WNT10A

Summary

WNT10A (Wnt family member 10A, HGNC:13829) is a protein-coding gene on chromosome 2q35, encoding Protein Wnt-10a (Q9GZT5). 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 is strongly expressed in the cell lines of promyelocytic leukemia and Burkitt’s lymphoma. In addition, it and another family member, the WNT6 gene, are strongly coexpressed in colorectal cancer cell lines. The gene overexpression may play key roles in carcinogenesis through activation of the WNT-beta-catenin-TCF signaling pathway. This gene and the WNT6 gene are clustered in the chromosome 2q35 region.

Source: NCBI Gene 80326 — RefSeq curated summary.

At a glance

• Gene–disease (curated): ectodermal dysplasia WNT10A related (Definitive, ClinGen) — +5 more curated relationships
• GWAS associations: 16
• Clinical variants (ClinVar): 612 total — 65 pathogenic, 28 likely-pathogenic
• Phenotypes (HPO): 86
• MANE Select transcript: NM_025216

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13829
Approved symbol	WNT10A
Name	Wnt family member 10A
Location	2q35
Locus type	gene with protein product
Status	Approved
Ensembl gene	ENSG00000135925
Ensembl biotype	protein_coding
OMIM	606268
Entrez	80326

Gene structure

Transcript identifiers

Ensembl transcripts: 6 — 4 protein_coding, 2 protein_coding_CDS_not_defined

ENST00000258411, ENST00000458582, ENST00000483911, ENST00000489887, ENST00000865256, ENST00000964557

RefSeq mRNA: 1 — MANE Select: NM_025216 NM_025216

CCDS: CCDS2426

Canonical transcript exons

ENST00000258411 — 4 exons

Exon	Start	End
ENSE00000922345	218882161	218882423
ENSE00000922346	218889984	218890363
ENSE00001276787	218892774	218893928
ENSE00001276796	218880852	218881108

Expression profiles

Bgee: expression breadth ubiquitous, 151 present calls, max score 91.31.

FANTOM5 (CAGE): breadth broad, TPM avg 2.9759 / max 237.9124, expressed in 434 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
25407	1.0855	196
25406	0.9429	181
25409	0.5282	137
25411	0.2528	145
25405	0.0813	36
25408	0.0685	40
25410	0.0167	5

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	91.31	gold quality
lower esophagus mucosa	UBERON:0035834	81.97	gold quality
bone marrow cell	CL:0002092	78.30	gold quality
skin of abdomen	UBERON:0001416	76.09	gold quality
esophagus mucosa	UBERON:0002469	74.59	gold quality
skin of leg	UBERON:0001511	73.32	gold quality
zone of skin	UBERON:0000014	72.08	gold quality
granulocyte	CL:0000094	71.72	gold quality
lymph node	UBERON:0000029	68.25	gold quality
pituitary gland	UBERON:0000007	68.18	gold quality
ileal mucosa	UBERON:0000331	67.91	silver quality
mucosa of transverse colon	UBERON:0004991	67.83	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	67.27	gold quality
adenohypophysis	UBERON:0002196	67.16	gold quality
minor salivary gland	UBERON:0001830	66.02	gold quality
spleen	UBERON:0002106	65.31	gold quality
tibialis anterior	UBERON:0001385	64.89	silver quality
mouth mucosa	UBERON:0003729	64.63	gold quality
pancreatic ductal cell	CL:0002079	64.29	silver quality
germinal epithelium of ovary	UBERON:0001304	63.63	silver quality
upper arm skin	UBERON:0004263	63.20	gold quality
saliva-secreting gland	UBERON:0001044	62.55	gold quality
vermiform appendix	UBERON:0001154	62.32	gold quality
duodenum	UBERON:0002114	61.54	gold quality
metanephros cortex	UBERON:0010533	60.94	gold quality
nucleus accumbens	UBERON:0001882	60.83	gold quality
prefrontal cortex	UBERON:0000451	60.61	gold quality
rectum	UBERON:0001052	60.56	gold quality
anterior cingulate cortex	UBERON:0009835	60.56	gold quality
vagina	UBERON:0000996	60.53	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-HCAD-11	yes	18.33
E-ANND-3	yes	3.15
E-MTAB-8060	no	40.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

