WNT10A Gene

WNT10A (WNT10A is the acronym for Wingless-Type MMTV Integration Site Family Member 10A) is a protein-coding gene located on chromosome 2q35. Germline mutations in WNT10A underlie several forms of autosomal recessive ectodermal dysplasia, in which heterozygous carriers may also have some less pronounced ectodermal abnormalities (Doolan BJ et al. 2021). In the general population, multiple heterozygous WNT10A variants can cause skin, hair, sweat gland or dental abnormalities.

Signaling pathways affected include presynaptic function of kainate receptors and transcription of androgen receptor nuclear signaling.WNT10A variants have also been associated with hair thickness, male androgenetic alopecia, hair curl, acne vulgaris, lipodystrophy, keloids, wound healing, tooth size, dental agenesis, hypodontia, taurodontia, and oral clefting. Furthermore, WNT10A mutations are also associated with renal fibrosis, keratoconus, as well as gastrointestinal tumors and neuropathic pain (Doolan BJ et al. 2021). Diseases associated with WNT10A include:

• Schöpf-Schulz-Passarge syndrome (OMIM 224750).
• Odontoonychodermal dysplasia (OMIM 257980)
• selective dental agenesis (OMIM 150400)

An important paralog of this gene is WNT10B.

The WNT10A gene is a member of the WNT gene family. The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins are associated with oncogenesis and various developmental processes, including cell fate regulation and patterning during embryogenesis. The WNT10A gene is highly expressed in promyelocytic leukemia and Burkitt lymphoma cell lines. Furthermore, the gene along with the WNT6 gene, is overexpressed in cell lines of colorectal cancer. Overexpression of the gene may play a key role in carcinogenesis through activation of the WNT-beta-catenin-TCF pathway.

The encoded WNT protein is a glycoprotein and ligand for members of the Frizzled receptor family and is involved in signaling pathways critical for organ development and tissue regeneration (see WnT signaling pathway below). Of the 19 known WNT ligands, WNT10A, has particular importance in skin, its appendages and teeth. It Plays a role in normal ectoderm development.

WNT is required for:

• normal tooth development.
• The normal postnatal development and maintenance of lingual papillae and sweat ducts.
• the normal proliferation of basal cells in the filiform papillae of the tongue, the plantar epithelium and the sweat ducts.
• the normal expression of keratins in lingual papillae.
• the normal expression of KRT9 in the epithelium of the sole of the foot.
• normal hair follicle function.

• Doolan BJ et al (2021) WNT10A, dermatology and dentistry. Br J Dermatol 185:1105-1111.
• Mues G et al (2014) The WNT10A gene in ectodermal dysplasias and selective tooth agenesis. Am J Med Genet A 164A:2455-2460.
• Nawaz S et al (2009) WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome. Eur J Hum Genet 17:1600-1605.
• Xu M et al. (2017) WNT10A mutation causes ectodermal dysplasia by impairing progenitor cell proliferation and KLF4-mediated differentiation. Nat Commun. 2017 Jun 7;8:15397.