16:78109831:GTTGA:G	donor_gain	1.0000
16:78109832:T:G	donor_gain	1.0000
16:78109832:TTGA:T	donor_gain	1.0000
16:78109833:TGA:T	donor_gain	1.0000
16:78109834:GA:G	donor_gain	1.0000
16:78109834:GAG:G	donor_gain	1.0000
16:78109835:AG:A	donor_loss	1.0000
16:78109836:G:GG	donor_gain	1.0000
16:78109836:GTAAG:G	donor_loss	1.0000
16:78109837:T:TC	donor_loss	1.0000
16:78114974:A:AG	acceptor_gain	1.0000
16:78114975:G:GC	acceptor_gain	1.0000
16:78114975:GCC:G	acceptor_gain	1.0000
16:78114975:GCCAT:G	acceptor_gain	1.0000
16:78115149:GAA:G	donor_gain	1.0000
16:78115151:ATAGG:A	donor_loss	1.0000
16:78115152:TAGGT:T	donor_loss	1.0000
16:78115153:AGGT:A	donor_loss	1.0000
16:78115154:GGTAG:G	donor_loss	1.0000
16:78115155:G:T	donor_loss	1.0000
16:78115156:T:G	donor_loss	1.0000
16:78164181:A:AG	acceptor_gain	1.0000
16:78164181:AG:A	acceptor_gain	1.0000
16:78164182:G:GG	acceptor_gain	1.0000
16:78164182:GG:G	acceptor_gain	1.0000
16:78164287:TGG:T	donor_gain	1.0000

AlphaMissense

2709 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
16:78099842:T:A	W22R	1.000
16:78099842:T:C	W22R	1.000
16:78109792:T:A	W63R	1.000
16:78109792:T:C	W63R	1.000
16:78109794:G:C	W63C	0.999
16:78109794:G:T	W63C	0.999
16:78099844:G:C	W22C	0.998
16:78099844:G:T	W22C	0.998
16:78099875:T:G	Y33D	0.998
16:78108445:T:A	W44R	0.998
16:78108445:T:C	W44R	0.998
16:78108447:G:C	W44C	0.998
16:78108447:G:T	W44C	0.998
16:78109793:G:C	W63S	0.998
16:78115011:G:C	R89T	0.998
16:78115011:G:T	R89I	0.998
16:78115012:A:C	R89S	0.998
16:78115012:A:T	R89S	0.998
16:78115019:T:C	F92L	0.998
16:78115021:T:A	F92L	0.998
16:78115021:T:G	F92L	0.998
16:78115005:A:G	D87G	0.997
16:78115008:C:A	P88Q	0.997
16:78425040:C:T	S259F	0.997
16:78432661:A:G	H322R	0.997
16:78432667:G:A	G324E	0.997
16:79211614:G:A	G355R	0.997
16:79211614:G:C	G355R	0.997
16:79211620:G:C	A357P	0.997
16:79211621:C:A	A357D	0.997

dbSNP variants (sampled 300 via entrez): RS1000001231 (16:79148547 A>G), RS1000002102 (16:78307012 T>C), RS1000002644 (16:78184276 A>G), RS1000006398 (16:78951235 G>A,C,T), RS1000007576 (16:78763381 G>C), RS1000008819 (16:78608739 T>G), RS1000009339 (16:78510787 GTGTT>G), RS1000010968 (16:78665983 C>A,G,T), RS1000012825 (16:78650758 T>G), RS1000013260 (16:78450043 C>G,T), RS1000015882 (16:78546184 G>A), RS1000016073 (16:78597811 A>C), RS1000021252 (16:78326452 C>A,T), RS1000022637 (16:78764770 T>C,G), RS1000025356 (16:79017361 C>T)

Disease associations

OMIM: gene MIM:605131 | disease phenotypes: MIM:308350, MIM:614322, MIM:616211, MIM:133239, MIM:181500, MIM:117100, MIM:616221

