WNT2

Summary

WNT2 (Wnt family member 2, HGNC:12780) is a protein-coding gene on chromosome 7q31.2, encoding Protein Wnt-2 (P09544). Ligand for members of the frizzled family of seven transmembrane receptors.

This gene is a member of the WNT gene family. The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. Alternatively spliced transcript variants have been identified for this gene.

Source: NCBI Gene 7472 — RefSeq curated summary.

At a glance

• GWAS associations: 10
• Clinical variants (ClinVar): 50 total
• Phenotypes (HPO): 1
• Druggable target: yes
• MANE Select transcript: NM_003391

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12780
Approved symbol	WNT2
Name	Wnt family member 2
Location	7q31.2
Locus type	gene with protein product
Status	Approved
Aliases	IRP
Ensembl gene	ENSG00000105989
Ensembl biotype	protein_coding
OMIM	147870
Entrez	7472

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 3 protein_coding, 2 nonsense_mediated_decay, 1 retained_intron

ENST00000265441, ENST00000449446, ENST00000461427, ENST00000491214, ENST00000647844, ENST00000950642

RefSeq mRNA: 1 — MANE Select: NM_003391 NM_003391

CCDS: CCDS5771

Canonical transcript exons

ENST00000265441 — 5 exons

Exon	Start	End
ENSE00000881922	117315071	117315348
ENSE00000881923	117320567	117320793
ENSE00001129911	117322907	117323058
ENSE00001801693	117275451	117278384
ENSE00003526440	117297612	117297876

Expression profiles

Bgee: expression breadth ubiquitous, 154 present calls, max score 97.61.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5064 / max 79.9881, expressed in 246 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
85834	0.8789	186
85837	0.2497	103
85836	0.1380	71
85835	0.1205	49
85833	0.0635	40
85838	0.0558	29

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
stromal cell of endometrium	CL:0002255	97.61	gold quality
placenta	UBERON:0001987	90.97	gold quality
lower lobe of lung	UBERON:0008949	83.52	gold quality
upper lobe of left lung	UBERON:0008952	81.62	gold quality
upper lobe of lung	UBERON:0008948	81.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	81.45	silver quality
right lung	UBERON:0002167	80.80	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	80.40	gold quality
lung	UBERON:0002048	80.13	gold quality
visceral pleura	UBERON:0002401	79.70	gold quality
decidua	UBERON:0002450	79.39	gold quality
endometrium	UBERON:0001295	79.08	gold quality
amniotic fluid	UBERON:0000173	75.01	gold quality
diaphragm	UBERON:0001103	74.60	gold quality
pleura	UBERON:0000977	71.85	gold quality
smooth muscle tissue	UBERON:0001135	71.76	gold quality
uterus	UBERON:0000995	70.35	gold quality
mammary duct	UBERON:0001765	70.15	silver quality
epithelium of mammary gland	UBERON:0003244	70.02	silver quality
epithelial cell of pancreas	CL:0000083	67.53	gold quality
parietal pleura	UBERON:0002400	67.15	silver quality
prostate gland	UBERON:0002367	66.46	gold quality
myometrium	UBERON:0001296	66.15	gold quality
choroid plexus epithelium	UBERON:0003911	65.61	gold quality
endothelial cell	CL:0000115	65.51	gold quality
tongue squamous epithelium	UBERON:0006919	64.96	gold quality
skin of hip	UBERON:0001554	64.75	gold quality
germinal epithelium of ovary	UBERON:0001304	64.74	silver quality
thoracic mammary gland	UBERON:0005200	64.40	gold quality
mammary gland	UBERON:0001911	64.37	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-24	yes	1147.22
E-MTAB-10662	yes	490.46
E-MTAB-6701	yes	71.22
E-ANND-3	yes	6.80

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AP1, AR, ATF3, CDX1, CUX1, EMX2, ERG, ESR2, EZH2, GATA6, GLI3, HHEX, HNF4A, MSX2, MYC, MYF5, NFAT5, NR1H4, NR2E1, OTX2, PITX2, RORA, SNAI1, SP1, SP5, TP53, VAX2, ZNF384

miRNA regulators (miRDB)