32 targeting WNT10A, 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-3646	100.00	73.56	5283
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-454-3P	99.91	74.01	1925
HSA-MIR-301B-3P	99.90	73.19	1836
HSA-MIR-130A-3P	99.90	73.31	1861
HSA-MIR-130B-3P	99.90	73.27	1850
HSA-MIR-301A-3P	99.90	73.15	1839
HSA-MIR-3666	99.90	73.24	1833
HSA-MIR-4295	99.90	73.11	1838
HSA-MIR-548AJ-5P	99.78	71.12	3085
HSA-MIR-548F-5P	99.78	71.02	3093
HSA-MIR-548G-5P	99.78	71.12	3085
HSA-MIR-548X-5P	99.78	71.12	3085
HSA-MIR-378G	99.71	64.90	1106
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-5004-5P	99.68	66.63	1294
HSA-MIR-7515	99.31	68.22	1795
HSA-MIR-361-3P	99.19	66.45	1381
HSA-MIR-138-2-3P	98.91	68.33	1643
HSA-MIR-6864-5P	98.38	66.59	1079
HSA-MIR-6882-3P	98.23	67.01	1119
HSA-MIR-337-3P	97.90	69.37	1052
HSA-MIR-7113-5P	97.88	67.33	1735
HSA-MIR-3116	97.07	65.78	1324
HSA-MIR-5194	96.77	63.91	1021
HSA-MIR-6782-5P	96.45	64.42	612
HSA-MIR-7109-3P	94.23	67.19	743

Literature-anchored findings (GeneRIF, showing 40)

• c.697G–>T (p.Glu233X) homozygous nonsense mutation in exon 3 of the WNT10A gene in an autosomal recessive ectodermal dysplasia: odonto-onycho-dermal dysplasia (PMID:17847007)
• mantle cell lymphoma highly and consistently expressed Wnt3 and Wnt10. (PMID:18787224)
• The first inherited missense mutation in WNT10A with associated ectodermal features, is reported. (PMID:19471313)
• Study reports on 12 patients, from 11 unrelated families, with ectodermal dysplasia caused by five previously undescribed WNT10A mutations (PMID:19559398)
• Results demonstrated significant up-regulation of WNT-3, WNT-4, WNT-5B, WNT-7B, WNT-9A, WNT-10A, and WNT-16B in patients with CLL compared to normal subjects. (PMID:19863181)
• patients harboring WNT10A mutations displayed distinctive clinical features (marked dental phenotype, no facial dysmorphism) (PMID:20979233)
• Mutations in the WNT10A gene are associated with ectodermal dysplasia presenting as palmoplantar keratoderma in two families. (PMID:21143469)
• WNT10A may be a novel angio/stromagenic growth factor (PMID:21203463)
• Case Reports: Single pedigree study provides a detailed illustration of the phenotypic spectrum of ectodermal abnormalities associated with WNT10A gene pathology. (PMID:21279306)
• We observed a marginally significant interaction between WNT10 rs10177996 (intron 1) and an individual’s proportion of calories from saturated fat. (PMID:21547848)
• In a panel of 34 patients with isolated hypodontia, the candidate gene WNT10A and the genes MSX1, PAX9, IRF6 and AXIN2 have been sequenced. WNT10A mutations were identified in 56% of the cases with non-syndromic hypodontia. (PMID:22581971)
• WNT10A acts as an autocrine oncogene both in renal cell carcinoma carcinogenesis and progression by activating WNT/beta-catenin signaling. (PMID:23094073)
• the expression level of Wnt10a is higher in endometrioid carcinoma than in non-endometrioid subtypes; however, the underlying mechanism remains unclear. (PMID:23135473)
• Nine pathogenic mutations within the coding region of the WNT10A gene were identified in 26 out of 42 (62%) Polish patients with non-syndromic tooth agenesis. (PMID:23167694)
• Expression studies in human hair follicle tissue suggests that WNT10A has a functional role in androgenetic alopecia etiology. (PMID:23358095)
• Mutations in WNT10A are frequently involved in oligodontia associated with minor signs of ectodermal dysplasia. (PMID:23401279)
• WNT10A variants were associated with non-syndromic tooth agenesis from mild to severe tooth agenesis, and the more severe tooth agenesis, the stronger association. (PMID:24043634)
• Our study has demonstrated for the first time that agenesis of the maxillary permanent canines is a distinct entity, associated with mutations in WNT10A. (PMID:24311251)
• WNT10A and EDA digenic mutations could result in oligodontia and syndromic tooth agenesis in the Chinese population. Moreover, our results will greatly expand the genotypic spectrum of tooth agenesis. (PMID:24312213)
• WNT10A mutations account for (1/4) of population-based isolated oligodontia and show phenotypic correlations. (PMID:24449199)
• Barrel-shaped mandibular incisors and severe hypodontia appear to be associated with homozygous or compound heterozygous mutations of WNT10A. (PMID:24458874)
• involvement of PAX9, EDA, SPRY2, SPRY4, and WNT10A as risk factors for MLIA. uncovered 3 strong synergistic interactions between MLIA liability and MSX1-TGFA, AXIN2-TGFA, and SPRY2-SPRY4 gene pairs. 1st evidence of sprouty genes in MLIA susceptibility. (PMID:24554542)
• Patients with bi-allelic WNT10A mutations have severe tooth agenesis. (PMID:24700731)
• The novel c.-14_7delinsC mutation might be the etiological variant of the WNT10A gene responsible for the permanent tooth agenesis in the Egyptian family. (PMID:24798981)
• transmission disequilibrium test showed transmitted disequilibrium in C392T. we found an association between the C392T variant and nonsyndromic oral clefts. (PMID:24957471)
• WNT10A may induce kidney fibrosis and associate with kidney dysfunction in acute interstitial nephritis. (PMID:25054240)
• WNT10A promotes the proliferation of DPCs and negatively regulates their odontoblastic differentiation. (PMID:25134734)
• p.Arg113Cys, p.Phe228Ile, newly identified p.Arg171Leu may represent aetiological mutations underlying MLIA w/associated dental anomalies, implicating coding variants in WNT10A gene (PMID:25545742)
• this study demonstrated that common variations in WNT10A have pleiotropic effects on the morphology of ectodermal appendages. (PMID:25612571)
• High WNT10A expression promotes an invasive and self-renewing phenotype in esophageal squamous cell carcinoma (PMID:25795715)
• WNT10A exonic variant increases the risk of keratoconus by decreasing corneal thickness (PMID:26049155)
• risk of hypodontia may be related to the WNT10A polymorphism. Our results also confirm the importance of the Wnt pathway in tooth development. (PMID:27050986)
• The development of maxillary canine, maxillary second molar and mandibular second molar was statistically significantly delayed in patients with WNT10A variants compared with patients without variants. The impact of WNT10A variants on dental development increases with presence of the nonsense c.(321C>A p.(C107*)) variant and the number of missing teeth (PMID:27650966)
• Wnt10a/beta-catenin signaling pathway is able to exacerbate keloid cell proliferation and inhibit the apoptosis of keloid cells through its interaction with TERT. (PMID:27771714)
• miR-378a-3p suppresses hepatic stellate cell activation, at least in part, via targeting of Wnt10a, supporting its potential utility as a novel therapeutic target for liver fibrosis. (PMID:27832641)
• Results from genetic analysis revealed that all seven individuals were homozygous or compound heterozygous for WNT10A mutations suggesting that tooth agenesis and/or peg-shaped crowns of primary mandibular incisors, severe oligodontia of permanent dentition as well as ectodermal symptoms of varying severity may be predictors of bi-allelic WNT10A mutations of importance for diagnosis, counselling and follow-up. (PMID:27881089)
• Mild to severe oligodontia was observed in all patients bearing biallelic WNT10A mutations. (PMID:28105635)
• Human and mouse WNT10A mutant palmoplantar and tongue epithelia also display specific differentiation defects that are mimicked by loss of the transcription factor KLF4. (PMID:28589954)
• High WNT10A expression is associated with papillary thyroid carcinoma. (PMID:28677753)
• The study confirmed that Phe228Ile is the most frequent WNT10A variant in Caucasian populations, and that WNT10A mutations are associated with large variability in EDI. (PMID:28976000)

