FERMT1

This gene encodes a member of the fermitin family, and contains a FERM domain and a pleckstrin homology domain. The encoded protein is involved in integrin signaling and linkage of the actin cytoskeleton to the extracellular matrix. Mutations in this gene have been linked to Kindler syndrome. [provided by RefSeq, Dec 2009]

Fermitin Family Member 1

Involved in cell adhesion. Contributes to integrin activation. When coexpressed with talin, potentiates activation of ITGA2B. Required for normal keratinocyte proliferation. Required for normal polarization of basal keratinocytes in skin, and for normal cell shape. Required for normal adhesion of keratinocytes to fibronectin and laminin, and for normal keratinocyte migration to wound sites. May mediate TGF-beta 1 signaling in tumor progression.

Basement membrane organization Source: Ensembl
Cell adhesion Source: UniProtKB
Cell-matrix adhesion Source: GO_Central
Establishment of epithelial cell polarity Source: UniProtKB
Integrin-mediated signaling pathway Source: InterPro
Keratinocyte migration Source: UniProtKB
Keratinocyte proliferation Source: UniProtKB
Negative regulation of canonical Wnt signaling pathway Source: Ensembl
Negative regulation of gene expression Source: Ensembl
Negative regulation of protein import into nucleus Source: Ensembl
Negative regulation of stem cell proliferation Source: Ensembl
Negative regulation of timing of anagen Source: Ensembl
Positive regulation of cell adhesion mediated by integrin Source: Ensembl
Positive regulation of cell-matrix adhesion Source: Ensembl
Positive regulation of integrin activation Source: ARUK-UCL
Positive regulation of transforming growth factor beta production Source: Ensembl
Positive regulation of transforming growth factor beta receptor signaling pathway Source: Ensembl
Positive regulation of wound healing, spreading of epidermal cells Source: ARUK-UCL

Cytoskeleton; Ruffle membrane; Focal adhesion. Constituent of focal adhesions. Localized at the basal aspect of skin keratinocytes, close to the cell membrane. Colocalizes with filamentous actin. Upon TGFB1 treatment, it localizes to membrane ruffles.

Kindler syndrome (KNDLRS):
The disease is caused by variants affecting the gene represented in this entry. Although most FERMT1 mutations are predicted to lead to premature termination of translation, and to loss of FERMT1 function, significant clinical variability is observed among patients. There is an association of FERMT1 missense and in-frame deletion mutations with milder disease phenotypes, and later onset of complications (PubMed:21936020).
An autosomal recessive skin disorder characterized by skin blistering, photosensitivity, progressive poikiloderma, and extensive skin atrophy. Additional clinical features include gingival erosions, ocular, esophageal, gastrointestinal and urogenital involvement, and an increased risk of mucocutaneous malignancy.