WNT11

Summary

WNT11 (Wnt family member 11, HGNC:12776) is a protein-coding gene on chromosome 11q13.5, encoding Protein Wnt-11 (O96014). Ligand for members of the frizzled family of seven transmembrane receptors.

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. This gene is a member of the WNT gene family. It encodes a protein which shows 97%, 85%, and 63% amino acid identity with mouse, chicken, and Xenopus Wnt11 protein, respectively. This gene may play roles in the development of skeleton, kidney and lung, and is considered to be a plausible candidate gene for High Bone Mass Syndrome.

Source: NCBI Gene 7481 — RefSeq curated summary.

At a glance

• Gene–disease (curated): osteoporosis (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 32
• Clinical variants (ClinVar): 64 total
• Phenotypes (HPO): 1
• MANE Select transcript: NM_004626

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12776
Approved symbol	WNT11
Name	Wnt family member 11
Location	11q13.5
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000085741
Ensembl biotype	protein_coding
OMIM	603699
Entrez	7481

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 17 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000322563, ENST00000529461, ENST00000532150, ENST00000864022, ENST00000864023, ENST00000864024, ENST00000961017, ENST00000961018, ENST00000961019, ENST00000961020, ENST00000961021, ENST00000961022, ENST00000961023, ENST00000961024, ENST00000961025, ENST00000961026, ENST00000961027, ENST00000961028

RefSeq mRNA: 1 — MANE Select: NM_004626 NM_004626

CCDS: CCDS8242

Canonical transcript exons

ENST00000322563 — 5 exons

Exon	Start	End
ENSE00000741724	76191564	76191856
ENSE00000989632	76196483	76196718
ENSE00000989633	76194567	76194844
ENSE00001335387	76186325	76187239
ENSE00002147815	76206325	76206502

Expression profiles

Bgee: expression breadth ubiquitous, 178 present calls, max score 90.35.

FANTOM5 (CAGE): breadth broad, TPM avg 2.2292 / max 301.1142, expressed in 485 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
121384	1.4496	348
121382	0.7377	193
121383	0.0419	21

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
omental fat pad	UBERON:0010414	90.35	gold quality
peritoneum	UBERON:0002358	90.22	gold quality
adipose tissue of abdominal region	UBERON:0007808	89.70	gold quality
hindlimb stylopod muscle	UBERON:0004252	89.06	gold quality
subcutaneous adipose tissue	UBERON:0002190	88.26	gold quality
tendon of biceps brachii	UBERON:0008188	87.36	gold quality
right adrenal gland cortex	UBERON:0035827	87.28	gold quality
adipose tissue	UBERON:0001013	86.19	gold quality
adrenal tissue	UBERON:0018303	86.16	gold quality
left adrenal gland cortex	UBERON:0035825	86.15	gold quality
right adrenal gland	UBERON:0001233	85.89	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	85.64	gold quality
left adrenal gland	UBERON:0001234	85.40	gold quality
connective tissue	UBERON:0002384	85.16	gold quality
adrenal cortex	UBERON:0001235	84.76	gold quality
right lobe of thyroid gland	UBERON:0001119	84.32	gold quality
apex of heart	UBERON:0002098	84.04	gold quality
adrenal gland	UBERON:0002369	83.80	gold quality
muscle of leg	UBERON:0001383	82.02	gold quality
gastrocnemius	UBERON:0001388	81.98	gold quality
left lobe of thyroid gland	UBERON:0001120	81.79	gold quality
thyroid gland	UBERON:0002046	80.45	gold quality
tendon	UBERON:0000043	79.92	gold quality
body of pancreas	UBERON:0001150	79.87	gold quality
heart left ventricle	UBERON:0002084	79.23	gold quality
popliteal artery	UBERON:0002250	78.97	gold quality
tibial artery	UBERON:0007610	78.96	gold quality
cardiac ventricle	UBERON:0002082	78.67	gold quality
muscle organ	UBERON:0001630	78.58	gold quality
right atrium auricular region	UBERON:0006631	77.95	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.46

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CTNNB1, ERG, ESRRA, KLF12

miRNA regulators (miRDB)