70 targeting WNT2, 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-3134	100.00	66.43	777
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-5696	99.98	72.36	4487
HSA-MIR-4803	99.98	71.99	3117
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-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-302C-5P	99.97	72.56	3642
HSA-MIR-548AT-5P	99.96	70.83	2666
HSA-MIR-548AA	99.96	70.64	3753
HSA-MIR-548AP-3P	99.96	70.64	3753
HSA-MIR-548T-3P	99.96	70.64	3753
HSA-MIR-4666A-3P	99.96	71.71	3434
HSA-MIR-329-3P	99.91	66.56	1234
HSA-MIR-362-3P	99.91	66.38	1267
HSA-MIR-627-3P	99.90	71.42	3316
HSA-MIR-579-3P	99.86	71.66	3628
HSA-MIR-664B-3P	99.84	71.65	3590
HSA-MIR-204-5P	99.79	71.62	2439
HSA-MIR-211-5P	99.79	71.65	2440
HSA-MIR-4517	99.76	69.19	1867
HSA-MIR-6885-3P	99.75	70.36	3187
HSA-MIR-4446-5P	99.72	69.19	2544
HSA-MIR-670-5P	99.67	69.94	1565
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-4666B	99.64	68.69	1282
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-4649-3P	99.56	66.90	1783

Literature-anchored findings (GeneRIF, showing 40)

• Up-regulation of WNT2 mRNA by estrogen might play a key role in some cases of human breast cancer through activation of the beta-catenin - TCF signaling pathway. (PMID:11712082)
• Activating mutations of the WNT2 gene are not a major contributor to the development of autistic disorder. (PMID:11840514)
• REVIEW: role in human gastrointestinal cancer (PMID:14533014)
• Our interpretation of these findings is that it is unlikely that DNA variations in RELN and WNT2 play a significant role in the genetic predisposition to autism. (PMID:15048648)
• Target genes involved in tumor WNT pathways in response to TGF-beta1 were found in cervix cancer cells. (PMID:15878915)
• Wnt/beta-catenin signalling pathway is activated in most of gastric cancers, which may play pivotal roles either in gastric cancer formation or in tumour invasion and dissemination (PMID:15896469)
• Inhibition of Wnt2 by monoclonal antibodies is of therapeutic interest in the development of more effective treatments for malignnt pleueral mesothelioma. (PMID:15900580)
• The increased Wnt2 expression in gastric cancers is paralleled with reduction of membranous E-cadherin. (PMID:16132582)
• The WNT2 gene is upregulated along the progression from low-grade dysplasia to esophageal adenocarcioma. (PMID:16407829)
• Regulation of Fz4 expression by Wnt2. (PMID:17386109)
• inhibition of both Wnt-2 and Gal-3 had synergistic effects on suppressing canonical Wnt signaling and inducing apoptosis, suggesting that aberrant canonical Wnt/beta-catenin signaling in colorectal cancer can be regulated at multiple levels (PMID:17534895)
• potential coordinative effects of Wnt, NF-kappaB and/or Stat3 activation on gastric cancer formation presumably by promoting the transcription of their common target genes. (PMID:18184402)
• Persistent upregulation in colorectal carcinoma cases studied. (PMID:18600204)
• Wnt (Wnt2), Stat3, and Notch-1 and -2 signaling are correlated in human epidermal tumors. (PMID:18703315)
• Knockdown of Wnt2 by siRNA in human U251 glioma cells inhibited cell proliferation and invasive ability, and induced apoptotic cell death (PMID:18949017)
• The results suggest that WNT2 could act through its receptor FZD9 to regulate the beta-CATENIN pathway in cumulus cells, recruiting beta-CATENIN into plasma membranes and promoting the formation of adherens junctions involving CDH1. (PMID:19038973)
• up-regulation of the Wnt-2 protein might play a role in the development of colorectal cancers. (PMID:19239325)
• RNA samples from 21 neuroblastoma showed a highly significant FZD1 and/or MDR1 overexpression after treatment, underlining a role for FZD1-mediated Wnt/beta-catenin pathway in clinical chemoresistance. (PMID:19421142)
