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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

NPPC Gene

protein-coding GIFtS: 53
GCID: GC02M232786

natriuretic peptide C

(Previous name: natriuretic peptide precursor C )

Explore 45 diseases affiliated with
NPPC via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Natriuretic Peptide C¹ ²
CNP¹ ²
Natriuretic Peptide Precursor C¹ ²
CNP2² ³
C-Type Natriuretic Peptide²

External Ids:	HGNC: 7941¹	Entrez Gene: 4880²	Ensembl: ENSG00000163273⁷	OMIM: 600296⁵	UniProtKB: P23582³

Export aliases for NPPC gene to outside databases

Previous GC identifers: GC02M230849 GC02M231521 GC02M232755 GC02M232992 GC02M232615 GC02M232498 GC02M224641

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for NPPC:

The protein encoded by this gene is proteolytically processed to form a secreted hormone of the natriuretic peptide

family. The encoded hormone regulates the growth and differentiation of cartilaginous growth plate chondrocytes and

may also be vasoactive and natriuretic. (provided by RefSeq, Sep 2011)

UniProtKB/Swiss-Prot: ANFC_HUMAN, P23582

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)

Gene Wiki entry for NPPC (Natriuretic peptide precursor C)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000002.11 NC_018913.1 NT_005403.17

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the NPPC gene promoter:
HOXA9B HOXA9 AP-4 HNF-4alpha2 RORalpha2 HNF-4alpha1 AREB6 Meis-1a Ik-1 Meis-1
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: NPPC promoter sequence

Search SABiosciences Chromatin IP Primers for NPPC

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat NPPC

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q24-qter Ensembl cytogenetic band: 2q37.1 HGNC cytogenetic band: 2q24-qter

NPPC Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
NPPC gene location

GeneLoc information about chromosome 2 GeneLoc Exon Structure

GeneLoc location for GC02M232786: view genomic region (about GC identifiers)

Start:	232,786,530 bp from pter	End:	232,791,113 bp from pter
Size:	4,584 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: ANFC_HUMAN, P23582 (See protein sequence)

Recommended Name: C-type natriuretic peptide precursor

Size: 126 amino acids; 13246 Da

Subcellular location: Secreted

1 PDB 3D structure from and Proteopedia for NPPC:

1JDP (3D)

Secondary accessions: Q4ZG41

Explore the universe of human proteins at neXtProt for NPPC: NX_P23582

NPPC Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_077720.1

ENSEMBL proteins:

ENSP00000387159 ENSP00000295440

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	Uscn Proteins for NPPC

Gene Ontology (GO): 2 cellular component terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	NAS	--
GO:0005615	extracellular space	IEA	--

NPPC for ontologies About GeneDecksing

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	Uscn ELISAs and CLIAs for NPPC

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

NPPC for domains About GeneDecksing

2 InterPro domains/families:

IPR000663 Natr_peptide

IPR002406 C_natriurtcpep

Graphical View of Domain Structure for InterPro Entry P23582

ProtoNet protein and cluster: P23582

1 Blocks protein family: IPB002406 C-type natriuretic peptide signature

UniProtKB/Swiss-Prot: ANFC_HUMAN, P23582

Similarity: Belongs to the natriuretic peptide family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: ANFC_HUMAN, P23582

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)

Genatlas biochemistry entry for NPPC:

natriuretic peptide precursor C homolog of mouse C type (CNP),most strongly expressed in the brain,also expressed in

vascular endothelial cells and other tissues,present at extremely low level in circulation,potentially playing a

paracrine/autocrine role

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In Situ Assay
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Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NPPC

Gene Ontology (GO): 4 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005102	receptor binding	IPI	1660465
GO:0005179	hormone activity	IEA	--
GO:0042803	protein homodimerization activity	IEA	--
GO:0051428	peptide hormone receptor binding	IEA	--

NPPC for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-out Nppc^tm1Yog for NPPC
     9 MGI mutant phenotypes (inferred from 3 alleles) (MGI details for Nppc):

craniofacial	endocrine/exocrine gland	growth/size	homeostasis/metabolism	limbs/digits/tail
mortality/aging	nervous system	reproductive system	skeleton

NPPC for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for NPPC

STRING Interaction Network Preview (showing 3 interactants - click image to see more details)

3 Interacting proteins for NPPC (P23582³ ENSP00000295440⁴) via UniProtKB, MINT, STRING, and/or I2D

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
NPR2	P20594³, ENSP00000341083⁴	I2D: score=2 STRING: ENSP00000341083
NPR3	P17342³, ENSP00000398028⁴	I2D: score=2 STRING: ENSP00000398028
MME	P08473³, ENSP00000353679⁴	I2D: score=1 STRING: ENSP00000353679

