WIF1

Summary

WIF1 (Wnt inhibitory factor 1, HGNC:18081) is a protein-coding gene on chromosome 12q14.3, encoding Wnt inhibitory factor 1 (Q9Y5W5). Binds to WNT proteins and inhibits their activities.

The protein encoded by this gene functions to inhibit WNT proteins, which are extracellular signaling molecules that play a role in embryonic development. This protein contains a WNT inhibitory factor (WIF) domain and five epidermal growth factor (EGF)-like domains, and is thought to be involved in mesoderm segmentation. This gene functions as a tumor suppressor gene, and has been found to be epigenetically silenced in various cancers.

Source: NCBI Gene 11197 — RefSeq curated summary.

At a glance

• GWAS associations: 13
• Clinical variants (ClinVar): 81 total
• MANE Select transcript: NM_007191

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:18081
Approved symbol	WIF1
Name	Wnt inhibitory factor 1
Location	12q14.3
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000156076
Ensembl biotype	protein_coding
OMIM	605186
Entrez	11197

Gene structure

Transcript identifiers

Ensembl transcripts: 11 — 11 protein_coding

ENST00000286574, ENST00000543094, ENST00000546001, ENST00000904761, ENST00000904762, ENST00000904763, ENST00000904764, ENST00000954483, ENST00000954484, ENST00000954485, ENST00000954486

RefSeq mRNA: 1 — MANE Select: NM_007191 NM_007191

CCDS: CCDS8971

Canonical transcript exons

ENST00000286574 — 10 exons

Exon	Start	End
ENSE00001024346	65056031	65056126
ENSE00001024351	65055118	65055213
ENSE00001291687	65120417	65120556
ENSE00001292676	65066641	65066736
ENSE00001297515	65050626	65051470
ENSE00001297646	65068764	65068904
ENSE00001305730	65067695	65067790
ENSE00001309501	65077746	65077854
ENSE00001313446	65062481	65062576
ENSE00001313678	65121044	65121305

Expression profiles

Bgee: expression breadth ubiquitous, 239 present calls, max score 98.40.

FANTOM5 (CAGE): breadth broad, TPM avg 5.0932 / max 915.4752, expressed in 294 samples.

FANTOM5 promoters (13 alternative TSS)

Promoter ID	TPM avg	Samples expressed
131879	1.5224	182
131878	1.1161	175
131887	0.8962	180
131884	0.6315	150
131880	0.3235	122
131886	0.1286	68
131885	0.1127	61
131876	0.0748	37
131875	0.0739	26
131883	0.0690	32

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lower lobe of lung	UBERON:0008949	98.40	gold quality
periodontal ligament	UBERON:0008266	98.25	gold quality
tibia	UBERON:0000979	97.17	gold quality
parotid gland	UBERON:0001831	96.59	gold quality
caudate nucleus	UBERON:0001873	96.46	gold quality
putamen	UBERON:0001874	96.45	gold quality
corpus epididymis	UBERON:0004359	95.73	gold quality
cauda epididymis	UBERON:0004360	95.59	gold quality
nucleus accumbens	UBERON:0001882	95.31	gold quality
trabecular bone tissue	UBERON:0002483	95.23	gold quality
skin of hip	UBERON:0001554	94.13	gold quality
endothelial cell	CL:0000115	93.77	gold quality
amygdala	UBERON:0001876	93.40	gold quality
Brodmann (1909) area 23	UBERON:0013554	92.86	gold quality
lung	UBERON:0002048	92.70	gold quality
visceral pleura	UBERON:0002401	92.44	gold quality
temporal lobe	UBERON:0001871	92.41	gold quality
CA1 field of hippocampus	UBERON:0003881	91.59	gold quality
right lung	UBERON:0002167	91.28	gold quality
cranial nerve II	UBERON:0000941	91.25	gold quality
entorhinal cortex	UBERON:0002728	91.16	gold quality
adult organism	UBERON:0007023	90.32	gold quality
orbitofrontal cortex	UBERON:0004167	90.31	gold quality
upper arm skin	UBERON:0004263	90.10	gold quality
upper lobe of lung	UBERON:0008948	89.88	gold quality
mammary duct	UBERON:0001765	89.80	gold quality
pharyngeal mucosa	UBERON:0000355	89.72	gold quality
hair follicle	UBERON:0002073	89.68	gold quality
right frontal lobe	UBERON:0002810	89.57	gold quality
telencephalon	UBERON:0001893	89.47	gold quality

Single-cell (SCXA)

Detected in 9 experiment(s), a significant marker in 9.

Experiment	Marker?	Max mean expression
E-MTAB-7316	yes	7370.71
E-GEOD-137537	yes	6763.04
E-MTAB-8221	yes	1902.09
E-MTAB-10885	yes	960.07
E-MTAB-11121	yes	886.51
E-MTAB-7407	yes	592.53
E-HCAD-1	yes	74.32
E-GEOD-84465	yes	11.43
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): AHR, CTNNB1, DNMT1, DNMT3A, DNMT3B, ESR1, MYC, NKX3-1, SP1, ZBTB17

miRNA regulators (miRDB)

65 targeting WIF1, 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-3163	100.00	77.23	8605
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-4668-3P	100.00	68.74	2635
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-144-3P	99.94	73.98	2698
HSA-MIR-552-5P	99.93	68.56	1583
HSA-MIR-6835-3P	99.93	70.49	2904
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-95-5P	99.89	72.17	3973
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-1299	99.77	71.24	2389

Literature-anchored findings (GeneRIF, showing 40)

• the methylation-status of the CpG island within the functional WIF-1 promoter region is an important key in Wnt activation in human cancer (PMID:15351726)
• novel mechanism of Wnt pathway regulation whereby activation of Rac1 amplifies signaling activity of stabilized/mutated beta-catenin by promoting accumulation in nucleus, and synergizing with beta-catenin to augment TCF/LEF-dependent gene transcription (PMID:15377999)
• Wnt signaling is involved in Akt activation in prostate cancer cells. Our data also indicate the possibility that Wnt and its signaling pathway can be therapeutic targets for PTEN-mutated advanced prostate carcinoma. (PMID:15389810)
• results provide evidence for the involvement of the Wnt/beta-catenin pathway in the pathogenesis of acute myeloid leukemia (PMID:15735743)
• WIF-1 silencing due to promoter hypermethylation is an important mechanism underlying aberrant activation of the Wnt signaling pathway in carcinogenesis of the digestive organs (PMID:16007117)
• aberrant Wnt signaling is a common event in NPC carcinogenesis linked with WIF-1 silencing (PMID:16427602)
• Epigenetic inactivation of Wnt inhibitory factor-1 is associated with bladder cancer through aberrant canonical Wnt/beta-catenin signaling pat (PMID:16428476)
• WIF domains may have a role as a recognition motif of Wnt and Drosophila hedgehog proteins that are activated by palmitoylation. (PMID:16476441)
• Taken together, our studies suggest that WIF-1 silencing due to its promoter hypermethylation is an important mechanism underlying the constitutively activated Wnt signaling in mesothelioma. (PMID:16516163)
• The Wif-1 methylation was the only independent factor negatively impacting on disease-free survival. (PMID:16525492)
• The methylation level of WIF-1 was significantly higher and mRNA level wassignificantly lower in bladder tumor than in bladder mucosa. (PMID:16609023)
• Valproic acid causes a change in acetylation of this gene. (PMID:17012225)
• Modification of the Wnt-signaling pathway are often associated with development of tumor and may play a significant role in carcinogenesis [review] (PMID:17094650)
• WIF1 is a recurrent target in human salivary gland oncogenesis and that downregulation of WIF1 plays a role in the development and/or progression of pleomorphic adenomas. (PMID:17171686)
• Thus, WIF1 functions as a tumor suppressor for both NPC and ESCC through suppressing the Wnt-signaling pathway, but is frequently silenced by epigenetic mechanism in a tumor-specific way. (PMID:17384664)
• Silencing of WIF-1 through promoter hypermethylation is an early and common event in the carcinogenesis of Barrett’s esophagus. (PMID:18005197)
• WIF1 may be a tumor suppressor, specifically in nonfunctioning pituitary tumors, and that the Wnt pathways are important in pituitary tumorigenesis. (PMID:18079202)
• WIF1 was among the genes differentially expressed in an in vivo-in vivo comparison between unfused and prematurely fused calvarial tissue. (PMID:18093228)
• The results suggest a role of the WIF domain as a palmitoyl binding domain required for WIF-1 binding to palmitoylated Wnt and signaling inhibition. (PMID:18256869)
• Using silencing RNA approaches, we confirmed that downregulation of Sp1 resulted in an increased expression of WIF1 and decreased methylation of WIF1 promoter (PMID:18701434)
• WIF-1 promoter region MSP might be used as an adjuvant tool to complement cytologic examination for the diagnosis of NSCLC-related malignant pleural effusion. (PMID:19085002)
• Mechanisms of WIF1-induced G(1) arrest include (a) SKP2 down-regulation leading to p27/Kip1 accumulation and (b) c-myc down-regulation releasing p21/WAF1 transcription. (PMID:19174556)
• analyzed 5 osteosarcoma cell lines in a high-throughput screen for epigenetically silenced tumor suppressor genes and identified Wnt inhibitory factor 1 (WIF1) as a candidate tumor suppressor gene (PMID:19307728)
• Data suggest that aberrant promoter methylation and decreased expression of DKK-3 and WIF-1 may be an important mechanism in hepatocellular carcinoma, and may be useful for early diagnosis and therapy of HCC. (PMID:19496188)
• Promoter methylation of Wnt inhibitory factor-1 is associated with lung cancer. (PMID:19528461)
• Wnt antagonist genes WIF1 and DKK3 show a very similar frequency of promoter methylation in human breast cancer, but only DKK3 methylation proves as a novel prognostic marker (PMID:19570204)
• Wnt antagonist WIF1 inhibits Wnt signaling and exerts potent antitumor activity by increasing the apoptosis rate in tumor cells and by impairing tumor vascularization (PMID:19690140)
• Tumor-specific methylation of APC, MGMT, RASSF2A, and Wif-1 genes might be a valuable biomarker in plasma for the early detection of colorectal cancer. (PMID:19773381)
• hypermethylation of the p16 and Wif-1 genes has potential as biomarkers that may be used to predict the prognosis of stage IA NSCLC. (PMID:19787276)
• procaine and procainamide reactivate WIF-1 in lung cancer cells and downregulate the Wnt canonical pathway (PMID:19885602)
• the WIF-1 is downregulated by promoter methylation and functions as a tumor suppressor gene by inducing apoptosis in human renal cell carcinoma cells. (PMID:19887605)
• WIF-1 silencing as a result of its promoter hypermethylation may be a frequent event in hepatocellular carcinoma. (PMID:20119713)
• WIF-1 exerts potent antiosteosarcoma effect in vivo in mouse models. Therefore, the reexpression of WIF-1 in WIF-1-deficient osteosarcoma represents a potential novel treatment and preventive strategy. (PMID:20197388)
• study suggest a shift away from canonical Wnt signaling toward noncanonical pathways driven by interactions between Wnt-5a and its cognate receptors in psoriasis, accompanied by impaired homeostatic inhibition of Wnt signaling by WIF-1 and dickkopf (PMID:20376066)
• Blocking Wnt signaling in PCa by WIF1 may represent a novel strategy in the future to reduce metastatic disease burden in PCa patients (PMID:20573255)
• WIF1 promoter methylation is a common event in mesothelioma. (PMID:20596629)
• Transient knockdown or somatic knockout of c-Myc in DLD-1 failed to restore WIF-1 expression suggesting that c-Myc is involved in initiating rather than maintaining WIF-1 epigenetic silencing (PMID:20697356)
• This study suggests that a cause of catenin delocalization in oral cancer could be due to WNT pathway activation, by epigenetic alterations of SFRP-1, SFRP-2, SFRP-4, SFRP-5, WIF-1, DKK-3 genes (PMID:20811686)
• Data show that the WIF-1 promoter was methylated in 89.7% of tumors, whereas all normal mucosa were unmethylated. (PMID:20874008)
• Down-regulation of WIF-1 mRNA expression is associated with hepatocellular carcinoma. (PMID:21052890)

