VLDLR very low density lipoprotein receptor [Homo sapiens (human)] - Gene

Summary

Official Symbol: VLDLRprovided by HGNC
Official Full Name: very low density lipoprotein receptorprovided by HGNC
Primary source: HGNC:HGNC:12698
See related: Ensembl:ENSG00000147852 MIM:192977; AllianceGenome:HGNC:12698
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: CAMRQ1; CARMQ1; CHRMQ1; VLDL-R; VLDLRCH
Summary: The low density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. This gene encodes a lipoprotein receptor that is a member of the LDLR family and plays important roles in VLDL-triglyceride metabolism and the reelin signaling pathway. Mutations in this gene cause VLDLR-associated cerebellar hypoplasia. Alternative splicing generates multiple transcript variants encoding distinct isoforms for this gene. [provided by RefSeq, Aug 2009]
Expression: Broad expression in ovary (RPKM 37.5), heart (RPKM 20.5) and 18 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 9p24.2

Exon count:: 19

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	9	NC_000009.12 (2621787..2660056)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	9	NC_060933.1 (2624554..2662816)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	9	NC_000009.11 (2621787..2660056)

Chromosome 9 - NC_000009.12 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 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?

The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes.
Title: The receptor VLDLR binds Eastern Equine Encephalitis virus through multiple distinct modes.
Identification of the miR-423-3p/VLDLR Regulatory Network for Glioma Using Transcriptome Analysis.
Title: Identification of the miR-423-3p/VLDLR Regulatory Network for Glioma Using Transcriptome Analysis.
ADAM17 mediates ectodomain shedding of the soluble VLDL receptor fragment in the retinal epithelium.
Title: ADAM17 mediates ectodomain shedding of the soluble VLDL receptor fragment in the retinal epithelium.
Expression level of VLDL receptor and VLDL-c levels in the malignant and benign breast tumors: The correlation with miRNA-4465 and miRNA-1297.
Title: Expression level of VLDL receptor and VLDL-c levels in the malignant and benign breast tumors: The correlation with miRNA-4465 and miRNA-1297.
Four single nucleotide polymorphisms (SNPs); rs6921438 and rs4416670 in LOC100132354-C6orf223, rs6993770 in ZFPM2, and rs10738760 in VLDLR-KCNV2 were reported to explain up to 50% of the heritability of vascular endothelial growth factor circulating levels. These SNPs were also studied for possible associations with circulating lipid levels in supposedly healthy European individuals and in a limited number of Iranian indi
Title: Association between SNPs of Circulating Vascular Endothelial Growth Factor Levels, Hypercholesterolemia and Metabolic Syndrome.
Postprandial VLDL particles are strongly bound and internalized into cells expressing the VLDL receptor. The presence of various specific ligands in VLDL remnants may enhance the capacity for binding to the VLDL receptor, which play the role primarily for energy delivery to the peripheral tissues, but is also a causal factor in atherogenic diseases when excessively and/or continuously remained in plasma.
Title: The VLDL receptor plays a key role in the metabolism of postprandial remnant lipoproteins.
This study presents the nuclear magnetic resonance solution structure of the recombinant VLDLR(2-4) fragment containing all three fibrin-binding cysteine-rich (CR) domains of this receptor.
Title: Nuclear Magnetic Resonance Solution Structure of the Recombinant Fragment Containing Three Fibrin-Binding Cysteine-Rich Domains of the Very Low Density Lipoprotein Receptor.
In summary, ER retention of pathogenic VLDLR mutants involves binding to calnexin, elevated endoplasmic reticulum stress, and delayed degradation which is dependent on SEL1L.
Title: Degradation routes of trafficking-defective VLDLR mutants associated with Dysequilibrium syndrome.
Our findings described an atherogenic phenotype characterized by low VLDL-C but high VLDLR mRNA expression in peripheral WBCs, which suggested that VLDLR in all types of peripheral WBCs may be involved in lipid deposition, and VLDL-C and VLDLR may co-determine the development of atherosclerosis.
Title: Low Very low-Density Lipoprotein Cholesterol but High Very low-Density Lipoprotein Receptor mRNA Expression in Peripheral White Blood Cells: An Atherogenic Phenotype for Atherosclerosis in a Community-Based Population.
In the second family, we identified a previously unreported homozygous missense change, c.154T > C (p.Cys52Arg) in the VLDLR gene
Title: Whole exome sequencing is necessary to clarify ID/DD cases with de novo copy number variants of uncertain significance: Two proof-of-concept examples.

