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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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ISYNA1
inositol-3-phosphate synthase 1
Chromosome 19 · 19p13.11
NCBI Gene: 51477Ensembl: ENSG00000105655.20HGNC: HGNC:29821UniProt: A0A140VK73
62PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindinginositol biosynthetic processinositol-3-phosphate synthase activitycytoplasmneurodegenerative diseasebreast carcinomaAbruptio Placentaesystemic lupus erythematosus
✦AI Summary

ISYNA1 encodes inositol-3-phosphate synthase 1, the rate-limiting enzyme in myo-inositol biosynthesis that catalyzes the conversion of glucose 6-phosphate to myo-inositol 1-phosphate 1. This enzyme is essential for de novo inositol synthesis, as demonstrated by the "inositol-less death" phenotype observed in ISYNA1 knockout cells when deprived of inositol 1. The gene plays a paradoxical role in cancer, functioning as both a tumor suppressor and oncogene depending on cellular context 2. ISYNA1 exhibits tumor-suppressive properties in ovarian cancer by suppressing stemness through Notch1 pathway inhibition 3 and in pancreatic cancer through p21/ZEB-1 signaling 4. However, it is overexpressed in bladder cancer where it promotes proliferation and inhibits apoptosis 5. In acute myeloid leukemia, ISYNA1 is frequently silenced through DNA hypermethylation, creating a synthetic lethal dependency on the myo-inositol transporter SLC5A3 6. The enzyme's expression is regulated by E2F1 transcription factor 7, and genetic polymorphisms may influence spina bifida risk through interactions with glucose metabolism 8. Inositol depletion affects phospholipid metabolism and activates stress signaling pathways 1.

Sources cited
1
ISYNA1 is the rate-limiting enzyme catalyzing glucose 6-phosphate to myo-inositol 1-phosphate conversion and is essential for cell viability
PMID: 35247568
2
ISYNA1 plays a paradoxical role in cancer as both tumor suppressor and oncogene depending on cellular context
PMID: 35462605
3
ISYNA1 suppresses ovarian cancer stemness through Notch1 pathway regulation
PMID: 37105506
4
ISYNA1 functions as tumor suppressor in pancreatic cancer through p21/ZEB-1 pathway
PMID: 32779876
5
ISYNA1 is overexpressed in bladder cancer and promotes proliferation while inhibiting apoptosis
PMID: 31495492
6
ISYNA1 silencing in AML creates synthetic lethal dependency on SLC5A3 myo-inositol transporter
PMID: 34531253
7
ISYNA1 expression is upregulated by E2F1 transcription factor
PMID: 15464731
8
ISYNA1 genetic polymorphisms may influence spina bifida risk through glucose metabolism interactions
PMID: 15172003
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.31Weak
breast carcinomaOpen Targets
0.27Weak
Abruptio PlacentaeOpen Targets
0.16Weak
systemic lupus erythematosusOpen Targets
0.15Weak
neoplasmOpen Targets
0.12Weak
psoriasisOpen Targets
0.11Weak
substance-related disorderOpen Targets
0.11Weak
infectionOpen Targets
0.10Weak
myocardial infarctionOpen Targets
0.10Weak
cancerOpen Targets
0.10Weak
breast cancerOpen Targets
0.10Weak
triple-negative breast cancerOpen Targets
0.10Suggestive
obesityOpen Targets
0.10Suggestive
Pallister-Hall syndromeOpen Targets
0.10Suggestive
experimental autoimmune encephalomyelitisOpen Targets
0.10Suggestive
luminal A breast carcinomaOpen Targets
0.09Suggestive
oral squamous cell carcinomaOpen Targets
0.09Suggestive
hepatocellular carcinomaOpen Targets
0.09Suggestive
colorectal cancerOpen Targets
0.09Suggestive
colitisOpen Targets
0.09Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
IMPA1Protein interaction91%IMPA2Protein interaction91%INPP1Protein interaction91%INPP4AProtein interaction91%INPP4BProtein interaction91%BPNT2Protein interaction91%
Tissue Expression6 tissues
Ovary
100%
Heart
32%
Bone Marrow
23%
Brain
20%
Lung
18%
Liver
17%
Gene Interaction Network
Click a node to explore
ISYNA1IMPA1IMPA2INPP1INPP4AINPP4BBPNT2
PROTEIN STRUCTURE
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AlphaFoldAI-predicted · UniProt Q9NPH2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.00LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.75 [0.57–1.00]
RankingsWhere ISYNA1 stands among ~20K protein-coding genes
  • #7,471of 20,598
    Most Researched62
  • #9,729of 17,882
    Most Constrained (LOEUF)1.00
Genes detectedISYNA1
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
ISYNA1 is overexpressed in bladder carcinoma and regulates cell proliferation and apoptosis.
PMID: 31495492
Biochem Biophys Res Commun · 2019
1.00
2
E2F1 regulation of the human myo-inositol 1-phosphate synthase (ISYNA1) gene promoter.
PMID: 15464731
Arch Biochem Biophys · 2004
0.90
3
The myo-inositol biosynthesis rate-limiting enzyme ISYNA1 suppresses the stemness of ovarian cancer via Notch1 pathway.
PMID: 37105506
Cell Signal · 2023
0.80
4
The paradoxical role of inositol in cancer: a consequence of the metabolic state of a tumor.
PMID: 35462605
Cancer Metastasis Rev · 2022
0.70
5
Musashi2 promotes the progression of pancreatic cancer through a novel ISYNA1-p21/ZEB-1 pathway.
PMID: 32779876
J Cell Mol Med · 2020
0.60