NPR2
natriuretic peptide receptor 2, the group of Transmembrane guanylate cyclases|DENN domain containing
Basic information
Region (hg38): 9:35791003-35809732
Previous symbols: [ "ANPRB", "NPRB", "AMDM" ]
Links
Phenotypes
GenCC
Source:
- acromesomelic dysplasia 1, Maroteaux type (Definitive), mode of inheritance: AR
- acromesomelic dysplasia 1, Maroteaux type (Definitive), mode of inheritance: AR
- tall stature-scoliosis-macrodactyly of the great toes syndrome (Moderate), mode of inheritance: AD
- short stature with nonspecific skeletal abnormalities 1 (Moderate), mode of inheritance: AD
- acromesomelic dysplasia 1, Maroteaux type (Supportive), mode of inheritance: AR
- tall stature-scoliosis-macrodactyly of the great toes syndrome (Supportive), mode of inheritance: AD
- acromesomelic dysplasia 1, Maroteaux type (Strong), mode of inheritance: AR
- tall stature-scoliosis-macrodactyly of the great toes syndrome (Strong), mode of inheritance: AD
- short stature with nonspecific skeletal abnormalities 1 (Strong), mode of inheritance: AD
- tall stature-scoliosis-macrodactyly of the great toes syndrome (Moderate), mode of inheritance: AD
Clinical Genomic Database
Source:
| Condition | Inheritance | Intervention Categories | Intervention/Rationale | Manifestation Categories | References |
|---|---|---|---|---|---|
| Epiphyseal chondrodysplasia, Miura type; Short stature with nonspecific skeletal abnormalities 1; Acromesomelic dysplasia 1 | AD/AR | General | Genetic knowledge may be beneficial related to issues such as selection of optimal supportive care, informed medical decision-making, prognostic considerations, and avoidance of unnecessary testing | Musculoskeletal | 15146390; 16384845; 22691581; 22870295; 24001744; 24057292; 24259409; 24471569; 26336901; 26537434 |
ClinVar
This is a list of variants' phenotypes submitted to
- Acromesomelic_dysplasia_1,_Maroteaux_type (497 variants)
- Tall_stature-scoliosis-macrodactyly_of_the_great_toes_syndrome (449 variants)
- not_provided (92 variants)
- Inborn_genetic_diseases (74 variants)
- Short_stature_with_nonspecific_skeletal_abnormalities (28 variants)
- not_specified (27 variants)
- NPR2-related_disorder (18 variants)
- Epilepsy,_familial_focal,_with_variable_foci_2 (5 variants)
- Short_stature_with_nonspecific_skeletal_abnormalities_1 (5 variants)
- Trident_hand (2 variants)
- Craniosynostosis_syndrome (2 variants)
- Limb_undergrowth (2 variants)
- Growth_delay (2 variants)
- Intellectual_disability (1 variants)
- Disproportionate_short_stature (1 variants)
- Short_stature (1 variants)
- Cardiac_anomalies_-_developmental_delay_-_facial_dysmorphism_syndrome (1 variants)
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the NPR2 gene is commonly pathogenic or not. These statistics are base on transcript: NM_000003995.4. Only rare variants are included in the table.
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.
| Effect | PathogenicP | Likely pathogenicLP | VUSVUS | Likely benignLB | BenignB | Sum |
|---|---|---|---|---|---|---|
| synonymous | 96 | 107 | ||||
| missense | 14 | 26 | 322 | 370 | ||
| nonsense | 21 | 30 | ||||
| start loss | 0 | |||||
| frameshift | 10 | 10 | 21 | |||
| splice donor/acceptor (+/-2bp) | 8 | |||||
| Total | 46 | 51 | 333 | 104 | 2 |
Highest pathogenic variant AF is 0.000010945784
Loading clinvar variants...
