WNT10A

Wnt family member 10A, the group of Wnt family

Basic information

Region (hg38): 2:218880851-218899581

Links

ENSG00000135925 ∙ NCBI:80326 ∙ OMIM:606268 ∙ HGNC:13829 ∙ Uniprot:Q9GZT5 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• odonto-onycho-dermal dysplasia (Supportive), mode of inheritance: AR
• autosomal recessive hypohidrotic ectodermal dysplasia (Supportive), mode of inheritance: AR
• SchC6pf-Schulz-Passarge syndrome (Supportive), mode of inheritance: AD
• tooth agenesis (Supportive), mode of inheritance: AD
• odonto-onycho-dermal dysplasia (Strong), mode of inheritance: AR
• ectodermal dysplasia WNT10A related (Definitive), mode of inheritance: Semidominant
• tooth agenesis, selective, 4 (Strong), mode of inheritance: AD
• ectodermal dysplasia WNT10A related (Definitive), mode of inheritance: Semidominant

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Odontoonychodermal dysplasia; Schopf-Schulz-Passarge syndrome; Tooth agenesis, selective, 4	AR	General	Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing	Dental; Dermatologic	4281327; 6837628; 15316967; 17847007; 19471313; 19559398; 20163410; 20418069; 21143469; 21484994; 21834823; 24449199

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the WNT10A gene.

• Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia (165 variants)
• Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4 (152 variants)
• SchC6pf-Schulz-Passarge syndrome (92 variants)
• Tooth agenesis, selective, 4 (68 variants)
• Odonto-onycho-dermal dysplasia (67 variants)
• not provided (45 variants)
• Inborn genetic diseases (19 variants)
• not specified (8 variants)
• Odonto-onycho-dermal dysplasia;SchC6pf-Schulz-Passarge syndrome;Tooth agenesis, selective, 4 (6 variants)
• WNT10A-related condition (5 variants)
• Tooth agenesis (4 variants)
• Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia;SchC6pf-Schulz-Passarge syndrome (3 variants)
• Abnormality of the dentition (2 variants)
• Tooth agenesis, selective, 2 (2 variants)
• Tooth agenesis, selective, 4;SchC6pf-Schulz-Passarge syndrome (2 variants)
• Ectodermal dysplasia (2 variants)
• SchC6pf-Schulz-Passarge syndrome;Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4 (2 variants)
• Selective tooth agenesis (1 variants)
• Bladder exstrophy-epispadias-cloacal extrophy complex (1 variants)
• Hypohidrotic ectodermal dysplasia (1 variants)
• Stiff skin;Arthralgia;Palmoplantar keratoderma (1 variants)
• Oligodontia (1 variants)
• WNT10A-Related Disorders (1 variants)
• SchC6pf-Schulz-Passarge syndrome;Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia (1 variants)
• Tooth agenesis, selective, 4;SchC6pf-Schulz-Passarge syndrome;Odonto-onycho-dermal dysplasia (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the WNT10A gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous				171	2	173
missense	2	14	76	10	1	103
nonsense	15	4	1			20
start loss	1	2				3
frameshift	25	3				28
inframe indel			2			2
splice donor/acceptor (+/-2bp)	1	1				2
splice region			1	3		4
non coding			11	8	1	20
Total	44	24	90	189	4

Highest pathogenic variant AF is 0.000834

Variants in WNT10A

This is a list of pathogenic ClinVar variants found in the WNT10A region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
2-218880873-C-A		SchC6pf-Schulz-Passarge syndrome • Tooth agenesis, selective, 4 • Odonto-onycho-dermal dysplasia • Odonto-onycho-dermal dysplasia;SchC6pf-Schulz-Passarge syndrome;Tooth agenesis, selective, 4	Uncertain significance (Jul 15, 2021)
2-218880926-G-C		Odonto-onycho-dermal dysplasia • Tooth agenesis, selective, 4 • SchC6pf-Schulz-Passarge syndrome	Uncertain significance (Apr 27, 2017)
2-218880974-AGCCCGTCAGGGCCTGCGCGCCATGGGCAGC-A		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely pathogenic (Jan 29, 2024)
2-218880996-A-G		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Pathogenic (Dec 15, 2023)
2-218880996-A-T		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Pathogenic (Sep 27, 2022)
2-218880996-ATGGGCAGCGCCCACCCTCGCCCC-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Pathogenic (Dec 24, 2022)
2-218880998-G-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely pathogenic (May 16, 2022)
2-218880999-G-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia • SchC6pf-Schulz-Passarge syndrome	Likely benign (Jan 31, 2024)
2-218881002-A-T		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Uncertain significance (Sep 01, 2021)
2-218881016-C-G		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely benign (Nov 07, 2022)
2-218881016-C-T		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely benign (Apr 22, 2022)
2-218881021-G-A		Tooth agenesis, selective, 4	Pathogenic (-)
2-218881022-G-A		Odonto-onycho-dermal dysplasia	Pathogenic (Jul 01, 2009)
2-218881028-G-A		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely benign (Feb 05, 2023)
2-218881031-C-G		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely benign (Feb 28, 2022)
2-218881031-C-T		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely benign (Sep 28, 2022)
2-218881032-C-T		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Pathogenic (Mar 12, 2023)
2-218881033-G-C		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4 • Inborn genetic diseases	Uncertain significance (Jan 03, 2024)
2-218881034-A-T		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely benign (Apr 23, 2022)
2-218881037-C-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely benign (Apr 26, 2023)
2-218881040-G-A		Odonto-onycho-dermal dysplasia;Tooth agenesis, selective, 4	Likely benign (Apr 21, 2020)
2-218881047-C-CCG		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Pathogenic (Oct 31, 2021)
2-218881049-G-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely benign (Nov 21, 2023)
2-218881049-G-C		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Likely benign (Feb 09, 2022)
2-218881054-C-A		Tooth agenesis, selective, 4;Odonto-onycho-dermal dysplasia	Uncertain significance (Jan 31, 2024)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
WNT10A	protein_coding	protein_coding	ENST00000258411	4	19219