• Wnt2 acts as an angiogenic factor for non-sinusoidal endothelium in vitro and in vivo. (PMID:19444628)
• These data demonstrate that mesenchymal stem cells from mice and humans produce Wnt proteins and TGF-beta1 that respectively stimulate lung fibroblast proliferation and matrix production. (PMID:19734317)
• Wnt2/beta-catenin signaling pathway is constitutively activated in esophageal squamous cell carcinoma (ESCC) cells, indicating that Wnt2/beta-catenin pathway plays an essential role in carcinogenesis of the esophagus. (PMID:19857041)
• findings provide evidence for a significant association between WNT2 and autism. (PMID:19895723)
• The present study does not support a major role for WNT2 in schizophrenia. (PMID:20492734)
• DNA methylation within the WNT2 promoter in human placenta is associated with low birthweight. (PMID:21474991)
• a haplotype of WNT2 (rs2896218-rs6950765: G-G) is significantly associated with ASDs. (PMID:21575668)
• Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition (PMID:22041457)
• significant association with SNP rs4730775 locus on chromosome 7 with genetic susceptibility to Peyronie’s disease (PMID:22489561)
• The WNT2 gene may play a suggestive role in language development in autistic disorder. (PMID:22522212)
• Expression of WNT2 in pancreatic cancer cells suppresses anoikis, enhances anchorage-independent sphere formation, and increases metastatic propensity in vivo. (PMID:22763454)
• Pdgf signaling potentiates Wnt2-Wnt7b signaling to promote high levels of Wnt activity in mesenchymal progenitors that is required for proper development of endoderm-derived organs, such as the lung (PMID:22949635)
• The skin lesions of scleroderma patients showed obviously increased expression of cytoplasmic Wnt 2, nuclear Wnt 3a and beta-catenin, but markedly lowered cell membrane expression of beta-catenin than normal skin. (PMID:23268410)
• Decreased placental expression of Wnt2 and increased placental expression of sFRP4 may be associated with the pathogenesis of severe preeclampsia. (PMID:23322712)
• The study demonistrated that expressions of Wnt-2 in high-grade brainstem gliomas were significantly higher than that in low-grade brainstem gliomas and normal brain tissues and were positively correlated with the expression of Ki-67. (PMID:23603171)
• Hypermethylation of WNT2 is associated with colorectal cancer. (PMID:23694962)
• We demonstrated an activation of Wnt-2 signaling via the Frizzled-8 receptor in non-small cell lung cancer cells (PMID:23815780)
• High expression of Wnt2 is associated with pancreatic cancer progression promoted by pancreatic stellate cells. (PMID:25731618)
• Wnt2/beta-catenin signaling was involved in stromal-epithelial cells interaction in endometriosis. (PMID:26116230)
• Wnt2 complements Wnt/beta-catenin signaling in regulating colorectal cancer cell proliferation. (PMID:26484565)
• The WNT2 rs39315 G allele was associated with advanced tumor stage in hepatocellular carcinoma. (PMID:26968103)
• Chondrogenic potential was higher and Wnt/beta-catenin signaling was more potently activated by a GSK-3beta inhibitor in the posterior than in the anterior part of the human infant sclera. (PMID:27336854)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt2	ENSDARG00000041117
mus_musculus	Wnt2	ENSMUSG00000010797
rattus_norvegicus	Wnt2	ENSRNOG00000089988
drosophila_melanogaster	Wnt2	FBGN0004360
drosophila_melanogaster	Wnt5	FBGN0010194
drosophila_melanogaster	Wnt10	FBGN0031903
caenorhabditis_elegans		WBGENE00000857
caenorhabditis_elegans		WBGENE00000858
caenorhabditis_elegans	lin-44	WBGENE00003029