Cross-species orthologs

9 orthologs

Organism	Symbol	Gene ID
danio_rerio	wnt10a	ENSDARG00000017155
mus_musculus	Wnt10a	ENSMUSG00000026167
rattus_norvegicus	Wnt10a	ENSRNOG00000052510
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), WNT9A (ENSG00000143816), WNT3A (ENSG00000154342), WNT7A (ENSG00000154764), WNT9B (ENSG00000158955), WNT4 (ENSG00000162552), WNT10B (ENSG00000169884), WNT7B (ENSG00000188064)

Protein

Protein identifiers

Protein Wnt-10a — Q9GZT5 (reviewed: Q9GZT5)

All UniProt accessions (3): A0A2K8FR47, Q9GZT5, H7BZB8

UniProt curated annotations — full annotation on UniProt →

Function. Ligand for members of the frizzled family of seven transmembrane receptors. Functions in the canonical Wnt/beta-catenin signaling pathway. Plays a role in normal ectoderm development. Required for normal tooth development. Required for normal postnatal development and maintenance of tongue papillae and sweat ducts. Required for normal proliferation of basal cells in tongue filiform papillae, plantar epithelium and sweat ducts. Required for normal expression of keratins in tongue papillae. Required for normal expression of KRT9 in foot plant epithelium. Required for normal hair follicle function.

