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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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CDS2
CDP-diacylglycerol synthase 2
Chromosome 20 · 20p12.3
NCBI Gene: 8760Ensembl: ENSG00000101290.15HGNC: HGNC:1801UniProt: O95674
64PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
phosphatidate cytidylyltransferase activityprotein bindingCDP-diacylglycerol biosynthetic processlipid droplet formationpolypovarian carcinomaneoplasmdiabetes mellitus
✦AI Summary

CDS2 (CDP-diacylglycerol synthase 2) catalyzes the conversion of phosphatidic acid to CDP-diacylglycerol (CDP-DAG), a critical intermediate in phospholipid synthesis 1. The enzyme exhibits specificity for particular acyl chain compositions, preferring 1-stearoyl-2-arachidonoyl substrates 1. CDS2 plays important roles in regulating lipid droplet growth and maturation, which are central to lipid and energy homeostasis 23. CDS2 functions at the endoplasmic reticulum, where it catalyzes a rate-limiting step in phosphatidylinositol (PI) synthesis 4. Clinically, CDS2 represents a synthetic lethal vulnerability in cancers with low CDS1 expression, including uveal melanoma, mesenchymal-like cancers, and pancreatic ductal adenocarcinoma 567. CDS2 knockout disrupts phosphoinositide synthesis, impairs lipid homeostasis, and triggers apoptosis in these cancer contexts 56. Additionally, CDS2 is implicated in diabetic wound healing through METTL3-mediated RNA methylation affecting mitochondrial function 8. The CDS1/CDS2 axis represents a promising therapeutic target across multiple cancer types, with CDS2 being pharmacologically tractable through inhibition of its catalytic activity 6.

Sources cited
1
CDS2 catalyzes PA to CDP-DAG conversion with specificity for stearoyl-arachidonoyl substrates
PMID: 25375833
2
CDS2 plays important role in regulating lipid droplet growth and maturation
PMID: 26946540
3
CDS2 regulates lipid droplet maturation and energy homeostasis
PMID: 31548309
4
CDS2 catalyzes rate-limiting step in PI synthesis at endoplasmic reticulum
PMID: 31173893
5
CDS2 is synthetically lethal with low CDS1 in uveal melanoma; knockout disrupts phosphoinositide synthesis and increases apoptosis
PMID: 40615675
6
CDS2 is essential in mesenchymal-like cancers with low CDS1; synthetic lethality involves lipid homeostasis disruption and apoptosis
PMID: 40615674
7
CDS2 is synthetic lethal target in pancreatic cancer cells with epithelial-to-mesenchymal transition signatures
PMID: 40848256
8
CDS2 involved in diabetic wound healing through METTL3-mediated RNA methylation affecting mitochondrial function
PMID: 39424634
Disease Associationsⓘ20
polypOpen Targets
0.23Weak
ovarian carcinomaOpen Targets
0.17Weak
neoplasmOpen Targets
0.09Suggestive
diabetes mellitusOpen Targets
0.06Suggestive
food allergyOpen Targets
0.06Suggestive
neutropenia, severe congenital, 2, autosomal dominantOpen Targets
0.04Suggestive
combined immunodeficiency with skin granulomasOpen Targets
0.04Suggestive
X-Linked Combined Immunodeficiency DiseasesOpen Targets
0.03Suggestive
common variable immunodeficiencyOpen Targets
0.03Suggestive
immunodeficiency 18Open Targets
0.03Suggestive
immunodeficiency 15aOpen Targets
0.03Suggestive
immunodeficiency 84Open Targets
0.03Suggestive
cancerOpen Targets
0.01Suggestive
non-alcoholic steatohepatitisOpen Targets
0.01Suggestive
psoriasisOpen Targets
0.01Suggestive
cardiovascular diseaseOpen Targets
0.01Suggestive
achalasia-alacrima syndromeOpen Targets
0.01Suggestive
acute lymphoblastic leukemiaOpen Targets
0.01Suggestive
colitisOpen Targets
0.01Suggestive
psoriasis vulgarisOpen Targets
0.01Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CDIPTProtein interaction99%PGS1Protein interaction97%PLD3Protein interaction97%LPIN3Protein interaction96%LPIN1Protein interaction96%PLD4Protein interaction96%
Tissue Expression6 tissues
Brain
100%
Heart
94%
Bone Marrow
54%
Lung
36%
Ovary
26%
Liver
25%
Gene Interaction Network
Click a node to explore
CDS2CDIPTPGS1PLD3LPIN3LPIN1PLD4
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt O95674
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
0.94LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.69 [0.51–0.94]
RankingsWhere CDS2 stands among ~20K protein-coding genes
  • #7,251of 20,598
    Most Researched64
  • #8,802of 17,882
    Most Constrained (LOEUF)0.94
Genes detectedCDS2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.
PMID: 40615675
Nat Genet · 2025
1.00
2
Identification and characterization of CDS2, a mammalian homolog of the Drosophila CDP-diacylglycerol synthase gene.
PMID: 9889000
Genomics · 1999
0.90
3
Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers.
PMID: 40615674
Nat Genet · 2025
0.80
4
Integrative genomic identification of therapeutic targets for pancreatic cancer.
PMID: 40848256
Cell Rep · 2025
0.70
5
Genomic organization of human CDS2 and evaluation as a candidate gene for corneal hereditary endothelial dystrophy 2 on chromosome 20p13.
PMID: 12457874
Exp Eye Res · 2002
0.60