43 targeting WNT11, 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-190A-3P	100.00	80.35	5520
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-4283	100.00	66.42	2097
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-589-3P	99.91	69.62	2088
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-8062	99.88	68.43	995
HSA-MIR-4307	99.82	70.45	3374
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-4729	99.69	72.18	4233
HSA-MIR-7157-5P	99.66	69.33	1829
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-4310	99.59	68.84	2527
HSA-MIR-186-3P	99.51	66.24	1685
HSA-MIR-4480	99.42	66.02	735
HSA-MIR-6128	99.33	67.83	1581
HSA-MIR-410-3P	99.27	69.98	2457
HSA-MIR-4528	99.18	69.77	1936
HSA-MIR-3125	99.14	68.49	2269
HSA-MIR-3916	98.99	68.04	2155
HSA-MIR-6859-5P	98.99	68.07	2049
HSA-MIR-3196	98.96	63.91	326
HSA-MIR-583	98.71	67.44	1791
HSA-MIR-2115-5P	98.66	68.07	1191
HSA-MIR-4290	98.51	65.17	907

Literature-anchored findings (GeneRIF, showing 40)

• WNT11 mRNA was up-regulated in four cases of colorectal adenocarcinoma, and a case of renal cell carcinoma. Up-regulation of WNT11 mRNA might play an important role in human carcinogenesis through activation of the WNT signaling pathway. (PMID:11712081)
• Wnt11 stimulates proliferation, migration, cytoskeletal rearrangement, and contact-independent growth by a beta-catenin-independent mechanism (PMID:15084607)
• Wnt11 promotes cardiac differentiation via the non-canonical PKC-dependent signaling pathway (PMID:15701629)
• Wnt11 gene is expressed during early embryonic development and has a critical role in regulation of gastrulation movements. (PMID:15708567)
• Wnt5a and Wnt11 expression in EPC cells was induced by coculture with rat neonatal cardiomyocyte and was blocked by gamma-secretase inhibition. (PMID:17967789)
• Wnt-11 promotes cell viability and is involved in coordination of key signaling pathways. (PMID:18572162)
• Our study reveals an unappreciated role for noncanonical Wnt signaling in hESC specification that involves development of unique mesoderm precursors via morphogenic organization within human EBs. (PMID:19265664)
• These observations suggest a novel role for Wnt11 as a tumor suppressor during hepatocarcinogenesis because loss of expression promotes the malignant phenotype via both canonical and noncanonical Wnt signaling pathways. (PMID:20103596)
• These observations suggest that the increased level of Wnt-11 found in prostate cancer contributes to tumour progression by promoting neuroendocrine-like differentiation. (PMID:20219091)
• Data provide evidence for an autocrine regulatory loop involving transcriptional upregulation of WNT11 by ERRalpha and beta-cat that influences the migratory capacity of cancer cells. (PMID:20870744)
• WNT11 emerged as a direct target of ERG. (PMID:21242973)
• These observations highlight the distinct roles of WNT11 and WNT4 during the early stages of retinoic acid-induced neuronal differentiation. (PMID:21280163)
• Wnt11 is involved in the protection of the host intestinal cells by blocking the invasion of pathogenic bacteria, suppressing inflammation, and inhibiting apoptosis. (PMID:21903761)
• Wnt11 mRNA expression was significantly higher in the stage I, II, III, or IV colorectal tumor tissues than in non-tumor colon. (PMID:22161723)
• Notch1-induced WISP-1 expression appeared to be Wnt11-dependent, but Wnt1-independent (PMID:22715413)
• Data established a seven-gene (AR, ESR2, GATA3, GBX2, KRT16, MMP28 and WNT11) prognostic signature to define a subset of triple-negative breast cancer (TNBC). (PMID:23549873)
• Estrogen/progesterone treatment of mature myometrial cells induced expression of WNT11 and WNT16, which remained constitutively elevated in leiomyoma tissues. (PMID:24082114)
• differential Wnt11 immunoexpression in high-grade human serous ovarian cancer compared to low-grade human serous ovarian cancer could play important roles in serous ovarian cancer progression and may be modulated by Wnt5a expression levels. (PMID:24606488)
• High expression of Wnt-11 is associated with metastasis in cervical cancer. (PMID:24737009)
• Report high expression of Wnt11 in esophageal squamous cell carcinoma, which was significantly associated with AJCC stage. (PMID:26261605)
• The Wnt11 gene plays an important role in human mesenchymal stromal cells for enhancing the osteogenesis in an infectious environment. (PMID:26818191)
• Data suggest that Wnt-11 may serve as a target for cervical cancer therapy. (PMID:27034261)
• Demonstrate immunohistochemical expression of Wnt11 and BCL2A1 in complete moles and normal villi. (PMID:27386628)
• TGF-beta1-induced sm-alpha-actin expression is mediated by WNT-11 via RhoA activation and subsequent actin cytoskeletal remodeling. (PMID:27422998)
• The positive rates of Wnt11 protein in normal esophageal epithelium tissue was 29.8% and in esophageal carcinomas tissue was 31.9%; there was no significant difference between the two groups (PMID:27628667)
• Noncanonical Wnt signaling via Wnt5a/5b/11 may have role in the pathogenesis of aortic valve calcification. (PMID:27932350)
• we found that the hypoxic environment of the perivenular zone promotes Wnt11 expression in hepatocytes, which then regulates unique gene expression via activation of the non-canonical Wnt pathway (PMID:29244788)
• The study uncovers a critical role of Wnt11-mediated non-canonical Wnt signaling (CaMKII and JNK pathways) in secreted AGR2’s promoted migration of CRC cells. (PMID:29427622)
• FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription (PMID:29717114)
• Wnt11 impedes Multicellular tumor spheroid-like structures attachment to Extracellular matrix components and therefore can affect ovarian cancer progression. (PMID:29753625)
• Data indicate that Wnt family member 11 protein (Wnt11) is a mediator of osteoblast commitment of mesenchymal stem cells (MSCs), and increases in a surface-roughness dependent manner. (PMID:29872092)
• Downregulation of WNT11 results in fibrotic changes of bladder epithelial cells and is associated with the pathogenesis and differential diagnosis of non-Hunner-type interstitial cystitis. (PMID:29955137)
• that ABHD11-AS1 promotes CRC progression through the miR-1254-WNT11 pathway (PMID:30537177)
• Investigated the role of Wnt11 in neuroendocrine (NE) differentiation, cell proliferation, and epithelial-to-mesenchymal transition in small-cell lung cancer (SCLC). Ascl1 plays an important role in regulating the Wnt signaling pathway and is one of the driver molecules of Wnt11 in SCLC. Wnt11 controlled NE differentiation, cell proliferation, and E-cadherin expression under the regulation of Ascl1 in SCLC cell lines. (PMID:31231131)
• WNT11 mRNA was present in three different human pancreatic ductal adenocarcinoma (PDAC) cell lines. WNT11 loss affected epithelial-mesenchymal transition, expression of neuronal and stemness biomarkers associated with metastasis. Human biopsies of PDAC showed significantly higher WNT11 mRNA levels compared with matched adjacent tissues. Upregulation of WNT11 expression ultimately worsens patient survival. (PMID:31718047)
• Genetic variants in WNT3A and WNT11 were associated with the left-right asymmetry in the amount of palatal rugae. (PMID:31756673)
• Aberrant expression of Wnt/beta-catenin signaling pathway genes in aggressive malignant gastric gastrointestinal stromal tumors. (PMID:32147424)
• WNT11 is a direct target of early growth response protein 1. (PMID:32635983)
• WNT11-Conditioned Medium Promotes Angiogenesis through the Activation of Non-Canonical WNT-PKC-JNK Signaling Pathway. (PMID:33137935)
• Noncanonical Wnt Signaling Promotes Myofibroblast Differentiation in Pulmonary Fibrosis. (PMID:34107237)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt11	ENSDARG00000014796
mus_musculus	Wnt11	ENSMUSG00000015957
rattus_norvegicus	Wnt11	ENSRNOG00000015982
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), WNT2 (ENSG00000105989), 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-11 — O96014 (reviewed: O96014)