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.

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

Disease relevance. Odonto-onycho-dermal dysplasia (OODD) [MIM:257980] A rare autosomal recessive ectodermal dysplasia characterized by dry hair, severe hypodontia, smooth tongue with marked reduction of fungiform and filiform papillae, onychodysplasia, keratoderma and hyperhidrosis of palms and soles, and hyperkeratosis of the skin. The disease is caused by variants affecting the gene represented in this entry. Schopf-Schulz-Passarge syndrome (SSPS) [MIM:224750] A rare ectodermal dysplasia, characterized chiefly by cysts of the eyelid margins, palmoplantar keratoderma, hypodontia, hypotrichosis and nail dystrophy. Multiple eyelid apocrine hidrocystomas are the hallmark of this condition, although they usually appear in adulthood. The concomitant presence of eccrine syringofibroadenoma in most patients and of other adnexal skin tumors in some affected subjects indicates that Schopf-Schulz-Passarge syndrome is a genodermatosis with skin appendage neoplasms. The disease is caused by variants affecting the gene represented in this entry. Tooth agenesis, selective, 4 (STHAG4) [MIM:150400] 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). In STHAG4, the upper lateral incisors are absent or peg-shaped. Some STHAG4 patients manifest mild features of ectodermal dysplasia, including sparse hair, sparse eyebrows, short eyelashes, abnormalities of the nails, sweating anomalies and dry skin. STHAG4 inheritance is autosomal dominant or autosomal recessive. The disease is caused by variants affecting the gene represented in this entry.

Similarity. Belongs to the Wnt family.

RefSeq proteins (1): NP_079492* (*=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 (49 total): sequence variant 29, disulfide bond 11, glycosylation site 2, signal peptide 1, chain 1, region of interest 1, compositionally biased region 1, modified residue 1, sequence conflict 1, lipid moiety-binding region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9GZT5-F1	82.36	0.52

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): 59, 268

Disulfide bonds (11): 159–214, 262–276, 264–271, 346–377, 362–372, 376–416, 392–407, 394–404, 399–400, 96–107, 149–157

Glycosylation sites (2): 106, 363

Function

Pathways and Gene Ontology

Reactome pathways

2 pathways

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

MSigDB gene sets: 0 (showing top):

GO Biological Process (17): hair follicle development (GO:0001942), positive regulation of gene expression (GO:0010628), neural crest cell differentiation (GO:0014033), neuron differentiation (GO:0030182), hair follicle morphogenesis (GO:0031069), odontogenesis (GO:0042476), regulation of odontogenesis of dentin-containing tooth (GO:0042487), tongue development (GO:0043586), skin development (GO:0043588), cell fate commitment (GO:0045165), epidermis morphogenesis (GO:0048730), sebaceous gland development (GO:0048733), canonical Wnt signaling pathway (GO:0060070), cellular response to transforming growth factor beta stimulus (GO:0071560), multicellular organism development (GO:0007275), Wnt signaling pathway (GO:0016055), animal organ development (GO:0048513)

GO Molecular Function (4): frizzled binding (GO:0005109), cytokine activity (GO:0005125), receptor ligand activity (GO:0048018), signaling receptor binding (GO:0005102)

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

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Signaling by WNT	1
GPCR ligand binding	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
anatomical structure development	3
hair cycle process	2
cell differentiation	2
skin epidermis development	1
gene expression	1
regulation of gene expression	1
positive regulation of macromolecule biosynthetic process	1
mesenchymal cell differentiation	1
stem cell differentiation	1
generation of neurons	1
hair follicle development	1
anatomical structure morphogenesis	1
epidermis morphogenesis	1
animal organ morphogenesis	1
odontogenesis of dentin-containing tooth	1
regulation of odontogenesis	1
sensory organ development	1
animal organ development	1
cellular developmental process	1
morphogenesis of an epithelium	1
epidermis development	1
skin development	1
gland development	1
Wnt signaling pathway	1
cellular response to growth factor stimulus	1
response to transforming growth factor beta	1
multicellular organismal process	1
cell surface receptor signaling pathway	1
G protein-coupled receptor binding	1
receptor ligand activity	1
signaling receptor binding	1
signal transduction	1
signaling receptor activator activity	1
protein binding	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1050 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
WNT10A	EDA	Q92838	922
WNT10A	PAX9	P55771	863
WNT10A	LRP5	O75197	782
WNT10A	MSX1	P28360	761
WNT10A	LRP6	O75581	753
WNT10A	LTBP3	Q9NS15	752
WNT10A	FZD1	Q9UP38	751
WNT10A	LTBP2	Q14767	741
WNT10A	EDARADD	Q8WWZ3	728
WNT10A	FZD7	O75084	722
WNT10A	EDAR	Q9UNE0	710
WNT10A	FZD8	Q9H461	709
WNT10A	AXIN2	Q9Y2T1	693
WNT10A	FZD5	Q13467	690
WNT10A	FZD6	O60353	689

