Atlas of Genetics and Cytogenetics in Oncology and Haematology

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KLK10 (Kallikrein-related peptidase 10)

Written2007-08Liu-Ying Luo, Eleftherios P Diamandis
R&D Systems, Inc. 614 McKinley Place, N. E. Minneapolis, MN 55413, USA (LYL); Department of Pathology, Laboratory Medicine, Mount Sinai Hospital, 600 University Ave. Toronto, ON M5G 1X5, Canada (EPD)

(Note : for Links provided by Atlas : click)


Other namesNES1
HGNC (Hugo) KLK10
LocusID (NCBI) 5655
Atlas_Id 41076
Location 19q13.41  [Link to chromosome band 19q13]
Location_base_pair Starts at 51516000 and ends at 51523431 bp from pter ( according to hg19-Feb_2009)  [Mapping KLK10.png]
Local_order Telomere to centromere.
Fusion genes
(updated 2016)
KLK10 (19q13.41) / KLK10 (19q13.41)KLK10 (19q13.41) / ZSCAN29 (15q15.3)


Description Spanning 5.7 kb of genomic DNA, the KLK10 gene consists of 5 introns and six exons.
Transcription The KLK10 gene has several splice variants with different lengths of the first exon. The predominant form is 1443 bp. Since the first exon is untranslated, all splice variants encode the same protein.
Pseudogene Not identified so far.


Description KLK10 is a 30 kDa serine protease containing 276 amino acids. It consists of a signal peptide (aa 1-33), an activation peptide (aa 34-42), and a mature chain (aa 43-276).
Expression High levels of KLK10 expression are typically found in glandular epithelia in a wide variety of organs, such as salivary gland, gastrointestinal tract, prostate, lung, breast, and ovary.
Localisation KLK10 is synthesized as a precursor protein of 276 amino acids. Within the secretary pathway, its signal peptide is cleaved and it is secreted into the extracellular milieu as an inactive zymogen.
KLK10 has been identified in many biological fluids, such as blood, amniotic fluid, cerebrospinal fluid, milk, and nipple aspirate.
Function How KLK10 is activated remains undetermined. It is expected that upon activation, the peptide bond between arginine42 and lysine43 is proteolysed to release the mature chain. Mature KLK10 exhibits some typical characteristics of a trypsin-like serine protease, such as the catalytic triad (Histidine86, serine229, and aspartic acid137) and an aspartic acid in its substrate-binding pocket. However, its enzymatic activity has not been experimentally confirmed so far. Consequently, its potential physiologic substrates have not been identified.
Homology Human KLK10 shares 98.2% and 69% identity with chimpanzee and mouse/rat klk10, respectively.


Note No germinal or somatic mutations are identified to be associated with cancer so far.

Implicated in

Entity Various cancers with upragulated KLK10.
Disease Epithelial ovarian carcinoma, uterine serous papillary carcinoma, head and neck squamous cell carcinoma, lung squamous cell carcinoma, and gastrointestinal tract cancer.
Prognosis In these malignancies, KLK10 has been reported to be upregulated. Among them, epithelial ovarian carcinoma is by far studied the most. KLK10 is overexpressed in ovarian tumor tissue than in normal epithelium and stromal tissues both at the mRNA and protein levels. Due to increased leakage of KLK10 into the circulation, serum concentrations of KLK10 in ovarian cancer patients are elevated. High levels of KLK10 in tumor tissue or in serum are associated with more advanced disease stages and poor survival. In particular, preoperative serum KLK10 levels can serve as a complimentary biomarker for CA125, a well-established tumor marker routinely used in ovarian cancer. It has been demonstrated that nearly all CA125-negative tumors show KLK10 immunostaining positivity and that about 35% of CA125-negative patients have increased serum levels of KLK10. In combination with CA125, KLK10 can improve the diagnostic sensitivity by about 20% compared to that of CA125 alone.
Cytogenetics No cytogenetic abnormalities are identified so far.
Hybrid/Mutated Gene Not identified so far.
Entity Various cancers with down regulated KLK10.
Disease Breast cancer, testicular cancer, leukemia, and prostate cancer.
Prognosis In contrast to ovarian cancer, KLK10 is down regulated in these malignancies, with breast cancer as a prototype. Several lines of evidence have demonstrated that KLK10 is progressively down regulated during breast cancer development. In a clinical study, it is observed that essentially all normal breast specimens had KLK10 expression, whereas about 46% of ductal carcinoma in situ (DCIS) and the majority of infiltrating ductal carcinoma (IDC) had no detectable KLK10 expression. More importantly, the KLK10 negative-DCIS was found to subsequently develop to IDC. In in vitro studies, it has been shown that KLK10 is expressed in normal breast epithelial cells but dramatically reduced in breast cancer cell lines. Moreover, reintroduction of KLK10 expression into these cancer cells can suppress their tumorigenecity in nude mice. KLK10 was thus considered to function as a tumor suppressor in breast cancer. The mechanisms governing the down regulation of KLK10 in breast cancer is not clear. One explanation is CpG island hypermethylation of exon 3, as demonstrated in a number of cancer cell lines. Noteworthy, expression of KLK10 is modulated by some steroid hormones and retinoid acid. They may, under certain conditions, also contribute to the aberrant expression of KLK10 in tumor tissues. However, the paradoxical expression of KLK10 in different types of tumors remains obscure.