Paralogs (18): WNT16 (ENSG00000002745), WNT8A (ENSG00000061492), WNT8B (ENSG00000075290), WNT11 (ENSG00000085741), WNT3 (ENSG00000108379), WNT5B (ENSG00000111186), WNT5A (ENSG00000114251), WNT6 (ENSG00000115596), WNT1 (ENSG00000125084), WNT2B (ENSG00000134245), WNT10A (ENSG00000135925), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-2 — P09544 (reviewed: P09544)

Alternative names: Int-1-like protein 1, Int-1-related protein

All UniProt accessions (5): P09544, A0A384MDX3, A0A3B3ITC9, C9JUI2, F8WDR1

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt signaling pathway that results in activation of transcription factors of the TCF/LEF family. Functions as a upstream regulator of FGF10 expression. Plays an important role in embryonic lung development. May contribute to embryonic brain development by regulating the proliferation of dopaminergic precursors and neurons.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in brain in the thalamus, in fetal and adult lung and in placenta.

Post-translational modifications. Palmitoleoylation is required for efficient binding to frizzled receptors. Depalmitoleoylation leads to Wnt signaling pathway inhibition.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_003382* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR009140	Wnt2	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (18 total): disulfide bond 11, sequence variant 3, signal peptide 1, chain 1, lipid moiety-binding region 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P09544-F1	88.89	0.71

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 (1): 212

Disulfide bonds (11): 294–304, 308–348, 324–339, 326–336, 331–332, 76–87, 127–135, 137–157, 206–220, 208–215, 278–309

Glycosylation sites (1): 295

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)

MSigDB gene sets: 293 (showing top): GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_LABYRINTHINE_LAYER_DEVELOPMENT, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_LUNG_EPITHELIUM_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_REGULATION_OF_MORPHOGENESIS_OF_A_BRANCHING_STRUCTURE, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, MIDORIKAWA_AMPLIFIED_IN_LIVER_CANCER, GOBP_CELLULAR_RESPONSE_TO_LIPID, GOBP_REGULATION_OF_DEVELOPMENTAL_GROWTH, GOBP_EPITHELIAL_TUBE_BRANCHING_INVOLVED_IN_LUNG_MORPHOGENESIS

GO Biological Process (32): positive regulation of mesenchymal cell proliferation (GO:0002053), lens development in camera-type eye (GO:0002088), cell-cell signaling (GO:0007267), positive regulation of cell population proliferation (GO:0008284), mesenchymal cell proliferation (GO:0010463), neurogenesis (GO:0022008), neuron differentiation (GO:0030182), cell proliferation in midbrain (GO:0033278), cell fate commitment (GO:0045165), positive regulation of transcription by RNA polymerase II (GO:0045944), positive regulation of fibroblast proliferation (GO:0048146), positive regulation of neurogenesis (GO:0050769), atrial cardiac muscle tissue morphogenesis (GO:0055009), cardiac muscle cell proliferation (GO:0060038), positive regulation of cardiac muscle cell proliferation (GO:0060045), canonical Wnt signaling pathway (GO:0060070), cardiac epithelial to mesenchymal transition (GO:0060317), lung induction (GO:0060492), positive regulation of epithelial cell proliferation involved in lung morphogenesis (GO:0060501), epithelial cell proliferation involved in lung morphogenesis (GO:0060502), labyrinthine layer blood vessel development (GO:0060716), iris morphogenesis (GO:0061072), mammary gland epithelium development (GO:0061180), cellular response to retinoic acid (GO:0071300), cellular response to transforming growth factor beta stimulus (GO:0071560), midbrain dopaminergic neuron differentiation (GO:1904948), multicellular organism development (GO:0007275), Wnt signaling pathway (GO:0016055), animal organ development (GO:0048513), system development (GO:0048731), epithelial cell proliferation (GO:0050673), positive regulation of epithelial cell proliferation (GO:0050679)

GO Molecular Function (5): frizzled binding (GO:0005109), cytokine activity (GO:0005125), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (5): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular matrix (GO:0031012), Wnt signalosome (GO:1990909)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of cell population proliferation	3
cell differentiation	3
cell population proliferation	2
cellular anatomical structure	2
mesenchymal cell proliferation	1
regulation of mesenchymal cell proliferation	1
camera-type eye development	1
anatomical structure development	1
cell communication	1
signaling	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
nervous system development	1
generation of neurons	1
midbrain development	1
neural precursor cell proliferation	1
cellular developmental process	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
fibroblast proliferation	1
regulation of fibroblast proliferation	1
positive regulation of cell development	1
neurogenesis	1
regulation of neurogenesis	1
positive regulation of nervous system development	1
cardiac atrium morphogenesis	1
atrial cardiac muscle tissue development	1
cardiac muscle tissue morphogenesis	1
striated muscle cell proliferation	1
cardiac muscle tissue growth	1
positive regulation of cardiac muscle tissue growth	1
cardiac muscle cell proliferation	1
regulation of cardiac muscle cell proliferation	1
Wnt signaling pathway	1
epithelial to mesenchymal transition	1
heart morphogenesis	1
organ induction	1
regulation of embryonic development	1
lung field specification	1

Protein interactions and networks

STRING

2248 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT2	LRP6	O75581	949
WNT2	LRP5	O75197	949
WNT2	FZD9	O00144	897
WNT2	FZD8	Q9H461	873
WNT2	FZD2	Q14332	834
WNT2	FZD4	Q9ULV1	818
WNT2	FZD7	O75084	791
WNT2	FZD1	Q9UP38	779
WNT2	CTNNB1	P35222	753
WNT2	FZD3	Q9NPG1	748
WNT2	DKK1	O94907	747
WNT2	FZD5	Q13467	747
WNT2	CAPZA2	P47755	713
WNT2	EGFR	P00533	710
WNT2	FZD6	O60353	707

IntAct

9 interactions, top by confidence:

A	B	Type	Score
WNT2	HSPA5	psi-mi:“MI:0915”(physical association)	0.560
WNT2	SFRP1	psi-mi:“MI:0915”(physical association)	0.400
WNT2	AQP5	psi-mi:“MI:0915”(physical association)	0.370
WNT2	HCK	psi-mi:“MI:0915”(physical association)	0.370
WNT2	UQCR11	psi-mi:“MI:0915”(physical association)	0.370
WNT2	RRAGC	psi-mi:“MI:0915”(physical association)	0.370
DCAF4	IGLL5	psi-mi:“MI:0914”(association)	0.350
WNT2	ZZEF1	psi-mi:“MI:0914”(association)	0.350

BioGRID (19): NME7 (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), WNT2 (Affinity Capture-MS), WNT2 (Co-localization), SFRP1 (Affinity Capture-Western), NOTCH1 (Affinity Capture-MS), GPC1 (Affinity Capture-MS), SORL1 (Affinity Capture-MS), ZZEF1 (Affinity Capture-MS), PASK (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), WLS (Affinity Capture-MS), PPP6R3 (Affinity Capture-MS), NOTCH2 (Affinity Capture-MS), PPP6R2 (Affinity Capture-MS)

ESM2 similar proteins: A0M8S1, A0M8T2, A1X153, A4D7S0, O00755, P09544, P21552, P22725, P22726, P28465, P87387, Q07DV4, Q07DW8, Q07DX7, Q07DY7, Q07DZ8, Q07E18, Q07E31, Q07E44, Q09YI4, Q09YJ6, Q09YK7, Q09YN1, Q108U2, Q1KYK4, Q1KYK5, Q1KYK6, Q1KYK7, Q1KYK9, Q1KYL1, Q2IBB0, Q2IBB5, Q2IBE2, Q2IBF4, Q2IBG1, Q2QL76, Q2QL85, Q2QL96, Q2QLA5, Q2QLB6

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, B2GUT4, O00755, O13267, O15978, O42122, O70283, P04426, P04628, P09544, P09615, P10108, P17553, P21551, P21552, P22724, P22725, P22726, P22727, P24257, P24383, P27467, P28047, P28465, P31285, P31286, P33945, P34888, P34889, P41221, P43446, P47793, P49337, P49338, P49339, P49340, P49893

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
WNT2	up-regulates	LRP5	binding
WNT2	up-regulates	LRP6	binding
SOSTDC1	“down-regulates activity”	WNT2

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	45
Likely benign	1
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

966 predictions. Top by Δscore:

Variant	Effect	Δscore
7:117297607:CTTA:C	donor_loss	1.0000
7:117297608:TTA:T	donor_loss	1.0000
7:117297609:TA:T	donor_loss	1.0000
7:117297610:A:AC	donor_gain	1.0000
7:117297610:AC:A	donor_gain	1.0000
7:117297610:ACCT:A	donor_loss	1.0000
7:117297610:ACCTG:A	donor_gain	1.0000
7:117297611:C:CC	donor_gain	1.0000
7:117297611:C:CT	donor_loss	1.0000
7:117297611:CC:C	donor_gain	1.0000
7:117297611:CCT:C	donor_gain	1.0000
7:117297611:CCTG:C	donor_gain	1.0000
7:117297611:CCTGC:C	donor_gain	1.0000
7:117297877:C:A	acceptor_loss	1.0000
7:117297878:T:A	acceptor_loss	1.0000
7:117297881:C:CT	acceptor_gain	1.0000
7:117315073:T:A	donor_gain	1.0000
7:117278384:CCTG:C	acceptor_loss	0.9900
7:117278385:C:CC	acceptor_gain	0.9900
7:117278385:CTG:C	acceptor_loss	0.9900
7:117278386:T:A	acceptor_loss	0.9900
7:117297614:G:A	donor_gain	0.9900
7:117297873:CAGC:C	acceptor_gain	0.9900
7:117297874:AGC:A	acceptor_gain	0.9900
7:117297875:GC:G	acceptor_gain	0.9900
7:117297876:CC:C	acceptor_gain	0.9900
7:117297877:C:CC	acceptor_gain	0.9900
7:117297881:C:T	acceptor_gain	0.9900
7:117297882:G:T	acceptor_gain	0.9900
7:117320565:A:AC	donor_gain	0.9900