Cross-species orthologs

11 orthologs

Organism	Symbol	Gene ID
danio_rerio	wif1	ENSDARG00000005541
mus_musculus	Wif1	ENSMUSG00000020218
rattus_norvegicus	Wif1	ENSRNOG00000004476
caenorhabditis_elegans		WBGENE00000168
caenorhabditis_elegans		WBGENE00012018
caenorhabditis_elegans		WBGENE00013480
caenorhabditis_elegans		WBGENE00013486
caenorhabditis_elegans		WBGENE00013487
caenorhabditis_elegans		WBGENE00018906
caenorhabditis_elegans		WBGENE00019901
caenorhabditis_elegans		WBGENE00022858

Paralogs (8): DLL3 (ENSG00000090932), CD93 (ENSG00000125810), FBLN7 (ENSG00000144152), CRELD1 (ENSG00000163703), DLK2 (ENSG00000171462), CD248 (ENSG00000174807), CLEC14A (ENSG00000176435), CRELD2 (ENSG00000184164)

Protein

Protein identifiers

Wnt inhibitory factor 1 — Q9Y5W5 (reviewed: Q9Y5W5)

All UniProt accessions (3): Q9Y5W5, F5H8A3, H0YFK7

UniProt curated annotations — full annotation on UniProt →

Function. Binds to WNT proteins and inhibits their activities. May be involved in mesoderm segmentation.

Subunit / interactions. Interacts with MYOC.

Subcellular location. Secreted.

RefSeq proteins (1): NP_009122* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000742	EGF	Domain
IPR003306	WIF	Domain
IPR013032	EGF-like_CS	Conserved_site
IPR013309	Wnt-inh	Family
IPR038677	WIF_sf	Homologous_superfamily
IPR050969	Dev_Signal_Modulators	Family

Pfam: PF02019, PF12661, PF21700

UniProt features (46 total): disulfide bond 15, strand 13, domain 6, helix 3, glycosylation site 2, sequence conflict 2, signal peptide 1, chain 1, turn 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

5 structures.

PDB	Method	Resolution (Å)
2YGN	X-RAY DIFFRACTION	1.85
2YGO	X-RAY DIFFRACTION	1.85
2YGP	X-RAY DIFFRACTION	2.22
2YGQ	X-RAY DIFFRACTION	3.95
2D3J	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y5W5-F1	79.57	0.40

Functional residue map

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

Disulfide bonds (15): 140–177, 182–192, 186–198, 200–209, 214–224, 218–230, 232–241, 246–256, 250–262, 278–288, 282–294, 296–305, 310–320, 314–326, 328–337

Glycosylation sites (2): 88, 245

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

ID	Pathway
R-HSA-201681	TCF dependent signaling in response to WNT
R-HSA-3772470	Negative regulation of TCF-dependent signaling by WNT ligand antagonists

MSigDB gene sets: 151 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_UP, AAGCAAT_MIR137, LEE_NEURAL_CREST_STEM_CELL_DN, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOBP_POSITIVE_REGULATION_OF_FAT_CELL_DIFFERENTIATION, GOCC_CELL_SURFACE, GOBP_REGULATION_OF_WNT_SIGNALING_PATHWAY, MODULE_66, GOBP_POSITIVE_REGULATION_OF_CELL_DIFFERENTIATION, GRE_C, SCHAEFFER_PROSTATE_DEVELOPMENT_12HR_UP, SCHAEFFER_PROSTATE_DEVELOPMENT_48HR_UP, GOBP_FAT_CELL_DIFFERENTIATION, ZHANG_BREAST_CANCER_PROGENITORS_UP, GOBP_POSITIVE_REGULATION_OF_DEVELOPMENTAL_PROCESS

GO Biological Process (4): signal transduction (GO:0007165), Wnt signaling pathway (GO:0016055), negative regulation of Wnt signaling pathway (GO:0030178), positive regulation of fat cell differentiation (GO:0045600)

GO Molecular Function (3): signaling receptor binding (GO:0005102), Wnt-protein binding (GO:0017147), protein binding (GO:0005515)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
TCF dependent signaling in response to WNT	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	2
cellular anatomical structure	2
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
cell surface receptor signaling pathway	1
negative regulation of signal transduction	1
Wnt signaling pathway	1
regulation of Wnt signaling pathway	1
fat cell differentiation	1
positive regulation of cell differentiation	1
regulation of fat cell differentiation	1
binding	1