GenCC curated gene-disease

Disease	Classification	Inheritance
autosomal recessive spinocerebellar ataxia 12	Strong	Autosomal recessive
developmental and epileptic encephalopathy, 28	Strong	Autosomal recessive
46,XY partial gonadal dysgenesis	Supportive	Autosomal dominant
undetermined early-onset epileptic encephalopathy	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
genetic developmental and epileptic encephalopathy	Definitive	AR

Mondo (18): developmental and epileptic encephalopathy, 1 (MONDO:0010632), autosomal recessive spinocerebellar ataxia 12 (MONDO:0013687), developmental and epileptic encephalopathy, 28 (MONDO:0014533), congenital nervous system disorder (MONDO:0002320), esophageal cancer (MONDO:0007576), disorder of sexual differentiation (MONDO:0002145), schizophrenia (MONDO:0005090), esophageal squamous cell carcinoma (MONDO:0005580), primary ovarian failure (MONDO:0005387), autism spectrum disorder (MONDO:0005258), self-limited epilepsy with centrotemporal spikes (MONDO:0007295), amelogenesis imperfecta type 1H (MONDO:0014540), infantile spasms (MONDO:0018097), hereditary breast ovarian cancer syndrome (MONDO:0003582), intellectual disability (MONDO:0001071)

Orphanet (13): Autosomal recessive cerebellar ataxia-epilepsy-intellectual disability syndrome due to WWOX deficiency (Orphanet:284282), Non-specific early-onset epileptic encephalopathy (Orphanet:442835), Squamous cell carcinoma of the esophagus (Orphanet:99977), Difference of sex development (Orphanet:90771), Self-limited epilepsy with centrotemporal spikes (Orphanet:1945), Amelogenesis imperfecta (Orphanet:88661), West syndrome (Orphanet:3451), Infantile epileptic spasms syndrome (Orphanet:697160), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Schizophrenia (Orphanet:3140), NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619), NON RARE IN EUROPE: Autism (Orphanet:106), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

118 total (30 of 118 shown, HPO-id order):

HPO	Term
HP:0000007	Autosomal recessive inheritance
HP:0000027	Azoospermia
HP:0000028	Cryptorchidism
HP:0000030	Testicular gonadoblastoma
HP:0000045	Abnormal scrotum morphology
HP:0000047	Hypospadias
HP:0000054	Micropenis
HP:0000058	Abnormal labia morphology
HP:0000062	Ambiguous genitalia
HP:0000100	Nephrotic syndrome
HP:0000133	Gonadal dysgenesis
HP:0000142	Abnormal vagina morphology
HP:0000149	Ovarian gonadoblastoma
HP:0000150	Gonadoblastoma
HP:0000252	Microcephaly
HP:0000253	Progressive microcephaly
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000348	High forehead
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000512	Abnormal electroretinogram
HP:0000546	Retinal degeneration
HP:0000582	Upslanted palpebral fissure
HP:0000592	Blue sclerae
HP:0000639	Nystagmus
HP:0000640	Gaze-evoked nystagmus

GWAS associations

72 associations (top):