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
4.17e-9	0.201	125560	0	187	125747	0.000744

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	-0.449	281	261	1.08	0.0000148	2659
Missense in Polyphen		115	114.89	1.0009		1241
Synonymous	-0.0973	113	112	1.01	0.00000649	871
Loss of Function	0.458	14	16.0	0.876	9.50e-7	142

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000550	0.000550
Ashkenazi Jewish	0.00	0.00
East Asian	0.000444	0.000435
Finnish	0.0000924	0.0000924
European (Non-Finnish)	0.00145	0.00143
Middle Eastern	0.000444	0.000435
South Asian	0.0000681	0.0000653
Other	0.000326	0.000326

dbNSFP

Source: dbNSFP

• Function: FUNCTION: Ligand for members of the frizzled family of seven transmembrane receptors (Probable). Functions in the canonical Wnt/beta-catenin signaling pathway (By similarity). Plays a role in normal ectoderm development (PubMed:17847007, PubMed:28589954). Required for normal tooth development (PubMed:17847007, PubMed:29178643, PubMed:28589954). Required for normal postnatal development and maintenance of tongue papillae and sweat ducts (PubMed:28589954). 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 (By similarity). Required for normal expression of KRT9 in foot plant epithelium (PubMed:28589954). Required for normal hair follicle function (PubMed:28589954). {ECO:0000250|UniProtKB:P70701, ECO:0000269|PubMed:17847007, ECO:0000269|PubMed:28589954, ECO:0000269|PubMed:29178643, ECO:0000305}.
• Disease: DISEASE: 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. {ECO:0000269|PubMed:17847007, ECO:0000269|PubMed:19471313, ECO:0000269|PubMed:19559398, ECO:0000269|PubMed:24458874, ECO:0000269|PubMed:28589954}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:19559398, ECO:0000269|PubMed:21143469}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: 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. {ECO:0000269|PubMed:20979233, ECO:0000269|PubMed:21484994, ECO:0000269|PubMed:22581971, ECO:0000269|PubMed:23401279, ECO:0000269|PubMed:24311251, ECO:0000269|PubMed:24449199, ECO:0000269|PubMed:27657131, ECO:0000269|PubMed:29178643}. Note=The disease is caused by mutations affecting the gene represented in this entry.
• Pathway: Gastric cancer - Homo sapiens (human);mTOR signaling pathway - Homo sapiens (human);Cushing,s syndrome - Homo sapiens (human);Breast cancer - Homo sapiens (human);HTLV-I infection - Homo sapiens (human);Signaling pathways regulating pluripotency of stem cells - Homo sapiens (human);Basal cell carcinoma - Homo sapiens (human);Hepatocellular carcinoma - Homo sapiens (human);Hippo signaling pathway - Homo sapiens (human);Proteoglycans in cancer - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Wnt signaling pathway - Homo sapiens (human);Melanogenesis - Homo sapiens (human);Human papillomavirus infection - Homo sapiens (human);Hair Follicle Development- Induction (Part 1 of 3);ESC Pluripotency Pathways;Wnt Signaling Pathway and Pluripotency;Wnt Signaling in Kidney Disease;EMT transition in Colorectal Cancer;Wnt Signaling Pathway;DNA Damage Response (only ATM dependent);Signaling by GPCR;Signaling by WNT;Signal Transduction;GPCR signaling-G alpha q;GPCR signaling-cholera toxin;GPCR signaling-pertussis toxin;Class B/2 (Secretin family receptors);GPCR ligand binding;GPCR signaling-G alpha s Epac and ERK;GPCR signaling-G alpha s PKA and ERK;WNT ligand biogenesis and trafficking;GPCR signaling-G alpha i;Wnt Canonical;Wnt Mammals (Consensus)

Recessive Scores

• pRec: 0.203

Haploinsufficiency Scores

• pHI: 0.243
• hipred: Y
• hipred_score: 0.694
• ghis: 0.643

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: E
• gene_indispensability_score: 0.501

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium

Mouse Genome Informatics

• Gene name: Wnt10a
• Phenotype: skeleton phenotype; limbs/digits/tail phenotype; digestive/alimentary phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); cellular phenotype; craniofacial phenotype; endocrine/exocrine gland phenotype; taste/olfaction phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); growth/size/body region phenotype

Zebrafish Information Network

• Gene name: wnt10a
• Affected structure: cranial cartilage
• Phenotype tag: abnormal
• Phenotype quality: morphology

Gene ontology

• Biological process: hair follicle development;regulation of signaling receptor activity;positive regulation of gene expression;neural crest cell differentiation;Wnt signaling pathway;neuron differentiation;hair follicle morphogenesis;odontogenesis;regulation of odontogenesis of dentin-containing tooth;tongue development;skin development;cell fate commitment;epidermis morphogenesis;sebaceous gland development;canonical Wnt signaling pathway;cellular response to transforming growth factor beta stimulus
• Cellular component: extracellular region;extracellular space
• Molecular function: frizzled binding;receptor ligand activity