Submit: New GeneRIF Correction See all GeneRIFs (64)

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
Cerebellar ataxia, intellectual disability, and dysequilibrium syndrome 1 MedGen: C4551552 OMIM: 224050 GeneReviews: VLDLR Cerebellar Hypoplasia	Compare labs

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association analysis of age-at-onset in Alzheimer's disease. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study of a quantitative disordered gambling trait. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of cis- and trans-acting genetic variants explaining up to half the variation in circulating vascular endothelial growth factor levels. 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 VLDLR	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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Markers

WI-18746 (e-PCR)
- UniSTS:48439

VLDLR (e-PCR)
- UniSTS:505995

SHGC-12535 (e-PCR)
- UniSTS:60113

GDB:631759 (e-PCR)
- UniSTS:158427

GDB:631760 (e-PCR)
- UniSTS:158428

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables apolipoprotein binding	IBA Inferred from Biological aspect of Ancestor more info
enables apolipoprotein binding	IDA Inferred from Direct Assay more info	PubMed
enables apolipoprotein binding	ISS Inferred from Sequence or Structural Similarity more info
enables calcium ion binding	IEA Inferred from Electronic Annotation more info
enables calcium-dependent protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables cargo receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor activity	TAS Traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables reelin receptor activity	ISS Inferred from Sequence or Structural Similarity more info
enables very-low-density lipoprotein particle binding	IDA Inferred from Direct Assay more info	PubMed
enables very-low-density lipoprotein particle receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables very-low-density lipoprotein particle receptor activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in cholesterol metabolic process	IEA Inferred from Electronic Annotation more info
involved_in dendrite morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in glycoprotein transport	IDA Inferred from Direct Assay more info	PubMed
involved_in lipid transport	IEA Inferred from Electronic Annotation more info
involved_in memory	TAS Traceable Author Statement more info	PubMed
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of dendrite development	ISS Inferred from Sequence or Structural Similarity more info
involved_in receptor-mediated endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in reelin-mediated signaling pathway	ISS Inferred from Sequence or Structural Similarity more info
involved_in regulation of synapse assembly	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in ventral spinal cord development	IEA Inferred from Electronic Annotation more info
involved_in very-low-density lipoprotein particle clearance	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in clathrin-coated pit	IEA Inferred from Electronic Annotation more info
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
located_in lysosomal membrane	TAS Traceable Author Statement more info
located_in membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	TAS Traceable Author Statement more info
part_of receptor complex	IDA Inferred from Direct Assay more info	PubMed
part_of very-low-density lipoprotein particle	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: very low-density lipoprotein receptor

Names: VLDL receptor

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_012741.2 RefSeqGene

Range

5002..43271

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001018056.3 → NP_001018066.1 very low-density lipoprotein receptor isoform b precursor

See identical proteins and their annotated locations for NP_001018066.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 3' coding region compared to variant 1. The resulting protein (isoform b) is shorter than isoform a.

Source sequence(s)

AL450467, BC144245, DA386669

Consensus CDS

CCDS34979.1

UniProtKB/TrEMBL

Q5VVF5, Q8NAN7

Related

ENSP00000506072.1, ENST00000681306.1

Conserved Domains (7) summary

smart00192
Location:71 → 103

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:505 → 547

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:396 → 426

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:33 → 67

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 ...

pfam00057
Location:237 → 273

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:568 → 608

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:360 → 394

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001322225.2 → NP_001309154.1 very low-density lipoprotein receptor isoform c precursor

Status: REVIEWED

Source sequence(s)

AL450467

Consensus CDS

CCDS94376.1

UniProtKB/TrEMBL

A0A7P0T897, Q8NAN7

Related

ENSP00000505030.1, ENST00000680746.1

Conserved Domains (8) summary

smart00192
Location:71 → 103

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:464 → 506

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:355 → 385

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:33 → 67

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 ...

pfam01456
Location:710 → 772

Mucin; Mucin-like glycoprotein

pfam00057
Location:196 → 232

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:527 → 567

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:319 → 353

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_001322226.2 → NP_001309155.1 very low-density lipoprotein receptor isoform d precursor

Status: REVIEWED

Source sequence(s)

AL450467

Consensus CDS

CCDS94377.1

UniProtKB/TrEMBL

A0A7P0T9P7, Q8NAN7

Related

ENSP00000505773.1, ENST00000681618.1

Conserved Domains (7) summary

smart00192
Location:71 → 103

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:464 → 506

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:355 → 385

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:33 → 67

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 ...

pfam00057
Location:196 → 232

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:527 → 567

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:319 → 353

FXa_inhibition; Coagulation Factor Xa inhibitory site
NM_003383.5 → NP_003374.3 very low-density lipoprotein receptor isoform a precursor

See identical proteins and their annotated locations for NP_003374.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AL450467, BC136562, DA386669

Consensus CDS

CCDS6446.1

UniProtKB/Swiss-Prot

B2RMZ7, D3DRH6, P98155, Q5VVF6

UniProtKB/TrEMBL

Q8NAN7

Related

ENSP00000371532.2, ENST00000382100.8

Conserved Domains (8) summary

smart00192
Location:71 → 103

LDLa; Low-density lipoprotein receptor domain class A

smart00135
Location:505 → 547

LY; Low-density lipoprotein-receptor YWTD domain

smart00179
Location:396 → 426

EGF_CA; Calcium-binding EGF-like domain

cd00112
Location:33 → 67

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 ...

pfam01456
Location:751 → 813

Mucin; Mucin-like glycoprotein

pfam00057
Location:237 → 273

Ldl_recept_a; Low-density lipoprotein receptor domain class A

pfam00058
Location:568 → 608

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

pfam14670
Location:360 → 394

FXa_inhibition; Coagulation Factor Xa inhibitory site