CleftGeneDB-Search

Gene: Lrp6

Basic information

Tag	Content
Uniprot ID	O88572
Entrez ID	16974
Genbank protein ID	AAH60704.1; AAC33007.1;
Genbank nucleotide ID	NM_008514.4
Ensembl protein ID
Ensembl nucleotide ID
Gene name	Low-density lipoprotein receptor-related protein 6
Gene symbol	Lrp6
Organism	Mus musculus
NCBI taxa ID	10090
Cleft type	CPO,CLP
Developmental stage	E14.5
Data sources	Manually collected
Reference	21237142; 19700620; 19653321;
Functional description	Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin. Required for posterior patterning of the epiblast during gastrulation (By similarity).
Sequence	MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF 60 GHGLIYWSDV SEEAIKRTEF NKSESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE 120 VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFVIINTE 180 IYWPNGLTLD YQERKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDTLYWT 240 DWNTHSILAC NKYTGEGLRE IHSNIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 300 PVKPFYQCAC PTGVKLMENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR 360 HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT 420 DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD 480 RVVLVNTSLG WPNGLALDYD EGTIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL 540 LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TSVHRVIGSN PCAEDNGGCS 600 HLCLYRPQGL RCACPIGFEL IGDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG 660 VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY 720 WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG 780 SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSDM LGLNREVIAD DLPHPFGLTQ 840 YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQAGW NECASSNGHC 900 SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APSTFLLFSQ KSAINRMVID EQQSPDIILP 960 IHSLRNVRAI DYDPLDKQLY WIDSRQNSIR KAHEDGGQGF NVVANSVANQ NLEIQPYDLS 1020 IDIYSRYIYW TCEATNVIDV TRLDGRSVGV VLKGEQDRPR AIVVNPEKGY MYFTNLQERS 1080 PKIERAALDG TEREVLFFSG LSKPIALALD SKLGKLFWAD SDLRRIESSD LSGANRIVLE 1140 DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 1200 EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGD 1260 IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK 1320 NCEVLCLIDQ FRCANGQCVG KHKKCDHSVD CSDRSDELDC YPTEEPAPQA TNTVGSVIGV 1380 IVTIFVSGTI YFICQRMLCP RMKGDGETMT NDYVVHSPAS VPLGYVPHPS SLSGSLPGMS 1440 RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 1500 EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDV 1560 NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS 1613

Abbreviation :
CLO : cleft lip only. CPO : cleft palate only. CLP : cleft lip and palate. CL/P : cleft lip with/without cleft palate.
For humans: CL/P, CLO, CPO, and CLP. For mice: CLO, CLP, and CPO.

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

There is no orthologous record for this gene !

Other genetic variants/mutations

ID	Variant	Type	Disease	Chromosome\Coordinate	Evidence
	p.Arg886Trp	Missense	-	-	UniProt

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO ID	GO Term	Evidence
GO:0005041	low-density lipoprotein particle receptor activity	ISO
GO:0005041	low-density lipoprotein particle receptor activity	IBA
GO:0005102	signaling receptor binding	ISO
GO:0005109	frizzled binding	ISO
GO:0005515	protein binding	IPI
GO:0015026	coreceptor activity	IBA
GO:0017147	Wnt-protein binding	ISO
GO:0017147	Wnt-protein binding	IPI
GO:0019210	kinase inhibitor activity	ISO
GO:0019534	toxin transmembrane transporter activity	IMP
GO:0034185	apolipoprotein binding	IBA
GO:0042802	identical protein binding	ISO
GO:0042803	protein homodimerization activity	ISO
GO:0042813	Wnt-activated receptor activity	IEA
GO:0071936	coreceptor activity involved in Wnt signaling pathway	ISO

GO:Biological Process

GO ID	GO Term	Evidence
GO:0001702	gastrulation with mouth forming second	IGI
GO:0001702	gastrulation with mouth forming second	IBA
GO:0001756	somitogenesis	IGI
GO:0001843	neural tube closure	IMP
GO:0001843	neural tube closure	IGI
GO:0001843	neural tube closure	IBA
GO:0001933	negative regulation of protein phosphorylation	ISO
GO:0001947	heart looping	IGI
GO:0002053	positive regulation of mesenchymal cell proliferation	IMP
GO:0003344	pericardium morphogenesis	IGI
GO:0003344	pericardium morphogenesis	IBA
GO:0003401	axis elongation	IMP
GO:0006355	regulation of transcription, DNA-templated	ISO
GO:0006469	negative regulation of protein kinase activity	ISO
GO:0007204	positive regulation of cytosolic calcium ion concentration	ISO
GO:0007268	chemical synaptic transmission	ISO
GO:0007268	chemical synaptic transmission	IBA
GO:0009880	embryonic pattern specification	IMP
GO:0009880	embryonic pattern specification	IBA
GO:0009950	dorsal/ventral axis specification	IMP
GO:0009952	anterior/posterior pattern specification	IGI
GO:0009952	anterior/posterior pattern specification	IMP
GO:0009952	anterior/posterior pattern specification	IBA
GO:0010976	positive regulation of neuron projection development	IGI
GO:0014029	neural crest formation	ISO
GO:0014029	neural crest formation	IBA
GO:0014033	neural crest cell differentiation	ISO
GO:0014033	neural crest cell differentiation	IBA
GO:0016055	Wnt signaling pathway	ISO
GO:0021587	cerebellum morphogenesis	IMP
GO:0021587	cerebellum morphogenesis	IBA
GO:0021794	thalamus development	IMP
GO:0021794	thalamus development	IBA
GO:0021795	cerebral cortex cell migration	IMP
GO:0021861	forebrain radial glial cell differentiation	IGI
GO:0021872	forebrain generation of neurons	IMP
GO:0021874	Wnt signaling pathway involved in forebrain neuroblast division	IGI
GO:0021874	Wnt signaling pathway involved in forebrain neuroblast division	IMP
GO:0021915	neural tube development	IGI
GO:0021943	formation of radial glial scaffolds	IGI
GO:0021987	cerebral cortex development	IMP
GO:0021987	cerebral cortex development	IBA
GO:0030278	regulation of ossification	IBA
GO:0030326	embryonic limb morphogenesis	IGI
GO:0030326	embryonic limb morphogenesis	IBA
GO:0030900	forebrain development	IMP
GO:0030901	midbrain development	IMP
GO:0030901	midbrain development	IBA
GO:0030917	midbrain-hindbrain boundary development	IMP
GO:0030917	midbrain-hindbrain boundary development	IBA
GO:0034392	negative regulation of smooth muscle cell apoptotic process	ISO
GO:0035108	limb morphogenesis	IMP
GO:0035108	limb morphogenesis	IGI
GO:0035115	embryonic forelimb morphogenesis	IMP
GO:0035115	embryonic forelimb morphogenesis	IGI
GO:0035116	embryonic hindlimb morphogenesis	IGI
GO:0035116	embryonic hindlimb morphogenesis	IMP
GO:0035261	external genitalia morphogenesis	IMP
GO:0035261	external genitalia morphogenesis	IBA
GO:0036342	post-anal tail morphogenesis	IMP
GO:0036342	post-anal tail morphogenesis	IGI
GO:0042074	cell migration involved in gastrulation	IGI
GO:0042127	regulation of cell population proliferation	IMP
GO:0042475	odontogenesis of dentin-containing tooth	IBA
GO:0042475	odontogenesis of dentin-containing tooth	IMP
GO:0042733	embryonic digit morphogenesis	IGI
GO:0042733	embryonic digit morphogenesis	IMP
GO:0043065	positive regulation of apoptotic process	IMP
GO:0045599	negative regulation of fat cell differentiation	IMP
GO:0045778	positive regulation of ossification	IMP
GO:0045780	positive regulation of bone resorption	IMP
GO:0045787	positive regulation of cell cycle	ISO
GO:0045893	positive regulation of transcription, DNA-templated	ISO
GO:0045893	positive regulation of transcription, DNA-templated	IDA
GO:0045944	positive regulation of transcription by RNA polymerase II	ISO
GO:0045944	positive regulation of transcription by RNA polymerase II	IBA
GO:0046849	bone remodeling	IGI
GO:0046849	bone remodeling	IBA
GO:0048596	embryonic camera-type eye morphogenesis	IMP
GO:0048596	embryonic camera-type eye morphogenesis	IBA
GO:0048699	generation of neurons	IMP
GO:0048705	skeletal system morphogenesis	IMP
GO:0050680	negative regulation of epithelial cell proliferation	IMP
GO:0051091	positive regulation of DNA-binding transcription factor activity	ISO
GO:0051091	positive regulation of DNA-binding transcription factor activity	IMP
GO:0051091	positive regulation of DNA-binding transcription factor activity	IBA
GO:0051593	response to folic acid	IMP
GO:0060021	roof of mouth development	IMP
GO:0060021	roof of mouth development	IBA
GO:0060026	convergent extension	IGI
GO:0060026	convergent extension	IBA
GO:0060042	retina morphogenesis in camera-type eye	IMP
GO:0060059	embryonic retina morphogenesis in camera-type eye	IMP
GO:0060059	embryonic retina morphogenesis in camera-type eye	IBA
GO:0060070	canonical Wnt signaling pathway	ISO
GO:0060070	canonical Wnt signaling pathway	ISS
GO:0060070	canonical Wnt signaling pathway	IGI
GO:0060070	canonical Wnt signaling pathway	IMP
GO:0060284	regulation of cell development	IMP
GO:0060325	face morphogenesis	IMP
GO:0060325	face morphogenesis	IBA
GO:0060349	bone morphogenesis	IBA
GO:0060444	branching involved in mammary gland duct morphogenesis	IMP
GO:0060444	branching involved in mammary gland duct morphogenesis	IBA
GO:0060535	trachea cartilage morphogenesis	IGI
GO:0060535	trachea cartilage morphogenesis	IBA
GO:0060596	mammary placode formation	IMP
GO:0060603	mammary gland duct morphogenesis	IGI
GO:0061310	canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development	IMP
GO:0061324	canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation	IMP
GO:0071397	cellular response to cholesterol	ISO
GO:0071542	dopaminergic neuron differentiation	IMP
GO:0071901	negative regulation of protein serine/threonine kinase activity	ISO
GO:0072659	protein localization to plasma membrane	ISO
GO:0090009	primitive streak formation	IGI
GO:0090009	primitive streak formation	IBA
GO:0090118	receptor-mediated endocytosis involved in cholesterol transport	IMP
GO:0090118	receptor-mediated endocytosis involved in cholesterol transport	IBA
GO:0090244	Wnt signaling pathway involved in somitogenesis	IMP
GO:0090244	Wnt signaling pathway involved in somitogenesis	IBA
GO:0090245	axis elongation involved in somitogenesis	IGI
GO:0090245	axis elongation involved in somitogenesis	IBA
GO:0098609	cell-cell adhesion	ISO
GO:0110135	Norrin signaling pathway	IDA
GO:1901998	toxin transport	IEA
GO:2000051	negative regulation of non-canonical Wnt signaling pathway	IGI
GO:2000149	negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis	IGI
GO:2000151	negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis	IGI
GO:2000162	negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis	IGI
GO:2000164	negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis	IGI
GO:2000166	negative regulation of planar cell polarity pathway involved in pericardium morphogenesis	IGI
GO:2000168	negative regulation of planar cell polarity pathway involved in neural tube closure	IGI

