Property Summary

NCBI Gene PubMed Count 70
PubMed Score 449.69
PubTator Score 141.82

Knowledge Summary

Patent

No data available

Expression

  Differential Expression (13)

Disease log2 FC p
esophageal adenocarcinoma -3.500 3.0e-02
Rhinitis 1.200 4.4e-02
psoriasis 1.300 3.3e-04
medulloblastoma, large-cell 1.200 1.4e-04
intraductal papillary-mucinous adenoma (... 2.800 1.2e-03
intraductal papillary-mucinous carcinoma... 2.300 1.6e-02
intraductal papillary-mucinous neoplasm ... 3.100 2.3e-03
colon cancer -3.100 3.7e-05
lung cancer -1.700 2.0e-04
pancreatic cancer 1.200 2.4e-02
cystic fibrosis 2.500 1.2e-03
nasopharyngeal carcinoma -2.200 2.5e-04
spina bifida -1.921 3.5e-02

Gene RIF (65)

PMID Text
26865388 This report discloses a prevalent SPINK5 founder mutation in Finland and illustrates Netherton syndrome phenotype variability
26031502 New mutation leading to the full variety of typical features of the Netherton syndrome.
25233048 The results suggest that SPINK5 and ADRB2 haplotypes might play a role in the susceptibility to childhood-onset asthma
24894987 The effect of GATA3 on SPINK5 expression was indirect and GATA3 alone was insufficient for final differentiation of keratinocytes where full SPINK5 expression was observed.
24831437 these results support epistasis between SPINK5 and TSLP, which contributes to childhood asthma.
24577329 Netherton syndrome is caused by mutations in SPINK5, which encodes the serine protease inhibitor LEKTI.
24390132 mesotrypsin contributes to the desquamation process by activating KLKs and degrading the intrinsic KLKs' inhibitor LEKTI
24015757 Herein we report three patients with Netherton syndrome who had growth retardation associated with GH deficiency and responded well to GH therapy.
22730493 The E420K LEKTI variant alters LEKTI proteolytic activation and results in protease deregulation.
22588119 major binding partners of LEKTI were found to be the antimicrobial peptide dermcidin and the serine protease cathepsin G and no kallikreins.
22570283 Lowered SPINK5 protein expression might be a contributing factor for the development of chronic rhinosinusitis.
22377713 Our study represents the first identification of a Netherton disease-causing SPINK5 mutation that alters splicing without affecting canonical splice sites.
22089833 New SPINK5 defects in 12 patients, who presented a clinical triad suggestive of Netherton syndrome with variations in inter- and intra-familial disease expression were disclosed.
22017185 Distinct SPINK5 and IL-31 gene variants (SNPs) were associated with the development of atopic eczema and non-atopic hand dermatitis in Taiwanese nurses.
21585560 the SPINK5 gene polymorphisms was found not to be associated with atopic dermatitis (AD) in regard to either serum IgE levels, concurrent allergic asthma or early onset of AD
21564178 The novel mutation, p.Gln333X, in the SPINK5 gene, is responsible for a mild Netherton syndrome phenotype in a Turkish pedigree.
21087323 Six SNPs (rs17718511, rs17860502, KN0001820, rs60978485, rs17718737, and rs1422985) and the haplotype TAA (rs60978485, rs6892205, rs2303064) in the SPINK5 gene were associated with atopic dermatitis in Koreans.
21087323 Observational study of gene-disease association and gene-gene interaction. (HuGE Navigator)
20800603 Observational study of gene-disease association. (HuGE Navigator)
20701904 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
20628086 Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
20533828 Caspase 14 has been implicated as a novel target of LEKTI, which has the potential to act as both a serine and a cysteine protease inhibitor.
20395963 Observational study of gene-disease association. (HuGE Navigator)
20107740 study reports two male siblings affected by Netherton syndrome, which resulted from a previously undescribed splicing mutation in SPINK5
20085599 Highly significant associations were detected between SPINK5 single nucleotide polymorphisms and visible eczema (but not IgE levels) and between IL13 variants and total IgE.
20085599 Observational study of gene-disease association. (HuGE Navigator)
19996348 Observational study of gene-disease association. (HuGE Navigator)
19913121 Observational study of gene-disease association. (HuGE Navigator)
19674346 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
19534795 -206G>A polymorphism in the SPINK5 is associated with asthma susceptibility in a Chinese Han population
19534795 Observational study of gene-disease association. (HuGE Navigator)
19522716 Even though the number of investigated subjects was small and hydrolytic activity was only slightly increased, the results denote that LEKTI might be diminished in atopic dermatitis