All UniProt accessions (1): O96014

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Probable developmental protein. May be a signaling molecule which affects the development of discrete regions of tissues. Is likely to signal over only few cell diameters.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Expressed in fetal lung, kidney, adult heart, liver, skeletal muscle, and pancreas.

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_004617* (*=MANE)

Domains & families (InterPro)

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

Pfam: PF00110

UniProt features (22 total): disulfide bond 11, glycosylation site 5, sequence conflict 3, signal peptide 1, chain 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O96014-F1	90.35	0.80

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): 215

Disulfide bonds (11): 140–157, 209–223, 211–218, 283–314, 299–309, 313–353, 329–344, 331–341, 336–337, 80–91, 130–138

Glycosylation sites (5): 40, 90, 160, 300, 304

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-4086398	Ca2+ pathway
R-HSA-4086400	PCP/CE pathway
R-HSA-9830674	Formation of the ureteric bud

MSigDB gene sets: 317 (showing top): GSE45365_HEALTHY_VS_MCMV_INFECTION_CD8_TCELL_IFNAR_KO_DN, GOBP_CARDIAC_CHAMBER_DEVELOPMENT, GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, SHEPARD_BMYB_MORPHOLINO_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, GOBP_CARDIAC_SEPTUM_DEVELOPMENT, GOBP_VENTRICULAR_SEPTUM_MORPHOGENESIS, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_CARTILAGE_DEVELOPMENT, KEGG_HEDGEHOG_SIGNALING_PATHWAY, GOBP_SKELETAL_SYSTEM_DEVELOPMENT, GOBP_CARDIAC_CHAMBER_MORPHOGENESIS, GOBP_REGULATION_OF_CARTILAGE_DEVELOPMENT

