WNT10B

Summary

WNT10B (Wnt family member 10B, HGNC:12775) is a protein-coding gene on chromosome 12q13.12, encoding Protein Wnt-10b (O00744). Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade.

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 may be involved in breast cancer, and its protein signaling is likely a molecular switch that governs adipogenesis. This protein is 96% identical to the mouse Wnt10b protein at the amino acid level. This gene is clustered with another family member, WNT1, in the chromosome 12q13 region.

Source: NCBI Gene 7480 — RefSeq curated summary.

At a glance

• Gene–disease (curated): split hand-foot malformation 6 (Definitive, GenCC) — +3 more curated relationships
• GWAS associations: 1
• Clinical variants (ClinVar): 138 total — 12 pathogenic, 12 likely-pathogenic
• Phenotypes (HPO): 41
• MANE Select transcript: NM_003394

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12775
Approved symbol	WNT10B
Name	Wnt family member 10B
Location	12q13.12
Locus type	gene with protein product
Status	Approved
Aliases	WNT-12, SHFM6
Ensembl gene	ENSG00000169884
Ensembl biotype	protein_coding
OMIM	601906
Entrez	7480

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 5 protein_coding, 1 retained_intron

ENST00000301061, ENST00000403957, ENST00000407467, ENST00000413630, ENST00000420388, ENST00000475740

RefSeq mRNA: 1 — MANE Select: NM_003394 NM_003394

CCDS: CCDS8775

Canonical transcript exons

ENST00000301061 — 5 exons

Exon	Start	End
ENSE00001163470	48967946	48968319
ENSE00001163479	48970089	48970351
ENSE00001319004	48970456	48970569
ENSE00001820462	48965340	48966553
ENSE00001835599	48971455	48971735

Expression profiles

Bgee: expression breadth ubiquitous, 197 present calls, max score 94.24.

FANTOM5 (CAGE): breadth broad, TPM avg 1.5004 / max 41.4969, expressed in 418 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
130761	0.4944	203
130760	0.3566	183
130769	0.3560	117
130762	0.2271	127
130768	0.0663	36

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
type B pancreatic cell	CL:0000169	94.24	silver quality
olfactory bulb	UBERON:0002264	94.12	silver quality
diaphragm	UBERON:0001103	91.56	gold quality
orbitofrontal cortex	UBERON:0004167	91.31	gold quality
cervix squamous epithelium	UBERON:0006922	91.23	silver quality
tongue squamous epithelium	UBERON:0006919	90.70	silver quality
nucleus accumbens	UBERON:0001882	89.59	gold quality
Brodmann (1909) area 10	UBERON:0013541	88.61	gold quality
CA1 field of hippocampus	UBERON:0003881	88.37	gold quality
cingulate cortex	UBERON:0003027	87.01	gold quality
anterior cingulate cortex	UBERON:0009835	86.87	gold quality
Brodmann (1909) area 46	UBERON:0006483	86.83	gold quality
prefrontal cortex	UBERON:0000451	86.71	gold quality
triceps brachii	UBERON:0001509	86.62	gold quality
right frontal lobe	UBERON:0002810	86.23	gold quality
frontal cortex	UBERON:0001870	86.13	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	85.79	gold quality
entorhinal cortex	UBERON:0002728	85.56	gold quality
superior frontal gyrus	UBERON:0002661	85.55	gold quality
putamen	UBERON:0001874	85.29	gold quality
Brodmann (1909) area 9	UBERON:0013540	85.24	gold quality
neocortex	UBERON:0001950	85.17	gold quality
temporal lobe	UBERON:0001871	84.91	gold quality
amygdala	UBERON:0001876	84.87	gold quality
caudate nucleus	UBERON:0001873	84.48	gold quality
gluteal muscle	UBERON:0002000	84.42	gold quality
cerebral cortex	UBERON:0000956	84.21	gold quality
telencephalon	UBERON:0001893	84.16	gold quality
decidua	UBERON:0002450	83.37	gold quality
middle temporal gyrus	UBERON:0002771	83.25	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.91