Protein interactions and networks

STRING

2086 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WIF1	SFRP1	Q8N474	920
WIF1	WNT3A	P56704	903
WIF1	FRZB	Q92765	894
WIF1	LEMD3	Q9Y2U8	883
WIF1	DKK1	O94907	882
WIF1	GDF11	O95390	833
WIF1	DKK4	Q9UBT3	786
WIF1	DKK2	Q9UBU2	779
WIF1	WNT5A	P41221	777
WIF1	LRP5	O75197	775
WIF1	SOST	Q9BQB4	754
WIF1	SFRP2	Q96HF1	736
WIF1	CTNNB1	P35222	736
WIF1	DKK3	Q9UBP4	730
WIF1	WNT4	P56705	722

IntAct

47 interactions, top by confidence:

A	B	Type	Score
WIF1	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.720
KRTAP10-8	WIF1	psi-mi:“MI:0915”(physical association)	0.720
WIF1	Wnt3a	psi-mi:“MI:0407”(direct interaction)	0.680
Wnt3a	WIF1	psi-mi:“MI:0915”(physical association)	0.680
WIF1	Wnt3a	psi-mi:“MI:0915”(physical association)	0.680
WIF1	WNT7A	psi-mi:“MI:0407”(direct interaction)	0.620
	WIF1	psi-mi:“MI:0915”(physical association)	0.560
WIF1		psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	WIF1	psi-mi:“MI:0915”(physical association)	0.560
WIF1	Wnt5a	psi-mi:“MI:0407”(direct interaction)	0.540
Wnt5a	WIF1	psi-mi:“MI:0915”(physical association)	0.540
WIF1	Wnt5a	psi-mi:“MI:0915”(physical association)	0.540
GPN1	POLR3A	psi-mi:“MI:0914”(association)	0.530
CRADD	WIF1	psi-mi:“MI:0915”(physical association)	0.490
WIF1	CRADD	psi-mi:“MI:0915”(physical association)	0.490
WIF1	WNT5A	psi-mi:“MI:0407”(direct interaction)	0.440

BioGRID (145): KRTAP10-8 (Two-hybrid), KRTAP10-3 (Two-hybrid), WIF1 (Two-hybrid), WIF1 (Two-hybrid), WIF1 (Two-hybrid), WIF1 (Two-hybrid), KRTAP10-8 (Two-hybrid), CYSRT1 (Two-hybrid), IP6K1 (Affinity Capture-MS), CTSV (Affinity Capture-MS), SMCHD1 (Affinity Capture-MS), NDRG1 (Affinity Capture-MS), NMD3 (Affinity Capture-MS), MAP1S (Affinity Capture-MS), ZFR (Affinity Capture-MS)

ESM2 similar proteins: A4FV93, B2LW77, D3ZUK3, O00548, O70534, O89103, P06579, P15306, P35070, P80370, P97607, Q05928, Q09163, Q14114, Q501P1, Q53RD9, Q5G872, Q61483, Q61521, Q61592, Q63772, Q66PY1, Q6IN38, Q6NZL8, Q6UY11, Q7T3Q2, Q8AWW5, Q8IWY4, Q8IX30, Q8JZM4, Q8K1E3, Q8NFT8, Q8R4Y4, Q91V88, Q924X6, Q9ET61, Q9JJS0, Q9JLL0, Q9NQ36, Q9NY15

Diamond homologs: Q6IN38, Q9W6F8, Q9W6F9, Q9WUA1, Q9Y5W5

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
WIF1	down-regulates	WNT8A	binding

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	53
Likely benign	2
Benign	25

Top pathogenic / likely-pathogenic (0)

SpliceAI

2155 predictions. Top by Δscore:

Variant	Effect	Δscore
12:65055112:AC:A	donor_loss	1.0000
12:65055113:CTCA:C	donor_gain	1.0000
12:65055114:TCA:T	donor_loss	1.0000
12:65055116:A:AC	donor_gain	1.0000
12:65055117:C:CG	donor_gain	1.0000
12:65055117:CT:C	donor_gain	1.0000
12:65055209:GACAG:G	acceptor_gain	1.0000
12:65055211:CAG:C	acceptor_gain	1.0000
12:65055212:AG:A	acceptor_gain	1.0000
12:65055212:AGCT:A	acceptor_loss	1.0000
12:65055213:GC:G	acceptor_loss	1.0000
12:65055214:C:CC	acceptor_gain	1.0000
12:65055221:C:CT	acceptor_gain	1.0000
12:65055222:A:T	acceptor_gain	1.0000
12:65066738:T:C	acceptor_gain	1.0000
12:65066738:T:TC	acceptor_gain	1.0000
12:65067786:CTCAG:C	acceptor_gain	1.0000
12:65067795:A:T	acceptor_gain	1.0000
12:65068759:CTTA:C	donor_loss	1.0000
12:65068761:TACC:T	donor_loss	1.0000
12:65068762:A:C	donor_loss	1.0000
12:65068763:C:CG	donor_loss	1.0000
12:65068902:CAA:C	acceptor_gain	1.0000
12:65068903:AA:A	acceptor_gain	1.0000
12:65068905:C:CA	acceptor_loss	1.0000
12:65068905:C:CC	acceptor_gain	1.0000
12:65121039:CTTAC:C	donor_loss	1.0000
12:65121041:TAC:T	donor_loss	1.0000
12:65121043:C:CA	donor_loss	1.0000
12:65055117:CTT:C	donor_gain	0.9900

AlphaMissense

2485 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:65068777:T:A	K175N	0.998
12:65068777:T:G	K175N	0.998
12:65120439:A:G	F89S	0.998
12:65068772:C:G	C177S	0.997
12:65068773:A:T	C177S	0.997
12:65068772:C:T	C177Y	0.996
12:65068883:C:G	C140S	0.996
12:65068884:A:T	C140S	0.996
12:65077835:A:G	F103S	0.996
12:65120434:A:G	W91R	0.996
12:65120434:A:T	W91R	0.996
12:65120496:A:C	F70C	0.996
12:65120508:A:C	F66C	0.996
12:65067703:C:T	C209Y	0.995
12:65067772:C:G	C186S	0.995
12:65067773:A:T	C186S	0.995
12:65068773:A:G	C177R	0.995
12:65068884:A:G	C140R	0.995
12:65068889:A:C	F138C	0.995
12:65068889:A:G	F138S	0.995
12:65066648:A:C	C241W	0.994
12:65066649:C:G	C241S	0.994
12:65066649:C:T	C241Y	0.994
12:65066650:A:T	C241S	0.994
12:65067702:A:C	C209W	0.994
12:65067703:C:G	C209S	0.994
12:65067704:A:T	C209S	0.994
12:65067754:C:G	C192S	0.994
12:65067755:A:T	C192S	0.994
12:65068771:A:C	C177W	0.994

dbSNP variants (sampled 300 via entrez): RS1000153166 (12:65080694 C>G), RS1000155052 (12:65121589 A>G), RS1000206000 (12:65090490 A>C), RS1000261400 (12:65066199 T>C), RS1000274666 (12:65120742 G>A), RS1000309209 (12:65087080 G>A,C), RS1000397006 (12:65095365 C>CT), RS1000437777 (12:65093118 C>T), RS1000453083 (12:65117825 T>C), RS1000538346 (12:65078729 A>G), RS1000609968 (12:65080227 G>T), RS1000615627 (12:65085279 T>A,C,G), RS1000646669 (12:65085520 C>G,T), RS1000702882 (12:65087781 A>G), RS1000806236 (12:65094384 C>T)

Disease associations

OMIM: gene MIM:605186 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): hereditary breast ovarian cancer syndrome (MONDO:0003582)

Orphanet (1): Hereditary breast and/or ovarian cancer syndrome (Orphanet:145)

HPO phenotypes

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

GWAS associations

13 associations (top):