GO Biological Process (53): osteoblast differentiation (GO:0001649), epithelial to mesenchymal transition (GO:0001837), primary heart field specification (GO:0003138), secondary heart field specification (GO:0003139), outflow tract morphogenesis (GO:0003151), atrial septum development (GO:0003283), signal transduction (GO:0007165), Wnt signaling pathway, calcium modulating pathway (GO:0007223), mesenchymal cell proliferation (GO:0010463), neuron differentiation (GO:0030182), bone mineralization (GO:0030282), adrenal gland development (GO:0030325), response to nutrient levels (GO:0031667), positive regulation of transforming growth factor beta2 production (GO:0032915), intracellular signal transduction (GO:0035556), cell fate commitment (GO:0045165), maintenance of epithelial cell apical/basal polarity (GO:0045199), positive regulation of DNA-templated transcription (GO:0045893), paraxial mesoderm formation (GO:0048341), notochord morphogenesis (GO:0048570), embryonic skeletal system development (GO:0048706), artery morphogenesis (GO:0048844), convergent extension involved in axis elongation (GO:0060028), canonical Wnt signaling pathway (GO:0060070), Wnt signaling pathway, planar cell polarity pathway (GO:0060071), cloacal septation (GO:0060197), ventricular septum morphogenesis (GO:0060412), lung-associated mesenchyme development (GO:0060484), ureteric bud morphogenesis (GO:0060675), negative regulation of cartilage development (GO:0061037), somite development (GO:0061053), neuroendocrine cell differentiation (GO:0061101), secondary palate development (GO:0062009), bicellular tight junction assembly (GO:0070830), cellular response to mechanical stimulus (GO:0071260), cellular response to retinoic acid (GO:0071300), stem cell proliferation (GO:0072089), mesonephric duct development (GO:0072177), negative regulation of mesenchymal cell proliferation (GO:0072201), negative regulation of canonical Wnt signaling pathway (GO:0090090)

GO Molecular Function (5): frizzled binding (GO:0005109), cytokine activity (GO:0005125), protein kinase activator activity (GO:0030295), signaling receptor binding (GO:0005102), protein binding (GO:0005515)

GO Cellular Component (4): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615), cytoplasm (GO:0005737), extracellular matrix (GO:0031012)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Beta-catenin independent WNT signaling	2
Signaling by WNT	1
GPCR ligand binding	1
Kidney development	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	3
ossification	2
heart field specification	2
intracellular anatomical structure	2
cellular anatomical structure	2
mesenchymal cell differentiation	1
heart morphogenesis	1
anatomical structure morphogenesis	1
cardiac atrium development	1
cardiac septum development	1
cell communication	1
cellular process	1
signaling	1
regulation of cellular process	1
cellular response to stimulus	1
non-canonical Wnt signaling pathway	1
cell population proliferation	1
generation of neurons	1
biomineral tissue development	1
endocrine system development	1
gland development	1
response to stimulus	1
transforming growth factor beta2 production	1
regulation of transforming growth factor beta2 production	1
positive regulation of transforming growth factor beta production	1
signal transduction	1
cellular developmental process	1
maintenance of apical/basal cell polarity	1
establishment or maintenance of epithelial cell apical/basal polarity	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
positive regulation of RNA biosynthetic process	1
mesoderm formation	1
paraxial mesoderm morphogenesis	1
notochord development	1
embryonic organ morphogenesis	1
G protein-coupled receptor binding	1
receptor ligand activity	1
protein kinase activity	1
kinase activator activity	1

Protein interactions and networks

STRING

1910 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT11	RYK	P34925	993
WNT11	FZD6	O60353	986
WNT11	FZD7	O75084	970
WNT11	FZD3	Q9NPG1	963
WNT11	FZD9	O00144	952
WNT11	FZD4	Q9ULV1	933
WNT11	FZD8	Q9H461	929
WNT11	SFRP5	Q5T4F7	910
WNT11	DVL1	O14640	909
WNT11	RORA	P35397	905
WNT11	ROR2	Q01974	853
WNT11	LRP5	O75197	841
WNT11	VANGL2	Q9ULK5	816
WNT11	FZD2	Q14332	813
WNT11	FZD1	Q9UP38	774

IntAct

73 interactions, top by confidence:

A	B	Type	Score
WNT11	MDFI	psi-mi:“MI:0915”(physical association)	0.780
MDFI	WNT11	psi-mi:“MI:0915”(physical association)	0.780
KRTAP10-7	WNT11	psi-mi:“MI:0915”(physical association)	0.560
KRTAP10-9	WNT11	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP10-7	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP10-9	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP12-3	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP9-3	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP10-8	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP5-7	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP5-9	psi-mi:“MI:0915”(physical association)	0.560
KRTAP1-3	WNT11	psi-mi:“MI:0915”(physical association)	0.560
CCNDBP1	WNT11	psi-mi:“MI:0915”(physical association)	0.560
CYSRT1	WNT11	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP1-1	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP17-1	psi-mi:“MI:0915”(physical association)	0.560
RASSF10	WNT11	psi-mi:“MI:0915”(physical association)	0.560
WNT11	FUCA2	psi-mi:“MI:0915”(physical association)	0.560
WNT11	KRTAP1-5	psi-mi:“MI:0915”(physical association)	0.560
KRTAP5-8	WNT11	psi-mi:“MI:0915”(physical association)	0.560
KLRG2	GXYLT2	psi-mi:“MI:0914”(association)	0.530
PLA2G10	CHEK1	psi-mi:“MI:0914”(association)	0.530
WNT16	WNT11	psi-mi:“MI:0914”(association)	0.530

BioGRID (34): WNT11 (Two-hybrid), KRTAP10-7 (Two-hybrid), KRTAP10-9 (Two-hybrid), WNT11 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), WNT11 (Affinity Capture-MS), WNT11 (Two-hybrid), MDFI (Two-hybrid), CCNDBP1 (Two-hybrid), KRTAP17-1 (Two-hybrid), KRTAP10-8 (Two-hybrid), KRTAP1-1 (Two-hybrid), RASSF10 (Two-hybrid), CYSRT1 (Two-hybrid)

ESM2 similar proteins: B2GUT4, O00744, O13267, O42237, O73864, O96014, P04426, P04628, P09615, P10108, P10600, P17125, P21551, P22724, P22725, P22726, P24257, P31286, P33945, P41221, P43446, P47793, P48614, P48615, P49337, P49338, P49339, P49340, P49893, P51891, P56705, P70275, P87387, Q06442, Q06443, Q07258, Q27Q52, Q28J82, Q4VC17, Q5NVK2

Diamond homologs: A0M8S1, A0M8T2, A1X153, A4D7S0, A8XEH1, B2GUT4, O00755, O13267, O96014, P09544, P17553, P21552, P22725, P24383, P27467, P28047, P28105, P28106, P28108, P28111, P28116, P28127, P28135, P28138, P28143, P28465, P28466, P31283, P31284, P31285, P31286, P31287, P31288, P31289, P31290, P31292, P41221, P47793, P48615, P49337

SIGNOR signaling

12 interactions.

A	Effect	B	Mechanism
WNT11	“up-regulates activity”	FZD3	binding
WNT11	“up-regulates activity”	LRP6	binding
WNT11	“up-regulates activity”	FZD6	binding
WNT11	up-regulates	CHRNA1
WNT11	up-regulates	MUSK	binding
MUSK	up-regulates	WNT11	binding
WNT11	“up-regulates activity”	Frizzled	binding
ERG	“up-regulates quantity by expression”	WNT11	“transcriptional regulation”
SOSTDC1	“down-regulates activity”	WNT11
WNT11	“up-regulates activity”	FZD7	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 31 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
Keratinization	12	27.9×	2e-13

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	56
Likely benign	1
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

1054 predictions. Top by Δscore:

Variant	Effect	Δscore
11:76187236:CTGC:C	acceptor_gain	1.0000
11:76187237:TGC:T	acceptor_gain	1.0000
11:76187237:TGCC:T	acceptor_loss	1.0000
11:76187238:GC:G	acceptor_gain	1.0000
11:76187239:CC:C	acceptor_gain	1.0000
11:76187240:C:CA	acceptor_loss	1.0000
11:76187240:C:CC	acceptor_gain	1.0000
11:76187243:T:TC	acceptor_gain	1.0000
11:76187245:G:C	acceptor_gain	1.0000
11:76191852:AGAGC:A	acceptor_gain	1.0000
11:76191853:GAGC:G	acceptor_gain	1.0000
11:76191854:AGC:A	acceptor_gain	1.0000
11:76191855:GC:G	acceptor_gain	1.0000
11:76191856:CC:C	acceptor_gain	1.0000
11:76191857:C:CC	acceptor_gain	1.0000
11:76191858:T:A	acceptor_loss	1.0000
11:76194841:GTCC:G	acceptor_gain	1.0000
11:76194842:TCC:T	acceptor_gain	1.0000
11:76194843:CC:C	acceptor_gain	1.0000
11:76194843:CCC:C	acceptor_gain	1.0000
11:76194844:CC:C	acceptor_gain	1.0000
11:76194844:CCTG:C	acceptor_loss	1.0000
11:76194845:C:CC	acceptor_gain	1.0000
11:76196478:CCTA:C	donor_loss	1.0000
11:76196479:CTA:C	donor_loss	1.0000
11:76196481:ACCTC:A	donor_loss	1.0000
11:76196482:CCTCT:C	donor_gain	1.0000
11:76196744:C:CT	acceptor_gain	1.0000
11:76196745:G:T	acceptor_gain	1.0000
11:76196746:A:AC	acceptor_gain	1.0000

AlphaMissense

2296 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:76187132:T:C	Y333C	1.000
11:76187234:C:G	C299S	1.000
11:76187235:A:T	C299S	1.000
11:76191606:C:G	C283S	1.000
11:76191607:A:T	C283S	1.000
11:76191782:C:A	W224C	1.000
11:76191782:C:G	W224C	1.000
11:76196535:C:A	W89C	1.000
11:76196535:C:G	W89C	1.000
11:76196537:A:G	W89R	1.000
11:76196537:A:T	W89R	1.000
11:76187071:G:C	C353W	0.999
11:76187072:C:G	C353S	0.999
11:76187072:C:T	C353Y	0.999
11:76187073:A:G	C353R	0.999
11:76187073:A:T	C353S	0.999
11:76187108:C:G	C341S	0.999
11:76187108:C:T	C341Y	0.999
11:76187109:A:T	C341S	0.999
11:76187120:C:T	C337Y	0.999
11:76187125:C:A	W335C	0.999
11:76187125:C:G	W335C	0.999
11:76187138:C:G	C331S	0.999
11:76187138:C:T	C331Y	0.999
11:76187139:A:T	C331S	0.999
11:76187144:C:G	C329S	0.999
11:76187145:A:T	C329S	0.999
11:76187189:C:G	C314S	0.999
11:76187189:C:T	C314Y	0.999
11:76187190:A:T	C314S	0.999

dbSNP variants (sampled 300 via entrez): RS1000134848 (11:76188774 G>A,C), RS1000315104 (11:76204886 T>C), RS1000371662 (11:76199491 A>C,G), RS1000385923 (11:76194299 A>G), RS1000883951 (11:76189621 C>A,T), RS1000991338 (11:76195327 C>A), RS1001121663 (11:76194157 G>A), RS1001148574 (11:76204890 G>A,T), RS1001229491 (11:76206506 C>A,G,T), RS1001270699 (11:76188607 G>A), RS1001321506 (11:76188832 G>T), RS1001339868 (11:76195199 G>A), RS1001374218 (11:76200721 A>C,G), RS1001444895 (11:76200934 G>A), RS1001532185 (11:76209022 T>G)

Disease associations

OMIM: gene MIM:603699 | disease phenotypes: MIM:300633, MIM:600057

GenCC curated gene-disease

Disease	Classification	Inheritance
osteoporosis	Strong	Autosomal dominant
congenital heart disease	Limited	Autosomal recessive

Mondo (4): hypospadias (MONDO:0005345), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), osteoporosis (MONDO:0005298), congenital heart disease (MONDO:0005453)

Orphanet (2): Classic bladder exstrophy (Orphanet:93930), OBSOLETE: Familial hypospadias (Orphanet:440)

HPO phenotypes

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

HPO	Term
HP:0000047	Hypospadias

GWAS associations

32 associations (top):

Study	Trait	p-value
GCST000562_2	PR interval	3.000000e-08
GCST005038_132	Allergic disease (asthma, hay fever or eczema)	2.000000e-63
GCST005038_74	Allergic disease (asthma, hay fever or eczema)	2.000000e-40
GCST005038_75	Allergic disease (asthma, hay fever or eczema)	4.000000e-14
GCST007045_7	PR interval	4.000000e-08
GCST007797_1	Asthma onset (childhood vs adult)	6.000000e-19
GCST007797_12	Asthma onset (childhood vs adult)	5.000000e-17
GCST007797_41	Asthma onset (childhood vs adult)	7.000000e-18
GCST007798_131	Asthma	3.000000e-64
GCST007798_132	Asthma	9.000000e-42
GCST007798_133	Asthma	6.000000e-62
GCST007799_2	Asthma (adult onset)	3.000000e-31
GCST007800_39	Asthma (childhood onset)	1.000000e-93
GCST007800_54	Asthma (childhood onset)	6.000000e-74
GCST008916_84	Asthma	8.000000e-29
GCST010321_142	PR interval	2.000000e-10
GCST010796_5338	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-10
GCST010796_5339	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010796_5340	Electrocardiogram morphology (amplitude at temporal datapoints)	6.000000e-09
GCST010796_5341	Electrocardiogram morphology (amplitude at temporal datapoints)	3.000000e-09
GCST010796_5342	Electrocardiogram morphology (amplitude at temporal datapoints)	5.000000e-09
GCST010796_5343	Electrocardiogram morphology (amplitude at temporal datapoints)	4.000000e-09
GCST010796_5344	Electrocardiogram morphology (amplitude at temporal datapoints)	1.000000e-08
GCST010796_5345	Electrocardiogram morphology (amplitude at temporal datapoints)	2.000000e-08
GCST010984_27	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	3.000000e-12
GCST010984_47	Allergic disease (asthma, hay fever and/or eczema) (multivariate analysis)	2.000000e-18
GCST010985_10	Allergic disease (asthma, hay fever and/or eczema) (age of onset)	4.000000e-28
GCST012298_9	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	5.000000e-06
GCST012301_11	Schizophrenia, bipolar disorder or major depressive disorder x sex interaction	8.000000e-06
GCST90002400_469	Plateletcrit	4.000000e-11