IntAct

6 interactions, top by confidence:

A	B	Type	Score
WNT10A	AFM	psi-mi:“MI:0915”(physical association)	0.400
WNT10A	HSPA5	psi-mi:“MI:0914”(association)	0.350
HNF1A	WNT10A	psi-mi:“MI:0914”(association)	0.350
WNT10A	MANBA	psi-mi:“MI:0914”(association)	0.350
	WNT10A	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (36): WNT10A (Proximity Label-MS), ZMYND19 (Affinity Capture-MS), WNT10A (Affinity Capture-MS), HSPA5 (Affinity Capture-MS), RMND5A (Affinity Capture-MS), MAEA (Affinity Capture-MS), GID8 (Affinity Capture-MS), MKLN1 (Affinity Capture-MS), RANBP10 (Affinity Capture-MS), WDR26 (Affinity Capture-MS), ARMC8 (Affinity Capture-MS), RANBP9 (Affinity Capture-MS), DNAJC3 (Affinity Capture-MS), PASK (Affinity Capture-MS), UBR1 (Affinity Capture-MS)

ESM2 similar proteins: B2GUT4, O00744, O73864, O75173, O96014, P04426, P04628, P09531, P22724, P22727, P24257, P34820, P34821, P43446, P48614, P48615, P49339, P49340, P49893, P51891, P55103, P56705, P57110, P70701, Q28J82, Q5Q0T9, Q5RFQ8, Q5T4F7, Q641Q3, Q66II0, Q670P5, Q6ZVN8, Q7TQ32, Q7Z5Y6, Q801F7, Q8BNJ2, Q8C1Q4, Q8N7M5, Q91029, Q93097

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

SIGNOR signaling

5 interactions.

A	Effect	B	Mechanism
WNT10A	up-regulates	FZD3	binding
WNT10A	up-regulates	LRP5	binding
WNT10A	up-regulates	LRP6	binding
WNT10A	up-regulates	CTNNB1
SOSTDC1	“down-regulates activity”	WNT10A

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	65
Likely pathogenic	28
Uncertain significance	179
Likely benign	267
Benign	4

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1070433	NM_025216.3(WNT10A):c.648del (p.Asp217fs)	Pathogenic
1070444	NM_025216.3(WNT10A):c.295del (p.Gln99fs)	Pathogenic
1073272	NM_025216.3(WNT10A):c.495_502dup (p.Glu168fs)	Pathogenic
1073385	NM_025216.3(WNT10A):c.932del (p.Glu311fs)	Pathogenic
1074605	NM_025216.3(WNT10A):c.993del (p.Ser332fs)	Pathogenic
1075184	NM_025216.3(WNT10A):c.315G>A (p.Trp105Ter)	Pathogenic
1075261	NM_025216.3(WNT10A):c.490C>T (p.Arg164Ter)	Pathogenic
1075575	NM_025216.3(WNT10A):c.847_851del (p.Phe283fs)	Pathogenic
1076644	NM_025216.3(WNT10A):c.55_56dup (p.Pro20fs)	Pathogenic
1365136	NM_025216.3(WNT10A):c.532_536del (p.Gln178fs)	Pathogenic
1404347	NM_025216.3(WNT10A):c.85del (p.Leu29fs)	Pathogenic
1412867	NM_025216.3(WNT10A):c.1091dup (p.Ser365fs)	Pathogenic
1417009	NM_025216.3(WNT10A):c.580del (p.Glu194fs)	Pathogenic
1453389	NM_025216.3(WNT10A):c.354T>A (p.Tyr118Ter)	Pathogenic
1458073	NM_025216.3(WNT10A):c.1063del (p.Ala355fs)	Pathogenic
1460070	NC_000002.11:g.(?219745718)(219757993_?)del	Pathogenic
2030181	NM_025216.3(WNT10A):c.574del (p.Val192fs)	Pathogenic
2030582	NM_025216.3(WNT10A):c.1046del (p.Glu349fs)	Pathogenic
2034704	NM_025216.3(WNT10A):c.673del (p.Ser225fs)	Pathogenic
2076317	NM_025216.3(WNT10A):c.983_984del (p.Arg328fs)	Pathogenic
2084754	NM_025216.3(WNT10A):c.386del (p.Glu129fs)	Pathogenic
2131175	NM_025216.3(WNT10A):c.532C>T (p.Gln178Ter)	Pathogenic
2133011	NM_025216.3(WNT10A):c.982_986dup (p.Arg330fs)	Pathogenic
2143000	NM_025216.3(WNT10A):c.1018G>T (p.Glu340Ter)	Pathogenic
2426931	NC_000002.11:g.(?219745708)(219747155_?)del	Pathogenic
2576981	NM_025216.3(WNT10A):c.26G>A (p.Trp9Ter)	Pathogenic
2576983	NM_025216.3(WNT10A):c.1070C>T (p.Thr357Ile)	Pathogenic
2577029	NM_025216.3(WNT10A):c.1036del (p.Cys346fs)	Pathogenic
265293	NM_025216.3(WNT10A):c.742C>T (p.Arg248Ter)	Pathogenic
265294	NM_025216.3(WNT10A):c.803C>G (p.Ser268Ter)	Pathogenic

