Alt. symbols: VAKTI | LEKTI | LETKI | NETS | NS | FLJ21544 | FLJ97536 | FLJ97596 | FLJ99794 | DKFZp686K19184

Approved name: serine peptidase inhibitor Kazal type 5
Alt. names: serine protease inhibitor, Kazal type 5 | lymphoepithelial Kazal-type-related inhibitor

Location: 5q32: 148025683 - 148137382 (+)
Gene type: protein_coding, 10 transcripts.

Scores: LoFtool: 0.997000 | pLI: 0.00000000 | LOEUF: 0.930

HGNC: 15464

NCBI: 11005, RefSeq: NG_009633.1

Ensembl: ENSG00000133710.17

LRG_110 | Status: public

OMIM: 605010

Expression | ProteinAtlas

The SPINK5 gene provides instructions for making a protein called LEKT1. LEKT1 is a type of serine peptidase inhibitor. Serine peptidase inhibitors control the activity of enzymes called serine peptidases, which break down other proteins. LEKT1 is found in the skin and in the thymus, which is a gland located behind the breastbone that plays an important role in the immune system by producing white blood cells called lymphocytes. LEKT1 controls the activity of certain serine peptidases in the outer layer of skin (the epidermis), especially the tough outer surface known as the stratum corneum, which provides a sturdy barrier between the body and its environment. Serine peptidase enzymes are involved in normal skin shedding by helping to break the connections between cells of the stratum corneum. LEKT1 is also involved in normal hair growth, the development of lymphocytes in the thymus, and the control of peptidases that trigger immune system function.

At least 40 SPINK5 gene mutations have been identified associated with Netherton syndrome [MIM:256500]. This is a genetic disorder manifesting with skin and hair abnormalities and a high risk of allergies, asthma, and eczema. The majority of pathogenic mutations in SPINK5 are nonsense, frameshift, or splice-affecting mutations that result in no protein or in a LEKT1 protein that is unable to control serine peptidase activity. To date, only one missense mutation has been reported as pathogenic (p .Thr808Ile). The lack of LEKT1 function allows the serine peptidases to be abnormally active and break down too many proteins in the stratum corneum. As a result, excessive skin shedding takes place, and the stratum corneum is unusually thin and breaks down easily, resulting in the skin abnormalities that occur in Netherton syndrome. Loss of LEKT1 function also results in abnormal hair growth. The immune dysfunction that leads to allergies, asthma, and eczema in individuals with Netherton syndrome likely arises from a lack of LEKT1 control of peptidases involved in the triggering of immune system function. Excessive activation of the immune system caused by invasion of microbes in the abnormal skin is also thought to be involved. [Load More]