LRP1B

protein-coding

LDL receptor related protein 1B, the group of Low density lipoprotein receptors

Gene summary

This gene encodes a member of the low density lipoprotein (LDL) receptor family. These receptors play a wide variety of roles in normal cell function and development due to their interactions with multiple ligands. Disruption of this gene has been reported in several types of cancer. [provided by RefSeq, Jun 2016]

MANE transcript

NM_018557.3

Inheritance

—

ClinVar variants

P:6U:510B:114

Top phenotype

LRP1B-related disorder

gnomAD constraint

pLI —, LoF o/e 0.26

Max pathogenic AF

—

Genomic locus

chr2:140,231,423-142,131,016

External References & Databases

Ensembl (ENSG00000168702)

Transcript & Mutation Effects

hg38 • Region Span ~1,899.6 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to LRP1B variants in ClinVar

10 Conditions Cataloged

not specifiedTotal: 468

LRP1B-related disorderTotal: 103

not providedTotal: 65

Inborn genetic diseasesTotal: 6

Prostate cancerTotal: 2

LRP1B-associated developmental disorderTotal: 1

High myopiaTotal: 1

EBV-positive nodal T- and NK-cell lymphomaTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_018557.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous		1 clinvar	4 clinvar	40 clinvar	20 clinvar	65
missense		5 clinvar	486 clinvar	38 clinvar	16 clinvar	545
nonsense			3 clinvar			3
start loss						0
frameshift			3 clinvar			3
splice donor/acceptor (+/-2bp)			14 clinvar			14
Total	0	6	510	78	36	630

Highest pathogenic variant AF is 0.0000043384057

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Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 9 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_018557.3	RefSeq	NP_061027.2	91	MANE Select
ENST00000389484.8	Ensembl	ENSP00000374135.3	91	MANE Select
ENST00000434794.1	Ensembl	ENSP00000413239.1	14	Standard
ENST00000437977.5	Ensembl	ENSP00000415052.1	17	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

receptor-mediated endocytosis
protein transport

Molecular Function

calcium ion binding

Cellular Component

integral component of membrane
receptor complex

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000389484
Coding exons: 91
Length: 1900279
Individuals with no LoFs: 125622
Homozygous LoFs: 0
Heterozygous LoFs: 125
Defined: 125747
p: 0.000497

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.93	2148	2.41e+3	0.890	0.000126	30637
Missense (PolyPhen)		251	329.9	0.76083		3595
Synonymous	-2.56	936	842	1.11	0.0000458	8063
Loss of Function	10.8	63	245	0.257	0.0000125	3119

Population LoF Frequency

Population	CAF	p-value	Status
African	0.00037	0.00037	rare
Latino/Admixed American	0.00065	0.00058	rare
Ashkenazi Jewish	0.00044	0.00040	rare
East Asian	0.00098	0.00098	rare
Finnish	0.00037	0.00037	rare
European (Non-Finnish)	0.00037	0.00036	rare
South Asian	0.00086	0.00082	rare
Other	0.00055	0.00049	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis.;

Recessive Scores

pRec: 0.133

Intolerance Scores

LoFtool: 0.00916
RVIS EVS: -2.29
RVIS percentile EVS: 1.23

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.203

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	High
Cancer	Medium	Medium	Medium