NPR2 (natriuretic peptide receptor 2)

Gene

• Entrez ID: 4882
• Gene name: Natriuretic peptide receptor 2
• Gene symbol: NPR2
• Synonyms: AMD1, AMDM, ANPRB, ANPb, ECDM, GC-B, GCB, GUC2B, GUCY2B, NPRB, NPRBi, SNSK
• Chromosome: 9
• Chromosome location: 9p13.3
• Summary: This gene encodes natriuretic peptide receptor B, one of two integral membrane receptors for natriuretic peptides. Both NPR1 and NPR2 contain five functional domains: an extracellular ligand-binding domain, a single membrane-spanning region, and intracell

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs28929479	T>A	Pathogenic	Intron variant, missense variant, genic upstream transcript variant, coding sequence variant, upstream transcript variant
rs28931581	C>A,G	Pathogenic	Intron variant, missense variant, genic upstream transcript variant, coding sequence variant, upstream transcript variant
rs28931582	T>G	Pathogenic	Intron variant, missense variant, genic upstream transcript variant, coding sequence variant, upstream transcript variant
rs121912739	C>T	Pathogenic	Genic upstream transcript variant, 5 prime UTR variant, stop gained, coding sequence variant, upstream transcript variant
rs139036657	G>A,C	Pathogenic	Genic upstream transcript variant, 5 prime UTR variant, intron variant, coding sequence variant, missense variant
rs587777596	C>T	Pathogenic	Missense variant, coding sequence variant
rs587777597	G>A,C	Pathogenic	Missense variant, coding sequence variant
rs753644648	G>A,T	Likely-pathogenic	Missense variant, intron variant, genic upstream transcript variant, upstream transcript variant, coding sequence variant
rs757744435	A>G,T	Likely-pathogenic	Missense variant, intron variant, genic upstream transcript variant, 5 prime UTR variant, coding sequence variant
rs758478717	C>T	Pathogenic	Missense variant, intron variant, genic upstream transcript variant, upstream transcript variant, coding sequence variant
rs766256429	C>G,T	Pathogenic	Coding sequence variant, missense variant
rs796065355	T>A,C	Pathogenic	Upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant, intron variant
rs796065356	C>A,G	Pathogenic	Upstream transcript variant, coding sequence variant, missense variant, genic upstream transcript variant, 5 prime UTR variant
rs879255257	T>-	Pathogenic	Upstream transcript variant, coding sequence variant, genic upstream transcript variant, 5 prime UTR variant, frameshift variant
rs886042851	ATCA>-	Likely-pathogenic	Coding sequence variant, 5 prime UTR variant, frameshift variant
rs969576919	C>T	Likely-pathogenic	Stop gained, coding sequence variant
rs1057518817	GTGGTCCTTTC>-	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1057519324	C>T	Pathogenic	Coding sequence variant, stop gained, missense variant
rs1057519333	T>C	Pathogenic	Coding sequence variant, missense variant
rs1057519334	C>-	Pathogenic	Coding sequence variant, stop gained
rs1057519335	T>A	Pathogenic	Genic upstream transcript variant, intron variant, missense variant, coding sequence variant, upstream transcript variant
rs1085307906	G>A	Likely-pathogenic	5 prime UTR variant, genic upstream transcript variant, missense variant, coding sequence variant, upstream transcript variant
rs1085308030	C>T	Likely-pathogenic	Genic upstream transcript variant, intron variant, missense variant, coding sequence variant, upstream transcript variant
rs1554672061	G>C	Likely-pathogenic	Genic upstream transcript variant, splice acceptor variant, upstream transcript variant, intron variant
rs1554672893	G>C	Likely-pathogenic	5 prime UTR variant, genic upstream transcript variant, upstream transcript variant, splice donor variant
rs1554673485	A>T	Likely-pathogenic	Coding sequence variant, stop gained
rs1554673888	->T	Likely-pathogenic	Coding sequence variant, frameshift variant
rs1588057922	T>G	Likely-pathogenic	5 prime UTR variant, genic upstream transcript variant, stop gained, coding sequence variant, upstream transcript variant
rs1588068987	G>-	Pathogenic	Frameshift variant, coding sequence variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT1191215	hsa-miR-129-5p	CLIP-seq
MIRT1191216	hsa-miR-2113	CLIP-seq
MIRT1191217	hsa-miR-4464	CLIP-seq
MIRT1191218	hsa-miR-4474-3p	CLIP-seq
MIRT1191219	hsa-miR-4748	CLIP-seq
MIRT1191220	hsa-miR-548ag	CLIP-seq
MIRT1191221	hsa-miR-548ai	CLIP-seq
MIRT2055382	hsa-miR-153	CLIP-seq
MIRT1191218	hsa-miR-4474-3p	CLIP-seq
MIRT2055383	hsa-miR-448	CLIP-seq
MIRT2055384	hsa-miR-4687-3p	CLIP-seq
MIRT2055385	hsa-miR-587	CLIP-seq