Study	Trait	p-value
GCST001485_3	Hippocampal volume	7.000000e-11
GCST003264_1084	Post bronchodilator FEV1/FVC ratio	4.000000e-06
GCST006871_5	Total hippocampal volume	2.000000e-20
GCST006874_1	Hippocampal subfield CA1 volume (corrected for total hippocampal volume)	8.000000e-19
GCST006886_4	Subiculum volume	2.000000e-13
GCST006887_3	Hippocampal subfield CA1 volume	6.000000e-28
GCST006888_2	Hippocampal subfield CA3 volume	9.000000e-19
GCST006889_1	Hippocampal subfield CA4 volume	3.000000e-19
GCST006890_5	Dentate gyrus granule cell layer volume	5.000000e-21
GCST006891_4	Dentate gyrus molecular layer volume	6.000000e-17
GCST006892_1	Hippocampal fissure volume	2.000000e-13
GCST006976_98	Macular thickness	1.000000e-08
GCST010703_95	Brain morphology (MOSTest)	3.000000e-46

EFO canonical traits (6, from GWAS)

EFO ID	Trait name
EFO:0005035	hippocampal volume
EFO:0004713	FEV/FVC ratio
EFO:0009394	hippocampal CA1 volume
EFO:0009395	hippocampal CA3 volume
EFO:0009396	hippocampal CA4 volume
EFO:0004346	neuroimaging measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
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

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
rs10878232	Efficacy	3	Platinum compounds	Non-Small Cell Lung Carcinoma

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs10878232	WIF1	3	3.00	1	Platinum compounds

CTD chemical–gene interactions

28 total (human), top 28 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, affects expression	7
Decitabine	affects methylation, affects expression, affects cotreatment, increases expression, decreases methylation	4
trichostatin A	affects cotreatment, increases expression	2
entinostat	increases expression, affects cotreatment	2
p-Chloromercuribenzoic Acid	affects cotreatment, decreases expression	2
sporidesmin	affects expression, affects reaction	1
perfluorooctanoic acid	increases expression	1
perfluoro-n-nonanoic acid	increases expression	1
deguelin	increases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	1
belinostat	decreases expression	1
dorsomorphin	increases expression, decreases expression, affects cotreatment	1
(+)-JQ1 compound	decreases expression	1
Arsenic Trioxide	decreases expression	1
Air Pollutants	increases abundance, increases expression	1
Aspirin	increases expression	1
Benzo(a)pyrene	increases methylation	1
Dexamethasone	affects cotreatment, increases expression	1
Etoposide	increases response to substance	1
Formaldehyde	increases expression	1
Latex	decreases expression	1
Tetrachlorodibenzodioxin	decreases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, increases expression	1
8-Bromo Cyclic Adenosine Monophosphate	affects cotreatment, increases expression	1
Isotretinoin	increases expression	1
Aflatoxin B1	decreases methylation	1
Paclitaxel	increases response to substance	1
Particulate Matter	increases abundance, increases expression	1