Study	Trait	p-value
GCST000441_4	Cardiac structure and function	3.000000e-06
GCST000823_12	Radiation response	1.000000e-06
GCST000885_9	Response to antipsychotic treatment in schizophrenia (reasoning)	1.000000e-06
GCST001057_4	Obesity	8.000000e-07
GCST001251_13	Pulmonary function	2.000000e-07
GCST001351_10	Type 2 diabetes	9.000000e-07
GCST001651_49	Response to amphetamines	8.000000e-06
GCST001784_11	Pulmonary function (smoking interaction)	1.000000e-07
GCST001784_9	Pulmonary function (smoking interaction)	8.000000e-08
GCST001820_8	Metabolite levels (5-HIAA)	9.000000e-06
GCST001961_11	Anorexia nervosa	7.000000e-06
GCST002306_18	Bipolar disorder (body mass index interaction)	2.000000e-06
GCST002483_5	Lung function (forced vital capacity)	1.000000e-08
GCST002707_17	Serum thyroid-stimulating hormone levels	8.000000e-06
GCST002777_6	Clozapine-induced cytotoxicity	7.000000e-06
GCST002937_7	Molybdenum levels	2.000000e-06
GCST003264_1022	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_1092	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST003264_1614	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003264_188	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_479	Post bronchodilator FEV1/FVC ratio	3.000000e-06
GCST003264_843	Post bronchodilator FEV1/FVC ratio	1.000000e-06
GCST003485_15	Response to fenofibrate (HDL cholesterol levels)	3.000000e-07
GCST003518_69	Daytime sleep phenotypes	5.000000e-07
GCST003941_12	Acute graft versus host disease in bone marrow transplantation (recipient effect)	2.000000e-07
GCST004025_13	Systemic juvenile idiopathic arthritis	2.000000e-06
GCST004068_58	Venous thromboembolism adjusted for sickle cell variant rs77121243-T	8.000000e-07
GCST004138_5	Early-onset Parkinson’s disease	3.000000e-27
GCST004482_74	Peripheral arterial disease (traffic-related air pollution interaction)	3.000000e-06
GCST004735_38	Epstein-Barr virus copy number in lymphoblastoid cell lines	7.000000e-06

EFO canonical traits (41, from GWAS)

EFO ID	Trait name
EFO:0004298	cardiovascular measurement
EFO:0004350	reasoning
EFO:0003892	pulmonary function measurement
EFO:0004314	forced expiratory volume
EFO:0005132	5-HIAA measurement
EFO:0004340	body mass index
EFO:0004312	vital capacity
EFO:0006952	cytotoxicity measurement
EFO:0004713	FEV/FVC ratio
EFO:0007805	HDL cholesterol change measurement
EFO:0007828	daytime rest measurement
EFO:0004599	acute graft vs. host disease
EFO:0007908	traffic air pollution measurement
EFO:0004761	uric acid measurement
EFO:0008370	infant white matter volume measurement
EFO:0009094	idiopathic dilated cardiomyopathy
EFO:0006953	family history of lung cancer
EFO:0004685	hip geometry
EFO:0009718	peak expiratory flow
EFO:1001870	late-onset Alzheimers disease
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0007660	neuroticism measurement
EFO:0010362	lysophosphatidylcholine 20:3 measurement
EFO:0010475	deoxycholate measurement
EFO:0009766	asparagine measurement
EFO:0010116	choline measurement
EFO:0004346	neuroimaging measurement
EFO:0008336	disease progression measurement
EFO:0004530	triglyceride measurement
EFO:0008343	sex interaction measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D012734	Disorders of Sex Development	C12.050.351.875.253; C12.200.706.316; C12.800.316; C16.131.939.316; C19.391.119
D004827	Epilepsy	C10.228.140.490
D000077277	Esophageal Squamous Cell Carcinoma	C04.557.470.200.400.330; C04.557.470.700.400.565; C04.588.274.476.205.500; C04.588.443.353.500; C06.301.371.205.500; C06.405.117.430.500; C06.405.249.205.500
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

PharmGKB clinical annotations

1 annotations.

Variant	Type	Level	Drugs	Phenotypes
rs9927200	Toxicity	3	sorafenib	Diarrhea

PharmGKB variants

5 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs2550731	WWOX		0.00	0
rs4502225	WWOX		0.00	0
rs11644322	WWOX		0.00	0
rs13338697	WWOX		0.00	0
rs9927200	WWOX	3	3.00	1	sorafenib

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, increases expression, affects methylation	10
Aflatoxin B1	affects expression, affects methylation, decreases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression	6
bisphenol A	increases expression, affects cotreatment, decreases methylation, decreases expression, increases methylation	3
sodium arsenite	affects expression, affects methylation, decreases expression, decreases reaction	3
Decitabine	affects expression, affects cotreatment, decreases expression, decreases reaction	3
lasiocarpine	decreases expression	2
methyleugenol	decreases expression	2
entinostat	affects cotreatment, increases expression	2
Air Pollutants	affects expression, increases abundance, decreases expression	2
Formaldehyde	decreases expression	2
Hydrogen Peroxide	affects expression, affects cotreatment, decreases expression, increases expression	2
N-Nitrosopyrrolidine	decreases expression	2
Silicon Dioxide	increases expression, decreases expression	2
aristolochic acid I	decreases expression	1
quercitrin	decreases expression	1
trichostatin A	affects cotreatment, affects expression	1
beta-lapachone	decreases expression	1
manganese chloride	decreases expression, increases abundance	1
benzo(e)pyrene	increases methylation	1
aflatoxin B2	increases methylation	1
glycidamide	decreases expression	1
U 0126	decreases expression, decreases reaction	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, 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
bisphenol S	decreases methylation	1
jinfukang	increases expression	1
Sunitinib	increases expression	1
Arsenic Trioxide	increases expression	1