EFO canonical traits (7, from GWAS)

EFO ID	Trait name
EFO:0004462	PR interval
EFO:0004847	age at onset
EFO:1002011	adult onset asthma
EFO:0004327	electrocardiography
EFO:0008343	sex interaction measurement
EFO:0007985	platelet crit
EFO:0004309	platelet count

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D006330	Heart Defects, Congenital	C14.240.400; C14.280.400; C16.131.240.400
D007021	Hypospadias	C12.050.351.875.466; C12.100.500.494.400; C12.200.294.494.400; C12.200.706.516; C12.800.516; C16.131.939.516
D010024	Osteoporosis	C05.116.198.579; C18.452.104.579

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	increases expression, increases methylation	4
sodium arsenite	increases expression	3
Tetrachlorodibenzodioxin	increases expression	3
Cadmium Chloride	increases abundance, increases expression, decreases expression	3
Valproic Acid	increases expression, increases methylation	2
sotorasib	affects cotreatment, decreases expression	1
propionaldehyde	increases expression	1
bisphenol A	affects cotreatment, increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	affects expression, decreases reaction	1
S-(1,2-dichlorovinyl)cysteine	increases expression, affects cotreatment, affects response to substance	1
pentanal	increases expression	1
deguelin	increases expression	1
bisphenol S	decreases expression	1
jinfukang	affects cotreatment, increases expression	1
apatinib	affects cotreatment, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
Sunitinib	increases expression	1
Zoledronic Acid	affects cotreatment, increases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Leflunomide	increases expression	1
Fluvastatin	affects cotreatment, increases expression	1
Microplastics	decreases expression, increases abundance	1
Aldehydes	increases expression	1
Arsenic	affects methylation	1
Cadmium	increases expression, increases abundance	1
Chelating Agents	affects binding, increases expression	1
Cisplatin	increases expression, affects cotreatment	1

