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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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KLK12
kallikrein related peptidase 12
Chromosome 19 · 19q13.41
NCBI Gene: 43849Ensembl: ENSG00000186474.17HGNC: HGNC:6360UniProt: A0A024R4M4
33PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Protease
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
peptidase activityserine-type peptidase activityproteolysissecretory granulebreast cancercolorectal cancertriple-negative breast cancerbreast carcinoma
✦AI Summary

KLK12 (kallikrein related peptidase 12) is a serine protease that functions primarily in extracellular matrix remodeling and cellular regulation. The enzyme efficiently cleaves extracellular matrix proteins including fibronectin and tenascin, generating fragments that regulate endothelial cell adhesion and migration 1. KLK12's proteolytic activity antagonizes fibronectin polymerization and promotes endothelial cell migration, contributing to angiogenesis 1. The protein exhibits differential expression patterns across cancer types, being overexpressed in colorectal cancer where it promotes cell viability, migration, and invasion through AMPK and mTOR signaling pathways 2. Conversely, KLK12 expression is downregulated in breast cancer tissues, with the KLK12sv3 splice variant serving as a favorable prognostic marker associated with lower tumor grade and longer disease-free survival 3 4. In infectious disease contexts, KLK12 regulates matrix metalloproteinases (MMP-1 and MMP-9) via bradykinin receptors in tuberculosis, serving as a diagnostic biomarker for differentiating latent and active disease states 5. Additionally, KLK12 plays a role in pancreatic endocrine progenitor cell motility during development 6. The gene undergoes alternative splicing, producing multiple variants with distinct expression patterns and potential clinical significance 7.

Sources cited
1
KLK12 cleaves fibronectin and tenascin, promotes endothelial cell migration through matrix remodeling
PMID: 29679011
2
KLK12 is overexpressed in colorectal cancer and regulates cell behavior via AMPK/mTOR pathways
PMID: 31485623
3
KLK12sv3 splice variant serves as favorable prognostic marker in breast cancer
PMID: 22351561
4
KLK12 is downregulated in breast cancer tissues and upregulated by steroid hormones
PMID: 11056051
5
KLK12 regulates MMP-1 and MMP-9 via bradykinin receptors in tuberculosis
PMID: 36293113
6
KLK12 plays a role in pancreatic endocrine progenitor cell motility
PMID: 37591246
7
KLK12 undergoes alternative splicing producing multiple variants with distinct expression patterns
PMID: 29874189
Disease Associationsⓘ20
breast cancerOpen Targets
0.08Suggestive
colorectal cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.06Suggestive
breast carcinomaOpen Targets
0.05Suggestive
neoplasmOpen Targets
0.04Suggestive
non-small cell lung carcinomaOpen Targets
0.04Suggestive
esophageal adenocarcinomaOpen Targets
0.03Suggestive
gastric cancerOpen Targets
0.03Suggestive
infectionOpen Targets
0.03Suggestive
Townes-Brocks syndromeOpen Targets
0.03Suggestive
cancerOpen Targets
0.03Suggestive
lymph node metastatic carcinomaOpen Targets
0.03Suggestive
systemic sclerodermaOpen Targets
0.02Suggestive
tuberculosisOpen Targets
0.02Suggestive
Alzheimer diseaseOpen Targets
0.02Suggestive
prostate cancerOpen Targets
0.02Suggestive
posterior cortical atrophyOpen Targets
0.02Suggestive
breast neoplasmOpen Targets
0.02Suggestive
esophageal squamous cell carcinomaOpen Targets
0.01Suggestive
oral squamous cell carcinomaOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
KLK10Shared pathway100%KLK11Shared pathway100%PRSS57Shared pathway100%KLK9Shared pathway100%PRSS58Shared pathway100%TASP1Shared pathway100%
Tissue Expression6 tissues
Ovary
100%
Brain
63%
Lung
50%
Bone Marrow
25%
Liver
25%
Heart
0%
Gene Interaction Network
Click a node to explore
KLK12KLK10KLK11PRSS57KLK9PRSS58TASP1
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q49AM7
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.56LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF1.10 [0.79–1.56]
RankingsWhere KLK12 stands among ~20K protein-coding genes
  • #11,362of 20,598
    Most Researched33
  • #15,466of 17,882
    Most Constrained (LOEUF)1.56
Genes detectedKLK12
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Knockdown of KLK12 inhibits viability and induces apoptosis in human colorectal cancer HT-29 cell line.
PMID: 31485623
Int J Mol Med · 2019
1.00
2
Human kallikrein-related peptidase 12 stimulates endothelial cell migration by remodeling the fibronectin matrix.
PMID: 29679011
Sci Rep · 2018
0.90
3
KLK12 Regulates MMP-1 and MMP-9 via Bradykinin Receptors: Biomarkers for Differentiating Latent and Active Bovine Tuberculosis.
PMID: 36293113
Int J Mol Sci · 2022
0.80
4
Human kallikrein-related peptidase 12 (KLK12) splice variants expression in breast cancer and their clinical impact.
PMID: 22351561
Tumour Biol · 2012
0.70
5
KLK12 is a novel serine protease and a new member of the human kallikrein gene family-differential expression in breast cancer.
PMID: 11056051
Genomics · 2000
0.60