19438860 Haploinsufficiency of SPINK5 can cause the Netherton syndrome phenotype in the presence of one null mutation with homozygous G1258A polymorphisms in SPINK5, and this could impair the function of LEKTI and therefore acts as a true mutation.
19247692 Observational study of gene-disease association. (HuGE Navigator)
19118981 reduced expression of LEKTI and increased expression of SCCE and SCTE in human epidermal keratinocytes after UVB irradiation may contribute to desquamation of the stratum corneum.
18774391 SPINK5 mutation confers a risk of eczema when maternally inherited but is not a major eczema risk factor; no interaction between the SPINK5 risk allele or the putative KLK7 risk allele and FLG mutations ws found
18774391 Observational study of gene-disease association. (HuGE Navigator)
18588753 SPINK5 (LEKTI) protein was detected in sinonasal tissue and was significantly decreased in polyp samples using IHC.
17989887 Observational study of gene-disease association. (HuGE Navigator)
17989887 study in children and adults with atopic dermatitis found that an association with SPINK5 E420K SNP was not confirmed. However, this was associated with high IgE serum levels (p=0.011).
17989726 SPINK5 mutations, causing NS, lead to truncated LEKTI; each Netherton syndrome patient possesses LEKTI of a different length, depending on the location of mutations
17936012 LEKTI domain 15 is a functional Kazal-type proteinase inhibitor.
17596512 These results identify KLK5, a key actor of the desquamation process, as the major target of LEKTI.
17415575 Uniparental disomy of maternal SPINK5 allele was indicated in the mutation analysis of two Taiwanese patients with Netherton syndrome.
17333166 Observational study of gene-disease association and gene-environment interaction. (HuGE Navigator)
16601670 Mutations in SPINK5 encoding the serine protease (SP) inhibitor, lymphoepithelial-Kazal-type 5 inhibitor (LEKTI), cause Netherton syndrome (NS). SP activation correlated with clinical severity, and inversely with residual LEKTI expression.
16519819 Observational study of gene-disease association. (HuGE Navigator)
16374478 Variable amounts of SPINK5 alternative transcripts are detected in all SPINK5 transcriptionally active tissues.
15986064 Observational study of gene-disease association. (HuGE Navigator)
15942217 Homozygous frameshift mutation in SPINK5 associated with Netherton syndrome.
15820494 Observational study of genetic testing. (HuGE Navigator)
15680911 We showed that LEKTI is a potent inhibitor of a family of serine proteinases involved in extracellular matrix remodeling and its expression is downregulated in head and neck squamous cell carcinomas.
15675955 in normal skin the LG system transports and secretes LEKTI earlier than KLK7 and KLK5 preventing premature loss of stratum corneum integrity/cohesion.
15466487 deficiency is related to epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin
15366933 The sequence from Leu32 to Ile38 of a chimeric double-mutant domain 1 of LEKTI is a chameleon sequence that converts a short 3(10)-helix into an extended loop conformation and parts of the COOH-terminal alpha-helix of domain 1 into a beta-hairpin.
15304086 LEKTI deficiency in the epidermis and in hair roots at the protein level and an aberrant expression of other proteins, especially transglutaminase1 and 3, which may account for the impaired epidermal barrier in Netherton syndrome
15005725 Observational study of gene-disease association. (HuGE Navigator)
14551605 There is an association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese.
12915442 LETKI proteolytic processing was studied in cultured keratinocytes as well as its tissue distribution and defective expression in Netherton syndrome.
12752122 Observational study of gene-disease association. (HuGE Navigator)
12437098 REVIEW: molecular cloning, characterization of the gene, tissue distribution, congenital disases associated with mutations
11943586 This is a multidomain serine proteinase inhibitor with physiopathological significance.
11874482 the defective inhibitory regulation of desquamation due to SPINK5 gene mutations may cause over-desquamation of corneocytes in Netherton syndrome, leading to severe skin permeability barrier dysfunction.
11841556 the intron-exon organization of the gene and characterize the spink5 mutations. five mutations, one of which resulted in perinatal lethal disease, were associated with ethnic groups
11796258 SPINK5's role in atopic dermatitis and skin diseases is described