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0001503	Process	Ossification	IEA
GO:0001653	Function	Peptide receptor activity	IBA	21873635
GO:0004383	Function	Guanylate cyclase activity	IBA	21873635
GO:0004383	Function	Guanylate cyclase activity	IDA	1672777
GO:0004383	Function	Guanylate cyclase activity	IMP	26980729
GO:0004672	Function	Protein kinase activity	IEA
GO:0005515	Function	Protein binding	IPI	16870210
GO:0005524	Function	ATP binding	IEA
GO:0005525	Function	GTP binding	IEA
GO:0005886	Component	Plasma membrane	IBA	21873635
GO:0005886	Component	Plasma membrane	IDA	24001744, 24471569
GO:0005886	Component	Plasma membrane	TAS
GO:0005887	Component	Integral component of plasma membrane	IDA	26980729
GO:0006182	Process	CGMP biosynthetic process	IBA	21873635
GO:0006182	Process	CGMP biosynthetic process	IDA	1672777
GO:0006468	Process	Protein phosphorylation	IEA
GO:0007165	Process	Signal transduction	IBA	21873635
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IBA	21873635
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IDA	1672777
GO:0007168	Process	Receptor guanylyl cyclase signaling pathway	IMP	26980729
GO:0008217	Process	Regulation of blood pressure	TAS	10082481
GO:0010753	Process	Positive regulation of cGMP-mediated signaling	IEA
GO:0016941	Function	Natriuretic peptide receptor activity	IBA	21873635
GO:0016941	Function	Natriuretic peptide receptor activity	IDA	1660465, 1672777
GO:0016941	Function	Natriuretic peptide receptor activity	IMP	26980729
GO:0017046	Function	Peptide hormone binding	IBA	21873635
GO:0017046	Function	Peptide hormone binding	IPI	1660465, 26980729
GO:0019934	Process	CGMP-mediated signaling	IEA
GO:0022414	Process	Reproductive process	IEA
GO:0042562	Function	Hormone binding	IPI	1672777
GO:0042802	Function	Identical protein binding	IEA
GO:0051447	Process	Negative regulation of meiotic cell cycle	IEA
GO:0060348	Process	Bone development	IEA
GO:0097011	Process	Cellular response to granulocyte macrophage colony-stimulating factor stimulus	IEP	14687666
GO:1900194	Process	Negative regulation of oocyte maturation	IEA
GO:1903779	Process	Regulation of cardiac conduction	TAS

Other IDs

• MIM: 108961
• HGNC: 7944
• e!Ensembl: ENSG00000159899

Protein

• UniProt ID: P20594
• Protein name: Atrial natriuretic peptide receptor 2 (EC 4.6.1.2) (Atrial natriuretic peptide receptor type B) (ANP-B) (ANPR-B) (NPR-B) (Guanylate cyclase B) (GC-B)
• Protein 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|
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF01094	ANF_receptor	44 → 399	Receptor family ligand binding region	Family
  PF07714	PK_Tyr_Ser-Thr	518 → 786	Protein tyrosine and serine/threonine kinase	Domain
  PF00211	Guanylate_cyc	852 → 1038	Adenylate and Guanylate cyclase catalytic domain	Domain

• Sequence:

  MALPSLLLLVAALAGGVRPPGARNLTLAVVLPEHNLSYAWAWPRVGPAVALAVEALGRAL
  PVDLRFVSSELEGACSEYLAPLSAVDLKLYHDPDLLLGPGCVYPAASVARFASHWRLPLL
  TAGAVASGFSAKNDHYRTLVRTGPSAPKLGEFVVTLHGHFNWTARAALLYLDARTDDRPH
  YFTIEGVFEALQGSNLSVQHQVYAREPGGPEQATHFIRANGRIVYICGPLEMLHEILLQA
  QRENLTNGDYVFFYLDVFGESLRAGPTRATGRPWQDNRTREQAQALREAFQTVLVITYRE
  PPNPEYQEFQNRLLIRAREDFGVELGPSLMNLIAGCFYDGILLYAEVLNETIQEGGTRED
  GLRIVEKMQGRRYHGVTGLVVMDKNNDRETDFVLWAMGDLDSGDFQPAAHYSGAEKQIWW
  TGRPIPWVKGAPPSDNPPCAFDLDDPSCDKTPLSTLAIVALGTGITFIMFGVSSFLIFRK
  LMLEKELASMLWRIRWEELQFGNSERYHKGAGSRLTLSLRGSSYGSLMTAHGKYQIFANT
  GHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCP
  RGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKI
  TDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALR
  SGPFYLEGLDLSPKEIVQKVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERPDFG
  QIKGFIRRFNKEGGTSILDNLLLRMEQYANNLEKLVEERTQAYLEEKRKAEALLYQILPH
  SVAEQLKRGETVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNF
  DVYKVETIGDAYMVVSGLPGRNGQRHAPEIARMALALLDAVSSFRIRHRPHDQLRLRIGV
  HTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELGCFQLELR
  GDVEMKGKGKMRTYWLLGERKGPPGLL

• Sequence length: 1047

Pathways

KEGG:

Purine metabolism
Metabolic pathways
cGMP-PKG signaling pathway
Hormone signaling
Vascular smooth muscle contraction
Oxytocin signaling pathway

Reactome:

Physiological factors

Associated diseases

Causal
Disease name	Disease term	dbSNP ID	References
Acromesomelic dysplasia	ACROMESOMELIC DYSPLASIA, MAROTEAUX TYPE	rs863223287, rs28936683, rs121909350, rs121909351, rs28931582, rs28929479, rs121912739, rs879255257, rs863225041, rs863225042, rs745854387, rs1057519324, rs1057519335, rs1057519334, rs1057519333, rs1057519336, rs1177728492, rs753644648, rs771373457, rs749952755, rs1828106198, rs1311857509, rs1828226013, rs1827867580, rs1828356952, rs1828565145, rs1828107536	22691581, 15146390, 17652215, 23065701, 26980729
Brachydactyly	Brachydactyly	rs121908949, rs28937580, rs121909082, rs104894122, rs863223289, rs863223290, rs104894121, rs1587657302, rs863223292, rs74315386, rs74315387, rs28936397, rs753691079, rs121909348, rs121917852, rs121917853, rs121917854, rs121917855, rs121917859, rs121917861, rs267606873, rs267606872, rs267606985, rs267606986, rs267606987, rs267606988, rs28933082, rs397514519, rs869025613, rs869025614, rs886039878, rs1553540620, rs1057518333, rs1948841937, rs1948868228, rs1948842030, rs1948842142
Craniosynostosis	Craniosynostosis	rs104893895, rs587777006, rs587777007, rs587777008, rs587777010, rs281865153, rs281865154, rs864321680, rs864321681, rs1057517670, rs1085307122, rs1064794325, rs1884302, rs1555750816, rs1599823350
Epilepsy	EPILEPSY, FAMILIAL FOCAL, WITH VARIABLE FOCI 2	rs113994140, rs119454947, rs28937874, rs1589762127, rs104894166, rs28939075, rs2134001459, rs104894167, rs119488099, rs119488100, rs1805032, rs387906420, rs121917752, rs121918622, rs121434579, rs1581220270, rs281865564, rs387907313, rs397514564, rs397514670, rs768241563, rs587776973, rs587776974, rs587776975, rs879255234, rs587776976, rs587776977, rs121917993, rs398123588, rs13306758, rs587777363, rs587777364, rs587777458, rs587777459, rs541024038, rs797044545, rs730882240, rs786205703, rs794726859, rs796053126, rs796053035, rs796053216, rs796052839, rs869025201, rs797044999, rs797044998, rs797045045, rs794726762, rs869312971, rs869312972, rs879255652, rs886037938, rs886037958, rs886037959, rs886037960, rs886037961, rs886037962, rs886037965, rs886037966, rs886039245, rs886039246, rs886039251, rs886039252, rs772872014, rs886039253, rs886039256, rs757511744, rs886039261, rs886039263, rs578185749, rs886039266, rs886039268, rs886039269, rs886039273, rs368820286, rs1057518801, rs1057518688, rs1057519107, rs1057519273, rs752753379, rs767795673, rs1057519424, rs755946598, rs760609867, rs1057521066, rs1057524233, rs1060501488, rs1060501487, rs755127868, rs751533302, rs771373457, rs1475605360, rs1555401942, rs1553567864, rs200661329, rs766667249, rs1556607762, rs1555882921, rs1555882867, rs1555900914, rs1553546836, rs77216276, rs755595256, rs1554169267, rs747661902, rs2105890565, rs1021001959, rs1555441032, rs1555439541, rs1556526609, rs1315483224, rs759952667, rs1555885023, rs1553456695, rs1555942720, rs1569083500, rs1559127505, rs1206309859, rs1567139896, rs1567134495, rs1431914212, rs1569166925, rs1569255443, rs1568955379, rs1567152003, rs374158137, rs1567129567, rs1569523728, rs1568991466, rs1569186093, rs1569254004, rs1372605067, rs1569067939, rs1568963062, rs1563959514, rs1569012755, rs1559118914, rs1602338615, rs1596522356, rs1364913665, rs1596522300, rs1596526976, rs1229740428, rs1596385588, rs1596500172, rs1596505517, rs1601925213, rs1601970168, rs1602010382, rs1602903591, rs1603014297, rs1603014708, rs1601875057, rs1601970824, rs1601755632, rs1587393982, rs1592977444, rs1575562076, rs1570998206, rs1588057922, rs1596528731, rs1602349641, rs1587401875, rs2065899210, rs1596526915, rs2093486364, rs2056165149, rs2056100951, rs781482552, rs1899868619, rs1900088045, rs1898675878, rs1898686157, rs1898837245, rs1898844513, rs2082841677, rs2085727988, rs2092933941, rs2091657024, rs1899864955, rs1898844907, rs2083056830, rs2084070588, rs1899713412, rs2082695884, rs1977106116, rs1977105425, rs1443687532
Epiphyseal dysplasia	Epiphyseal dysplasia	rs137852652, rs28936668, rs1600786629, rs1600786748, rs606231367, rs1569763139, rs1569763108, rs1085307973, rs1555821817
Scoliosis	Scoliosis, unspecified	rs1057518828, rs147296805, rs758163506, rs1555613564, rs1596852902, rs1596853067, rs1596853085
Short stature with nonspecific skeletal abnormalities	SHORT STATURE WITH NONSPECIFIC SKELETAL ABNORMALITIES	rs879255257, rs796065355, rs1057519324, rs1311857509	24001744, 24471569
Tall stature, scoliosis, macrodactyly of great toe syndrome	Tall stature-scoliosis-macrodactyly of the great toes syndrome	rs587777595, rs587777596, rs587777597

Unknown
Disease name	Disease term	dbSNP ID	References
Arachnodactyly	Arachnodactyly
Clinodactyly	Clinodactyly of fingers
Congenital hypoplasia of radius	Congenital hypoplasia of radius
Dolichocephaly	Long narrow head
Dysmorphic features	Dysmorphic features		15146390, 25703509, 24259409
Epiphyseal chondrodysplasia	EPIPHYSEAL CHONDRODYSPLASIA, MIURA TYPE		23065701, 24057292, 23827346, 22870295, 15146390, 24259409
Frontal bossing	Frontal bossing
Osteopenia	Osteopenia
Sprengel deformity	Sprengel deformity