GO:Cellular Component

GO ID	GO Term	Evidence
GO:0005623	cell	IEA
GO:0005769	early endosome	IDA
GO:0005783	endoplasmic reticulum	IEA
GO:0005886	plasma membrane	ISO
GO:0005886	plasma membrane	IGI
GO:0005886	plasma membrane	IDA
GO:0009986	cell surface	ISO
GO:0009986	cell surface	IBA
GO:0016020	membrane	IDA
GO:0016021	integral component of membrane	IEA
GO:0031410	cytoplasmic vesicle	ISO
GO:0043025	neuronal cell body	ISO
GO:0043025	neuronal cell body	IBA
GO:0045202	synapse	ISO
GO:0045202	synapse	IBA
GO:1990851	Wnt-Frizzled-LRP5/6 complex	ISO
GO:1990909	Wnt signalosome	ISO
GO:0005769	early endosome	ISO
GO:0005794	Golgi apparatus	ISO
GO:0005901	caveola	ISO

Reactome Pathway

Reactome ID	Reactome Term	Evidence
R-MMU-162582	Signal Transduction	IEA
R-MMU-195721	Signaling by WNT	IEA
R-MMU-201681	TCF dependent signaling in response to WNT	IEA
R-MMU-3772470	Negative regulation of TCF-dependent signaling by WNT ligand antagonists	IEA
R-MMU-4641262	Disassembly of the destruction complex and recruitment of AXIN to the membrane	IEA
R-MMU-4641263	Regulation of FZD by ubiquitination	IEA

Functional annotations

Keywords

Keyword ID	Keyword Term
KW-1003	Cell membrane
KW-0217	Developmental protein
KW-0225	Disease mutation
KW-1015	Disulfide bond
KW-0245	EGF-like domain
KW-0254	Endocytosis
KW-0256	Endoplasmic reticulum
KW-0325	Glycoprotein
KW-1017	Isopeptide bond
KW-0449	Lipoprotein
KW-0472	Membrane
KW-0564	Palmitate
KW-0597	Phosphoprotein
KW-0621	Polymorphism
KW-0675	Receptor
KW-1185	Reference proteome
KW-0677	Repeat
KW-0732	Signal
KW-0812	Transmembrane
KW-1133	Transmembrane helix
KW-0832	Ubl conjugation
KW-0879	Wnt signaling pathway

Interpro

InterPro ID	InterPro Term
IPR011042	6-blade_b-propeller_TolB-like
IPR000742	EGF-like_dom
IPR036055	LDL_receptor-like_sf
IPR023415	LDLR_class-A_CS
IPR000033	LDLR_classB_rpt
IPR002172	LDrepeatLR_classA_rpt
IPR017049	LRP5/6

PROSITE

PROSITE ID	PROSITE Term
PS01186	EGF_2
PS01209	LDLRA_1
PS50068	LDLRA_2
PS51120	LDLRB

Pfam

Pfam ID	Pfam Term
PF00057	Ldl_recept_a
PF00058	Ldl_recept_b

Gene: Lrp6

Basic information

Gene expression information

Gene expression during embryonic days (E11.5~E18.5) ~ adult days (Ps) in the lip and palate tissues. (X-axis: days, Y-axis: tissues)

Protein structural annotations

3D structure in PDB database

There is no related protein structure for this gene.

Protein disorder information

Orthologous information

There is no orthologous record for this gene !

Other genetic variants/mutations

Gene Ontology (GO)/biological pathways

GO:Molecular Function

GO:Biological Process

GO:Cellular Component

Reactome Pathway

Functional annotations

Keywords

Interpro

PROSITE

Pfam

Protein-protein interaction

Protein-miRNA interaction