LRP6 LDL receptor related protein 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRP6provided by HGNC
Official Full Name: LDL receptor related protein 6provided by HGNC
Primary source: HGNC:HGNC:6698
See related: Ensembl:ENSG00000070018 MIM:603507; AllianceGenome:HGNC:6698
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ADCAD2; STHAG7
Summary: This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]
Expression: Ubiquitous expression in placenta (RPKM 10.1), ovary (RPKM 7.4) and 24 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 12p13.2

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
110	current	GRCh38.p14 (GCF_000001405.40)	12	NC_000012.12 (12116025..12267044, complement)
110	current	T2T-CHM13v2.0 (GCF_009914755.1)	12	NC_060936.1 (11985150..12136111, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	12	NC_000012.11 (12268959..12419978, complement)

Chromosome 12 - NC_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a Caucasian family.
Title: An LRP6 mutation (Arg360His) associated with low bone mineral density but not cardiovascular events in a Caucasian family.
Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.
Title: Mutations in LRP6 highlight the role of WNT signaling in oral exostoses and dental anomalies.
Variants in the Wnt co-receptor LRP6 are associated with familial exudative vitreoretinopathy.
Title: Variants in the Wnt co-receptor LRP6 are associated with familial exudative vitreoretinopathy.
SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/beta-catenin signaling.
Title: SIK2 maintains breast cancer stemness by phosphorylating LRP6 and activating Wnt/β-catenin signaling.
circLRP6 contributes to osteosarcoma progression by regulating the miR1413p/HDAC4/HMGB1 axis.
Title: circ‑LRP6 contributes to osteosarcoma progression by regulating the miR‑141‑3p/HDAC4/HMGB1 axis.
Lrp6 Genotype affects Individual Susceptibility to Nonalcoholic Fatty Liver Disease and Silibinin Therapeutic Response via Wnt/beta-catenin-Cyp2e1 Signaling.
Title: Lrp6 Genotype affects Individual Susceptibility to Nonalcoholic Fatty Liver Disease and Silibinin Therapeutic Response via Wnt/β-catenin-Cyp2e1 Signaling.
Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer.
Title: Transmembrane protein 97 exhibits oncogenic properties via enhancing LRP6-mediated Wnt signaling in breast cancer.
The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.
Title: The complex role of Wnt ligands in type 2 diabetes mellitus and related complications.
PUM1 modulates trophoblast cell proliferation and migration through LRP6.
Title: PUM1 modulates trophoblast cell proliferation and migration through LRP6.
MicroRNA-513c-5p is involved in the pathogenesis of preeclampsia by regulating of low-density lipoprotein receptor-associated protein 6.
Title: MicroRNA-513c-5p is involved in the pathogenesis of preeclampsia by regulating of low-density lipoprotein receptor-associated protein 6.

Submit: New GeneRIF Correction See all GeneRIFs (186)

Phenotypes

Go to the top of the page Help

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Coronary artery disease, autosomal dominant 2 MedGen: C1970440 OMIM: 610947 GeneReviews: Not available	Compare labs
Tooth agenesis, selective, 7 MedGen: C4225231 OMIM: 616724 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genetics of coronary artery calcification among African Americans, a meta-analysis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See Variation Viewer (GRCh37.p13)

