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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
β“˜GeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
AGK
acylglycerol kinase
Chromosome 7 Β· 7q34
NCBI Gene: 55750Ensembl: ENSG00000006530.18HGNC: HGNC:21869UniProt: A0A3B3ISZ0
142PubMed Papers
22Diseases
0Drugs
50Pathogenic Variants
FUNCTIONAL ROLE
Kinase
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
mitochondrial membraneTIM22 mitochondrial import inner membrane insertion complexmitochondrionprotein bindingSengers syndromecataract 38Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathyearly-onset non-syndromic cataract
✦AI Summary

AGK (acylglycerol kinase) is a lipid kinase that phosphorylates monoacylglycerols and diacylglycerols to produce lysophosphatidic acid (LPA) and phosphatidic acid (PA), respectively 1. It also phosphorylates ceramide and shows substrate preference for 1,2-dioleoylglycerol over regioisomers 1. Beyond its kinase function, AGK acts as a kinase-independent component of the TIM22 mitochondrial import complex, mediating insertion of multi-pass transmembrane proteins into the mitochondrial inner membrane 23. Within TIM22, AGK is specifically required for importing metabolite carriers like ANT1 and SLC25A24 2. AGK overexpression increases LPA formation and secretion, activating EGFR and downstream MAPK signaling to promote cell growth 1. AGK deficiency impairs mitochondrial complex I function and is associated with non-alcoholic steatohepatitis (NASH) progression through disrupted mitochondrial fatty acid metabolism 4. Clinically, AGK mutations cause Mitochondrial DNA Depletion Syndrome 10, characterized by impaired mtDNA synthesis and systemic organ dysfunction 5. AGK mutations also cause Sengers syndrome, presenting with congenital cataracts, cardiomyopathy, myopathy, and lactic acidosis 4. These disease associations underscore AGK's critical dual role in lipid metabolism and mitochondrial protein import.

Sources cited
1
AGK phosphorylates monoacylglycerols and diacylglycerols to form LPA and PA; does not phosphorylate sphingosine; overexpression increases LPA secretion and EGFR/MAPK signaling
PMID: 15939762
2
AGK is a component of the TIM22 complex mediating mitochondrial protein import; required for import of metabolite carriers ANT1 and SLC25A24
PMID: 28712724
3
TIM22 complex mediates import and insertion of multi-pass transmembrane proteins into mitochondrial inner membrane using membrane potential as driving force
PMID: 28712726
4
AGK deficiency impairs mitochondrial complex I function and aggravates NASH; AGK interacts with complex I subunits NDUFS2 and NDUFA10 via kinase-independent pathway; AGK mutations cause Sengers syndrome
PMID: 35547757
5
AGK is among nuclear genes crucial for mtDNA maintenance; AGK pathogenic variants cause Mitochondrial DNA Depletion Syndrome 10
PMID: 28215579
Disease Associationsβ“˜22
Sengers syndromeOpen Targets
0.82Strong
cataract 38Open Targets
0.73Strong
Congenital cataract - hypertrophic cardiomyopathy - mitochondrial myopathyOpen Targets
0.71Strong
early-onset non-syndromic cataractOpen Targets
0.56Moderate
cancerOpen Targets
0.55Moderate
genetic disorderOpen Targets
0.49Moderate
mitochondrial diseaseOpen Targets
0.44Moderate
Developmental cataractOpen Targets
0.42Moderate
Total congenital cataractOpen Targets
0.37Weak
total early-onset cataractOpen Targets
0.37Weak
Syndromic diarrheaOpen Targets
0.34Weak
psoriasisOpen Targets
0.32Weak
enteritisOpen Targets
0.28Weak
ovarian neoplasmOpen Targets
0.20Weak
scoliosisOpen Targets
0.15Weak
ankylosing spondylitisOpen Targets
0.12Weak
brain diseaseOpen Targets
0.12Weak
neoplasmOpen Targets
0.10Suggestive
breast cancerOpen Targets
0.08Suggestive
nasopharyngeal carcinomaOpen Targets
0.08Suggestive
Cataract 38UniProt
Mitochondrial DNA depletion syndrome 10UniProt
