NPPC

protein-coding

natriuretic peptide C, the group of Neuropeptides

Gene summary

This gene encodes a preproprotein that is proteolytically processed to generate multiple protein products. These products include the cardiac natriuretic peptides CNP-53, CNP-29 and CNP-22, which belong to the natriuretic family of peptides. The encoded peptides exhibit vasorelaxation activity in laboratory animals and elevated levels of CNP-22 have been observed in the plasma of chronic heart failure patients. [provided by RefSeq, Oct 2015]

MANE transcript

NM_024409.4

Inheritance

ClinVar variants

U:53B:17

Top phenotype

Acromesomelic type of short stature

gnomAD constraint

pLI —, LoF o/e 0.54

Max pathogenic AF

—

Genomic locus

chr2:231,921,809-231,926,396

External References & Databases

Ensembl (ENSG00000163273)

Transcript & Mutation Effects

hg38 • Region Span ~4.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

short stature with nonspecific skeletal abnormalities 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014551

Submitter: PanelApp Australia

short stature with nonspecific skeletal abnormalities 1LIMITED

Inheritance Pattern: AD

Disease ID:MONDO:0014551

Submitter: Franklin by Genoox

Two families with short stature and small hands underwent DNA examination which revealed heterozygous mutations in NPPC gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to NPPC variants in ClinVar

3 Conditions Cataloged

not providedTotal: 64

not specifiedTotal: 16

Acromesomelic type of short statureTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_024409.4. 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			1 clinvar	10 clinvar	2 clinvar	13
missense			47 clinvar	3 clinvar	2 clinvar	52
nonsense			3 clinvar			3
start loss			1 clinvar			1
frameshift			1 clinvar			1
splice donor/acceptor (+/-2bp)						0
Total	0	0	53	13	4	70

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 12 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_024409.4	RefSeq	NP_077720.1	2	MANE Select
ENST00000409852.2	Ensembl	ENSP00000387159.1	2	MANE Select
ENST00000295440.2	Ensembl	ENSP00000295440.2	2	Standard
ENST00000295440.3	Ensembl	ENSP00000295440.2	2	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Pathways ConsensusPathDB

Fluid shear stress and atherosclerosis - Homo sapiens (human)
Physiological factors
Cardiac conduction
Muscle contraction

Biological Process

ossification
response to hypoxia
growth plate cartilage chondrocyte differentiation
growth plate cartilage chondrocyte proliferation
cGMP biosynthetic process

Molecular Function

signaling receptor binding
hormone activity
hormone receptor binding

Cellular Component

extracellular region
extracellular space
secretory granule
protein-containing complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000409852
Coding exons: 2
Length: 4584
Individuals with no LoFs: 123355
Homozygous LoFs: 0
Heterozygous LoFs: 3
Defined: 123358
p: 0.0000122

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.323	58	65.3	0.888	0.00000297	765
Missense (PolyPhen)		12	11.941	1.005		106
Synonymous	0.613	27	31.4	0.861	0.00000141	289
Loss of Function	0.820	2	3.70	0.540	1.60e-7	48

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0	0.0	absent
Ashkenazi Jewish	0	0.0	absent
East Asian	0	0.0	absent
Finnish	0	0.0	absent
European (Non-Finnish)	0.000028	0.000027	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Hormone which plays a role in endochondral ossification through regulation of cartilaginous growth plate chondrocytes proliferation and differentiation. May also be vasoactive and natriuretic. Specifically binds and stimulates the cGMP production of the NPR2 receptor. Binds the clearance receptor NPR3 (By similarity). {ECO:0000250, ECO:0000269|PubMed:1672777}.;

Recessive Scores

pRec: 0.241

Intolerance Scores

LoFtool: 0.517
RVIS EVS: 0.04
RVIS percentile EVS: 56.25

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.731

Gene Damage Prediction

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