About this table

Gene Ontology (GO): 5/20 biological process terms (GO ID links to tree view) (see all 20): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001503	ossification	IEA	--
GO:0001666	response to hypoxia	IEA	--
GO:0003418	growth plate cartilage chondrocyte differentiation	ISS	--
GO:0003419	growth plate cartilage chondrocyte proliferation	ISS	--
GO:0006182	cGMP biosynthetic process	IDA	1672777

NPPC for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

NPPC for compounds About GeneDecksing

Browse Small Molecules at EMD Millipore

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for NPPC
10/55 Novoseek chemical compound relationships for NPPC gene (see all 55) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
urodilatin	90.8	25	17032349 (3), 16565701 (2), 10073597 (2), 8097089 (1) (see all 18)
cgmp	85.2	191	8172609 (6), 12958024 (4), 7611424 (4), 2164803 (4) (see all 71)
guanylate	74.4	21	9115758 (2), 7679284 (1), 12632516 (1), 18472099 (1) (see all 17)
8-bromo cgmp	72.6	13	14749356 (3), 11292628 (2), 7611424 (2), 11984695 (1) (see all 8)
2',3'-cyclic nucleotide	65.1	8	8065530 (2), 8390968 (1), 1666129 (1), 1710279 (1) (see all 6)
ly 83583	64.3	8	12632516 (1), 17466389 (1)
hanp	63.2	7	18850266 (1), 12608696 (1), 9582102 (1)
kt 5823	60.7	1	15564589 (1)
zaprinast	54.1	3	17466389 (1)
thiorphan	52.3	4	9887994 (2), 11304521 (1)

Search CenterWatch for drugs/clinical trials and news about NPPC / ANFC

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for NPPC gene:

NM_024409.2

Unigene Clusters for NPPC:

Natriuretic peptide C

Hs.247916 , Hs.627236

Unigene Representative Sequences: BF976889, NM_024409

2 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000409852(uc002vsl.2) ENST00000295440(uc021vye.1)

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		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat NPPC
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		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat NPPC

Additional cDNA sequence:

HQ419060.1 JF420840.1

1 DOTS entry:

DT.91917815

2 AceView cDNA sequences:

NM_024409 BC069120

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

NPPC expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AGCGGCCTGG

About this image

NPPC expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

2 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Ovary

Ovary

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See NPPC Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for NPPC

SOURCE GeneReport for Unigene clusters: Hs.247916 Hs.627236

SABiosciences Expression via Pathway-Focused PCR Array including NPPC:

Hypertension in human mouse rat

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In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for NPPC

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of chordates.

Orthologs for NPPC gene from 3/9 species (see all 9) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
mouse (Mus musculus)	Mammalia	Nppc^{1 , 5}	natriuretic peptide type C^{1, 5}	88.36(n)¹ 91.27(a)¹		1 (43.98 cM)⁵ 18159¹ NM_010933.5¹ NP_035063.1¹ 86666293⁵
African clawed frog (Xenopus laevis)	Amphibia	Xl.8803²	Xenopus laevis transcribed sequence with weak similarity more	72.63(n)		AW159572.1
zebrafish (Danio rerio)	Actinopterygii	CU928218.2⁶ si:ch211-126j24.3⁶	si:ch211-126j24.3	42(a) 42(a)	many → 1 many → 1	22(41578654-41584044) 22(41667719-41674270)

ENSEMBL Gene Tree for NPPC (if available)
TreeFam Gene Tree for NPPC (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 2 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs146734520^1,2		--	232786407(+)	`ATCCAC/GAATTG`	1	--	ds500¹		0	--	--	--	--
rs967511^1,2	H	--	232786472(-)	`GCTGAG/AAAAGA`	1	--	ds500¹		4		NS EA	418
rs112122738^1,2		--	232786487(+)	`GTCCTG/AAAAAA`	1	--	ds500¹		1		CSA	2
rs7564402^1,2	C,F,	--	232786567(+)	`TTTTAA/GCTAGT`	1	--	ds500¹		4		NA WA	124
rs189850160^1,2		--	232786733(+)	`CTGTCA/GGTCTC`	1	--	ds500¹		0	--	--	--	--
rs181124128^1,2		--	232786881(+)	`TAAAAA/CAGCTG`	1	--	ut3¹		0	--	--	--	--
rs186139446^1,2		--	232786916(+)	`AAAAAA/GAAAGA`	1	--	ut3¹		0	--	--	--	--
rs188033305^1,2		--	232786947(+)	`AGCCAC/TATTGC`	1	--	ut3¹		0	--	--	--	--
rs181960059^1,2		--	232786953(+)	`ATTGCA/GTTGGA`	1	--	ut3¹		0	--	--	--	--
rs186186383^1,2		--	232786975(+)	`ATGCTA/GGAGGC`	1	--	ut3¹		0	--	--	--	--