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

D12S1310 (e-PCR)
- UniSTS:73986

RH70320 (e-PCR)
- UniSTS:58218

RH80314 (e-PCR)
- UniSTS:89732

G41288 (e-PCR)
- UniSTS:20362

Lrp6 (e-PCR), detects polymorphism
- UniSTS:507036

BTA05_16075:706838514:1 (e-PCR)
- UniSTS:267949

MARC_16075-16076:1041970786:1 (e-PCR)
- UniSTS:267949

Lrp6 (e-PCR), detects polymorphism
- UniSTS:528050

G41286 (e-PCR)
- UniSTS:80060

RH104205 (e-PCR)
- UniSTS:98530

LRP6_4011 (e-PCR)
- UniSTS:462321

Homology

Homologs of the LRP6 gene: The LRP6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, and frog.
Orthologs from Annotation Pipeline: 438 organisms have orthologs with human gene LRP6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables Wnt receptor activity	IEA Inferred from Electronic Annotation more info
enables Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables Wnt-protein binding	TAS Traceable Author Statement more info	PubMed
enables coreceptor activity involved in Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
enables coreceptor activity involved in canonical Wnt signaling pathway	NAS Non-traceable Author Statement more info	PubMed
enables frizzled binding	IPI Inferred from Physical Interaction more info	PubMed
enables identical protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables kinase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables low-density lipoprotein particle receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
enables signaling receptor binding	IPI Inferred from Physical Interaction more info	PubMed
NOT enables toxin transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables toxin transmembrane transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
involved_in Wnt signaling pathway involved in somitogenesis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info	PubMed
acts_upstream_of_or_within canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in canonical Wnt signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in canonical Wnt signaling pathway	TAS Traceable Author Statement more info	PubMed
involved_in canonical Wnt signaling pathway involved in neural crest cell differentiation	IC Inferred by Curator more info	PubMed
involved_in canonical Wnt signaling pathway involved in regulation of cell proliferation	IC Inferred by Curator more info	PubMed
involved_in cell-cell adhesion	IEA Inferred from Electronic Annotation more info
involved_in cellular response to cholesterol	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chemical synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in dopaminergic neuron differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in midbrain dopaminergic neuron differentiation	TAS Traceable Author Statement more info	PubMed
involved_in negative regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of smooth muscle cell apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neural crest cell differentiation	IDA Inferred from Direct Assay more info	PubMed
involved_in neural crest formation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in positive regulation of DNA-binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of DNA-templated transcription	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in protein localization to plasma membrane	IPI Inferred from Physical Interaction more info	PubMed
involved_in receptor-mediated endocytosis involved in cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info	PubMed
involved_in response to peptide hormone	IEA Inferred from Electronic Annotation more info
involved_in toxin transport	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
colocalizes_with Golgi apparatus	IDA Inferred from Direct Assay more info	PubMed
part_of Wnt signalosome	IDA Inferred from Direct Assay more info	PubMed
part_of Wnt signalosome	NAS Non-traceable Author Statement more info	PubMed
part_of Wnt-Frizzled-LRP5/6 complex	IDA Inferred from Direct Assay more info	PubMed
part_of Wnt-Frizzled-LRP5/6 complex	IPI Inferred from Physical Interaction more info	PubMed
part_of Wnt-Frizzled-LRP5/6 complex	TAS Traceable Author Statement more info	PubMed
colocalizes_with caveola	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome membrane	TAS Traceable Author Statement more info
located_in endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
located_in extracellular region	TAS Traceable Author Statement more info
located_in neuronal cell body	IEA Inferred from Electronic Annotation more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in synapse	IEA Inferred from Electronic Annotation more info

General protein information

Go to the top of the page Help

Preferred Names: low-density lipoprotein receptor-related protein 6

Names: LRP-6

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016168.2 RefSeqGene

Range

4834..155853

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001414244.1 → NP_001401173.1 low-density lipoprotein receptor-related protein 6 isoform a precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414245.1 → NP_001401174.1 low-density lipoprotein receptor-related protein 6 isoform b precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414246.1 → NP_001401175.1 low-density lipoprotein receptor-related protein 6 isoform c precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414247.1 → NP_001401176.1 low-density lipoprotein receptor-related protein 6 isoform d precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414248.1 → NP_001401177.1 low-density lipoprotein receptor-related protein 6 isoform e precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414249.1 → NP_001401178.1 low-density lipoprotein receptor-related protein 6 isoform f precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414250.1 → NP_001401179.1 low-density lipoprotein receptor-related protein 6 isoform g precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414251.1 → NP_001401180.1 low-density lipoprotein receptor-related protein 6 isoform h precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414252.1 → NP_001401181.1 low-density lipoprotein receptor-related protein 6 isoform i

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414253.1 → NP_001401182.1 low-density lipoprotein receptor-related protein 6 isoform i

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414254.1 → NP_001401183.1 low-density lipoprotein receptor-related protein 6 isoform i

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_001414255.1 → NP_001401184.1 low-density lipoprotein receptor-related protein 6 isoform j precursor

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603
NM_002336.3 → NP_002327.2 low-density lipoprotein receptor-related protein 6 isoform b precursor

See identical proteins and their annotated locations for NP_002327.2

Status: REVIEWED

Source sequence(s)

AA126261, AC007537, AC007621, AF074264, BC126405, BP229563

Consensus CDS

CCDS8647.1

UniProtKB/Swiss-Prot

O75581, Q17RZ2

Related

ENSP00000261349.4, ENST00000261349.9

Conserved Domains (6) summary

smart00135
Location:483 → 524

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1326 → 1360

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd05819
Location:55 → 93

NHL; NHL repeat [structural motif]

pfam00058
Location:150 → 190

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:592 → 627

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:55 → 272

NHL; NHL repeat unit of beta-propeller proteins

RNA

NR_182264.1 RNA Sequence

Status: REVIEWED

Source sequence(s)

AC007537, AC007621, KF455603

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 110 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

12116025..12267044 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011520671.4 → XP_011518973.1 low-density lipoprotein receptor-related protein 6 isoform X3

Conserved Domains (4) summary

smart00135
Location:332 → 373

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1175 → 1209

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

pfam00058
Location:1 → 39

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:441 → 476

FXa_inhibition; Coagulation Factor Xa inhibitory site
XM_006719078.5 → XP_006719141.1 low-density lipoprotein receptor-related protein 6 isoform X1

UniProtKB/Swiss-Prot

O75581, Q17RZ2

Related

ENSP00000445083.1, ENST00000538239.5

Conserved Domains (6) summary

smart00135
Location:483 → 524

LY; Low-density lipoprotein-receptor YWTD domain

cd00112
Location:1326 → 1360

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cd05819
Location:55 → 93

NHL; NHL repeat [structural motif]

pfam00058
Location:150 → 190

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:592 → 627

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:55 → 272

NHL; NHL repeat unit of beta-propeller proteins
XM_047428844.1 → XP_047284800.1 low-density lipoprotein receptor-related protein 6 isoform X2