AlphaMissense

2398 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
7:117278255:A:C	F328C	0.999
7:117278357:C:G	C294S	0.999
7:117278358:A:T	C294S	0.999
7:117320622:C:A	W85C	0.999
7:117320622:C:G	W85C	0.999
7:117278254:G:C	F328L	0.998
7:117278254:G:T	F328L	0.998
7:117278256:A:G	F328L	0.998
7:117315169:C:A	G164W	0.998
7:117278195:C:G	C348S	0.997
7:117278196:A:T	C348S	0.997
7:117278248:C:A	W330C	0.997
7:117278248:C:G	W330C	0.997
7:117278357:C:T	C294Y	0.997
7:117297802:C:A	W221C	0.997
7:117297802:C:G	W221C	0.997
7:117315089:G:C	N190K	0.997
7:117315089:G:T	N190K	0.997
7:117315189:C:G	C157S	0.997
7:117315190:A:T	C157S	0.997
7:117315197:C:A	W154C	0.997
7:117315197:C:G	W154C	0.997
7:117315322:C:G	A113P	0.997
7:117320713:C:G	C55S	0.997
7:117320714:A:T	C55S	0.997
7:117278231:C:G	C336S	0.996
7:117278232:A:T	C336S	0.996
7:117278315:C:G	C308S	0.996
7:117278316:A:T	C308S	0.996
7:117278356:G:C	C294W	0.996

dbSNP variants (sampled 300 via entrez): RS1000007052 (7:117291338 T>C), RS1000106174 (7:117318063 A>G), RS1000244555 (7:117276225 G>T), RS1000265588 (7:117321855 C>G), RS1000323884 (7:117321564 C>A,G,T), RS1000331353 (7:117323438 C>G,T), RS1000430912 (7:117278085 A>T), RS1000571024 (7:117300457 T>A), RS1000764147 (7:117279547 G>A,C), RS1000766952 (7:117314281 G>A), RS1000792374 (7:117276014 C>T), RS1000845301 (7:117317865 A>T), RS1000849329 (7:117323584 C>G,T), RS1000899740 (7:117286336 G>T), RS1001085024 (7:117293720 A>G)

Disease associations

OMIM: gene MIM:147870 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): renal cell carcinoma (MONDO:0005086)

Orphanet (1): Renal cell carcinoma (Orphanet:217071)

HPO phenotypes

1 total (1 of 1 shown, HPO-id order):

HPO	Term
HP:0005584	Renal cell carcinoma

GWAS associations

10 associations (top):

Study	Trait	p-value
GCST001144_4	Dupuytren’s disease	3.000000e-08
GCST001629_2	Response to platinum-based chemotherapy in non-small-cell lung cancer	4.000000e-07
GCST003995_35	Tonsillectomy	4.000000e-08
GCST004131_127	Inflammatory bowel disease	4.000000e-06
GCST004133_45	Ulcerative colitis	6.000000e-06
GCST004858_7	Dupuytren’s disease	4.000000e-23
GCST005014_120	Tonsillectomy	4.000000e-08
GCST009158_12	Uterine fibroids	5.000000e-08
GCST90020025_366	Waist-to-hip ratio adjusted for BMI	2.000000e-08
GCST90020027_1323	Waist-hip index	2.000000e-08

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004229	Dupuytren Contracture
EFO:0007924	tonsillectomy risk measurement
EFO:0007788	BMI-adjusted waist-hip ratio

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D002292	Carcinoma, Renal Cell	C04.557.470.200.025.390; C04.588.945.947.535.160; C12.050.351.937.820.535.160; C12.050.351.968.419.473.160; C12.200.758.820.750.160; C12.200.777.419.473.160; C12.900.820.535.160; C12.950.419.473.160; C12.950.983.535.160

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1255132 (SINGLE PROTEIN)

