HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
50 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
KL
klotho
Chromosome 13 · 13q13.1
NCBI Gene: 9365Ensembl: ENSG00000133116.8HGNC: HGNC:6344UniProt: Q9UEF7
529PubMed Papers
21Diseases
0Drugs
0Pathogenic Variants
RESEARCH IMPACT
Highly StudiedTrending
CLINICAL
OMIM Disease Gene
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
fibroblast growth factor bindingpositive regulation of bone mineralizationextracellular exosomefibroblast growth factor receptor bindingtype 2 diabetes mellitustumoral calcinosis, hyperphosphatemic, familial, 3diabetes mellitusfamilial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndrome
✦AI Summary

KL (klotho) is a multifunctional protein that serves as both a membrane-bound receptor and circulating hormone involved in aging regulation and metabolic processes. The protein exists in three forms: full-length transmembrane, truncated soluble, and secreted α-Klotho, each with potentially different functions 1. KL functions as an aging-suppressor gene, with overexpression extending lifespan in mice while mutations shorten it 1. The protein regulates phosphate, calcium, and vitamin D metabolism and may function as an anti-aging hormone by inhibiting insulin/IGF1 signaling pathways 1. KL suppresses insulin and Wnt signaling pathways, inhibits oxidative stress, and regulates phosphatase and calcium absorption 1. In respiratory diseases, KL deficiency contributes to chr13 obstructive pulmonary disease (COPD) pathogenesis by regulating club cell senescence and differentiation, with reduced KL expression associated with increased age-related markers and pulmonary inflammation 2. Point mutations in the human KL gene are associated with hypertension and kidney disease, suggesting its essential role in maintaining normal renal function 1. The protein's role in aging regulation and metabolic homeostasis makes it clinically significant for understanding age-related diseases and potential therapeutic interventions.

Sources cited
1
KL functions as aging-suppressor gene, exists in three protein forms, regulates phosphate/calcium/vitamin D metabolism, and suppresses insulin/Wnt signaling
PMID: 25695404
2
KL deficiency contributes to COPD pathogenesis by regulating club cell senescence and is associated with pulmonary inflammation
PMID: 39930762
⚠Limited data available — This gene has 2 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ21
type 2 diabetes mellitusOpen Targets
0.56Moderate
tumoral calcinosis, hyperphosphatemic, familial, 3Open Targets
0.50Moderate
diabetes mellitusOpen Targets
0.48Moderate
familial hyperphosphatemic tumoral calcinosis/hyperphosphatemic hyperostosis syndromeOpen Targets
0.40Weak
cancerOpen Targets
0.40Weak
Abnormal nasolacrimal system morphologyOpen Targets
0.33Weak
male infertilityOpen Targets
0.33Weak
VitiligoOpen Targets
0.32Weak
liver diseaseOpen Targets
0.32Weak
temporomandibular joint disorderOpen Targets
0.29Weak
hamartomaOpen Targets
0.23Weak
nevusOpen Targets
0.19Weak
ocular hypotensionOpen Targets
0.18Weak
amenorrheaOpen Targets
0.14Weak
chronic kidney diseaseOpen Targets
0.12Weak
familial tumoral calcinosisOpen Targets
0.12Weak
neoplasmOpen Targets
0.12Weak
Bruising susceptibilityOpen Targets
0.12Weak
acute kidney injuryOpen Targets
0.12Weak
diabetic nephropathyOpen Targets
0.11Weak
Tumoral calcinosis, hyperphosphatemic, familial, 3UniProt
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
FGF3Protein interaction100%FGF7Protein interaction100%FGF8Protein interaction100%GALNT3Protein interaction100%RENProtein interaction100%FGF18Protein interaction100%
Tissue Expression6 tissues
Lung
100%
Heart
81%
Brain
25%
Bone Marrow
13%
Ovary
7%
Liver
5%
Gene Interaction Network
Click a node to explore
KLFGF3FGF7FGF8GALNT3RENFGF18
PROTEIN STRUCTURE
Preparing viewer…
PDB7YSH · 2.74 Å · EM
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.92LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.74 [0.60–0.92]
RankingsWhere KL stands among ~20K protein-coding genes
  • #480of 20,598
    Most Researched529 · top 5%
  • #8,390of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedKL
Sources retrieved50 papers
Response time—
📄 Sources
50▼
1
Molecular basis of Klotho: from gene to function in aging.
PMID: 25695404
Endocr Rev · 2015
1.00
2
Genetically determined α-Klotho levels and causal association with aging-related lung diseases.
PMID: 40180194
Respir Med · 2025
0.90
3
Research progress of KL-6 in respiratory system diseases.
PMID: 38773736
Crit Rev Clin Lab Sci · 2024
0.90
4
Investigating the Antifibrotic Effects of β-Citronellol on a TGF-β1-Stimulated LX-2 Hepatic Stellate Cell Model.
PMID: 39062514
Biomolecules · 2024
0.88
5
Prognostic bioindicators in severe COVID-19 patients.
PMID: 33548798
Cytokine · 2021
0.84