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B9U7	Abcam A-549 WIF1 KO	Cancer cell line	Male
CVCL_D9VR	Ubigene HEK293 WIF1 KO	Transformed cell line	Female
CVCL_WS32	LN-2669GS_WIF1	Cancer cell line	Male
CVCL_WS33	LN-229_indWIF1	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT02562170	PHASE4	COMPLETED	Protexa® Versus TiLoopBra® in Immediate Breast Reconstruction- A Pilot Study
NCT00673335	PHASE3	COMPLETED	Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation
NCT00685256	PHASE3	COMPLETED	Standard Genetic Counseling With or Without a Decision Guide in Improving Communication Between Mothers Undergoing BRCA1/2 Testing and Their Minor-Age Children
NCT03162276	PHASE3	UNKNOWN	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00253539	PHASE2	COMPLETED	Arzoxifene or Tamoxifen in Preventing Breast Cancer in Premenopausal Women at High Risk for Breast Cancer
NCT00305695	PHASE2	COMPLETED	Zoledronate or Observation in Maintaining Bone Mineral Density in Patients Who Are Undergoing Surgery to Remove Both Ovaries
NCT00321633	PHASE2	COMPLETED	Carboplatin or Docetaxel in Treating Women With Metastatic Genetic Breast Cancer
NCT01333748	PHASE2	COMPLETED	Search Allelic Imbalance of Expression of BRCA Genes in Hereditary Risk of Breast and/or Ovarian Cancer
NCT01367639	PHASE2	COMPLETED	Trial of Inquiry Based Stress Reduction (IBSR) Program for BRCA1/2 Mutation Carriers
NCT00535119	PHASE1	COMPLETED	Veliparib, Carboplatin, and Paclitaxel in Treating Patients With Advanced Solid Cancer
NCT00892736	PHASE1	COMPLETED	Veliparib in Treating Patients With Malignant Solid Tumors That Do Not Respond to Previous Therapy
NCT03832985	EARLY_PHASE1	COMPLETED	Pediatric Reporting of Adult-Onset Genomic Results
NCT00005095	Not specified	RECRUITING	Specimen and Data Study for Ovarian Cancer Early Detection and Prevention
NCT00609505	Not specified	COMPLETED	Telemedicine vs. Face-to-Face Cancer Genetic Counseling
NCT01273909	Not specified	UNKNOWN	Outcomes After Perforator Flap Reconstruction for Breast Reconstruction and/or Lymphedema Treatment
NCT01445275	Not specified	WITHDRAWN	Cost of Cancer Risk Management in Women at Elevated Genetic Risk for Ovarian Cancer Who Participated on GOG-0199
NCT01608074	Not specified	ACTIVE_NOT_RECRUITING	Radical Fimbriectomy for Young BRCA Mutation Carriers
NCT02087592	Not specified	COMPLETED	Feasibility of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02302742	Not specified	RECRUITING	Triple Negative Breast Cancer and Germline Hereditary Breast and Ovarian Cancer Mutation Carrier Registry
NCT02324062	Not specified	COMPLETED	Cancer Genetics Hereditary Cancer Panel Testing
NCT02516540	Not specified	UNKNOWN	Efficacy of Lifestyle Intervention in BRCA1/2 Mutation Carriers
NCT02653105	Not specified	ACTIVE_NOT_RECRUITING	Women at Risk of Breast Cancer and OLFM4
NCT02705924	Not specified	TERMINATED	Impact of a Psychoeducational Intervention on Expectations and Coping in Young Women Exposed to a High HBOC Risk
NCT02760849	Not specified	ACTIVE_NOT_RECRUITING	Surgery in Preventing Ovarian Cancer in Patients With Genetic Mutations
NCT02786147	Not specified	COMPLETED	Identification and Referral of Women at Risk for Hereditary Breast/Ovarian Cancer
NCT02956681	Not specified	COMPLETED	Statewide Communication to Reach Diverse Low Income Women
NCT03015376	Not specified	UNKNOWN	Inherited Susceptible Genes Among Epithelial Ovarian Cancer
NCT03050268	Not specified	RECRUITING	Familial Investigations of Childhood Cancer Predisposition
NCT03075540	Not specified	COMPLETED	Enhancing At-risk Latina Women’s Use of Genetic Counseling for Hereditary Breast and Ovarian Cancer
NCT03124212	Not specified	RECRUITING	Cascade Genetic Testing for Hereditary Breast/Ovarian Cancer and Lynch Syndrome in Switzerland
NCT03246841	Not specified	ACTIVE_NOT_RECRUITING	Investigation of Tumour Spectrum of Germline Mutations in Breast and Ovarian Cancer Genes.
NCT03294343	Not specified	UNKNOWN	Risk-Reducing Surgeries for Hereditary Ovarian Cancer
NCT03421327	Not specified	COMPLETED	Genetic Risk: Whether, When, and How to Tell Adolescents
NCT03510689	Not specified	COMPLETED	Genetics and Heart Health After Cancer Therapy
NCT03511690	Not specified	COMPLETED	Testing an Intelligent Tutoring System to Enhance Genetic Risk Assessment
NCT03784859	Not specified	COMPLETED	Tissue Expansion in Breast Reconstruction Without Drains
NCT03979612	Not specified	UNKNOWN	Evaluation of the Adhesion to the GENEPY Network
NCT04197856	Not specified	ACTIVE_NOT_RECRUITING	Direct Information to At-risk Relatives
NCT04407611	Not specified	COMPLETED	Scalable Communication Modalities for Returning Genetic Research Results
NCT04508764	Not specified	TERMINATED	Implementation of the Families Accelerating Cascade Testing Toolkit (FACTT) for Hereditary Breast and Ovarian Cancer and Lynch Syndrome