Pathogenic Variants50
NM_018238.4(AGK):c.297+2T>CPathogenic
not provided|Sengers syndrome;Cataract 38|AGK-related disorder
β˜…β˜…β˜†β˜†2026
NM_018238.4(AGK):c.523_524del (p.Ile175fs)Pathogenic
Sengers syndrome|not provided|Cataract 38;Sengers syndrome
β˜…β˜…β˜†β˜†2025β†’ Residue 175
NM_018238.4(AGK):c.409C>T (p.Arg137Ter)Pathogenic
Sengers syndrome|not provided|Trichohepatoenteric syndrome 1|Sengers syndrome;Cataract 38
β˜…β˜…β˜†β˜†2025β†’ Residue 137
NM_018238.4(AGK):c.841C>T (p.Arg281Ter)Pathogenic
Sengers syndrome|not provided|Cataract 38;Sengers syndrome
β˜…β˜…β˜†β˜†2024β†’ Residue 281
NM_018238.4(AGK):c.412C>T (p.Arg138Ter)Pathogenic
Cataract 38;Sengers syndrome|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024β†’ Residue 138
NM_018238.4(AGK):c.222-2A>CLikely pathogenic
Sengers syndrome;Cataract 38
β˜…β˜…β˜†β˜†2024
NM_018238.4(AGK):c.424-3C>GPathogenic
Cataract 38|Sengers syndrome|Autosomal recessive AGK-related phenotype|Inborn genetic diseases
β˜…β˜…β˜†β˜†2024
NM_018238.4(AGK):c.672C>A (p.Tyr224Ter)Pathogenic
not provided|Sengers syndrome|Cataract 38;Sengers syndrome
β˜…β˜…β˜†β˜†2023β†’ Residue 224
NM_018238.4(AGK):c.518+1G>APathogenic
Sengers syndrome|AGK-related disorder
β˜…β˜…β˜†β˜†2023
NM_018238.4(AGK):c.1047-2A>TPathogenic
not provided|Sengers syndrome;Cataract 38
β˜…β˜…β˜†β˜†2023
NM_018238.4(AGK):c.1141_1142dup (p.Ser382fs)Pathogenic
not provided|Cataract 38;Sengers syndrome
β˜…β˜…β˜†β˜†2022β†’ Residue 382
NM_018238.4(AGK):c.1150_1154del (p.Phe383_Ser384insTer)Likely pathogenic
Sengers syndrome;Cataract 38
β˜…β˜†β˜†β˜†2025β†’ Residue 383
NM_018238.4(AGK):c.25C>T (p.Arg9Ter)Pathogenic
Cataract 38;Sengers syndrome
β˜…β˜†β˜†β˜†2025β†’ Residue 9
NM_018238.4(AGK):c.221+1dupPathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_018238.4(AGK):c.1131+2T>CPathogenic
Sengers syndrome|Sengers syndrome;Cataract 38
β˜…β˜†β˜†β˜†2024
NM_018238.4(AGK):c.1035dup (p.Ile346fs)Pathogenic
Cataract 38;Sengers syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 346
NM_018238.4(AGK):c.1166_1167dup (p.Tyr390fs)Pathogenic
Sengers syndrome;Cataract 38
β˜…β˜†β˜†β˜†2024β†’ Residue 390
NM_018238.4(AGK):c.976-1G>CLikely pathogenic
Sengers syndrome;Cataract 38
β˜…β˜†β˜†β˜†2024
NM_018238.4(AGK):c.269T>G (p.Leu90Ter)Pathogenic
Sengers syndrome;Cataract 38
β˜…β˜†β˜†β˜†2024β†’ Residue 90
NM_018238.4(AGK):c.356dup (p.Ile120fs)Pathogenic
Cataract 38;Sengers syndrome
β˜…β˜†β˜†β˜†2024β†’ Residue 120
View on ClinVar β†—
Related Genes
TIMM10BProtein interaction100%GPAMProtein interaction100%GPAT2Protein interaction98%PNLIPRP3Protein interaction92%AGPAT1Protein interaction91%AGPAT2Protein interaction91%
Tissue Expression6 tissues
Heart
100%
Brain
52%
Liver
48%
Ovary
42%
Lung
39%
Bone Marrow
36%
Gene Interaction Network
Click a node to explore
AGKTIMM10BGPAMGPAT2PNLIPRP3AGPAT1AGPAT2
PROTEIN STRUCTURE
Preparing viewer…
PDB7CGP Β· 3.70 Γ… Β· EM
View on RCSB β†—
Constraintβ“˜
LOEUFβ“˜
0.92LoF Tolerant
pLIβ“˜
0.00Tolerant
Observed/Expected LoF0.65 [0.47–0.92]
RankingsWhere AGK stands among ~20K protein-coding genes
  • #3,210of 20,598
    Most Researched142 Β· top quartile
  • #1,331of 5,498
    Most Pathogenic Variants50 Β· top quartile
  • #8,408of 17,882
    Most Constrained (LOEUF)0.92
Genes detectedAGK
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
Perioperative Durvalumab with Neoadjuvant Chemotherapy in Operable Bladder Cancer.
PMID: 39282910
N Engl J Med Β· 2024
1.00
2
Oral Iptacopan Monotherapy in Paroxysmal Nocturnal Hemoglobinuria.
PMID: 38477987
N Engl J Med Β· 2024
0.90
3
Mitochondrial DNA maintenance defects.
PMID: 28215579
Biochim Biophys Acta Mol Basis Dis Β· 2017
0.80
4
AGK regulates the progression to NASH by affecting mitochondria complex I function.
PMID: 35547757
Theranostics Β· 2022
0.70
5
IL-33-activated ILC2s induce tertiary lymphoid structures in pancreatic cancer.
PMID: 39814891
Nature Β· 2025
0.60