NPR2 Gene - Natriuretic Peptide Receptor 2
Guanylyl Cyclase B (GC-B) Receptor for C-Type Natriuretic Peptide (CNP)
Gene Information Card
| Symbol | NPR2 |
|---|---|
| Full Name | Natriuretic Peptide Receptor 2 |
| Gene Type | protein-coding |
| Chromosomal Location | 9p13.3 |
| NCBI Gene ID | 4882 ncbi.nlm.nih.gov/gene/4882 |
| Ensembl ID | ENSG00000159899 |
| UniProt ID | P20594 |
| OMIM ID | 108961 |
| HGNC ID | 7944 |
| Aliases | GUC2B, GUCY2B, ANPb, NPRB, GC-B |
Description
The NPR2 gene encodes natriuretic peptide receptor 2 (NPR2), also known as guanylyl cyclase B (GC-B). This receptor specifically binds C-type natriuretic peptide (CNP) and, upon activation, catalyzes the synthesis of cyclic GMP (cGMP). NPR2 plays a critical role in endochondral ossification and skeletal growth. Loss-of-function mutations cause acromesomelic dysplasia, Maroteaux type (AMDM), while gain-of-function mutations are associated with epiphyseal chondrodysplasia, Miura type (ECDM).
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Acromesomelic Dysplasia, Maroteaux Type (AMDM) | Loss-of-function mutations in NPR2 impair CNP/cGMP signaling, disrupting endochondral bone growth, leading to short stature and skeletal abnormalities. | OMIM #602875; multiple homozygous/compound heterozygous variants reported. |
| Epiphyseal Chondrodysplasia, Miura Type (ECDM) | Gain-of-function mutations (e.g., p.Arg655Cys) increase basal cGMP production, causing tall stature and enlarged epiphyses. | OMIM #615923; heterozygous activating mutations. |
| Short Stature (idiopathic) | Heterozygous loss-of-function variants in NPR2 are associated with mild short stature without the full AMDM phenotype. | ClinVar; multiple studies (e.g., Vasques et al., 2013). |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone (cartilage) | High | High |
| Lung | Medium | Medium |
| Kidney | Medium | Medium |
| Heart | Low | Low |
| Brain | Low | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| Chondrocytes | High | Primary cell type for NPR2 function |
| Osteoblasts | Medium | Expressed during bone formation |
| HEK293 | Low | Used in recombinant expression studies |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.271dupA (p.Thr91Asnfs*12) | Frameshift | Rare | Loss-of-function; AMDM |
| c.1963C>T (p.Arg655Cys) | Missense | Rare | Gain-of-function; ECDM |
| c.2071G>A (p.Val691Met) | Missense | Rare | Loss-of-function; AMDM |
| c.3448C>T (p.Arg1150*) | Nonsense | Rare | Loss-of-function; AMDM |
Mutation functional classification
Loss of Function (LOF)
Most NPR2 mutations in AMDM are loss-of-function (nonsense, frameshift, missense) that reduce or abolish guanylyl cyclase activity, leading to impaired CNP signaling and skeletal growth defects.
Gain of Function (GOF)
Activating missense mutations (e.g., p.Arg655Cys) increase basal cGMP production, resulting in overgrowth and epiphyseal abnormalities in ECDM.
Dominant Negative (DN)
Some heterozygous missense variants may exert a dominant-negative effect by forming inactive dimers with wild-type NPR2, contributing to short stature.
View complete mutation data：
Gene Ontology (GO)
| • GO:0004383 (guanylate cyclase activity) | • GO:0005524 (ATP binding) |
| • GO:0005901 (caveola) | • GO:0007165 (signal transduction) |
| • GO:0008078 (mesodermal cell differentiation) | • GO:0010640 (regulation of platelet-derived growth factor receptor signaling pathway) |
| • GO:0030018 (Z disc) | • GO:0035556 (intracellular signal transduction) |
| • GO:0042802 (identical protein binding) | • GO:0043410 (positive regulation of MAPK cascade) |
| • GO:0045907 (positive regulation of vasoconstriction) | • GO:0045944 (positive regulation of transcription by RNA polymerase II) |
| • GO:0051592 (response to calcium ion) | • GO:0060348 (bone development) |
| • GO:0071872 (cellular response to epinephrine stimulus) | • GO:1900076 (regulation of cellular response to insulin stimulus) |
Pathways
• cGMP-PKG signaling pathway (KEGG: hsa04022)
• Natriuretic peptide signaling (Reactome: R-HSA-418594)
• Guanylate cyclase pathway (WikiPathways: WP286)
Protein Summary
Natriuretic peptide receptor 2 (NPR2) is a single-pass transmembrane receptor with an extracellular ligand-binding domain, a transmembrane domain, and an intracellular guanylyl cyclase domain. It forms a homodimer and, upon binding CNP, converts GTP to cGMP. NPR2 is essential for longitudinal bone growth via regulation of chondrocyte proliferation and differentiation. Mutations in NPR2 cause skeletal dysplasias with either short or tall stature.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NPR2 Knockout HEK293 Cell Line | EDJ-KQ1840 | Human | 4882 | Details Get a Quote |
| NPR2 Knockout A-549 Cell Line | EDJ-KQ21694 | Human | 4882 | Details Get a Quote |
| NPR2 Knockout HCT 116 Cell Line | EDJ-KQ21695 | Human | 4882 | Details Get a Quote |
| NPR2 Knockout HeLa Cell Line | EDC90020 | Human | 4882 | Details Get a Quote |
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