NPR1

Chr 1

natriuretic peptide receptor 1

Also known as: ANP-A, ANPRA, ANPa, GC-A, GUC2A, GUCY2A, NPRA

Guanylyl cyclases, catalyzing the production of cGMP from GTP, are classified as soluble and membrane forms (Garbers and Lowe, 1994 [PubMed 7982997]). The membrane guanylyl cyclases, often termed guanylyl cyclases A through F, form a family of cell-surface receptors with a similar topographic structure: an extracellular ligand-binding domain, a single membrane-spanning domain, and an intracellular region that contains a protein kinase-like domain and a cyclase catalytic domain. GC-A and GC-B function as receptors for natriuretic peptides; they are also referred to as atrial natriuretic peptide receptor A (NPR1) and type B (NPR2; MIM 108961). Also see NPR3 (MIM 108962), which encodes a protein with only the ligand-binding transmembrane and 37-amino acid cytoplasmic domains. NPR1 is a membrane-bound guanylate cyclase that serves as the receptor for both atrial and brain natriuretic peptides (ANP (MIM 108780) and BNP (MIM 600295), respectively).[supplied by OMIM, May 2009]

OMIMResearchGenerating clinical summary…

Clinical highlights

Interpreting a novel variant
This gene is strongly intolerant of loss-of-function variation in the population, so LoF variants warrant close attention. No curated mechanism annotation is available — see the mechanism card for the computational prediction and its caveats.Based on population constraint only.
0
Active trials
137
Pubs (1 yr)
P/LP submissions
P/LP missense
0.48
LOEUF
Multiple*
Mechanism· predicted

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint?
0.48LOEUF
pLI 0.000
Z-score 4.49
OE 0.32 (0.210.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint?
2.82Z-score
OE missense 0.68 (0.630.74)
414 obs / 610.0 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios?
LoF OE?0.32 (0.210.48)
00.351.4
Missense OE?0.68 (0.630.74)
00.61.4
Synonymous OE?0.90
01.21.6
LoF obs/exp: 16 / 50.3Missense obs/exp: 414 / 610.0Syn Z: 1.29

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

NPR1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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