AQP5 Gene

AQP5 (aquaporin 5) is a protein-coding gene located on chromosome 12q13.12. The encoded protein is a so-called cell membrane water channel protein, aquaporin 5.

Associated metabolic pathways include aquaporin-mediated transport (water channels) and stabilization and expansion of E-cadherin adherence. An important paralog of this gene is AQP2.

Diseases associated with AQP5 include:

• An autosomal dominant form of diffuse non-epidermolytic palmoplantar keratoderma (Bothnian-type palmoplantar keratosis) (see below Palmoplantar keratosis aquagene with mutation in AQP5). The mutation in AQP5 results in impaired epidermal water barrier function in the epidermis of the palms and soles.

and

• Sicca syndrome of the eye

Aquaporins (AQPs) are integral membrane proteins that facilitate the transport of water across biological membranes along an osmotic gradient (water channels). In humans and rodents, 13 AQP isoforms (AQP0-AQP12) have been identified to date.

In mammals, aquaporins (AQP1) regulate the water balance of e.g. erythrocytes, kidney cells, keratinocytes and other cells. An erythrocyte, for example, has about 200,000 water channels per cell. In the alveoli, such "channels" provide the fluid film necessary for gas exchange. Malfunctions of the aquaporins are responsible for diseases such as diabetes insipidus, atopic eczema, cataracts and glaucoma. Aquaporin-3 is expressed more frequently in atopic eczema. This would be among others an explanation for the disturbance of the barrier function in atopics. Retinoids are also able to upregulate AQPs.

Mutaions in AQP5 lead to a mild form of palmoplantar keratosis (see above) with atypical swelling behaviour of the horny layer on contact with water.

Furthermore, aquaporins play an important role in fluid secretion in salivary glands. Together with TRPV4 they control the regulatory volume decrease in salivary epithelial cells. Aquaporins play a redundant role in water transport in the eye, lung and sweat glands.

1. Abdul-Wahab A et al. (2016) Autosomal dominant diffuse nonepidermolytic palmoplantar keratoderma due to a recurrent mutation in aquaporin-5. Br J Dermatol 174:430-432.
2. Blaydon DC et al (2013) Mutations in AQP5, encoding a water-channel protein, cause autosomal-dominant diffuse nonepidermolytic palmoplantar keratoderma. Am J Hum Genet 93:330-335.
3. Krøigård AB et al. (2016) The first Danish family reported with an AQP5 mutation presenting diffuse nonepidermolytic palmoplantar keratoderma of Bothnian type, hyperhidrosis and frequent Corynebacterium infections: a case report. BMC Dermatol 16:7.
4. Nadal M et al. (2015) Aquagenic palmar keratoderma in a patient heterozygous for the mutation c.3197G>C in the CFTR gene. Ann Dermatol Venereol 142:201-205.