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CEBPB, CREB1, DLX5, HNF4A, MSX2, MYC, NR2F2, RBPJ, SP7, SREBF1, XBP1

miRNA regulators (miRDB)

34 targeting WNT10B, 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-1252-5P	100.00	69.80	2774
HSA-MIR-4533	100.00	69.48	2758
HSA-MIR-12118	100.00	65.88	1270
HSA-MIR-188-3P	100.00	68.76	1240
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-6891-5P	99.98	66.53	1372
HSA-MIR-3173-3P	99.98	66.49	1217
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-130B-5P	99.83	68.50	1888
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-148A-3P	99.74	73.77	1700
HSA-MIR-148B-3P	99.74	73.75	1700
HSA-MIR-152-3P	99.74	73.75	1703
HSA-MIR-4428	99.73	66.41	1733
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-6081	99.48	66.07	1446
HSA-MIR-5695	99.41	67.48	1047
HSA-MIR-32-3P	99.36	68.20	2517
HSA-MIR-4777-5P	99.33	67.53	1148
HSA-MIR-6501-3P	98.71	67.45	1480
HSA-MIR-4468	98.01	66.85	1187
HSA-MIR-450A-2-3P	97.91	67.56	1459
HSA-MIR-4446-3P	97.91	64.29	991
HSA-MIR-6893-3P	97.79	64.91	1238
HSA-MIR-4521	97.73	67.64	684
HSA-MIR-4797-3P	97.48	67.14	989
HSA-MIR-2467-5P	97.36	67.71	991

Literature-anchored findings (GeneRIF, showing 40)