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| NPR2 | protein_coding | protein_coding | ENST00000342694 | 22 | 17579 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.0000420 | 1.00 | 125717 | 0 | 31 | 125748 | 0.000123 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.96 | 398 | 602 | 0.661 | 0.0000410 | 6760 |
| Missense in Polyphen | 94 | 197.84 | 0.47513 | 2323 | ||
| Synonymous | 0.461 | 223 | 232 | 0.962 | 0.0000138 | 2197 |
| Loss of Function | 4.54 | 18 | 54.0 | 0.333 | 0.00000360 | 580 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.000330 | 0.000329 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.0000544 | 0.0000544 |
| Finnish | 0.000139 | 0.000139 |
| European (Non-Finnish) | 0.000115 | 0.000114 |
| Middle Eastern | 0.0000544 | 0.0000544 |
| South Asian | 0.000196 | 0.000196 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Receptor for the C-type natriuretic peptide NPPC/CNP hormone. Has guanylate cyclase activity upon binding of its ligand. May play a role in the regulation of skeletal growth. {ECO:0000269|PubMed:15146390, ECO:0000269|PubMed:1672777, ECO:0000269|PubMed:24001744, ECO:0000269|PubMed:24471569, ECO:0000269|PubMed:26980729}.;
- Disease
- DISEASE: Acromesomelic dysplasia, Maroteaux type (AMDM) [MIM:602875]: An autosomal recessive acromesomelic chondrodysplasia. Acromesomelic chondrodysplasias are rare hereditary skeletal disorders characterized by short stature, very short limbs and hand/foot malformations. The severity of limb abnormalities increases from proximal to distal with profoundly affected hands and feet showing brachydactyly and/or rudimentary fingers (knob-like fingers). AMDM is characterized by axial skeletal involvement with wedging of vertebral bodies. In AMDM all skeletal elements are present but show abnormal rates of linear growth. {ECO:0000269|PubMed:15146390, ECO:0000269|PubMed:17652215, ECO:0000269|PubMed:26980729}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Epiphyseal chondrodysplasia, Miura type (ECDM) [MIM:615923]: An overgrowth syndrome characterized by tall stature, long hands and feet with arachnodactyly, macrodactyly of the great toes, scoliosis, coxa valga and slipped capital femoral epiphysis. {ECO:0000269|PubMed:22870295, ECO:0000269|PubMed:23827346, ECO:0000269|PubMed:24057292, ECO:0000269|PubMed:24259409}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Short stature with non-specific skeletal abnormalities (SNSK) [MIM:616255]: A condition characterized by short stature, defined as a height less than 2 SD below normal, and no endocrine abnormalities. {ECO:0000269|PubMed:24001744, ECO:0000269|PubMed:24471569}. Note=The disease is caused by mutations affecting the gene represented in this entry.;
- Pathway
- Oxytocin signaling pathway - Homo sapiens (human);Vascular smooth muscle contraction - Homo sapiens (human);Purine metabolism - Homo sapiens (human);cGMP-PKG signaling pathway - Homo sapiens (human);Physiological factors;Purine metabolism;Cardiac conduction;Muscle contraction;Purine nucleotides nucleosides metabolism
(Consensus)
Recessive Scores
- pRec
- 0.266
Intolerance Scores
- loftool
- 0.202
- rvis_EVS
- -1.04
- rvis_percentile_EVS
- 7.71
Haploinsufficiency Scores
- pHI
- 0.200
- hipred
- Y
- hipred_score
- 0.708
- ghis
- 0.618
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.944
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Npr2
- Phenotype
- homeostasis/metabolism phenotype; muscle phenotype; craniofacial phenotype; growth/size/body region phenotype; endocrine/exocrine gland phenotype; respiratory system phenotype; behavior/neurological phenotype (the observable actions or reactions of mammalian organisms that are manifested through development and lifespan); immune system phenotype; skeleton phenotype; limbs/digits/tail phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; 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); 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);
Gene ontology
- Biological process
- ossification;cGMP biosynthetic process;protein phosphorylation;signal transduction;receptor guanylyl cyclase signaling pathway;regulation of blood pressure;positive regulation of cGMP-mediated signaling;cGMP-mediated signaling;reproductive process;negative regulation of meiotic cell cycle;bone development;cellular response to granulocyte macrophage colony-stimulating factor stimulus;negative regulation of oocyte maturation;regulation of cardiac conduction
- Cellular component
- plasma membrane;integral component of plasma membrane
- Molecular function
- peptide receptor activity;guanylate cyclase activity;protein kinase activity;protein binding;ATP binding;GTP binding;natriuretic peptide receptor activity;peptide hormone binding;hormone binding;identical protein binding