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GeneE
10 sources retrieved Β· Most recent: April 2026 Β· Index updated 14 days ago
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AGPS
alkylglycerone phosphate synthase
Chromosome 2 Β· 2q31.2
NCBI Gene: 8540Ensembl: ENSG00000018510.18HGNC: HGNC:327UniProt: B7Z3Q4
115PubMed Papers
21Diseases
0Drugs
30Pathogenic Variants
CLINICAL
OMIM Disease Gene
DATA QUALITY
βœ“ Experimental GO Evidenceβœ“ Swiss-Prot Reviewed
lipid biosynthetic processprotein bindingalkylglycerone-phosphate synthase activityperoxisomerhizomelic chondrodysplasia punctata type 3rhizomelic chondrodysplasia punctataneurodegenerative diseaseAbnormality of the skeletal system
✦AI Summary

AGPS (alkylglycerone phosphate synthase) is a key enzyme in ether lipid biosynthesis that catalyzes the formation of alkyl-dihydroxyacetonephosphate, the first ether-linked intermediate in this pathway 1. The enzyme is localized to peroxisomes and functions as the rate-limiting step in ether lipid synthesis 1. AGPS activity is tightly regulated through multiple mechanisms, including peroxisomal localization control and protein degradation pathways. Mechanistically, AGPS can be ubiquitinated and degraded by the E3 ligase MDM2, with this process enhanced by TrkA kinase phosphorylation at the Y451 site 2. The enzyme's expression and activity have significant disease relevance, particularly in cancer biology. AGPS promotes ferroptosis susceptibility in both prostate and gastric cancers by modulating ether lipid metabolism 23. In gastric cancer, Helicobacter pylori CagA increases AGPS expression through the MEK/ERK/SRF pathway, making cells more sensitive to ferroptosis and certain therapeutics like apatinib 3. Clinically, AGPS shows promise as both a prognostic biomarker and therapeutic target, with its expression levels correlating with patient survival and treatment response in various cancers 24.

Sources cited
1
AGPS is the rate-limiting enzyme for ether lipid synthesis and is localized to peroxisomes
PMID: 39169021
2
AGPS can be ubiquitinated by MDM2 and phosphorylated by TrkA kinase, and promotes ferroptosis in prostate cancer
PMID: 38200609
3
AGPS expression is increased by H. pylori CagA through MEK/ERK/SRF pathway and promotes ferroptosis susceptibility in gastric cancer
PMID: 38383581
4
AGPS is part of a prognostic model for laryngeal squamous cell carcinoma
PMID: 38610001
⚠Limited data available β€” This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsβ“˜21
rhizomelic chondrodysplasia punctata type 3Open Targets
0.82Strong
rhizomelic chondrodysplasia punctataOpen Targets
0.47Moderate
neurodegenerative diseaseOpen Targets
0.45Moderate
Abnormality of the skeletal systemOpen Targets
0.37Weak
alkylglycerone-phosphate synthase deficiencyOpen Targets
0.37Weak
insomniaOpen Targets
0.29Weak
cervical carcinomaOpen Targets
0.26Weak
placenta praeviaOpen Targets
0.23Weak
genetic disorderOpen Targets
0.19Weak
synpolydactylyOpen Targets
0.12Weak
refractive errorOpen Targets
0.09Suggestive
posterior cortical atrophyOpen Targets
0.08Suggestive
human african trypanosomiasisOpen Targets
0.06Suggestive
thyroid cancerOpen Targets
0.05Suggestive
azoospermiaOpen Targets
0.05Suggestive
Hypergonadotropic hypogonadism - cataract syndromeOpen Targets
0.05Suggestive
hypergonadotropic hypogonadism-cataract syndromeOpen Targets
0.05Suggestive
colobomatous microphthalmia - obesity - hypogenitalism - intellectual disability syndromeOpen Targets
0.05Suggestive
Colobomatous microphthalmia-obesity-hypogenitalism-intellectual disability syndromeOpen Targets
0.05Suggestive
prostate cancerOpen Targets
0.05Suggestive
Rhizomelic chondrodysplasia punctata 3UniProt