• pyrethroid insecticides and estrogen can enhance the expression of the WNT10B proto-oncogene (PMID:12437293)
• mutations represent the first naturally occurring missense variants of WNT10B (PMID:16477437)
• suggest that fibroblast growth factor switches WNT10B from a negative to a positive cell growth regulator (PMID:17761539)
• Metastatic osteosarcoma cell lines showed better chemotaxis response to Wnt10B than the non-metastatic osteosarcoma cell lines (PMID:18465804)
• By homozygosity mapping a novel Split-Hand/Foot Malformation locus at 12q13.11-q13 with a maximum multipoint lod score of 5.47; by subsequent candidate gene approach a homozygous missense WNT10b mutation was identified. (PMID:18515319)
• This analysis implicates the WNT10B locus as a genetic element in the regulation of bone mass and structural geometry. (PMID:19016593)
• In Wnt10b-expressing mammary tumors, levels of p27(KIP1) were extremely low; conversely, Wnt10b-null mammary cells expressed high levels of this protein, suggesting Wnt-dependent regulation of p27(KIP1). (PMID:19056892)
• S1P induces osteoblast precursor recruitment and promotes mature cell survival. Wnt10b and BMP6 also were significantly increased in mature osteoclasts, whereas sclerostin levels decreased during differentiation. (PMID:19075223)
• We have not found evidence for a robust association of common WNT10B gene allelic variants with either BMD or fractures in postmenopausal women. (PMID:19458884)
• This study is the first report of the association of common genetic polymorphism of WNT10B with human fat accumulation. (PMID:20579865)
• Homozygous nonsense mutation in WNT10B is associated with sporadic split-hand/foot malformation with autosomal recessive inheritance. (PMID:20635353)
• Wnt10b, but not Wnt3a, stimulates the NFkappaB and Notch pathways in U2OS osteosarcoma cells. (PMID:21321991)
• A novel sequence variant (c.986C>G, p.Thr329Arg) of WNT10B has been identified in familial split-hand/foot malformations in a large consanguineous Pakistani family. (PMID:21554266)
• Wnt/beta-catenin pathway forms a negative feedback loop during TGF-beta1 induced human normal skin fibroblast-to-myofibroblast transition (PMID:22041457)
• common variation in WNT10B was shown to be associated with BMI and weight in a case-control population of Belgian males. (PMID:22189080)
• we identified WNT10B as a direct target of miR-148a in cancer-associated fibroblasts from endometrial cancers (PMID:22890324)
• Variations in WNT10B do not contribute to human monogenic obesity in our population. (PMID:23104151)
• Results suggest that Wnt10b likely plays an important role in the development of endometrial cancer (EC). The results also identify a role for Wnt10b in EC cells through promoting proliferation and inhibiting apoptosis. (PMID:23135473)
• WNT10B/beta-catenin signalling induces HMGA2 and proliferation in metastatic breast cancer tumours devoid of ERalpha, PR and HER2 expression. (PMID:23307470)
• No association between WNT10B polymorphisms and adiposity parameters was found. However, a role for WNT10B variants in determining human bone mineral density was found. (PMID:23325361)
• Hypoxia-inducible factor-2alpha-dependent hypoxic induction of Wnt10b expression in adipogenic cells. (PMID:23900840)
• Sequence analysis of WNT10B gene revealed a novel 4-bp deletion mutation. (PMID:24211389)
• these findings clearly demonstrate that Wnt10b promotes epidermal keratinocyte transformation through induced Egf pathway (PMID:25995040)
• Data show that Wnt protein Wnt10b is expressed in cardiomyocytes and localized in the intercalated discs of mouse and human hearts. (PMID:26338900)
• WNT10B enhances proliferation through beta-catenin and RAC1 GTPase in human corneal endothelial cells. (PMID:26370090)
• findings provide the identification of autosomal-dominant WNT10B mutations in individuals with oligodontia, which increases the spectrum of congenital tooth agenesis and suggests attenuated Wnt signaling in endothelial differentiation of dental pulp stem cells. (PMID:27321946)
• These results present the first evidence for a recurrent rearrangement promoted by a mobile ht-WNT10B oncogene, as a relevant mechanism for Wnt involvement in human cancer. (PMID:27853307)
• this study provides novel insight into the mechanism of action of parathyroid hormone on human periodontal ligament cells and establish their interplay with T cells via the Wnt10b pathway as a modulating factor for the anabolic properties of the hormone in periodontal regeneration (PMID:28071181)
• Wnt10b is involved in forskolin/hCG-mediated BeWo cell fusion via beta-catenin/GCMa/syncytin pathway, which may also involve activation of PKA (PMID:28370659)
• In 7 families afflicted with dental anomalies we detected 4 heterozygous missense variants in WNT10B. We performed whole exome sequencing in the patients who had WNT10B mutations and found no mutations in other known hypodontia-associated genes..They also show that WNT10B variants are associated not only with oligodontia and isolated tooth agenesis, but also with microdontia, short tooth roots, dental pulp stones (PMID:29364501)
• We report an Indian girl with split-hand/foot malformation (SHFM), sparse hair, and interrupted eyebrows, who carries a novel homozygous deletion c.695_697delACA in WNT10B. The variant is deduced to cause an in-frame deletion of Asn residue 232 (p.Asn232del). (PMID:29427788)
• Treatment of secondary hyperparathyroidism with calcitriol improved the bone anabolism by inhibiting osteoclasts and promoting osteoblasts that might be achieved by increasing the Wnt 10b level. (PMID:30149605)
• Significant associations were found between individual SNPs and SNP combinations in WNT10A, WNT10B and GREM2 SNPs with isolated tooth agenesis. (PMID:30246922)
• Authors define WNT10B-dependent biomarkers for beta-CATENIN/HMGA2/EZH2 signaling predictive of reduced relapse-free survival. (PMID:30563890)
• No genotype-phenotype correlation is delineated but heterozygous individuals might have mild features of split hand/foot malformation, suggesting a dose-effect of the WNT10B loss-of-function (PMID:31050392)
• Study shows for the first time significant ultraviolet B induced upregulation of WNT7B, WNT10B and TCF7L2 in patients with psoriasis and suggests a potential role of these genes in psoriasis pathogenesis. (PMID:31089877)
• results suggest a dual role for Wnt family member 10B protein (WNT10B) in normal development and in prostate cancer progression with opposing functions depending on disease stage (PMID:31433503)
• Sequence Variants in the WNT10B and TP63 Genes Underlying Isolated Split-Hand/Split-Foot Malformation. (PMID:32762550)
• Functional characterization of ATF1, GREM2 AND WNT10B variants associated with tooth agenesis. (PMID:33369218)
• FZD6 triggers Wnt-signalling driven by WNT10B(IVS1) expression and highlights new targets in T-cell acute lymphoblastic leukemia. (PMID:33497493)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt10b	ENSDARG00000040925
mus_musculus	Wnt10b	ENSMUSG00000022996
rattus_norvegicus	Wnt10b	ENSRNOG00000061238
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), 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), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-10b — O00744 (reviewed: O00744)