SpliceAI

640 predictions. Top by Δscore:

Variant	Effect	Δscore
2:218892768:CCGCA:C	acceptor_loss	1.0000
2:218892769:CGCA:C	acceptor_loss	1.0000
2:218892770:GCAG:G	acceptor_loss	1.0000
2:218892771:CAGGC:C	acceptor_loss	1.0000
2:218892772:A:AG	acceptor_gain	1.0000
2:218892772:A:T	acceptor_loss	1.0000
2:218892773:G:GA	acceptor_gain	1.0000
2:218892773:GGCA:G	acceptor_gain	1.0000
2:218882158:CA:C	acceptor_loss	0.9900
2:218882159:A:AT	acceptor_loss	0.9900
2:218882160:GGTCA:G	acceptor_gain	0.9900
2:218882421:GAG:G	donor_gain	0.9900
2:218889979:CACAG:C	acceptor_loss	0.9900
2:218889981:CAGGT:C	acceptor_loss	0.9900
2:218890156:GCGTG:G	donor_gain	0.9900
2:218892769:C:A	acceptor_gain	0.9900
2:218892772:AG:A	acceptor_gain	0.9900
2:218892773:GG:G	acceptor_gain	0.9900
2:218892773:GGC:G	acceptor_gain	0.9900
2:218881106:CAGG:C	donor_loss	0.9800
2:218881107:AGG:A	donor_loss	0.9800
2:218881109:GT:G	donor_loss	0.9800
2:218881110:T:G	donor_loss	0.9800
2:218882152:T:G	acceptor_gain	0.9800
2:218882159:A:AG	acceptor_gain	0.9800
2:218882160:G:GG	acceptor_gain	0.9800
2:218882403:A:T	donor_gain	0.9800
2:218889976:A:AG	acceptor_gain	0.9800
2:218889982:A:AG	acceptor_gain	0.9800
2:218889983:G:GG	acceptor_gain	0.9800

AlphaMissense

2716 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:218882309:G:C	G88R	1.000
2:218882309:G:T	G88C	1.000
2:218882360:T:A	W105R	1.000
2:218882360:T:C	W105R	1.000
2:218882362:G:C	W105C	1.000
2:218882362:G:T	W105C	1.000
2:218890345:C:A	N246K	1.000
2:218890345:C:G	N246K	1.000
2:218892848:G:C	W277C	1.000
2:218892848:G:T	W277C	1.000
2:218892876:G:T	G287W	1.000
2:218893101:T:A	C362S	1.000
2:218893102:G:C	C362S	1.000
2:218893204:T:G	F396C	1.000
2:218893264:G:A	C416Y	1.000
2:218893265:C:G	C416W	1.000
2:218882310:G:A	G88D	0.999
2:218882333:T:A	C96S	0.999
2:218882333:T:C	C96R	0.999
2:218882334:G:A	C96Y	0.999
2:218882334:G:C	C96S	0.999
2:218882334:G:T	C96F	0.999
2:218882335:C:G	C96W	0.999
2:218882366:T:A	C107S	0.999
2:218882366:T:C	C107R	0.999
2:218882367:G:A	C107Y	0.999
2:218882367:G:C	C107S	0.999
2:218882367:G:T	C107F	0.999
2:218882368:C:G	C107W	0.999
2:218889995:A:C	S130R	0.999

dbSNP variants (sampled 300 via entrez): RS1000062194 (2:218888769 A>C,G), RS1000340948 (2:218885550 C>A,G), RS1000373571 (2:218885805 G>A), RS1000438849 (2:218882079 G>A,C,T), RS1000490109 (2:218879368 T>C), RS1000503344 (2:218891319 G>A,T), RS1000685216 (2:218889212 A>G), RS1000769227 (2:218883664 G>A,C), RS1000780829 (2:218875810 T>C), RS1000974096 (2:218874646 G>A), RS1001140940 (2:218872294 G>C), RS1001265422 (2:218879138 C>T), RS1001333454 (2:218877794 G>A), RS1001633530 (2:218886481 C>T), RS1001883653 (2:218880780 G>A,C)

