LRP4 LDL receptor related protein 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LRP4provided by HGNC
Official Full Name: LDL receptor related protein 4provided by HGNC
Primary source: HGNC:HGNC:6696
See related: Ensembl:ENSG00000134569 MIM:604270; AllianceGenome:HGNC:6696
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: CLSS; CMS17; LRP-4; LRP10; MEGF7; SOST2
Summary: This gene encodes a member of the low-density lipoprotein receptor-related protein family. The encoded protein may be a regulator of Wnt signaling. Mutations in this gene are associated with Cenani-Lenz syndrome. [provided by RefSeq, May 2010]
Expression: Broad expression in skin (RPKM 19.1), brain (RPKM 14.7) and 16 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 11p11.2

Exon count:: 41

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	11	NC_000011.10 (46856717..46918550, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	11	NC_060935.1 (47013618..47075418, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	11	NC_000011.9 (46878268..46940101, complement)

Chromosome 11 - NC_000011.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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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

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LRP4 site-specific variants in the third beta-propeller domain causes congenital myasthenic syndrome type 17.
Title: LRP4 site-specific variants in the third β-propeller domain causes congenital myasthenic syndrome type 17.
LRP4-related signalling pathways and their regulatory role in neurological diseases.
Title: LRP4-related signalling pathways and their regulatory role in neurological diseases.
A variant in the LDL receptor-related protein encoding gene LRP4 underlying polydactyly and phalangeal synostosis in a family of Pakistani origin.
Title: A variant in the LDL receptor-related protein encoding gene LRP4 underlying polydactyly and phalangeal synostosis in a family of Pakistani origin.
The collagen ColQ binds to LRP4 and regulates the activation of the Muscle-Specific Kinase-LRP4 receptor complex by agrin at the neuromuscular junction.
Title: The collagen ColQ binds to LRP4 and regulates the activation of the Muscle-Specific Kinase-LRP4 receptor complex by agrin at the neuromuscular junction.
Knockdown of long noncoding RNA HUMT inhibits the proliferation and metastasis by regulating miR-455-5p/LRP4 axis in hepatocellular carcinoma.
Title: Knockdown of long noncoding RNA HUMT inhibits the proliferation and metastasis by regulating miR-455-5p/LRP4 axis in hepatocellular carcinoma.
Novel variants in the LRP4 underlying Cenani-Lenz Syndactyly syndrome.
Title: Novel variants in the LRP4 underlying Cenani-Lenz Syndactyly syndrome.
Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third beta-Propeller Domain Can Cause Sclerosteosis.
Title: Identification of Compound Heterozygous Variants in LRP4 Demonstrates That a Pathogenic Variant outside the Third β-Propeller Domain Can Cause Sclerosteosis.
Correlation between BTG3, CASP9 and LRP4 single-nucleotide polymorphisms and susceptibility to papillary thyroid carcinoma.
Title: Correlation between BTG3, CASP9 and LRP4 single-nucleotide polymorphisms and susceptibility to papillary thyroid carcinoma.
The VWF/LRP4/alphaVbeta3-axis represents a novel pathway regulating proliferation of human vascular smooth muscle cells.
Title: The VWF/LRP4/αVβ3-axis represents a novel pathway regulating proliferation of human vascular smooth muscle cells.
A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2.
Title: A novel biallelic splice-site variant in the LRP4 gene causes sclerosteosis 2.

Submit: New GeneRIF Correction See all GeneRIFs (37)

Phenotypes

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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
Cenani-Lenz syndactyly syndrome MedGen: C1859309 OMIM: 212780 GeneReviews: Not available	Compare labs
Congenital myasthenic syndrome 17 MedGen: C4225377 OMIM: 616304 GeneReviews: Congenital Myasthenic Syndromes Overview	Compare labs
Sclerosteosis 2 MedGen: C3280402 OMIM: 614305 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Biological, clinical and population relevance of 95 loci for blood lipids. EBI GWAS Catalog EBI GWAS CatalogPubMed
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic predictors of fibrin D-dimer levels in healthy adults. EBI GWAS Catalog EBI GWAS CatalogPubMed
New sequence variants associated with bone mineral density. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of LRP4	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables apolipoprotein binding	IEA Inferred from Electronic Annotation more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables coreceptor activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein homodimerization activity	IEA Inferred from Electronic Annotation more info
enables receptor tyrosine kinase binding	ISS Inferred from Sequence or Structural Similarity more info
enables scaffold protein binding	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
involved_in Wnt signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in amyloid-beta clearance by cellular catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in dendrite morphogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in dorsal/ventral pattern formation	IEA Inferred from Electronic Annotation more info
involved_in embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in enzyme-linked receptor protein signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in generation of neurons	IBA Inferred from Biological aspect of Ancestor more info
involved_in hair follicle development	IEA Inferred from Electronic Annotation more info
involved_in kidney development	IDA Inferred from Direct Assay more info	PubMed
involved_in limb development	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of axonogenesis	ISS Inferred from Sequence or Structural Similarity more info
involved_in negative regulation of canonical Wnt signaling pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of canonical Wnt signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of canonical Wnt signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in negative regulation of ossification	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in odontogenesis of dentin-containing tooth	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of Rac protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of presynaptic membrane organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of skeletal muscle acetylcholine-gated channel clustering	IEA Inferred from Electronic Annotation more info
involved_in postsynaptic membrane assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in presynaptic membrane assembly	ISS Inferred from Sequence or Structural Similarity more info
involved_in proximal/distal pattern formation	IEA Inferred from Electronic Annotation more info
involved_in skeletal muscle acetylcholine-gated channel clustering	ISS Inferred from Sequence or Structural Similarity more info
involved_in synapse organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in synapse organization	ISS Inferred from Sequence or Structural Similarity more info
involved_in synaptic assembly at neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info

Component	Evidence Code	Pubs
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	ISS Inferred from Sequence or Structural Similarity more info
located_in dendrite	ISS Inferred from Sequence or Structural Similarity more info
located_in neuromuscular junction	ISS Inferred from Sequence or Structural Similarity more info
located_in neuronal cell body	ISS Inferred from Sequence or Structural Similarity more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISS Inferred from Sequence or Structural Similarity more info
located_in plasma membrane raft	ISS Inferred from Sequence or Structural Similarity more info
located_in postsynaptic density	ISS Inferred from Sequence or Structural Similarity more info
located_in synaptic membrane	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: low-density lipoprotein receptor-related protein 4

Names: multiple EGF like domains 7; multiple epidermal growth factor-like domains 7

NCBI Reference Sequences (RefSeq)

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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_021394.2 RefSeqGene

Range

5000..66833

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002334.4 → NP_002325.2 low-density lipoprotein receptor-related protein 4 precursor

See identical proteins and their annotated locations for NP_002325.2

Status: REVIEWED

Source sequence(s)

AC021573

Consensus CDS

CCDS31478.1

UniProtKB/Swiss-Prot

B2RN39, O75096, Q4AC85, Q5KTZ5

Related

ENSP00000367888.1, ENST00000378623.6

Conserved Domains (9) summary

smart00192
Location:311 → 343

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:505 → 545

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:395 → 434

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:270 → 304

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:1085 → 1123

NHL; NHL repeat [structural motif]

pfam00057
Location:70 → 105

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:1179 → 1219

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:1313 → 1348

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:1085 → 1277

NHL; NHL repeat unit of beta-propeller proteins

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000011.10 Reference GRCh38.p14 Primary Assembly

Range

46856717..46918550 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017017734.2 → XP_016873223.1 low-density lipoprotein receptor-related protein 4 isoform X1
XM_011520103.3 → XP_011518405.1 low-density lipoprotein receptor-related protein 4 isoform X2

Conserved Domains (8) summary

smart00192
Location:43 → 75

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:237 → 277

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:127 → 166

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:2 → 36

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:817 → 855

NHL; NHL repeat [structural motif]

pfam00058
Location:911 → 951

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:1045 → 1080

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:817 → 1009

NHL; NHL repeat unit of beta-propeller proteins
XM_011520104.3 → XP_011518406.1 low-density lipoprotein receptor-related protein 4 isoform X3

Conserved Domains (5) summary

smart00135
Location:63 → 105

LY; Low-density lipoprotein-receptor YWTD domain

cd05819
Location:340 → 378

NHL; NHL repeat [structural motif]

pfam00058
Location:434 → 474

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:568 → 603

FXa_inhibition; Coagulation Factor Xa inhibitory site

cl18310
Location:340 → 532

NHL; NHL repeat unit of beta-propeller proteins

Alternate T2T-CHM13v2.0

Genomic

NC_060935.1 Alternate T2T-CHM13v2.0

Range

47013618..47075418 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054368782.1 → XP_054224757.1 low-density lipoprotein receptor-related protein 4 isoform X1
XM_054368783.1 → XP_054224758.1 low-density lipoprotein receptor-related protein 4 isoform X2
XM_054368784.1 → XP_054224759.1 low-density lipoprotein receptor-related protein 4 isoform X3