Identification of molecular targets for immunotherapy of patients with head and neck squamous cell carcinoma.
Dasgupta S, Tripathi PK, Qin H, Bhattacharya-Chatterjee M, Valentino J, Chatterjee SK
Oral oncology. 2006 ; 42 (3) : 306-316.
PMID 16321566
Analysis of normal epithelial cell specific-1 (NES1)/kallikrein 10 mRNA expression by in situ hybridization, a novel marker for breast cancer.
Dhar S, Bhargava R, Yunes M, Li B, Goyal J, Naber SP, Wazer DE, Band V
Clinical cancer research : an official journal of the American Association for Cancer Research. 2001 ; 7 (11) : 3393-3398.
PMID 11705853
Clinical significance of human kallikrein 10 gene expression in colorectal cancer and gastric cancer.
Feng B, Xu WB, Zheng MH, Ma JJ, Cai Q, Zhang Y, Ji J, Lu AG, Qu Y, Li JW, Wang ML, Hu WG, Liu BY, Zhu ZG
Journal of gastroenterology and hepatology. 2006 ; 21 (10) : 1596-1603.
PMID 16928223
The role for NES1 serine protease as a novel tumor suppressor.
Goyal J, Smith KM, Cowan JM, Wazer DE, Lee SW, Band V
Cancer research. 1998 ; 58 (21) : 4782-4786.
PMID 9809976
Downregulation and CpG island hypermethylation of NES1/hK10 gene in the pathogenesis of human gastric cancer.
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Cancer letters. 2007 ; 251 (1) : 78-85.
PMID 17182177
CpG methylation as a basis for breast tumor-specific loss of NES1/kallikrein 10 expression.
Li B, Goyal J, Dhar S, Dimri G, Evron E, Sukumar S, Wazer DE, Band V
Cancer research. 2001 ; 61 (21) : 8014-8021.
PMID 11691827
Identification of a novel serine protease-like gene, the expression of which is down-regulated during breast cancer progression.
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Cancer research. 1996 ; 56 (14) : 3371-3379.
PMID 8764136
Structural characterization and mapping of the normal epithelial cell-specific 1 gene.
Luo L, Herbrick JA, Scherer SW, Beatty B, Squire J, Diamandis EP
Biochemical and biophysical research communications. 1998 ; 247 (3) : 580-586.
PMID 9647736
Steroid hormone regulation of the human kallikrein 10 (KLK10) gene in cancer cell lines and functional characterization of the KLK10 gene promoter.
Luo LY, Grass L, Diamandis EP
Clinica chimica acta; international journal of clinical chemistry. 2003 ; 337 (1-2) : 115-126.
PMID 14568187
The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis.
Luo LY, Katsaros D, Scorilas A, Fracchioli S, Bellino R, van Gramberen M, de Bruijn H, Henrik A, Stenman UH, Massobrio M, van der Zee AG, Vergote I, Diamandis EP
Cancer research. 2003 ; 63 (4) : 807-811.
PMID 12591730
Expression of the normal epithelial cell-specific 1 (NES1; KLK10) candidate tumour suppressor gene in normal and malignant testicular tissue.
Luo LY, Rajpert-De Meyts ER, Jung K, Diamandis EP
British journal of cancer. 2001 ; 85 (2) : 220-224.