Alternative names: Protein Wnt-12

All UniProt accessions (4): O00744, B5MCC8, C9J3H3, C9JCI2

UniProt curated annotations — full annotation on UniProt →

Function. Member of the Wnt ligand gene family that encodes for secreted proteins, which activate the Wnt signaling cascade. Specifically activates canonical Wnt/beta-catenin signaling and thus triggers beta-catenin/LEF/TCF-mediated transcriptional programs. Involved in signaling networks controlling stemness, pluripotency and cell fate decisions. Acts in the immune system, mammary gland, adipose tissue, bone and skin.

Subunit / interactions. Forms a soluble 1:1 complex with AFM; this prevents oligomerization and is required for prolonged biological activity. The complex with AFM may represent the physiological form in body fluids.

Subcellular location. Secreted. Extracellular space. Extracellular matrix.

Tissue specificity. Detected in most adult tissues. Highest levels were found in heart and skeletal muscle. Low levels are found in brain.

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

Disease relevance. Split-hand/foot malformation 6 (SHFM6) [MIM:225300] A limb malformation involving the central rays of the autopod and presenting with syndactyly, median clefts of the hands and feet, and aplasia and/or hypoplasia of the phalanges, metacarpals, and metatarsals. Some patients have been found to have intellectual disability, ectodermal and craniofacial findings, and orofacial clefting. The disease is caused by variants affecting the gene represented in this entry. Tooth agenesis, selective, 8 (STHAG8) [MIM:617073] A form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). STHAG8 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. Potential genotype-phenotype correlation between variants and the positions of missing teeth.

Similarity. Belongs to the Wnt family.

Isoforms (2)

UniProt ID	Names	Canonical?
O00744-1	1	yes
O00744-2	2

RefSeq proteins (1): NP_003385* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR005817	Wnt	Family
IPR013302	Wnt10	Family
IPR018161	Wnt_CS	Conserved_site
IPR043158	Wnt_C	Homologous_superfamily

Pfam: PF00110

UniProt features (31 total): disulfide bond 11, sequence variant 6, sequence conflict 4, splice variant 2, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O00744-F1	80.52	0.54

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 (2): 46, 253

Disulfide bonds (11): 146–199, 247–261, 249–256, 318–349, 334–344, 348–388, 364–379, 366–376, 371–372, 83–94, 136–144

Glycosylation sites (2): 93, 335

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-3238698	WNT ligand biogenesis and trafficking
R-HSA-373080	Class B/2 (Secretin family receptors)
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation

MSigDB gene sets: 447 (showing top): GOBP_POSITIVE_REGULATION_OF_EPITHELIAL_CELL_DIFFERENTIATION, GOBP_NEGATIVE_REGULATION_OF_EPITHELIAL_CELL_PROLIFERATION, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, CREL_01, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_FAT_CELL_DIFFERENTIATION, CAR_TNFRSF25, GOBP_BONE_TRABECULA_MORPHOGENESIS, GOBP_REGULATION_OF_PROTEASOMAL_UBIQUITIN_DEPENDENT_PROTEIN_CATABOLIC_PROCESS, GOBP_REGULATION_OF_SKELETAL_MUSCLE_TISSUE_DEVELOPMENT, GOBP_MUSCLE_TISSUE_DEVELOPMENT, BENPORATH_ES_WITH_H3K27ME3, MYOGENIN_Q6, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION

GO Biological Process (50): G2/M transition of mitotic cell cycle (GO:0000086), negative regulation of transcription by RNA polymerase II (GO:0000122), osteoblast differentiation (GO:0001649), chondrocyte differentiation (GO:0002062), transcription by RNA polymerase II (GO:0006366), lipid metabolic process (GO:0006629), smoothened signaling pathway (GO:0007224), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), myoblast differentiation involved in skeletal muscle regeneration (GO:0014835), neuron differentiation (GO:0030182), T cell differentiation (GO:0030217), positive regulation of bone mineralization (GO:0030501), epithelial cell differentiation (GO:0030855), positive regulation of epithelial cell differentiation (GO:0030858), regulation of proteasomal ubiquitin-dependent protein catabolic process (GO:0032434), positive regulation of apoptotic process (GO:0043065), cell fate commitment (GO:0045165), fat cell differentiation (GO:0045444), positive regulation of T cell differentiation (GO:0045582), negative regulation of fat cell differentiation (GO:0045599), positive regulation of osteoblast differentiation (GO:0045669), positive regulation of RNA polymerase II transcription preinitiation complex assembly (GO:0045899), myoblast development (GO:0048627), regulation of skeletal muscle tissue development (GO:0048641), skeletal muscle fiber development (GO:0048741), negative regulation of epithelial cell proliferation (GO:0050680), protein stabilization (GO:0050821), sensory perception of taste (GO:0050909), positive regulation of timing of anagen (GO:0051885), canonical Wnt signaling pathway (GO:0060070), bone trabecula formation (GO:0060346), fungiform papilla development (GO:0061196), cellular response to retinoic acid (GO:0071300), cellular response to cAMP (GO:0071320), cellular response to parathyroid hormone stimulus (GO:0071374), hematopoietic stem cell proliferation (GO:0071425), positive regulation of canonical Wnt signaling pathway (GO:0090263), negative regulation of cold-induced thermogenesis (GO:0120163), positive regulation of hematopoietic stem cell proliferation (GO:1902035), regulation of transcription by RNA polymerase II (GO:0006357)

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 (2): extracellular region (GO:0005576), obsolete extracellular space (GO:0005615)

Reactome top-level categories

Rollup of top-3 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1
Adipogenesis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cell differentiation	6
mitotic cell cycle	1
mitotic cell cycle phase transition	1
cell cycle G2/M phase transition	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
ossification	1
cartilage development	1
DNA-templated transcription	1
primary metabolic process	1
cell surface receptor signaling pathway	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
skeletal muscle tissue regeneration	1
myoblast differentiation	1
generation of neurons	1
lymphocyte differentiation	1
T cell activation	1
bone mineralization	1
regulation of bone mineralization	1
positive regulation of ossification	1
positive regulation of biomineral tissue development	1
epithelium development	1
epithelial cell differentiation	1
regulation of epithelial cell differentiation	1
positive regulation of cell differentiation	1
proteasome-mediated ubiquitin-dependent protein catabolic process	1
regulation of proteasomal protein catabolic process	1
regulation of ubiquitin-dependent protein catabolic process	1
apoptotic process	1
regulation of apoptotic process	1
positive regulation of programmed cell death	1
cellular developmental process	1
T cell differentiation	1
regulation of T cell differentiation	1
positive regulation of lymphocyte differentiation	1
positive regulation of T cell activation	1

Protein interactions and networks

STRING

1220 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT10B	LRP5	O75197	992
WNT10B	LRP6	O75581	936
WNT10B	FZD1	Q9UP38	834
WNT10B	FZD7	O75084	823
WNT10B	TP63	Q9H3D4	760
WNT10B	CTNNB1	P35222	731
WNT10B	FOXN1	O15353	720
WNT10B	FZD8	Q9H461	700
WNT10B	FZD5	Q13467	696
WNT10B	DKK1	O94907	686
WNT10B	FZD4	Q9ULV1	677
WNT10B	SFRP5	Q5T4F7	676
WNT10B	LEF1	Q9UJU2	647
WNT10B	AXIN2	Q9Y2T1	646
WNT10B	DLX5	P56178	632

IntAct

15 interactions, top by confidence:

A	B	Type	Score
WNT10B	APP	psi-mi:“MI:0915”(physical association)	0.560
WNT10B	LRP6	psi-mi:“MI:0914”(association)	0.530
WNT10B	PPP2R2D	psi-mi:“MI:0914”(association)	0.530
WNT10B	AFM	psi-mi:“MI:0915”(physical association)	0.400
PDGFRA	GXYLT2	psi-mi:“MI:0914”(association)	0.350
CLEC12B	GXYLT2	psi-mi:“MI:0914”(association)	0.350
NOTCH2	ZNF320	psi-mi:“MI:0914”(association)	0.350
OIT3	WNT10B	psi-mi:“MI:0914”(association)	0.350
WNT10B	NDUFA2	psi-mi:“MI:0914”(association)	0.350
RNF166	WASL	psi-mi:“MI:0914”(association)	0.350
WNT10B	VWA8	psi-mi:“MI:0914”(association)	0.350

BioGRID (32): PPP2R2D (Affinity Capture-MS), PPP6R2 (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), JMJD8 (Affinity Capture-MS), JMJD8 (Affinity Capture-MS), PPP2R2D (Affinity Capture-MS), FSTL1 (Affinity Capture-MS), COL6A2 (Affinity Capture-MS), LRP6 (Affinity Capture-MS), WNT10B (Two-hybrid), WNT10B (Positive Genetic), WNT10B (Affinity Capture-RNA), WNT10B (Affinity Capture-MS), WNT10B (Affinity Capture-MS)

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, B2GUT4, O00744, 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, P48614, P49337, P49338, P49340

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
WNT10B	up-regulates	FZD3	binding
WNT10B	up-regulates	LRP5	binding
WNT10B	“up-regulates activity”	LRP6	binding
WNT10B	up-regulates	CTNNB1
WNT10B	up-regulates	FZD5	binding
WNT10B	“up-regulates activity”	FZD1	binding
WNT10B	down-regulates	Adipogenesis
WNT10B	up-regulates	FZD1	binding
WNT10B	up-regulates	FZD2	binding
SOSTDC1	“down-regulates activity”	WNT10B

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	12
Likely pathogenic	12
Uncertain significance	79
Likely benign	20
Benign	7

Top pathogenic / likely-pathogenic (24)

Variant ID	HGVS	Classification
1333232	NM_003394.4(WNT10B):c.117_136del (p.Glu39fs)	Pathogenic
1695395	NM_003394.4(WNT10B):c.741del (p.Lys246_Cys247insTer)	Pathogenic
1698374	NM_003394.4(WNT10B):c.499_500del (p.Leu167fs)	Pathogenic
2098787	NM_003394.4(WNT10B):c.884_896del (p.Phe295fs)	Pathogenic
253057	NM_003394.4(WNT10B):c.632G>A (p.Arg211Gln)	Pathogenic
253058	NM_003394.4(WNT10B):c.786G>A (p.Trp262Ter)	Pathogenic
2971064	NM_003394.4(WNT10B):c.969dup (p.Met324fs)	Pathogenic
30237	NM_003394.4(WNT10B):c.458_461dup (p.Asp155fs)	Pathogenic
3376605	NM_003394.4(WNT10B):c.343C>T (p.Arg115Ter)	Pathogenic
522440	NM_003394.4(WNT10B):c.676C>T (p.Arg226Ter)	Pathogenic
634645	NM_003394.4(WNT10B):c.817del (p.Ala273fs)	Pathogenic
7630	NM_003394.4(WNT10B):c.994C>T (p.Arg332Trp)	Pathogenic
2136157	NM_003394.4(WNT10B):c.767G>A (p.Cys256Tyr)	Likely pathogenic
2502298	NM_003394.4(WNT10B):c.53T>A (p.Leu18Gln)	Likely pathogenic
2664721	NM_003394.4(WNT10B):c.115G>T (p.Glu39Ter)	Likely pathogenic
3391173	NM_003394.4(WNT10B):c.638T>G (p.Phe213Cys)	Likely pathogenic
4077745	NM_003394.4(WNT10B):c.953del (p.Cys318fs)	Likely pathogenic
4291871	NM_003394.4(WNT10B):c.148dup (p.Thr50fs)	Likely pathogenic
4795367	NM_003394.4(WNT10B):c.1165_1168del (p.Lys389fs)	Likely pathogenic
4845799	NM_003394.4(WNT10B):c.337_337+1delinsTGTGAGGA	Likely pathogenic
599263	NM_003394.4(WNT10B):c.689ACA[2] (p.Asn232del)	Likely pathogenic
634646	NM_003394.4(WNT10B):c.746G>T (p.Cys249Phe)	Likely pathogenic
634648	NM_003394.4(WNT10B):c.949T>A (p.Phe317Ile)	Likely pathogenic
638164	NM_003394.4(WNT10B):c.257A>C (p.Gln86Pro)	Likely pathogenic

