NPR3

protein-coding

natriuretic peptide receptor 3, the group of DENN domain containing

Gene summary

This gene encodes one of three natriuretic peptide receptors. Natriutetic peptides are small peptides which regulate blood volume and pressure, pulmonary hypertension, and cardiac function as well as some metabolic and growth processes. The product of this gene encodes a natriuretic peptide receptor responsible for clearing circulating and extracellular natriuretic peptides through endocytosis of the receptor. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2011]

Previous symbols:

NPRC
ANPRC
C5orf23

MANE transcript

NM_001204375.2

Inheritance

AR, AD

ClinVar variants

P:9U:115B:79

Top phenotype

Boudin-Mortier syndrome

gnomAD constraint

pLI —, LoF o/e 0.51

Max pathogenic AF

—

Genomic locus

chr5:32,689,070-32,791,724

External References & Databases

Ensembl (ENSG00000113389)

Transcript & Mutation Effects

hg38 • Region Span ~102.7 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

Boudin-Mortier syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859194

Submitter: PanelApp Australia

Boudin-Mortier syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859194

Submitter: G2P

Boudin-Mortier syndromeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0859194

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Boudin-Mortier syndromeAD

Manifestation: Cardiovascular; Musculoskeletal

Intervention: Cardiovascular

Rationale: The condition has been reported as including progressive dilation of the aortic root in some individuals, and awareness may allow surveillance and potential early management

Refs: 30032985

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPR3 variants in ClinVar

5 Conditions Cataloged

not providedTotal: 171

Inborn genetic diseasesTotal: 77

not specifiedTotal: 10

Boudin-Mortier syndromeTotal: 9

NPR3-related disorderTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_001204375.2. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous				72 clinvar	3 clinvar	75
missense		3 clinvar	114 clinvar	4 clinvar		121
nonsense						0
start loss						0
frameshift	3 clinvar	2 clinvar				5
splice donor/acceptor (+/-2bp)		1 clinvar	1 clinvar			2
Total	3	6	115	76	3	203

Highest pathogenic variant AF is 0.000009581782

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 24 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_001204375.2	RefSeq	NP_001191304.1	8	MANE Select
ENST00000265074.13	Ensembl	ENSP00000265074.8	8	MANE Select
NM_000908.4	RefSeq	NP_000899.1	8	Standard
NM_001204376.2	RefSeq	NP_001191305.1	8	Standard

Model Organisms & Knockout Phenotypes

Observed phenotypic effects in mouse and zebrafish models

Gene / Model	Organism	Observed Phenotype
npr3	Danio rerio	Structure: heart Quality: decreased size abnormal

Gene / Model

Organism

Observed Phenotype

npr3

Danio rerio

Structure: heart

Quality: decreased size

abnormal

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

miR-targeted genes in lymphocytes - TarBase

Biological Process

skeletal system development
osteoclast proliferation
adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
negative regulation of adenylate cyclase activity
phospholipase C-activating G protein-coupled receptor signaling pathway

Molecular Function

protein binding
G protein-coupled peptide receptor activity
natriuretic peptide receptor activity
peptide hormone binding
chloride ion binding

Cellular Component

integral component of plasma membrane
protein-containing complex
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000265074
Coding exons: 8
Length: 102644
Individuals with no LoFs: 124963
Homozygous LoFs: 0
Heterozygous LoFs: 25
Defined: 124988
p: 0.000100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.808	261	300	0.869	0.0000150	3489
Missense (PolyPhen)		87	112.94	0.77035		1246
Synonymous	0.491	118	125	0.944	0.00000665	1099
Loss of Function	2.23	12	23.7	0.506	0.00000134	268

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00015	0.00014	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.00012	0.00011	rare
South Asian	0.00013	0.00013	rare
Other	0.00033	0.00033	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Receptor for the natriuretic peptide hormones, binding with similar affinities atrial natriuretic peptide NPPA/ANP, brain natriuretic peptide NPPB/BNP, and C-type natriuretic peptide NPPC/CNP. May function as a clearance receptor for NPPA, NPPB and NPPC, regulating their local concentrations and effects. May regulate diuresis, blood pressure and skeletal development. Does not have guanylate cyclase activity. {ECO:0000250|UniProtKB:P70180}.;

Recessive Scores

pRec: 0.178

Intolerance Scores

LoFtool: 0.534
RVIS EVS: 0
RVIS percentile EVS: 53.73

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.432

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium