LDLRAP1 low density lipoprotein receptor adaptor protein 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LDLRAP1provided by HGNC
Official Full Name: low density lipoprotein receptor adaptor protein 1provided by HGNC
Primary source: HGNC:HGNC:18640
See related: Ensembl:ENSG00000157978 MIM:605747; AllianceGenome:HGNC:18640
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: ARH; ARH1; ARH2; FHCB1; FHCB2; FHCL4
Summary: The protein encoded by this gene is a cytosolic protein which contains a phosphotyrosine binding (PTD) domain. The PTD domain has been found to interact with the cytoplasmic tail of the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the disorder autosomal recessive hypercholesterolaemia. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in spleen (RPKM 14.0), lymph node (RPKM 12.3) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p36.11

Exon count:: 15

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (25543606..25590400)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (25380944..25427735)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (25870097..25895377)

Chromosome 1 - NC_000001.11 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?

A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia
Title: A Novel Splice Site Variant in the LDLRAP1 Gene Causes Familial Hypercholesterolemia.
Molecular insights into the coding region mutations of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) linked to familial hypercholesterolemia.
Title: Molecular insights into the coding region mutations of low-density lipoprotein receptor adaptor protein 1 (LDLRAP1) linked to familial hypercholesterolemia.
new variant in the LDLRAP1 gene associated with autosomal recessive hypercholesterolemia
Title: A case of autosomal recessive hypercholesterolemia caused by a new variant in the LDL receptor adaptor protein 1 gene.
Case Report: combined variants in LDLR/LDLRAP1 genes trigger a severe familial hypercholesterolemia phenotype.
Title: Novel combined variants of LDLR and LDLRAP1 genes causing severe familial hypercholesterolemia.
Pathogenic mutations in LDLR, APOB, PCSK9 and LDLRAP1 genes were found in 17 of 225 patients with familial hypercholesterolemia leading to premature myocardial infarction.
Title: Effects of familial hypercholesterolemia-associated genes on the phenotype of premature myocardial infarction.
The results show that phosphorylated ARH1 has more ordered structure than the non-phosphorylated type.
Title: Understanding the differences of the ligand binding/unbinding pathways between phosphorylated and non-phosphorylated ARH1 using molecular dynamics simulations.
LDLRAP1 associated with Familial Hypercholesterolemia and Polygenic Hypercholesterolemia in patients with Acute Coronary Syndrome , age </=65 years, and LDL-C levels >/=160 mg/dl.
Title: Genetically Confirmed Familial Hypercholesterolemia in Patients With Acute Coronary Syndrome.
Numb specifically regulates NPC1L1-mediated cholesterol absorption both in human intestine and liver, distinct from ARH and Dab2, which selectively participate in LDLR-mediated LDL uptake.
Title: The clathrin adaptor proteins ARH, Dab2, and numb play distinct roles in Niemann-Pick C1-Like 1 versus low density lipoprotein receptor-mediated cholesterol uptake.
Identification of ARH gene and characterization of its mutations in Autosomal Recessive Hypercholesterolemia patients [Review]
Title: The history of Autosomal Recessive Hypercholesterolemia (ARH). From clinical observations to gene identification.
cells that depend upon ARH for LDL uptake can control which lipoproteins are internalized by their LDLRs through changes in nitric oxide.
Title: S-nitrosylation of ARH is required for LDL uptake by the LDL receptor.

Submit: New GeneRIF Correction See all GeneRIFs (34)

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
Hypercholesterolemia, familial, 4 MedGen: C1863512 OMIM: 603813 GeneReviews: Familial Hypercholesterolemia	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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

G32710 (e-PCR)
- UniSTS:117292

G54707 (e-PCR)
- UniSTS:117809

ARH_9459 (e-PCR)
- UniSTS:468289

AL034214 (e-PCR)
- UniSTS:94040

SHGC-74391 (e-PCR)
- UniSTS:48757

A009O34 (e-PCR)
- UniSTS:62344

SHGC-144355 (e-PCR)
- UniSTS:172210

SHGC-74429 (e-PCR)
- UniSTS:72115

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables AP-1 adaptor complex binding	IDA Inferred from Direct Assay more info	PubMed
enables AP-2 adaptor complex binding	IDA Inferred from Direct Assay more info	PubMed
enables amyloid-beta binding	IPI Inferred from Physical Interaction more info	PubMed
enables clathrin adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables clathrin binding	IDA Inferred from Direct Assay more info	PubMed
enables low-density lipoprotein particle receptor binding	IPI Inferred from Physical Interaction more info	PubMed
enables phosphatidylinositol-4,5-bisphosphate binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphotyrosine residue binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables signaling adaptor activity	IDA Inferred from Direct Assay more info	PubMed
enables signaling receptor complex adaptor activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
involved_in amyloid precursor protein metabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to cytokine stimulus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol homeostasis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cholesterol metabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in cholesterol transport	NAS Non-traceable Author Statement more info	PubMed
involved_in low-density lipoprotein particle clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of cholesterol metabolic process	IC Inferred by Curator more info	PubMed
involved_in positive regulation of low-density lipoprotein particle clearance	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of receptor-mediated endocytosis involved in cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of vascular associated smooth muscle cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor internalization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in receptor-mediated endocytosis	IDA Inferred from Direct Assay more info	PubMed
involved_in receptor-mediated endocytosis involved in cholesterol transport	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein binding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of protein localization to plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in axon	ISS Inferred from Sequence or Structural Similarity more info
located_in basal plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in clathrin-coated endocytic vesicle membrane	TAS Traceable Author Statement more info
located_in cytoplasmic side of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
is_active_in early endosome	IBA Inferred from Biological aspect of Ancestor more info
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in neurofilament	ISS Inferred from Sequence or Structural Similarity more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
located_in recycling endosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: low density lipoprotein receptor adapter protein 1

Names: LDL receptor adaptor protein; autosomal recessive hypercholesterolemia protein

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_008932.1 RefSeqGene

Range

5001..30302

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_276

mRNA and Protein(s)

NM_015627.3 → NP_056442.2 low density lipoprotein receptor adapter protein 1

See identical proteins and their annotated locations for NP_056442.2

Status: REVIEWED

Source sequence(s)

AK091219, AL117654, AL606491, DA930479

Consensus CDS

CCDS30639.1

UniProtKB/Swiss-Prot

A2BHI5, Q5SW96, Q6TQS9, Q8N2Y0, Q9UFI9

UniProtKB/TrEMBL

B3KR97

Related

ENSP00000363458.4, ENST00000374338.5

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold

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_000001.11 Reference GRCh38.p14 Primary Assembly

Range

25543606..25590400

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006710560.5 → XP_006710623.1 low density lipoprotein receptor adapter protein 1 isoform X7

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_006710561.5 → XP_006710624.1 low density lipoprotein receptor adapter protein 1 isoform X9

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_011541211.4 → XP_011539513.1 low density lipoprotein receptor adapter protein 1 isoform X8

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_011541212.4 → XP_011539514.1 low density lipoprotein receptor adapter protein 1 isoform X11

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_017000995.3 → XP_016856484.1 low density lipoprotein receptor adapter protein 1 isoform X13
XM_047417473.1 → XP_047273429.1 low density lipoprotein receptor adapter protein 1 isoform X2
XM_011541209.4 → XP_011539511.1 low density lipoprotein receptor adapter protein 1 isoform X1

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_006710559.5 → XP_006710622.1 low density lipoprotein receptor adapter protein 1 isoform X5

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_011541210.4 → XP_011539512.1 low density lipoprotein receptor adapter protein 1 isoform X6

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:44 → 166

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_024446315.2 → XP_024302083.1 low density lipoprotein receptor adapter protein 1 isoform X10

UniProtKB/TrEMBL

B3KR97

Conserved Domains (1) summary

cd13159
Location:1 → 121

PTB_LDLRAP-mammal-like; Low Density Lipoprotein Receptor Adaptor Protein 1 (LDLRAP1) in mammals and similar proteins Phosphotyrosine-binding (PTB) PH-like fold
XM_047417497.1 → XP_047273453.1 low density lipoprotein receptor adapter protein 1 isoform X12
XM_017000994.3 → XP_016856483.1 low density lipoprotein receptor adapter protein 1 isoform X3

UniProtKB/TrEMBL

B3KR97
XM_047417482.1 → XP_047273438.1 low density lipoprotein receptor adapter protein 1 isoform X4

RNA

XR_946603.4 RNA Sequence
XR_007058621.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

NC_060925.1 Alternate T2T-CHM13v2.0

Range

25380944..25427735

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054335906.1 → XP_054191881.1 low density lipoprotein receptor adapter protein 1 isoform X7
XM_054335908.1 → XP_054191883.1 low density lipoprotein receptor adapter protein 1 isoform X9
XM_054335907.1 → XP_054191882.1 low density lipoprotein receptor adapter protein 1 isoform X8
XM_054335910.1 → XP_054191885.1 low density lipoprotein receptor adapter protein 1 isoform X11
XM_054335912.1 → XP_054191887.1 low density lipoprotein receptor adapter protein 1 isoform X13
XM_054335901.1 → XP_054191876.1 low density lipoprotein receptor adapter protein 1 isoform X2
XM_054335900.1 → XP_054191875.1 low density lipoprotein receptor adapter protein 1 isoform X1
XM_054335904.1 → XP_054191879.1 low density lipoprotein receptor adapter protein 1 isoform X5
XM_054335905.1 → XP_054191880.1 low density lipoprotein receptor adapter protein 1 isoform X6
XM_054335909.1 → XP_054191884.1 low density lipoprotein receptor adapter protein 1 isoform X10
XM_054335911.1 → XP_054191886.1 low density lipoprotein receptor adapter protein 1 isoform X12
XM_054335903.1 → XP_054191878.1 low density lipoprotein receptor adapter protein 1 isoform X4
XM_054335902.1 → XP_054191877.1 low density lipoprotein receptor adapter protein 1 isoform X3