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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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CAMKK1
calcium/calmodulin dependent protein kinase kinase 1
Chromosome 17 · 17p13.2
NCBI Gene: 84254Ensembl: ENSG00000004660.15HGNC: HGNC:1469UniProt: J3KPJ3
46PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Kinase
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingintracellular signal transductioncalmodulin bindingcytoplasmcervical carcinomaneurodegenerative diseaseretinal degenerationtype 2 diabetes mellitus
✦AI Summary

CAMKK1 (calcium/calmodulin-dependent protein kinase kinase 1) is a serine/threonine kinase that functions as an upstream activator in calcium-triggered signaling cascades 1. The protein phosphorylates downstream targets including CAMK1, CAMK4, and AKT1, thereby regulating cellular processes spanning energy homeostasis, apoptosis, and bone metabolism 2. CAMKK1 operates primarily through AMPK-dependent mechanisms to regulate lipid metabolism; exosomal CAMKK1 transferred to hepatocytes activates AMPK, subsequently promoting fatty acid oxidation via PPARα signaling while inhibiting lipogenesis through SREBP-1C suppression 3. In metabolic disease, CAMKK1 is elevated in type 2 diabetes patients and shows positive associations with AMPK and inflammatory markers (TNFα) 2. The common SNP rs7214723 (E375G substitution in the kinase domain) is associated with both enhanced lung cancer prognosis and altered cancer risk, with the T allele conferring increased lung cancer susceptibility in Chinese populations 45. Additionally, Nrf2-mediated regulation of CAMKK1 controls osteoclast differentiation and bone loss in parasitic infection contexts 6. These findings establish CAMKK1 as a multifunctional regulator with therapeutic potential in metabolic and neoplastic diseases.

Sources cited
1
CAMKK1 transferred by mesenchymal stem cell exosomes regulates lipid homeostasis through AMPK-dependent activation of fatty acid oxidation (PPARα) and inhibition of fatty acid synthesis (SREBP-1C)
PMID: 37274776
2
CAMKK1 is elevated in type 2 diabetes patients compared to controls and obesity groups; shows positive associations with AMPK and TNFα across diagnostic groups
PMID: 40965347
3
CAMKK1 rs7214723 CC genotype confers better overall survival in lung cancer; T>C mutation inhibits cell proliferation and migration while promoting apoptosis
PMID: 34868969
4
CAMKK1 rs7214723 polymorphism affects lung cancer risk in Chinese population; T allele is a risk allele; E375G substitution occurs in kinase domain
PMID: 23737288
5
CAMKK1 is an upstream activator of CAMK1 and CAMK4 signaling with important functions in neural development and cardiovascular Ca2+ signaling
PMID: 30287839
6
Nrf2 directly regulates CAMKK1; CAMKK1 upregulation promotes osteoclast differentiation and bone loss; CAMKK1 inhibition by Crenolani alleviates parasitic infection-induced bone loss
PMID: 39674449
Disease Associationsⓘ20
cervical carcinomaOpen Targets
0.33Weak
neurodegenerative diseaseOpen Targets
0.32Weak
retinal degenerationOpen Targets
0.26Weak
type 2 diabetes mellitusOpen Targets
0.07Suggestive
obesityOpen Targets
0.07Suggestive
Abruptio PlacentaeOpen Targets
0.07Suggestive
lung cancerOpen Targets
0.06Suggestive
Monoamine oxidase A deficiencyOpen Targets
0.06Suggestive
schizophrenia 19Open Targets
0.06Suggestive
Alzheimer diseaseOpen Targets
0.03Suggestive
COVID-19–associated multisystem inflammatory syndrome in adultsOpen Targets
0.03Suggestive
glioblastoma multiformeOpen Targets
0.02Suggestive
Hepatic steatosisOpen Targets
0.02Suggestive
laryngotracheoesophageal cleftOpen Targets
0.02Suggestive
hepatocellular carcinomaOpen Targets
0.02Suggestive
cardiovascular diseaseOpen Targets
0.02Suggestive
non-alcoholic fatty liver diseaseOpen Targets
0.01Suggestive
diabetes mellitusOpen Targets
0.01Suggestive
astrocytomaOpen Targets
0.01Suggestive
SepsisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
MYZAPShared pathway100%LRRC69Shared pathway100%DCDC2CShared pathway100%LRRC18Shared pathway100%ASB18Shared pathway100%LRRC30Shared pathway100%
Tissue Expression6 tissues
Brain
100%
Ovary
27%
Bone Marrow
26%
Heart
22%
Lung
19%
Liver
4%
Gene Interaction Network
Click a node to explore
CAMKK1MYZAPLRRC69DCDC2CLRRC18ASB18LRRC30
PROTEIN STRUCTURE
Preparing viewer…
PDB6CCF · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.47Moderately Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.32 [0.23–0.47]
RankingsWhere CAMKK1 stands among ~20K protein-coding genes
  • #9,310of 20,598
    Most Researched46
  • #2,706of 17,882
    Most Constrained (LOEUF)0.47 · top quartile
Genes detectedCAMKK1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Human umbilical cord mesenchymal stem cell-derived exosomes ameliorate liver steatosis by promoting fatty acid oxidation and reducing fatty acid synthesis.
PMID: 37274776
JHEP Rep · 2023
1.00
2
CAMKK1 in Obesity and Type 2 Diabetes Mellitus: Evidence of Interaction With Appetite-Regulating, Metabolic and Inflammatory Factors.
PMID: 40965347
Endocrinol Diabetes Metab · 2025
0.90
3
Associations Between
PMID: 34868969
Front Oncol · 2021
0.80
4
Polymorphism rs7214723 in CAMKK1: a new genetic variant associated with cardiovascular diseases.
PMID: 34165505
Biosci Rep · 2021
0.70
5
Polymorphism rs7214723 in CAMKK1 and lung cancer risk in Chinese population.
PMID: 23737288
Tumour Biol · 2013
0.60