AA Sequence

MKIATVSVLLPLALCLIQDAASKNEDQEMCHEFQAFMKNGKLFCPQDKKFFQSLDGIMFINKCATCKMIL      1 - 70
EKEAKSQKRARHLARAPKATAPTELNCDDFKKGERDGDFICPDYYEAVCGTDGKTYDNRCALCAENAKTG     71 - 140
SQIGVKSEGECKSSNPEQDVCSAFRPFVRDGRLGCTRENDPVLGPDGKTHGNKCAMCAELFLKEAENAKR    141 - 210
EGETRIRRNAEKDFCKEYEKQVRNGRLFCTRESDPVRGPDGRMHGNKCALCAEIFKQRFSEENSKTDQNL    211 - 280
GKAEEKTKVKREIVKLCSQYQNQAKNGILFCTRENDPIRGPDGKMHGNLCSMCQAYFQAENEEKKKAEAR    281 - 350
ARNKRESGKATSYAELCSEYRKLVRNGKLACTRENDPIQGPDGKVHGNTCSMCEVFFQAEEEEKKKKEGK    351 - 420
SRNKRQSKSTASFEELCSEYRKSRKNGRLFCTRENDPIQGPDGKMHGNTCSMCEAFFQQEERARAKAKRE    421 - 490
AAKEICSEFRDQVRNGTLICTREHNPVRGPDGKMHGNKCAMCASVFKLEEEEKKNDKEEKGKVEAEKVKR    491 - 560
EAVQELCSEYRHYVRNGRLPCTRENDPIEGLDGKIHGNTCSMCEAFFQQEAKEKERAEPRAKVKREAEKE    561 - 630
TCDEFRRLLQNGKLFCTRENDPVRGPDGKTHGNKCAMCKAVFQKENEERKRKEEEDQRNAAGHGSSGGGG    631 - 700
GNTQDECAEYREQMKNGRLSCTRESDPVRDADGKSYNNQCTMCKAKLEREAERKNEYSRSRSNGTGSESG    701 - 770
KDTCDEFRSQMKNGKLICTRESDPVRGPDGKTHGNKCTMCKEKLEREAAEKKKKEDEDRSNTGERSNTGE    771 - 840
RSNDKEDLCREFRSMQRNGKLICTRENNPVRGPYGKMHINKCAMCQSIFDREANERKKKDEEKSSSKPSN    841 - 910
NAKDECSEFRNYIRNNELICPRENDPVHGADGKFYTNKCYMCRAVFLTEALERAKLQEKPSHVRASQEED    911 - 980
SPDSFSSLDSEMCKDYRVLPRIGYLCPKDLKPVCGDDGQTYNNPCMLCHENLIRQTNTHIRSTGKCEESS    981 - 1050
TPGTTAASMPPSDE                                                           1051 - 1064
//

Text Mined References (72)

