HomeAboutRankingsData Sources
© 2026 GeneE
🧬
GeneE
8 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
ⓘGeneE is for informational purposes only. It is not a substitute for professional medical advice, diagnosis, or treatment.
CNPY4
canopy FGF signaling regulator 4
Chromosome 7 · 7q22.1
NCBI Gene: 245812Ensembl: ENSG00000166997.9HGNC: HGNC:28631UniProt: Q8N129
15PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein bindingpositive regulation of protein localization to plasma membranesignaling receptor bindingextracellular regiongenetic disorderautismazoospermiaMale infertility with spermatogenesis disorder due to single gene mutation
✦AI Summary

CNPY4 (canopy FGF signaling regulator 4) is a conserved saposin-like protein that regulates cellular signaling through multiple mechanisms. As a primary function, CNPY4 modulates cell surface expression of TLR4 and participates in protein localization to the plasma membrane 1. Mechanistically, CNPY4 acts as a negative regulator of Hedgehog (HH) pathway signaling by controlling membrane sterol lipid composition; Cnpy4 knockout embryos exhibit HH signaling perturbations including digit abnormalities, while Cnpy4 knockdown hyperactivates HH signaling and elevates membrane cholesterol levels 2. CNPY4 also functions as a substrate of the kinase FAM20C, where its phosphorylation contributes to proinflammatory adipocyte signaling and metabolic dysfunction 3. Disease relevance includes involvement in developmental processes, immune regulation, and metabolic disorders. Regarding clinical significance, CNPY4 expression is differentially regulated in endometrial stromal cells from women with recurrent pregnancy loss and repeated implantation failure compared to fertile controls, suggesting a potential biomarker role in reproductive pathology 4. CNPY4 interacts with the tumor suppressor LRIG1, implicating it in growth factor receptor regulation networks 5. Further research is needed to fully elucidate CNPY4's therapeutic potential in metabolic and immunological diseases.

Sources cited
1
CNPY4 is a conserved saposin-like protein involved in protein localization to plasma membrane and biological processes including immune responses and disease
PMID: 39869231
2
CNPY4 inhibits Hedgehog pathway signaling by modulating membrane sterol lipids; Cnpy4 knockout causes developmental defects and Cnpy4 knockdown hyperactivates HH signaling
PMID: 35504891
3
CNPY4 is a FAM20C substrate whose phosphorylation promotes proinflammatory adipocyte signaling and contributes to obesity-induced insulin resistance
PMID: 41148235
4
CNPY4 is differentially expressed in endometrial stromal cells from women with repeated implantation failure and recurrent pregnancy loss upon decidualization
PMID: 30612956
5
CNPY4 interacts with LRIG1, a tumor suppressor that regulates growth factor receptor signaling networks
PMID: 29317492
Disease Associationsⓘ20
genetic disorderOpen Targets
0.15Weak
autismOpen Targets
0.11Weak
azoospermiaOpen Targets
0.09Suggestive
Male infertility with spermatogenesis disorder due to single gene mutationOpen Targets
0.07Suggestive
Female infertility due to fertilization defectOpen Targets
0.07Suggestive
Rare genetic female infertilityOpen Targets
0.07Suggestive
partial chromosome Y deletionOpen Targets
0.07Suggestive
spermatogenic failure 3Open Targets
0.06Suggestive
spermatogenic failure 55Open Targets
0.06Suggestive
spermatogenic failure 26Open Targets
0.06Suggestive
spermatogenic failure 31Open Targets
0.06Suggestive
spermatogenic failure 53Open Targets
0.06Suggestive
spermatogenic failure 87Open Targets
0.06Suggestive
habitual abortionOpen Targets
0.06Suggestive
spermatogenic failure 23Open Targets
0.06Suggestive
spermatogenic failure 52Open Targets
0.06Suggestive
oocyte maturation defect 14Open Targets
0.06Suggestive
oocyte maturation defect 5Open Targets
0.06Suggestive
spermatogenic failure 61Open Targets
0.06Suggestive
spermatogenic failure 88Open Targets
0.06Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
LY96Protein interaction83%TLR4Protein interaction76%STACShared pathway50%STAC3Shared pathway33%STAC2Shared pathway33%PTPN9Shared pathway25%
Tissue Expression6 tissues
Ovary
100%
Heart
57%
Bone Marrow
45%
Lung
39%
Brain
34%
Liver
26%
Gene Interaction Network
Click a node to explore
CNPY4LY96TLR4STACSTAC3STAC2PTPN9
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q8N129
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.33LoF Tolerant
pLIⓘ
0.00Tolerant
Observed/Expected LoF0.98 [0.73–1.33]
RankingsWhere CNPY4 stands among ~20K protein-coding genes
  • #15,523of 20,598
    Most Researched15
  • #13,960of 17,882
    Most Constrained (LOEUF)1.33
Genes detectedCNPY4
Sources retrieved8 papers
Response time—
📄 Sources
8▼
1
Progress in Research on CNPY2 in Diseases.
PMID: 37259932
Mini Rev Med Chem · 2024
1.00
2
Secretory kinase FAM20C triggers adipocyte dysfunction, inciting insulin resistance and inflammation in obesity.
PMID: 41148235
J Clin Invest · 2026
0.88
3
The role of canopy family proteins: biological mechanism and disease function.
PMID: 39869231
Mol Biol Rep · 2025
0.75
4
CNPY4 inhibits the Hedgehog pathway by modulating membrane sterol lipids.
PMID: 35504891
Nat Commun · 2022
0.63
5
Endometrial stromal cell proteome mapping in repeated implantation failure and recurrent pregnancy loss cases and fertile women.
PMID: 30612956
Reprod Biomed Online · 2019
0.50