SpliceAI

953 predictions. Top by Δscore:

Variant	Effect	Δscore
12:48970088:CCGCG:C	donor_gain	1.0000
12:48970350:CC:C	acceptor_gain	1.0000
12:48970351:CC:C	acceptor_gain	1.0000
12:48970351:CCTG:C	acceptor_loss	1.0000
12:48970352:C:A	acceptor_loss	1.0000
12:48970352:C:CC	acceptor_gain	1.0000
12:48970353:T:G	acceptor_loss	1.0000
12:48970451:CTCA:C	donor_loss	1.0000
12:48970452:TCACC:T	donor_loss	1.0000
12:48970453:CAC:C	donor_loss	1.0000
12:48970455:C:CT	donor_loss	1.0000
12:48970455:CCGA:C	donor_gain	1.0000
12:48966549:ACCAC:A	acceptor_gain	0.9900
12:48966550:CCAC:C	acceptor_gain	0.9900
12:48966550:CCACC:C	acceptor_gain	0.9900
12:48966551:CACC:C	acceptor_gain	0.9900
12:48966552:AC:A	acceptor_gain	0.9900
12:48966553:CC:C	acceptor_gain	0.9900
12:48966554:CTA:C	acceptor_loss	0.9900
12:48966560:C:CT	acceptor_gain	0.9900
12:48966561:A:T	acceptor_gain	0.9900
12:48966563:C:CT	acceptor_gain	0.9900
12:48966564:A:T	acceptor_gain	0.9900
12:48970083:GCTCA:G	donor_loss	0.9900
12:48970084:CTCAC:C	donor_loss	0.9900
12:48970085:TCAC:T	donor_loss	0.9900
12:48970086:CA:C	donor_loss	0.9900
12:48970087:A:AC	donor_gain	0.9900
12:48970088:C:CC	donor_gain	0.9900
12:48970088:C:CT	donor_loss	0.9900

AlphaMissense

2514 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:48966155:C:A	W370C	1.000
12:48966155:C:G	W370C	1.000
12:48966161:G:C	F368L	1.000
12:48966161:G:T	F368L	1.000
12:48966162:A:C	F368C	1.000
12:48966163:A:G	F368L	1.000
12:48966479:C:A	W262C	1.000
12:48966479:C:G	W262C	1.000
12:48966514:C:A	G251C	1.000
12:48966519:C:G	C249S	1.000
12:48966520:A:T	C249S	1.000
12:48966101:A:C	C388W	0.999
12:48966102:C:T	C388Y	0.999
12:48966103:A:G	C388R	0.999
12:48966138:C:G	C376S	0.999
12:48966139:A:T	C376S	0.999
12:48966150:C:T	C372Y	0.999
12:48966153:C:G	C371S	0.999
12:48966154:A:T	C371S	0.999
12:48966162:A:G	F368S	0.999
12:48966264:C:G	C334S	0.999
12:48966264:C:T	C334Y	0.999
12:48966265:A:T	C334S	0.999
12:48966462:A:C	F268C	0.999
12:48966483:C:G	C261S	0.999
12:48966483:C:T	C261Y	0.999
12:48966484:A:T	C261S	0.999
12:48966498:C:A	C256F	0.999
12:48966498:C:G	C256S	0.999
12:48966498:C:T	C256Y	0.999

dbSNP variants (sampled 300 via entrez): RS1000071972 (12:48972543 G>A), RS1000240555 (12:48970392 C>G), RS1000361136 (12:48972847 G>A), RS1000841594 (12:48966717 A>C), RS1001074244 (12:48965659 G>T), RS1001246167 (12:48972226 C>A,T), RS1001250713 (12:48972224 A>G), RS1001298817 (12:48972564 T>C,G), RS1002030520 (12:48967135 C>T), RS1002196990 (12:48973381 C>G), RS1002655814 (12:48973701 G>A), RS1003088939 (12:48968875 G>A), RS1003688449 (12:48964940 A>C,G), RS1003816044 (12:48967103 G>A), RS1003986131 (12:48969761 G>GT)

Disease associations

OMIM: gene MIM:601906 | disease phenotypes: MIM:225300, MIM:617073

GenCC curated gene-disease

Disease	Classification	Inheritance
split hand-foot malformation 6	Definitive	Autosomal recessive
tooth agenesis, selective, 8	Strong	Autosomal dominant
split hand-foot malformation	Supportive	Autosomal dominant
tooth agenesis	Supportive	Autosomal dominant

Mondo (4): split hand-foot malformation 6 (MONDO:0009157), tooth agenesis, selective, 8 (MONDO:0014901), split hand-foot malformation (MONDO:0016576), tooth agenesis (MONDO:0005486)

Orphanet (2): Isolated split hand-split foot malformation (Orphanet:2440), Oligodontia (Orphanet:99798)

HPO phenotypes

41 total (30 of 41 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000407	Sensorineural hearing impairment
HP:0000526	Aniridia
HP:0000677	Oligodontia
HP:0000679	Taurodontia
HP:0000684	Delayed eruption of teeth
HP:0000685	Hypoplasia of teeth
HP:0000687	Widely spaced teeth
HP:0000689	Dental malocclusion
HP:0000690	Agenesis of maxillary lateral incisor
HP:0000691	Microdontia
HP:0000696	Delayed eruption of permanent teeth
HP:0000958	Dry skin
HP:0001171	Split hand
HP:0001592	Selective tooth agenesis
HP:0001770	Toe syndactyly
HP:0001839	Split foot
HP:0001849	Foot oligodactyly
HP:0003829	Typified by incomplete penetrance
HP:0004050	Absent hand
HP:0004058	Hand monodactyly
HP:0005216	Impaired mastication
HP:0006101	Finger syndactyly
HP:0006289	Agenesis of central incisor
HP:0006297	Enamel hypoplasia
HP:0006336	Short dental root
HP:0006342	Peg-shaped maxillary lateral incisors
HP:0006344	Abnormal primary molar morphology

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST008103_109	Bipolar disorder	4.000000e-06

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C567616	Split-Hand-Foot Malformation 6 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	increases expression	3
Panobinostat	affects cotreatment, increases expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Copper	affects binding, decreases expression	2
ETC-159	decreases expression	1
sotorasib	affects cotreatment, decreases expression	1
bufotalin	decreases reaction, increases expression	1
methyleugenol	increases expression	1
phenothrin	increases expression	1
cobaltiprotoporphyrin	affects expression	1
trichostatin A	increases expression	1
fenvalerate	increases expression	1
butyraldehyde	increases expression	1
perfluorooctanoic acid	decreases expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1
dorsomorphin	affects cotreatment, increases expression	1
bisphenol S	decreases methylation	1
apatinib	decreases expression, affects cotreatment	1
NSC 689534	affects binding, decreases expression	1
trametinib	affects cotreatment, decreases expression	1
(+)-JQ1 compound	decreases expression	1
NVP-BKM120	affects cotreatment, decreases expression	1
LGK974	decreases expression	1
Arsenic Trioxide	affects cotreatment, decreases expression	1
Microplastics	decreases expression, increases abundance	1
Air Pollutants	decreases methylation, increases abundance, increases expression	1

Cellosaurus cell lines

1 cell lines: 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D9VS	Ubigene HEK293 WNT10B KO	Transformed cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT01470235	Not specified	UNKNOWN	Hypodontia and Ovarian Cancer
NCT03445026	Not specified	UNKNOWN	Frequency of Hypodontia After Chemotherapy in Childhood Cancer Survivors Study
NCT05771246	Not specified	COMPLETED	Craniofacial Morphology And Sella Turcica Bridging Associated With Third Molar Agenesis.