Disease associations

OMIM: gene MIM:606268 | disease phenotypes: MIM:150400, MIM:224750, MIM:257980, MIM:602639, MIM:615510, MIM:600057, MIM:305100

GenCC curated gene-disease

Disease	Classification	Inheritance
ectodermal dysplasia WNT10A related	Definitive	Semidominant
tooth agenesis, selective, 4	Strong	Autosomal dominant
odonto-onycho-dermal dysplasia	Strong	Autosomal recessive
autosomal recessive hypohidrotic ectodermal dysplasia	Supportive	Autosomal recessive
Schöpf-Schulz-Passarge syndrome	Supportive	Autosomal dominant
tooth agenesis	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
ectodermal dysplasia WNT10A related	Definitive	SD

Mondo (12): tooth agenesis, selective, 4 (MONDO:0007881), Schöpf-Schulz-Passarge syndrome (MONDO:0009145), odonto-onycho-dermal dysplasia (MONDO:0009773), tooth agenesis, selective, 2 (MONDO:0011265), alacrima, achalasia, and intellectual disability syndrome (MONDO:0014219), paroxysmal nonkinesigenic dyskinesia (MONDO:0700088), bladder exstrophy-epispadias-cloacal exstrophy complex (MONDO:0700039), ectodermal dysplasia WNT10A related (MONDO:0100358), ectodermal dysplasia syndrome (MONDO:0019287), hypohidrotic ectodermal dysplasia (MONDO:0016535), autosomal recessive hypohidrotic ectodermal dysplasia (MONDO:0016619), tooth agenesis (MONDO:0005486)

Orphanet (8): Odonto-onycho-dermal dysplasia (Orphanet:2721), Schöpf-Schulz-Passarge syndrome (Orphanet:50944), Oligodontia (Orphanet:99798), Triple A syndrome (Orphanet:869), Paroxysmal non-kinesigenic dyskinesia (Orphanet:98810), Classic bladder exstrophy (Orphanet:93930), Ectodermal dysplasia syndrome (Orphanet:79373), Hypohidrotic ectodermal dysplasia (Orphanet:238468)

HPO phenotypes

86 total (30 of 86 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000007	Autosomal recessive inheritance
HP:0000202	Orofacial cleft
HP:0000320	Bird-like facies
HP:0000478	Abnormality of the eye
HP:0000613	Photophobia
HP:0000668	Hypodontia
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:0000962	Hyperkeratosis
HP:0000963	Thin skin
HP:0000966	Hypohidrosis
HP:0000968	Ectodermal dysplasia
HP:0000972	Palmoplantar hyperkeratosis
HP:0000975	Hyperhidrosis
HP:0000982	Palmoplantar keratoderma
HP:0001231	Abnormal fingernail morphology
HP:0001595	Abnormal hair morphology
HP:0001596	Alopecia
HP:0001792	Small nail
HP:0001798	Anonychia
HP:0001799	Short nail

GWAS associations

16 associations (top):

Study	Trait	p-value
GCST000519_15	Hair morphology	1.000000e-06
GCST000706_2	Common traits (Other)	3.000000e-14
GCST003983_12	Male-pattern baldness	2.000000e-16
GCST005116_18	Male-pattern baldness	1.000000e-19
GCST005191_5	Hair shape	8.000000e-26
GCST005389_4	Tooth agenesis	2.000000e-40
GCST006366_1	Central corneal thickness	5.000000e-13
GCST006661_114	Male-pattern baldness	2.000000e-16
GCST007234_8	Acne (severe)	2.000000e-12
GCST007234_9	Acne (severe)	4.000000e-07
GCST008295_45	Number of decayed, missing and filled tooth surfaces or use of dentures	2.000000e-22
GCST008306_28	Dentures	2.000000e-20
GCST008317_10	Central corneal thickness	5.000000e-11
GCST010002_409	Refractive error	2.000000e-17
GCST010173_53	Triglyceride levels	2.000000e-33
GCST011011_13	Youthful appearance (self-reported)	3.000000e-11

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0005038	hair morphology
EFO:0005213	central corneal thickness
EFO:0010078	dentures
EFO:0004530	triglyceride measurement