PMID Year Title
26865388 2016 Intrafamily and Interfamilial Phenotype Variation and Immature Immunity in Patients With Netherton Syndrome and Finnish SPINK5 Founder Mutation.
26031502 2015 New mutation leading to the full variety of typical features of the Netherton syndrome.
25233048 2015 SPINK5 and ADRB2 haplotypes are risk factors for asthma in Mexican pediatric patients.
25153381 2014 Netherton syndrome: defective kallikrein inhibition in the skin leads to skin inflammation and allergy.
25131691 2014 Mechanisms of abnormal lamellar body secretion and the dysfunctional skin barrier in patients with atopic dermatitis.
24894987 2014 Regulation of serine protease inhibitor Kazal type-5 (SPINK5) gene expression in the keratinocytes.
24831437 2014 Epistasis between serine protease inhibitor Kazal-type 5 (SPINK5) and thymic stromal lymphopoietin (TSLP) genes contributes to childhood asthma.
24577329 2014 Molecular analysis of a series of Israeli families with Comèl-Netherton syndrome.
24390132 2014 Keratinocyte-specific mesotrypsin contributes to the desquamation process via kallikrein activation and LEKTI degradation.
24015757 Netherton syndrome associated with growth hormone deficiency.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22730493 2012 The 420K LEKTI variant alters LEKTI proteolytic activation and results in protease deregulation: implications for atopic dermatitis.
22588119 2012 The identification of a new role for LEKTI in the skin: The use of protein 'bait' arrays to detect defective trafficking of dermcidin in the skin of patients with Netherton syndrome.
22570283 2012 Low SPINK5 expression in chronic rhinosinusitis.
22377713 2012 A synonymous mutation in SPINK5 exon 11 causes Netherton syndrome by altering exonic splicing regulatory elements.
22089833 2012 Clinical expression and new SPINK5 splicing defects in Netherton syndrome: unmasking a frequent founder synonymous mutation and unconventional intronic mutations.
22017185 2011 Distinct SPINK5 and IL-31 polymorphisms are associated with atopic eczema and non-atopic hand dermatitis in Taiwanese nursing population.
21697885 2011 Proteolytic activation cascade of the Netherton syndrome-defective protein, LEKTI, in the epidermis: implications for skin homeostasis.
21585560 2012 Association of SPINK5 gene polymorphisms with atopic dermatitis in Northeast China.
21564178 2011 New homozygous SPINK5 mutation, p.Gln333X, in a Turkish pedigree with Netherton syndrome.
21087323 2010 Hint for association of single nucleotide polymorphisms and haplotype in SPINK5 gene with atopic dermatitis in Koreans.
20800603 2010 Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study.
20701904 2010 Early life environment, neurodevelopment and the interrelation with atopy.
20628086 2010 Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
20533828 2010 New role for LEKTI in skin barrier formation: label-free quantitative proteomic identification of caspase 14 as a novel target for the protease inhibitor LEKTI.
20395963 2010 Replication of genetic association studies in asthma and related phenotypes.
20107740 2010 A new SPINK5 donor splice site mutation in siblings with Netherton syndrome.
20085599 2009 A multi-centre study of candidate genes for wheeze and allergy: the International Study of Asthma and Allergies in Childhood Phase 2.
19996348 2010 Positionally cloned genes and age-specific effects in asthma and atopy: an international population-based cohort study (ECRHS).
19913121 2009 Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
19674346 2009 Polymorphisms in inflammation genes, tobacco smoke and furred pets and wheeze in children.
19534795 2009 A functional polymorphism in the SPINK5 gene is associated with asthma in a Chinese Han Population.
19522716 2009 Serine protease inhibitor lymphoepithelial Kazal type-related inhibitor tends to be decreased in atopic dermatitis.
19438860 2009 A heterozygous null mutation combined with the G1258A polymorphism of SPINK5 causes impaired LEKTI function and abnormal expression of skin barrier proteins.
