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10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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KLK4
kallikrein related peptidase 4
Chromosome 19 Β· 19q13.41
NCBI Gene: 9622Ensembl: ENSG00000167749.12HGNC: HGNC:6365UniProt: A0A0C4DFQ5
97PubMed Papers
21Diseases
0Drugs
7Pathogenic Variants
FUNCTIONAL ROLE
Protease
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
amelogenesisprotein bindingserine-type endopeptidase activityextracellular matrix disassemblyHypomaturation amelogenesis imperfectaamelogenesis imperfectaGraves diseasegenetic disorder
✦AI Summary

KLK4 (kallikrein related peptidase 4) is a chymotrypsin-like serine protease that plays a critical role in dental enamel formation during tooth development 1. The enzyme is expressed during the transition from secretory to maturation stage of amelogenesis and functions throughout the maturation phase 1. KLK4's primary function is to aggressively degrade the retained organic matrix following termination of enamel protein secretion, facilitating the orderly replacement of organic matrix with mineral to generate harder, less porous enamel 2. Studies of Klk4-ablated mice demonstrate that without functional KLK4, enamel remains soft and protein-rich, with crystallites failing to properly interlock despite growing substantially in width and thickness 1. Mutations in KLK4 cause autosomal recessive amelogenesis imperfecta, characterized by soft, porous enamel containing residual protein 23. Beyond dental development, KLK4 has clinical significance in cancer, particularly ovarian carcinoma, where higher expression correlates with poor prognosis, increased tumor grade, and clinical stage 4. Genetic variations in KLK4 also contribute to dental caries susceptibility 56, highlighting its broader role in oral health.

Sources cited
1
KLK4 is a chymotrypsin-like serine protease expressed during enamel maturation that cleaves enamel matrix proteins
PMID: 25071586
2
KLK4 aggressively degrades organic matrix to facilitate mineral replacement and mutations cause amelogenesis imperfecta
PMID: 18627287
3
Klk4-ablated mice have soft, protein-rich enamel with crystallites that fail to interlock properly
PMID: 25071586
4
KLK4 mutations are associated with amelogenesis imperfecta phenotypes
PMID: 39321764
5
Higher KLK4 expression in ovarian cancer correlates with poor prognosis and increased tumor grade/stage
PMID: 11489816
6
Genetic variations in KLK4 contribute to dental caries susceptibility
PMID: 28445870
7
KLK4 is among genes involved in enamel formation that impact caries susceptibility
PMID: 28266114
Disease Associationsβ“˜21
Hypomaturation amelogenesis imperfectaOpen Targets
0.67Moderate
amelogenesis imperfectaOpen Targets
0.52Moderate
Graves diseaseOpen Targets
0.35Weak
genetic disorderOpen Targets
0.19Weak
male infertilityOpen Targets
0.11Weak
prostate cancerOpen Targets
0.10Weak
neoplasmOpen Targets
0.10Suggestive
COVID-19Open Targets
0.08Suggestive
metabolic syndromeOpen Targets
0.08Suggestive
acute kidney injuryOpen Targets
0.07Suggestive
Hypoplastic amelogenesis imperfectaOpen Targets
0.07Suggestive
dental cariesOpen Targets
0.07Suggestive
ovarian cancerOpen Targets
0.07Suggestive
posterior cortical atrophyOpen Targets
0.06Suggestive
cancerOpen Targets
0.06Suggestive
breast cancerOpen Targets
0.05Suggestive
amelogenesis imperfecta, type ijOpen Targets
0.05Suggestive
amelogenesis imperfecta type 1AOpen Targets
0.05Suggestive
amelogenesis imperfecta hypomaturation type 2A4Open Targets
0.05Suggestive
dentin dysplasia type IOpen Targets
0.05Suggestive
Amelogenesis imperfecta, hypomaturation type, 2A1UniProt
Pathogenic Variants7
NM_004917.5(KLK4):c.458G>A (p.Trp153Ter)Likely pathogenic
Amelogenesis imperfecta type 2A1|not provided
β˜…β˜…β˜†β˜†2024β†’ Residue 153
NM_004917.5(KLK4):c.632del (p.Leu211fs)Pathogenic
Amelogenesis imperfecta type 2A1|not provided
β˜…β˜…β˜†β˜†2021β†’ Residue 211
NM_004917.5(KLK4):c.224+2T>CLikely pathogenic
Amelogenesis imperfecta type 2A1
β˜…β˜†β˜†β˜†2024
NM_004917.5(KLK4):c.620_621del (p.Ser207fs)Likely pathogenic
Amelogenesis imperfecta type 2A1
β˜…β˜†β˜†β˜†2021β†’ Residue 207
NM_004917.5(KLK4):c.245del (p.Gly82fs)Pathogenic
Amelogenesis imperfecta type 2A1
β˜†β˜†β˜†β˜†2013β†’ Residue 82
NM_004917.5(KLK4):c.637T>C (p.Cys213Arg)Pathogenic
Amelogenesis imperfecta
β˜†β˜†β˜†β˜†β†’ Residue 213
NM_004917.5(KLK4):c.170C>A (p.Ser57Ter)Pathogenic
Amelogenesis imperfecta
β˜†β˜†β˜†β˜†β†’ Residue 57
View on ClinVar β†—
Related Genes
C1SProtein interaction100%AGTProtein interaction97%WDR72Protein interaction97%AMBNProtein interaction96%SPINK5Protein interaction87%SERPINA4Protein interaction85%
Tissue Expression6 tissues
Brain
100%
Lung
80%
Liver
40%
Bone Marrow
40%
Ovary
40%
Heart
0%
Gene Interaction Network
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KLK4C1SAGTWDR72AMBNSPINK5SERPINA4
PROTEIN STRUCTURE
Preparing viewer…
PDB4K8Y Β· 1.00 Γ… Β· X-ray
View on RCSB β†—
RankingsWhere KLK4 stands among ~20K protein-coding genes
  • #4,946of 20,598
    Most Researched97 Β· top quartile
  • #3,187of 5,498
    Most Pathogenic Variants7
Genes detectedKLK4
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Developmental Defects of Enamel.
PMID: 39321764
Monogr Oral Sci Β· 2024
1.00
2
Interaction of lifestyle, behaviour or systemic diseases with dental caries and periodontal diseases: consensus report of group 2 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases.
PMID: 28266114
J Clin Periodontol Β· 2017
0.90
3
KLK4 Gene and Dental Decay: Replication in a South Brazilian Population.
PMID: 28445870
Caries Res Β· 2017
0.80
4
Functions of KLK4 and MMP-20 in dental enamel formation.
PMID: 18627287
Biol Chem Β· 2008
0.70
5
Kallikrein-related peptidase-4 (KLK4): role in enamel formation and revelations from ablated mice.
PMID: 25071586
Front Physiol Β· 2014
0.60