MeSH disease descriptors (6)

Descriptor	Name	Tree numbers
D004476	Ectodermal Dysplasia	C16.131.077.350; C16.131.831.350; C16.320.850.250; C17.800.804.350; C17.800.827.250
D053360	Ectodermal Dysplasia, Hypohidrotic, Autosomal Recessive	C16.131.077.350.348; C16.131.831.350.348; C16.320.850.250.348; C17.800.804.350.348; C17.800.827.250.348
C537742	Odontoonychodermal dysplasia (supp.)
C565607	Schopf-Schulz-Passarge Syndrome (supp.)
C566513	Tooth Agenesis, Selective, 2 (supp.)
C563634	Tooth Agenesis, Selective, 4 (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Particulate Matter	increases abundance, decreases methylation, increases expression, decreases expression	3
bisphenol A	decreases expression, affects cotreatment, decreases methylation	2
Resveratrol	affects cotreatment, decreases expression	2
Air Pollutants	decreases methylation, increases expression, decreases expression, increases abundance	2
Estradiol	affects cotreatment, decreases expression	2
Valproic Acid	increases expression	2
FR900359	increases phosphorylation	1
ETC-159	decreases expression	1
kojic acid	decreases expression	1
11-nor-delta(9)-tetrahydrocannabinol-9-carboxylic acid	affects methylation, increases abundance	1
sodium arsenite	increases expression	1
butyraldehyde	increases expression	1
benzo(e)pyrene	increases methylation	1
tebuconazole	decreases expression	1
deguelin	increases expression	1
2-palmitoylglycerol	increases expression	1
erucylphospho-N,N,N-trimethylpropylammonium	decreases expression	1
abrine	increases expression	1
LGK974	decreases expression	1
Fulvestrant	affects cotreatment, decreases methylation	1
Microplastics	increases abundance, decreases expression	1
Arbutin	decreases expression	1
Arsenic	affects expression	1
Benzo(a)pyrene	decreases methylation	1
Cannabinoids	affects methylation, increases abundance	1
Diazinon	increases methylation	1
Ethyl Methanesulfonate	decreases expression	1
Formaldehyde	decreases expression	1
Methapyrilene	increases methylation	1
Methyl Methanesulfonate	decreases expression	1

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00001211	Not specified	COMPLETED	Clinical Study of Oral Endosseous Titanium Implants in Edentulous Subjects
NCT00266513	Not specified	TERMINATED	Studies of Disorders in Antibody Production and Related Primary Immunodeficiency States
NCT01108770	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia
NCT02896387	Not specified	TERMINATED	Ability of a Molecule (Prima) to Restore Physiological Differentiation in Epithelium Expressing Gene p63
NCT05954416	Not specified	RECRUITING	FARD (RaDiCo Cohort) (RaDiCo-FARD)
NCT06330324	Not specified	ENROLLING_BY_INVITATION	Reproductive Options in Inherited Skin Diseases
NCT06330350	Not specified	RECRUITING	Qualitative Study in Patients With Genodermatoses and Healthcare Professionals on Reproductive Counselling
NCT07468019	Not specified	RECRUITING	Organization’s Unique Protocol ID
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.
NCT01109290	Not specified	COMPLETED	Characterization of Sweat Gland Function in Patients With Recessively Inherited Hypohidrotic Ectodermal Dysplasia
NCT01293565	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected by Hypohidrotic Ectodermal Dysplasia - A
NCT01386775	Not specified	COMPLETED	Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia: Intrafamilial Variation
NCT01398397	Not specified	COMPLETED	Medical Record Review of Hypohidrotic Ectodermal Dysplasia Clinical Phenotype
NCT01398813	Not specified	COMPLETED	X-Linked Hypohidrotic Ectodermal Dysplasia (XLHED) Carrier Outlook Toward Reproduction Survey
NCT01629927	Not specified	COMPLETED	Evaluation of Phenotypic and Genetic Properties in Male Subjects Affected By Hypohidrotic Ectodermal Dysplasia (ECP-012)
NCT01629940	Not specified	COMPLETED	Phenotypic and Genetic Properties in Males at Risk for X-linked Hypohidrotic Ectodermal Dysplasia: Evaluation of an Early Diagnosis Technology and Tests to Assess Nutritional Status
NCT04741412	Not specified	COMPLETED	Pediatric SARS-CoV-2 Infections: Course of COVID-19, Immune Responses, Complications and Long-term Consequences
NCT05378932	Not specified	COMPLETED	Impact of Dysregulation of Core Body Temperature on Sleep in Patients With Hypohidrotic Ectodermal Dysplasia