Cellosaurus cell lines

7 cell lines: 4 cancer cell line, 3 induced pluripotent stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_C1TE	HUJIi001-A	Induced pluripotent stem cell	Male
CVCL_C1TF	HUJIi002-A	Induced pluripotent stem cell	Female
CVCL_C1TG	HUJIi003-A	Induced pluripotent stem cell	Male
CVCL_E2PA	HAP1 WWOX (-) 3	Cancer cell line	Male
CVCL_E2PB	HAP1 WWOX (-) 4	Cancer cell line	Male
CVCL_TY26	HAP1 WWOX (-) 1	Cancer cell line	Male
CVCL_XV14	HAP1 WWOX (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00333099	PHASE4	COMPLETED	INEC Study: Immuno-modulating Enteral Nutrition in Cancer
NCT00365508	PHASE4	COMPLETED	Counseling and Nicotine Replacement Therapy in Helping Adult Smokers Quit Smoking
NCT00666978	PHASE4	COMPLETED	Health Education Counseling With or Without Bupropion in Helping African Americans Stop Smoking
NCT00754468	PHASE4	COMPLETED	Study of CryoSpray Ablation(TM)to Determine Treatment Effect, Depth of Injury, and Side Effects in the Esophagus.
NCT00790140	PHASE4	UNKNOWN	Trial of Enteral Nutrition Enriched With Eicosapentaenoic Acid (EPA) in Upper Gastrointestinal Cancer Surgery
NCT00911092	PHASE4	COMPLETED	Predictive Proteomic Factors of the Response to Concomitant Radiochemotherapy in Esophageal Cancer
NCT01038154	PHASE4	UNKNOWN	Study to Evaluate the Efficacy of Pravastatin on Survival and Recurrence of Advanced Gastroesophageal Cancer
NCT01416077	PHASE4	COMPLETED	Decreasing Postoperative Complications by Goal-Directed Fluid Therapy During Esophageal Resection
NCT01927328	PHASE4	UNKNOWN	Iron Replacement in Oesophagogastric Neoplasia
NCT01962272	PHASE4	COMPLETED	The Effect of Nutritional Counseling for Cancer Patients
NCT02042313	PHASE4	UNKNOWN	Postoperative Pain Management After Minimally Invasive Esophagectomy
NCT02320734	PHASE4	COMPLETED	Deep Neuromuscular Relaxation in Patients for Thoraco-laparoscopic Esophagectomy
NCT03384511	PHASE4	COMPLETED	The Use of 18F-ALF-NOTA-PRGD2 PET/CT Scan to Predict the Efficacy and Adverse Events of Apatinib in Malignancies.
NCT03413436	PHASE4	COMPLETED	Lobaplation or Cisplatin in Adjuvant Chemotherapy for Esophageal Carcinoma
NCT03642093	PHASE4	UNKNOWN	HOPE - A Study to Evaluate the Effect of a Prehabilitation Program on GI Cancer Patients Planning to Undergo Surgery
NCT04269369	PHASE4	UNKNOWN	Implementation of Pre-emptive Geno- and Phenotyping in 5-Fluorouracil- or Capecitabine-treated Patients
NCT05183126	PHASE4	RECRUITING	Pharmacokinetic Study of Skeletal Muscle Area-based Paclitaxel Infusion in Patients With Cancer
NCT06437288	PHASE4	ENROLLING_BY_INVITATION	Hematoporphyrin Photodynamic Therapy for Esophageal Cancer
NCT07124351	PHASE4	RECRUITING	Intraoperative Imaging of Gastrointestinal Malignancies Using Pafolacianine (CYTALUX™)
NCT00002631	PHASE3	COMPLETED	Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00002883	PHASE3	COMPLETED	Surgery With or Without Combination Chemotherapy in Treating Patients With Cancer of the Esophagus
NCT00002884	PHASE3	UNKNOWN	Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00002897	PHASE3	COMPLETED	Surgery With or Without Chemotherapy in Treating Patients With Stage II or Stage III Cancer of the Esophagus
NCT00003118	PHASE3	COMPLETED	Surgery With or Without Chemotherapy and Radiation Therapy in Treating Patients With Cancer of the Esophagus
NCT00020787	PHASE3	COMPLETED	Vaccine Therapy Plus Chemotherapy in Treating Patients With Metastatic or Locally Recurrent Stomach Cancer or Esophageal Cancer
NCT00041262	PHASE3	UNKNOWN	Combination Chemotherapy in Treating Patients With Esophageal Cancer
NCT00047112	PHASE3	COMPLETED	Surgery With or Without Radiation Therapy and Chemotherapy in Treating Patients With Esophageal Cancer
NCT00052910	PHASE3	COMPLETED	Chemotherapy and Radiation Therapy After Surgery in Treating Patients With Stomach or Esophageal Cancer
NCT00165061	PHASE3	COMPLETED	Multi-Center Prospective Randomized Trial Comparing Standard Esophagectomy Against Chemo-Radiotherapy for Treatment of Squamous Esophageal Cancer - Early Results From the Chinese University Research Group for Esophageal Cancer (CURE)
NCT00193817	PHASE3	UNKNOWN	Three Field Radical Esophagectomy Versus Two Field Esophagectomy - a Prospective Trial
NCT00193882	PHASE3	COMPLETED	Advanced Oesophageal Cancer Study to Compare Quality of Life and Palliation of Dysphagia.
NCT00270166	PHASE3	COMPLETED	The Effect of Epoetin Alfa on the Anemia of Patients With Selected Cancers Receiving Chemotherapy
NCT00357682	PHASE3	COMPLETED	A Phase III, Randomized, Study of Aspirin and Esomeprazole Chemoprevention in Barrett’s Metaplasia
NCT00359645	PHASE3	COMPLETED	Randomized Trial to Assess the Impact of a Screening Program on Upper Aerodigestive Tract Cancer Mortality in a High Risk Population
NCT00387348	PHASE3	TERMINATED	Escitalopram in Treating Depression in Patients With Advanced Lung or Gastrointestinal Cancer
NCT00416858	PHASE3	COMPLETED	Radiation Therapy and Combination Chemotherapy With or Without Surgery in Treating Patients With Locally Advanced Esophageal Cancer That Can Be Removed By Surgery
NCT00525200	PHASE3	COMPLETED	p53-Adjusted Neoadjuvant Chemotherapy for Potentially Resectable Esophageal Cancer
NCT00655876	PHASE3	COMPLETED	Paclitaxel, Cisplatin, and Radiation Therapy With or Without Cetuximab in Treating Patients With Locally Advanced Esophageal Cancer
NCT00665197	PHASE3	COMPLETED	Palliative Radiotherapy and Brachytherapy for Oesophageal Cancer Dysphagia
NCT00686114	PHASE3	UNKNOWN	Concurrent Chemoradiotherapy Containing Paclitaxel&Cisplatin With/Without Tarceva in Locally Advanced Esophageal Cancer