Pathogenic Variants30
NM_003659.4(AGPS):c.926C>T (p.Thr309Ile)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3|Rhizomelic chondrodysplasia punctata
β˜…β˜…β˜†β˜†2025β†’ Residue 309
NM_003659.4(AGPS):c.544C>T (p.Arg182Ter)Pathogenic
not provided|Rhizomelic chondrodysplasia punctata type 3
β˜…β˜…β˜†β˜†2025β†’ Residue 182
NM_003659.4(AGPS):c.1543C>T (p.Arg515Ter)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 515
NM_003659.4(AGPS):c.1233+1G>ALikely pathogenic
not provided
β˜…β˜†β˜†β˜†2025
NM_003659.4(AGPS):c.1663_1666dup (p.Gly556fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 556
NM_003659.4(AGPS):c.549del (p.Phe184fs)Pathogenic
not provided
β˜…β˜†β˜†β˜†2025β†’ Residue 184
NM_003659.4(AGPS):c.1736dup (p.Tyr580fs)Pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 580
NM_003659.4(AGPS):c.638-1G>APathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024
NM_003659.4(AGPS):c.815del (p.Asn272fs)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 272
NM_003659.4(AGPS):c.505A>T (p.Lys169Ter)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 169
NM_003659.3(AGPS):c.1286delGLikely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024
NM_003659.4(AGPS):c.580delinsCC (p.Ile194fs)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2024β†’ Residue 194
NM_003659.4(AGPS):c.288G>A (p.Trp96Ter)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023β†’ Residue 96
NM_003659.4(AGPS):c.1608-1G>ALikely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023
NM_003659.4(AGPS):c.1557_1564del (p.Glu520fs)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023β†’ Residue 520
NM_003659.4(AGPS):c.557_562+5delLikely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023
NM_003659.4(AGPS):c.1546-84_1591dupLikely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023
NM_003659.4(AGPS):c.637+2T>ALikely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023
NM_003659.4(AGPS):c.1658_1659del (p.Lys553fs)Likely pathogenic
Rhizomelic chondrodysplasia punctata
β˜…β˜†β˜†β˜†2023β†’ Residue 553
NM_003659.4(AGPS):c.595G>T (p.Glu199Ter)Likely pathogenic
Rhizomelic chondrodysplasia punctata type 3
β˜…β˜†β˜†β˜†2023β†’ Residue 199
View on ClinVar β†—
Related Genes
PEX5LProtein interaction90%PHYHProtein interaction88%PEX6Protein interaction86%PEX10Protein interaction86%PEX2Protein interaction86%PEX5Protein interaction86%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
61%
Heart
56%
Liver
48%
Lung
35%
Ovary
25%
Gene Interaction Network
Click a node to explore
AGPSPEX5LPHYHPEX6PEX10PEX2PEX5
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted Β· UniProt O00116
View on AlphaFold β†—
Constraintβ“˜
LOEUFβ“˜
0.41Moderately Constrained
pLIβ“˜
1.00Intolerant
Observed/Expected LoF0.25 [0.16–0.41]
RankingsWhere AGPS stands among ~20K protein-coding genes
  • #4,102of 20,598
    Most Researched115 Β· top quartile
  • #1,801of 5,498
    Most Pathogenic Variants30
  • #2,079of 17,882
    Most Constrained (LOEUF)0.41 Β· top quartile
Genes detectedAGPS
Sources retrieved10 papers
Response timeβ€”
πŸ“„ Sources
10β–Ό
1
The lipid-metabolism enzyme ECI2 reduces neutrophil extracellular traps formation for colorectal cancer suppression.
PMID: 39169021
Nat Commun Β· 2024
1.00
2
TrkA promotes MDM2-mediated AGPS ubiquitination and degradation to trigger prostate cancer progression.
PMID: 38200609
J Exp Clin Cancer Res Β· 2024
0.90
3
Theatre ventilation.
PMID: 33645287
Ann R Coll Surg Engl Β· 2021
0.80
4
RUNX1-BMP2 promotes vasculogenic mimicry in laryngeal squamous cell carcinoma via activation of the PI3K-AKT signaling pathway.
PMID: 38610001
Cell Commun Signal Β· 2024
0.70
5
Tracheotomy in the SARS-CoV-2 pandemic.
PMID: 32342565
Head Neck Β· 2020
0.60