HapMap Linkage Disequilibrium report for NPPC (232786530 - 232791113 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for NPPC
1 CNV: 3408
Human Gene Mutation Database (HGMD): NPPC

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing NPPC

DNA2.0 Custom Variant and Variant Library Synthesis for NPPC

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

NPPC for disorders           About GeneDecksing

OMIM gene information: 600296    OMIM disorders: --

20/45 diseases for NPPC (see all 45):    About MalaCards

cor pulmonale aortic valve stenosis plasmodium falciparum malaria pre-eclampsia

acromesomelic dysplasia myocardial infarction congestive heart failure achondroplasia

acute myocardial infarction cystic fibrosis dwarfism coronary heart disease

dilated cardiomyopathy vascular disease hypercholesterolemia essential hypertension

eclampsia pheochromocytoma nephrotic syndrome chagas disease

4 diseases from the University of Copenhagen DISEASES database for NPPC:

Acromesomelic dysplasia Achondroplasia Congestive heart failure Hypertension

10/44 Novoseek disease relationships for NPPC gene (see all 44) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
heart failure	54.6	13	16006261 (2), 17428580 (2), 13678415 (1), 8087930 (1) (see all 11)
heart failure congestive	51.2	6	7878562 (3), 8117275 (1), 12909191 (1), 9034752 (1)
skeletal dysplasia	46.6	11	19282381 (3)
dwarfism	44	3	17681481 (1), 14702637 (1), 17116261 (1)
achondroplasia	40.3	5	14702637 (2), 19282381 (1)
cardiovascular diseases	37.1	9	8743538 (1), 8117275 (1), 15749162 (1), 19620509 (1) (see all 6)
fluid overload	29.2	1	8733825 (1)
cerebral vasospasm	26.2	6	9254093 (2), 11178224 (2)
cor pulmonale	14	5	7878562 (4), 8527262 (1)
vasospasm	11.1	1	11178224 (1)

Genetic Association Database (GAD): NPPC
Human Genome Epidemiology (HuGE) Navigator: NPPC (9 documents)

Export disorders for NPPC gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for NPPC gene, integrated from 9 sources (see all 343):
(articles sorted by number of sources associating them with NPPC)

Utopia: connect your pdf to the dynamic
world of online information

Molecular cloning and chromosomal assignment of the mouse C-type natriuretic peptide (CNP) gene (Nppc): comparison with the human CNP gene (NPPC). (PubMed id 7698765)^{1, 3, 9} Ogawa Y....Nakao K. (1994)
Isolation and identification of C-type natriuretic peptide in human monocytic cell line, THP-1. (PubMed id 1472040)^{1, 2, 9} Ishizaka Y....Matsuo H. (1992)
C-type natriuretic peptide (CNP) is the major natriuretic peptide in human cerebrospinal fluid. (PubMed id 8330189)^{1, 3, 9} Kaneko T....Hirai O. (1993)
Selective activation of the B natriuretic peptide receptor by C-type natriuretic peptide (CNP). (PubMed id 1672777)^{1, 2, 9} Koller K.J....Goeddel D.V. (1991)
Generation and annotation of the DNA sequences of human chromosomes 2 and 4. (PubMed id 15815621)^{1, 2} Hillier L.W....Wilson R.K. (2005)
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). (PubMed id 15489334)^{1, 2} Gerhard D.S....Malek J. (2004)
A single-nucleotide polymorphism in C-type natriuretic peptide gene may be associated with hypertension. (PubMed id 12452325)^{1, 4} Ono K....Iwai N. (2002)
Allosteric activation of a spring-loaded natriuretic peptide receptor dimer by hormone. (PubMed id 11533490)^{1, 2} He X.-L.... Garcia K.C. (2001)
Human C-type natriuretic peptide. Characterization of the gene and peptide. (PubMed id 1339402)^{1, 2} Ogawa Y.... Imura H. (1992)
Gene and precursor structures of human C-type natriuretic peptide. (PubMed id 2018508)^{1, 2} Tawaragi Y....Matsuo H. (1991)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 4880	HGNC: 7941	AceView: NPPC	Ensembl:ENSG00000163273	euGenes: HUgn4880
ECgene: NPPC	H-InvDB: NPPC

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for NPPC	Pharmacogenomics, SNPs, Pathways

Intellectual Property for NPPC gene
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Patent Information for NPPC gene:
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