19247692 2009 Analyses of associations with asthma in four asthma population samples from Canada and Australia.
19118981 2009 Dichotomous effect of ultraviolet B on the expression of corneodesmosomal enzymes in human epidermal keratinocytes.
18774391 2008 Analysis of the individual and aggregate genetic contributions of previously identified serine peptidase inhibitor Kazal type 5 (SPINK5), kallikrein-related peptidase 7 (KLK7), and filaggrin (FLG) polymorphisms to eczema risk.
18588753 Epithelial genes in chronic rhinosinusitis with and without nasal polyps.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
17989887 2007 Analysis of SPINK 5, KLK 7 and FLG genotypes in a French atopic dermatitis cohort.
17989726 2008 Correlation between SPINK5 gene mutations and clinical manifestations in Netherton syndrome patients.
17936012 2008 LEKTI domain 15 is a functional Kazal-type proteinase inhibitor.
17596512 2007 LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction.
17415575 2007 Netherton syndrome: mutation analysis of two Taiwanese families.
17333166 2007 The SPINK gene family and celiac disease susceptibility.
16601670 2006 Serine protease activity and residual LEKTI expression determine phenotype in Netherton syndrome.
16519819 2006 Analysis of polymorphisms in 16 genes in type 1 diabetes that have been associated with other immune-mediated diseases.
16374478 2006 SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing.
15986064 2005 Asthma severity and genetics in Taiwan.
15942217 2005 Netherton syndrome with extensive skin peeling and failure to thrive due to a homozygous frameshift mutation in SPINK5.
15820494 2005 Rapid detection of the SPINK5 polymorphism Glu420Lys by real-time PCR technology.
15680911 2005 Consequences of C-terminal domains and N-terminal signal peptide deletions on LEKTI secretion, stability, and subcellular distribution.
15675955 2005 LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum.
15466487 2004 Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice.
15372022 2004 The DNA sequence and comparative analysis of human chromosome 5.
15366933 2004 The solution structure of a chimeric LEKTI domain reveals a chameleon sequence.
15304086 2004 SPINK5 and Netherton syndrome: novel mutations, demonstration of missing LEKTI, and differential expression of transglutaminases.
15005725 2004 Association between polymorphisms in serine protease inhibitor, kazal type 5 and asthma phenotypes in a large German population sample.
14551605 2003 Association between polymorphisms in the SPINK5 gene and atopic dermatitis in the Japanese.
12915442 2003 LEKTI proteolytic processing in human primary keratinocytes, tissue distribution and defective expression in Netherton syndrome.
12752122 2003 Association of SPINK5 gene polymorphisms with atopic dermatitis in the Japanese population.
12684009 2003 Homologous proteins with different folds: the three-dimensional structures of domains 1 and 6 of the multiple Kazal-type inhibitor LEKTI.
12437098 Biochemical features, molecular biology and clinical relevance of the human 15-domain serine proteinase inhibitor LEKTI.
11943586 2002 LEKTI: a multidomain serine proteinase inhibitor with pathophysiological relevance.
11874482 2002 Elevated stratum corneum hydrolytic activity in Netherton syndrome suggests an inhibitory regulation of desquamation by SPINK5-derived peptides.
11841556 2002 Netherton syndrome: disease expression and spectrum of SPINK5 mutations in 21 families.
11594460 2001 Purification and partial amino acid sequence of proteins from human epidermal keratinocyte conditioned medium.
11544479 2001 Gene polymorphism in Netherton and common atopic disease.
11511292 2001 The spectrum of pathogenic mutations in SPINK5 in 19 families with Netherton syndrome: implications for mutation detection and first case of prenatal diagnosis.
10835624 2000 Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.
10712206 2000 Localization of the Netherton syndrome gene to chromosome 5q32, by linkage analysis and homozygosity mapping.
10419450 1999 LEKTI, a novel 15-domain type of human serine proteinase inhibitor.