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B8AG	Abcam Raji WNT11 KO	Cancer cell line	Male
CVCL_C0BB	Abcam THP-1 WNT11 KO	Cancer cell line	Male
CVCL_C7CY	Abcam PC-3 WNT11 KO	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00006180	PHASE4	COMPLETED	Bone Loss in Premenopausal Women With Depression
NCT00035256	PHASE4	COMPLETED	Sequential Use of Teriparatide and Raloxifene HCl in the Treatment of Postmenopausal Women With Osteoporosis
NCT00035971	PHASE4	COMPLETED	EVA: Evista Alendronate Comparison
NCT00114556	PHASE4	COMPLETED	The Effect of Zoledronic Acid on Bone Density in Liver Transplant Patients
NCT00130403	PHASE4	COMPLETED	OPTAMISE: Clinical Effectiveness of Teriparatide After Alendronate or Risedronate Therapy in Osteoporotic Postmenopausal Women
NCT00148915	PHASE4	COMPLETED	A Study To Assess the Quality and Strength of Bone in Women Participants With Osteoporosis Taking Oral Ibandronate Versus Placebo
NCT00157690	PHASE4	COMPLETED	Study of Alendronate to Prevent and Treat Osteoporosis in Cystic Fibrosis Patients
NCT00159419	PHASE4	COMPLETED	Bisphosphonate Therapy for Osteogenesis Imperfecta
NCT00165607	PHASE4	COMPLETED	Randomized, Open, Parallel, Active Controlled Study on Fracture Prevention in Antiosteoporosis Treatment (OF Study)
NCT00168909	PHASE4	COMPLETED	Influence of Alfacalcidol on Falls in Osteopenic/Osteoporotic Postmenopausal Women (ALFA Study)
NCT00182871	PHASE4	COMPLETED	Testosterone Effects on Bone and Frailty
NCT00191425	PHASE4	COMPLETED	2-Year Therapy With Teriparatide vs 1-yr Therapy Followed by 1-Year of Raloxifene or Calcium/Vit D in Severe Postmenopausal Osteoporosis
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00221299	PHASE4	COMPLETED	Risedronate and Parathyroid Hormone to Reverse Osteoporosis Caused by Chronic Steroid Use
NCT00252408	PHASE4	COMPLETED	Danish Osteoporosis Prevention Study
NCT00259298	PHASE4	COMPLETED	Evaluation of the Effects of Teriparatide on Skeleton Images in Postmenopausal Women With Osteoporosis
NCT00261625	PHASE4	COMPLETED	Can Alendronate Suppress Calcification and Improve Bone Density in Chronic Peritoneal Dialysis Patients?
NCT00271713	PHASE4	COMPLETED	Impact of Oral Ibandronate 150 mg Monthly on Structural Properties of Bone in Postmenopausal Osteoporosis (SPIMOS-3D)
NCT00294463	PHASE4	COMPLETED	Effects of Tibolone Treatment on the Endometrium
NCT00327990	PHASE4	COMPLETED	Evaluation Of Missed Osteoporosis Diagnoses, And Preference Between Once Monthly Ibandronate And Once Weekly Alendronate
NCT00357331	PHASE4	COMPLETED	The Effects of Potassium Citrate on Bone Metabolism
NCT00371956	PHASE4	COMPLETED	Raloxifene for Prevention of Bone Loss in Postmenopausal Patients Receiving Chronic Corticosteroid Therapy
NCT00372372	PHASE4	COMPLETED	The Efficacy of Risedronate in Prevention of Bone Loss in Patients Receiving High Dose Corticosteroid Treatment
NCT00376662	PHASE4	COMPLETED	HRT Versus Etidronate for Osteoporosis and Fractures in Asthmatics Receiving Glucocorticoids.
NCT00402441	PHASE4	COMPLETED	Risedronate in the Prevention of Osteoporosis in Postmenopausal Women
NCT00405392	PHASE4	COMPLETED	Study To Investigate Patient Preference On Dosing In Ibandronate And Risedronate In Korean Women With Postmenopausal Osteoporosis
NCT00431444	PHASE4	COMPLETED	Effects of Zoledronic Acid and Raloxifene on Bone Turnover Markers in Postmenopausal Women With Low Bone Mineral Density
NCT00446589	PHASE4	TERMINATED	The Effects of Ibandronate or Teriparatide Therapy on Bone Histology and Biochemical Indices in Patients on Hemodialysis With Low Bone Mineral Density
NCT00453492	PHASE4	COMPLETED	Risedronate Sodium in Post Menopausal Osteoporosis
NCT00460057	PHASE4	COMPLETED	The Change of Bone Markers After Low Dose Alendronate in Postmenopausal Women With Bone Loss
NCT00479037	PHASE4	COMPLETED	Effect of Full Length Parathyroid Hormone, PTH(1-84) or Strontium Ranelate on Bone Markers in Postmenopausal Women With Primary Osteoporosis (FP-006-IM)
NCT00485953	PHASE4	COMPLETED	Effect of Bisphosphonate on Bone Loss in Postmenopausal Women With Breast Cancer Initiating Aromatase Inhibitor Therapy
NCT00489424	PHASE4	COMPLETED	Acetaminophen or Fluvastatin Compared to Placebo on the Transient Post-Dose Symptoms (PDS) Following an Intravenous (i.v.) Infusion of a Single Dose of Zoledronic Acid 5mg, in Post-menopausal Women With Low Bone Mass
NCT00491920	PHASE4	COMPLETED	High Dosage Vitamin D and Osteoporosis
NCT00504166	PHASE4	COMPLETED	Alendronate Prevents Microarchitectural Deterioration of Trabecular Bone in Early Postmenopausal Women
NCT00544180	PHASE4	TERMINATED	ROSPA - Record on Satisfaction of Patients With Actonel 35 mg Once a Week
NCT00548509	PHASE4	COMPLETED	The Effect of Vitamin K2 on Bone Turnover
NCT00549068	PHASE4	COMPLETED	POWER Point of Care Effect on Satisfaction of Treatment
NCT00549965	PHASE4	COMPLETED	Satisfaction and Compliance of Risedronate in PMO
NCT00557310	PHASE4	COMPLETED	A Study Using Imaging Technology to Measure Changes in Bone Structure After Treatment With Teriparatide