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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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NPPC
natriuretic peptide C
Chromosome 2 · 2q37.1
NCBI Gene: 4880Ensembl: ENSG00000163273.5HGNC: HGNC:7941UniProt: E5LCN7
114PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein-containing complexhormone receptor bindingnegative regulation of meiotic cell cyclecGMP biosynthetic processknee fractureneurodegenerative diseaserespiratory failureAbnormality of the skeletal system
✦AI Summary

NPPC (natriuretic peptide C) encodes a hormone that regulates multiple physiological processes through cGMP signaling. The primary function of NPPC is maintaining oocyte meiotic arrest and developmental capacity 1. NPPC is produced by granulosa and mural cells in the ovary, where it binds the NPR2 receptor on cumulus cells to generate cGMP, which penetrates oocytes via gap junctions and inhibits phosphodiesterase 3A, thereby maintaining elevated cAMP levels that suppress meiosis resumption 2. During the luteinizing hormone surge, reduced NPPC/NPR2 signaling decreases cGMP, allowing cAMP hydrolysis and meiotic resumption 2. Beyond reproduction, NPPC plays a critical role in skeletal development through NPR2-mediated cGMP production 3. Disease relevance is demonstrated by mutations in NPPC causing autosomal dominant short stature in humans 3 and premature ovarian insufficiency, where aberrant post-translational cleavage impairs cGMP synthesis 4. Clinically, CNP analogs are in trials for achondroplasia treatment 3. NPPC mutations result in reduced ovarian size, abnormal chr2, impaired cumulus expansion, and decreased oocyte numbers 1, establishing NPPC as essential for both skeletal and reproductive health.

Sources cited
1
NPPC/NPR2/cGMP signaling maintains oocyte meiotic arrest and developmental capacity; defects cause small ovaries, abnormal chromosomes, and reduced oocyte numbers
PMID: 31078160
2
NPPC produced by granulosa cells binds NPR2 on cumulus cells to produce cGMP, which inhibits PDE3A in oocytes to maintain meiotic arrest through elevated cAMP
PMID: 35209923
3
NPPC mutations cause autosomal dominant short stature in humans; CNP analogs are in clinical trials for achondroplasia treatment
PMID: 28661490
4
NPPC mutations causing abnormal post-translational cleavage reduce cGMP synthetic activity and are associated with premature ovarian insufficiency
PMID: 35120671
⚠Limited data available — This gene has 4 indexed publications. Summary and analysis may be incomplete.
Disease Associationsⓘ20
knee fractureOpen Targets
0.32Weak
neurodegenerative diseaseOpen Targets
0.25Weak
respiratory failureOpen Targets
0.19Weak
Abnormality of the skeletal systemOpen Targets
0.14Weak
ovarian dysfunctionOpen Targets
0.10Suggestive
Benign Thyroid Gland NeoplasmOpen Targets
0.09Suggestive
liver diseaseOpen Targets
0.06Suggestive
alcohol drinkingOpen Targets
0.05Suggestive
Acromesomelic dysplasia, Grebe typeOpen Targets
0.05Suggestive
AcheiropodiaOpen Targets
0.05Suggestive
Eiken syndromeOpen Targets
0.05Suggestive
acromesomelic dysplasia 2BOpen Targets
0.05Suggestive
spondyloepimetaphyseal dysplasia, Isidor-Toutain typeOpen Targets
0.05Suggestive
Absent tibia - polydactylyOpen Targets
0.05Suggestive
tibia, hypoplasia or aplasia of, with polydactylyOpen Targets
0.05Suggestive
Metaphyseal chondrodysplasia, Schmid typeOpen Targets
0.05Suggestive
Schmid metaphyseal chondrodysplasiaOpen Targets
0.05Suggestive
chondrodysplasia punctata, tibial-metacarpal typeOpen Targets
0.04Suggestive
Fibular aplasia - ectrodactylyOpen Targets
0.04Suggestive
fibular aplasia-ectrodactyly syndromeOpen Targets
0.04Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
NPR3Protein interaction100%NPR1Protein interaction95%OSTNProtein interaction73%NPPBProtein interaction66%NPPAProtein interaction66%NPR2Protein interaction58%
Tissue Expression6 tissues
Brain
100%
Heart
48%
Ovary
24%
Bone Marrow
6%
Lung
0%
Liver
0%
Gene Interaction Network
Click a node to explore
NPPCNPR3NPR1OSTNNPPBNPPANPR2
PROTEIN STRUCTURE
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PDB1JDP · 2.00 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.04LoF Tolerant
pLIⓘ
0.22Tolerant
Observed/Expected LoF0.45 [0.22–1.04]
RankingsWhere NPPC stands among ~20K protein-coding genes
  • #4,158of 20,598
    Most Researched114 · top quartile
  • #10,290of 17,882
    Most Constrained (LOEUF)1.04
Genes detectedNPPC
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Signaling mechanisms and their regulation during in vivo or in vitro maturation of mammalian oocytes.
PMID: 35209923
Reprod Biol Endocrinol · 2022
1.00
2
Rejuvenation Modulation of Nucleus Pulposus Progenitor Cells Reverses Senescence-Associated Intervertebral Disc Degeneration.
PMID: 39969420
Adv Mater · 2025
0.90
3
Injectable ECM-mimetic dynamic hydrogels abolish ferroptosis-induced post-discectomy herniation through delivering nucleus pulposus progenitor cell-derived exosomes.
PMID: 40169595
Nat Commun · 2025
0.80
4
Nppc/Npr2/cGMP signaling cascade maintains oocyte developmental capacity.
PMID: 31078160
Cell Mol Biol (Noisy-le-grand) · 2019
0.70
5
Single-nucleus transcriptomics decodes the link between aging and lumbar disc herniation.
PMID: 40119681
Protein Cell · 2025
0.60