NPR3

natriuretic peptide receptor 3, the group of DENN domain containing

Basic information

Region (hg38): 5:32689069-32791724

Previous symbols: [ "NPRC", "ANPRC", "C5orf23" ]

Links

ENSG00000113389 ∙ NCBI:4883 ∙ OMIM:108962 ∙ HGNC:7945 ∙ Uniprot:P17342 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

• Boudin-Mortier syndrome (Strong), mode of inheritance: AR

Clinical Genomic Database

Source: CGD

Condition	Inheritance	Intervention Categories	Intervention/Rationale	Manifestation Categories	References
Boudin-Mortier syndrome	AD	Cardiovascular	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	Cardiovascular; Musculoskeletal	30032985

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the NPR3 gene.

• not provided (141 variants)
• Inborn genetic diseases (18 variants)
• Boudin-Mortier syndrome (2 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPR3 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type	Pathogenic	Likely pathogenic	VUS	Likely benign	Benign	Sum
synonymous			1	31	6	38
missense		2	60	3	1	66
nonsense						0
start loss						0
frameshift						0
inframe indel			3			3
splice donor/acceptor (+/-2bp)			2			2
splice region			1	3	1	5
non coding				15	23	38
Total	0	2	66	49	30

Variants in NPR3

This is a list of pathogenic ClinVar variants found in the NPR3 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position	Type	Phenotype	Significance	ClinVar
5-32710655-G-A		NPR3-related disorder	Benign (Jul 30, 2019)
5-32710680-G-A		NPR3-related disorder	Benign (Mar 20, 2019)
5-32711527-C-A			Benign (May 14, 2021)
5-32711547-A-ACTTTTT			Benign (May 13, 2021)
5-32711571-T-TC			Benign (May 14, 2021)
5-32711576-T-TTTTTA			Benign (May 14, 2021)
5-32711771-G-C		NPR3-related disorder	Benign (May 06, 2021)
5-32711784-C-G			Uncertain significance (Dec 01, 2021)
5-32711806-C-G			Likely benign (Nov 13, 2023)
5-32711806-C-T			Likely benign (Jan 29, 2024)
5-32711809-G-A			Likely benign (Aug 15, 2022)
5-32711819-C-G		Inborn genetic diseases	Uncertain significance (Nov 09, 2021)
5-32711827-G-C			Uncertain significance (Oct 18, 2022)
5-32711830-G-T			Likely benign (Dec 06, 2022)
5-32711833-G-C			Uncertain significance (Dec 06, 2022)
5-32711839-C-G			Likely benign (Apr 07, 2022)
5-32711840-G-A		Inborn genetic diseases	Uncertain significance (Jan 30, 2024)
5-32711848-C-A			Likely benign (Oct 05, 2023)
5-32711848-C-T			Likely benign (Nov 10, 2023)
5-32711851-TGGCGGTGGCGTTGGCGGCGGC-T			Uncertain significance (Jun 30, 2022)
5-32711863-T-TGGC			Uncertain significance (Dec 28, 2021)
5-32711867-G-A			Uncertain significance (Sep 07, 2022)
5-32711877-G-A			Uncertain significance (Jul 21, 2022)
5-32711884-G-A			Uncertain significance (Nov 23, 2021)
5-32711902-C-G			Likely benign (Aug 20, 2022)

GnomAD

Source: gnomAD

Gene	Type	Bio Type	Transcript	Coding Exons	Length
NPR3	protein_coding	protein_coding	ENST00000265074	8	102644

pLI Probability LOF Intolerant	pRec Probability LOF Recessive	Individuals with no LOFs	Individuals with Homozygous LOFs	Individuals with Heterozygous LOFs	Defined	p
0.0000101	0.987	124963	0	25	124988	0.000100

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible in Transcript
Missense	0.808	261	300	0.869	0.0000150	3489
Missense in 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

LoF frequencies by population

Ethnicity	Sum of pLOFs	p
African & African-American	0.000147	0.000147
Ashkenazi Jewish	0.00	0.00
East Asian	0.00	0.00
Finnish	0.0000465	0.0000464
European (Non-Finnish)	0.000117	0.000115
Middle Eastern	0.00	0.00
South Asian	0.000134	0.000131
Other	0.000331	0.000329

dbNSFP

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}.
• Pathway: miR-targeted genes in lymphocytes - TarBase (Consensus)

Recessive Scores

• pRec: 0.178

Intolerance Scores

• loftool: 0.534
• rvis_EVS: 0
• rvis_percentile_EVS: 53.73

Haploinsufficiency Scores

• pHI: 0.751
• hipred: Y
• hipred_score: 0.623
• ghis: 0.483

Essentials

• essential_gene_CRISPR: N
• essential_gene_CRISPR2: N
• essential_gene_gene_trap: N
• gene_indispensability_pred: N
• gene_indispensability_score: 0.432

Gene Damage Prediction

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

Mouse Genome Informatics

• Gene name: Npr3
• Phenotype: immune system phenotype; skeleton phenotype; renal/urinary system phenotype; limbs/digits/tail phenotype; hearing/vestibular/ear phenotype; hematopoietic system phenotype; cardiovascular system phenotype (the observable morphological and physiological characteristics of the mammalian heart, blood vessels, or circulatory system that are manifested through development and lifespan); reproductive system phenotype; mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); homeostasis/metabolism phenotype; craniofacial phenotype; growth/size/body region phenotype; adipose tissue phenotype (the observable morphological and physiological characteristics of mammalian fat tissue that are manifested through development and lifespan)

Zebrafish Information Network

• Gene name: npr3
• Affected structure: heart
• Phenotype tag: abnormal
• Phenotype quality: decreased size

Gene ontology

• 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;regulation of blood pressure;pancreatic juice secretion;regulation of osteoblast proliferation;positive regulation of urine volume;phosphatidylinositol-mediated signaling;negative regulation of smooth muscle cell proliferation;positive regulation of nitric-oxide synthase activity;negative regulation of cold-induced thermogenesis
• Cellular component: integral component of plasma membrane;protein-containing complex;extracellular exosome
• Molecular function: protein binding;G protein-coupled peptide receptor activity;natriuretic peptide receptor activity;peptide hormone binding;chloride ion binding;peptide binding;hormone binding;protein homodimerization activity