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases methylation	4
sodium arsenite	increases expression, affects cotreatment, decreases expression	2
Resveratrol	decreases expression	2
Benzo(a)pyrene	affects methylation, increases mutagenesis	2
bisphenol A	increases methylation, decreases reaction, decreases expression	1
lead acetate	affects cotreatment, decreases expression	1
ethyl-p-hydroxybenzoate	increases expression	1
arsenite	increases methylation	1
afimoxifene	increases expression	1
chromous chloride	affects cotreatment, decreases expression	1
chromic oxide	decreases expression, affects cotreatment	1
1-nitropyrene	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression, affects cotreatment	1
perfluorooctane sulfonic acid	decreases expression	1
deguelin	increases expression	1
entinostat	increases expression	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
(+)-JQ1 compound	decreases expression	1
Decitabine	decreases reaction, increases methylation	1
Fulvestrant	decreases expression	1
Microplastics	increases abundance, increases expression	1
Ethanol	increases expression	1
Doxorubicin	decreases expression	1
Estradiol	increases expression	1
Lipopolysaccharides	affects cotreatment, affects response to substance, increases expression	1
Methylnitronitrosoguanidine	increases expression	1
Oxygen	decreases reaction, increases expression	1
Polystyrenes	increases abundance, increases expression	1
Silicon Dioxide	increases expression	1

ChEMBL screening assays

2 unique, capped per target: 2 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1259663	Binding	Inhibition of Wnt2 signaling pathway in human A549 cells assessed as inhibition of beta-casein-mediated Tcf/Lef transcriptional activity after 24 hrs by dual luciferase reporter gene assay relative to control	Identification of 2,3,6-trisubstituted quinoxaline derivatives as a Wnt2/β-catenin pathway inhibitor in non-small-cell lung cancer cell lines. — Bioorg Med Chem Lett

Cellosaurus cell lines

3 cell lines: 3 embryonic stem cell

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

Cellosaurus	Name	Category	Sex
CVCL_A7V4	SEES3-1V human WNT2, clone1	Embryonic stem cell	Male
CVCL_A7V5	SEES3-1V human WNT2, clone2	Embryonic stem cell	Male
CVCL_A7V6	SEES3-1V human WNT2, clone3	Embryonic stem cell	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00414765	PHASE4	COMPLETED	Aldesleukin in Participants With Metastatic Renal Cell Carcinoma or Metastatic Melanoma
NCT00777504	PHASE4	UNKNOWN	Study to the Optimal Duration of Therapy With Oral Angiogenesis Inhibitors
NCT00930345	PHASE4	TERMINATED	Biological, Pathological and Imagery Markers in the First-line Treatment of Metastatic Clear-cell Renal Cell Carcinoma
NCT01206764	PHASE4	COMPLETED	A Trial of Everolimis in Patients With Advanced Renal Cell Carcinoma.
NCT01266837	PHASE4	COMPLETED	Open Label, Single Arm Trial to Characterize Patients With Metastatic RCC Treated With Everolimus After Failure of the First VEGF-targeted Therapy (MARC-2)
NCT02056587	PHASE4	COMPLETED	Everolimus in Patients With Metastatic Renal Cell Carcinoma Following Progression on Prior Bevacizumab Treatment
NCT02338570	PHASE4	TERMINATED	Outcome-related Factors in Patients With Metastatic Renal Cell Carcinoma Treated With Everolimus (ORCHIDEE)
NCT02596035	PHASE4	COMPLETED	An Investigational Immuno-therapy Safety Trial of Nivolumab in Patients With Advanced or Metastatic Renal Cell Carcinoma
NCT02982954	PHASE4	COMPLETED	A Study to Evaluate the Safety of Nivolumab and Ipilimumab in Subjects With Previously Untreated Advanced or Metastatic Renal Cell Cancer
NCT05949424	PHASE4	UNKNOWN	OPTI - DOSE: Optimal Dosing of Oral Anticancer Drugs in Older Adults
NCT07028125	PHASE4	RECRUITING	Digital Monitoring of Self-reported Symptoms by Patients Treated With Cabozantinib Plus Nivolumab for Advanced Clear-cell Renal Carcinoma
NCT07405086	PHASE4	RECRUITING	Morning Versus Afternoon Administration of Immunotherapy for the Treatment of Advanced or Metastatic Solid Tumors, The Knight SHIFT Study
NCT00033904	PHASE3	COMPLETED	Survival Study Of Oncophage® vs. Observation In Patients With Kidney Cancer
NCT00126178	PHASE3	TERMINATED	Clinical Trial Studying a Personalized Cancer Vaccine in Patients With Non-metastatic Kidney Cancer
NCT00291369	PHASE3	COMPLETED	Cytokines in Patients With Metastatic Renal Cell Carcinoma of Intermediate Prognosis
NCT00410124	PHASE3	COMPLETED	RAD001 Plus Best Supportive Care (BSC) Versus BSC Plus Placebo in Patients With Metastatic Carcinoma of the Kidney Which Has Progressed After Treatment With Sorafenib and/or Sunitinib
NCT00474786	PHASE3	COMPLETED	Temsirolimus Versus Sorafenib As Second-Line Therapy In Patients With Advanced RCC Who Have Failed First-Line Sunitinib
NCT00478114	PHASE3	COMPLETED	Efficacy and Safety of Sorafenib in Advanced Renal Cell Carcinoma (RCC)
NCT00606632	PHASE3	COMPLETED	Pre-surgical Detection of Clear Cell Renal Cell Carcinoma (ccRCC) Using Radiolabeled G250-Antibody
NCT00606866	PHASE3	COMPLETED	MRI Study of BAY 43-9006 in Metastatic Renal Cell Carcinoma
NCT00631371	PHASE3	COMPLETED	Study Comparing Bevacizumab + Temsirolimus vs. Bevacizumab + Interferon-Alfa In Advanced Renal Cell Carcinoma Subjects
NCT00732914	PHASE3	COMPLETED	Sequential Study to Treat Renal Cell Carcinoma
NCT00869011	PHASE3	UNKNOWN	Exercise for Patients With Renal Cell Cancer Receiving Sunitinib
NCT00930033	PHASE3	COMPLETED	Clinical Trial to Assess the Importance of Nephrectomy
NCT01030783	PHASE3	COMPLETED	A Study to Compare Tivozanib (AV-951) to Sorafenib in Subjects With Advanced Renal Cell Carcinoma
NCT01076010	PHASE3	COMPLETED	An Extension Treatment Protocol for Subjects Who Have Participated in a Study of Tivozanib Versus Sorafenib in Kidney Carcinoma (Protocol AV-951-09-301).
NCT01198158	PHASE3	TERMINATED	Everolimus With or Without Bevacizumab in Treating Patients With Advanced Kidney Cancer That Progressed After First-Line Therapy
NCT01223027	PHASE3	COMPLETED	Study of Dovitinib Versus Sorafenib in Patients With Metastatic Renal Cell Carcinoma
NCT01224288	PHASE3	ACTIVE_NOT_RECRUITING	Dynamic Contrast Enhancement Computed Tomography for Evaluating Tumor Perfusion in Patients With Metastatic Renal Cell Carcinoma Receiving Targeted Therapies: Renal Cell Carcinoma (RCC) Scramble
NCT01235962	PHASE3	COMPLETED	A Study to Evaluate Pazopanib as an Adjuvant Treatment for Localized Renal Cell Carcinoma (RCC)
NCT01265810	PHASE3	COMPLETED	Caphosol in Oral Mucositis Due to Targeted Therapy
NCT01265901	PHASE3	COMPLETED	IMA901 in Patients Receiving Sunitinib for Advanced/Metastatic Renal Cell Carcinoma
NCT01481870	PHASE3	UNKNOWN	Comparison of Sequential Therapies With Sunitinib and Sorafenib in Advanced Renal Cell Carcinoma
NCT01582672	PHASE3	TERMINATED	Phase 3 Trial of Autologous Dendritic Cell Immunotherapy Plus Standard Treatment of Advanced Renal Cell Carcinoma
NCT01613846	PHASE3	COMPLETED	Phase III Sequential Open-label Study to Evaluate the Efficacy and Safety of Sorafenib Followed by Pazopanib Versus Pazopanib Followed by Sorafenib in the Treatment of Advanced / Metastatic Renal Cell Carcinoma (SWITCH-II)
NCT01762592	PHASE3	WITHDRAWN	REDECT 2: REnal Masses: Pivotal Trial to DEteCT Clear Cell Renal Cell Carcinoma With PET/CT
NCT01865747	PHASE3	COMPLETED	A Study of Cabozantinib (XL184) vs Everolimus in Subjects With Metastatic Renal Cell Carcinoma
NCT02231749	PHASE3	COMPLETED	Nivolumab Combined With Ipilimumab Versus Sunitinib in Previously Untreated Advanced or Metastatic Renal Cell Carcinoma (CheckMate 214)
NCT02420821	PHASE3	COMPLETED	A Study of Atezolizumab in Combination With Bevacizumab Versus Sunitinib in Participants With Untreated Advanced Renal Cell Carcinoma (RCC)
NCT02811861	PHASE3	ACTIVE_NOT_RECRUITING	Lenvatinib/Everolimus or Lenvatinib/Pembrolizumab Versus Sunitinib Alone as Treatment of Advanced Renal Cell Carcinoma