PMID 11461080
Human kallikrein 10 expression in normal tissues by immunohistochemistry.
Petraki CD, Karavana VN, Luo LY, Diamandis EP
The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2002 ; 50 (9) : 1247-1261.
PMID 12185203
The normal epithelial cell-specific 1 (NES1) gene, a candidate tumor suppressor gene on chromosome 19q13.3-4, is downregulated by hypermethylation in acute lymphoblastic leukemia.
Roman-Gomez J, Jimenez-Velasco A, Agirre X, Castillejo JA, Barrios M, Andreu EJ, Prosper F, Heiniger A, Torres A
Leukemia : official journal of the Leukemia Society of America, Leukemia Research Fund, U.K. 2004 ; 18 (2) : 362-365.
PMID 14628074
Potential markers that complement expression of CA125 in epithelial ovarian cancer.
Rosen DG, Wang L, Atkinson JN, Yu Y, Lu KH, Diamandis EP, Hellstrom I, Mok SC, Liu J, Bast RC Jr
Gynecologic oncology. 2005 ; 99 (2) : 267-277.
PMID 16061277
Overexpression of kallikrein 10 (hK10) in uterine serous papillary carcinomas.
Santin AD, Diamandis EP, Bellone S, Marizzoni M, Bandiera E, Palmieri M, Papasakelariou C, Katsaros D, Burnett A, Pecorelli S
American journal of obstetrics and gynecology. 2006 ; 194 (5) : 1296-1302.
PMID 16647913
Overexpression of kallikrein 10 in epithelial ovarian carcinomas.
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Gynecologic oncology. 2003 ; 90 (1) : 44-50.
PMID 12821340
Downregulation of human kallikrein 10 (KLK10/NES1) by CpG island hypermethylation in breast, ovarian and prostate cancers.
Sidiropoulos M, Pampalakis G, Sotiropoulou G, Katsaros D, Diamandis EP
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2005 ; 26 (6) : 324-336.
PMID 16254462
A 10-gene classifier for distinguishing head and neck squamous cell carcinoma and lung squamous cell carcinoma.
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Clinical cancer research : an official journal of the American Association for Cancer Research. 2007 ; 13 (10) : 2905-2915.
PMID 17504990
Identification of new splice variants and differential expression of the human kallikrein 10 gene, a candidate cancer biomarker.
Yousef GM, White NM, Michael IP, Cho JC, Robb JD, Kurlender L, Khan S, Diamandis EP
Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine. 2005 ; 26 (5) : 227-235.
PMID 16103744
Loss of expression of the putative tumor suppressor NES1 gene in biopsy-proven ductal carcinoma in situ predicts for invasive carcinoma at definitive surgery.
Yunes MJ, Neuschatz AC, Bornstein LE, Naber SP, Band V, Wazer DE
International journal of radiation oncology, biology, physics. 2003 ; 56 (3) : 653-657.
PMID 12788170
The human kallikrein 10 promoter contains a functional retinoid response element.
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Biological chemistry. 2006 ; 387 (6) : 741-747.
PMID 16800735


This paper should be referenced as such :
Luo, LY ; Diamandis, EP
KLK10 (kallikrein-related peptidase 10)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(2):108-110.
Free journal version : [ pdf ]   [ DOI ]
On line version :

External links

HGNC (Hugo)KLK10   6358
Entrez_Gene (NCBI)KLK10  5655  kallikrein related peptidase 10
AliasesNES1; PRSSL1
GeneCards (Weizmann)KLK10
Ensembl hg19 (Hinxton)ENSG00000129451 [Gene_View]  chr19:51516000-51523431 [Contig_View]  KLK10 [Vega]
Ensembl hg38 (Hinxton)ENSG00000129451 [Gene_View]  chr19:51516000-51523431 [Contig_View]  KLK10 [Vega]
ICGC DataPortalENSG00000129451
TCGA cBioPortalKLK10
AceView (NCBI)KLK10
Genatlas (Paris)KLK10
SOURCE (Princeton)KLK10
Genetics Home Reference (NIH)KLK10
Genomic and cartography
GoldenPath hg19 (UCSC)KLK10  -     chr19:51516000-51523431 -  19q13   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)KLK10  -     19q13   [Description]    (hg38-Dec_2013)
EnsemblKLK10 - 19q13 [CytoView hg19]  KLK10 - 19q13 [CytoView hg38]
Mapping of homologs : NCBIKLK10 [Mapview hg19]  KLK10 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF024605 AK026045 AK292365 AK309456 AY561635
RefSeq transcript (Entrez)NM_001077500 NM_002776 NM_145888
RefSeq genomic (Entrez)NC_000019 NC_018930 NT_011109 NW_004929415
Consensus coding sequences : CCDS (NCBI)KLK10
Cluster EST : UnigeneHs.275464 [ NCBI ]
CGAP (NCI)Hs.275464
Alternative Splicing GalleryENSG00000129451
Gene ExpressionKLK10 [ NCBI-GEO ]   KLK10 [ EBI - ARRAY_EXPRESS ]   KLK10 [ SEEK ]   KLK10 [ MEM ]
Gene Expression Viewer (FireBrowse)KLK10 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5655
GTEX Portal (Tissue expression)KLK10
Protein : pattern, domain, 3D structure
UniProt/SwissProtO43240 (Uniprot)
NextProtO43240  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO43240
Splice isoforms : SwissVarO43240 (Swissvar)
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   
Domaine pattern : Prosite (Expaxy)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)   
Domains : Interpro (EBI)Peptidase_S1_PA    Peptidase_S1A    Trypsin_dom    TRYPSIN_HIS   
Domain families : Pfam (Sanger)Trypsin (PF00089)   
Domain families : Pfam (NCBI)pfam00089   
Domain families : Smart (EMBL)Tryp_SPc (SM00020)  
DMDM Disease mutations5655
Blocks (Seattle)KLK10
Human Protein AtlasENSG00000129451
Peptide AtlasO43240
Protein Interaction databases
IntAct (EBI)O43240
Ontologies - Pathways
Ontology : AmiGOserine-type endopeptidase activity  extracellular region  proteolysis  cell cycle  serine-type peptidase activity  
Ontology : EGO-EBIserine-type endopeptidase activity  extracellular region  proteolysis  cell cycle  serine-type peptidase activity  
NDEx NetworkKLK10
Atlas of Cancer Signalling NetworkKLK10
Wikipedia pathwaysKLK10
Orthology - Evolution
GeneTree (enSembl)ENSG00000129451
Phylogenetic Trees/Animal Genes : TreeFamKLK10
Homologs : HomoloGeneKLK10
Homology/Alignments : Family Browser (UCSC)KLK10
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerKLK10 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)KLK10
Exome Variant ServerKLK10
ExAC (Exome Aggregation Consortium)KLK10 (select the gene name)
Genetic variants : HAPMAP5655
Genomic Variants (DGV)KLK10 [DGVbeta]
DECIPHER (Syndromes)19:51516000-51523431  ENSG00000129451
CONAN: Copy Number AnalysisKLK10 
ICGC Data PortalKLK10 
TCGA Data PortalKLK10 
Broad Tumor PortalKLK10
OASIS PortalKLK10 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICKLK10 
Mutations and Diseases : HGMDKLK10
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch KLK10
DgiDB (Drug Gene Interaction Database)KLK10
DoCM (Curated mutations)KLK10 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)KLK10 (select a term)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry KLK10
NextProtO43240 [Medical]
Huge Navigator KLK10 [HugePedia]
snp3D : Map Gene to Disease5655
BioCentury BCIQKLK10
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD5655
Chemical/Pharm GKB GenePA30147
Clinical trialKLK10
canSAR (ICR)KLK10 (select the gene name)
PubMed60 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon Oct 10 11:36:40 CEST 2016

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