LRP3

protein-coding

LDL receptor related protein 3, the group of Low density lipoprotein receptors

Gene summary

Involved in negative regulation of fat cell differentiation; positive regulation of osteoblast differentiation; and regulation of gene expression. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_002333.4

Inheritance

—

ClinVar variants

U:152B:8

Top phenotype

—

gnomAD constraint

pLI —, LoF o/e 0.48

Max pathogenic AF

—

Genomic locus

chr19:33,177,603-33,208,864

External References & Databases

Ensembl (ENSG00000130881)

Transcript & Mutation Effects

hg38 • Region Span ~31.3 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 LRP3 variants in ClinVar

2 Conditions Cataloged

not specifiedTotal: 149

not providedTotal: 6

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_002333.4. 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			2 clinvar	3 clinvar	1 clinvar	6
missense			149 clinvar	3 clinvar	1 clinvar	153
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			1 clinvar			1
Total	0	0	152	6	2	160

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 20 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_002333.4	RefSeq	NP_002324.2	7	MANE Select
ENST00000253193.9	Ensembl	ENSP00000253193.6	7	MANE Select
ENST00000592484.5	Ensembl	ENSP00000476735.1	3	Standard
ENST00000998314.1	Ensembl	ENSP00000668131.1	7	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

receptor-mediated endocytosis

Cellular Component

clathrin-coated pit
integral component of membrane

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000253193
Coding exons: 7
Length: 30186
Individuals with no LoFs: 125714
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125737
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	1.41	386	472	0.818	0.0000345	4782
Missense (PolyPhen)		171	231.88	0.73744		2198
Synonymous	-0.513	221	212	1.04	0.0000169	1590
Loss of Function	2.49	13	26.9	0.483	0.00000145	280

Population LoF Frequency

Population	CAF	p-value	Status
African	0.000063	0.000062	rare
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0.00022	0.00020	rare
East Asian	0.000060	0.000054	rare
Finnish	0	0.0	absent
European (Non-Finnish)	0.00015	0.00014	rare
South Asian	0	0.0	absent
Other	0.00018	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Probable receptor, which may be involved in the internalization of lipophilic molecules and/or signal transduction. Its precise role is however unclear, since it does not bind to very low density lipoprotein (VLDL) or to LRPAP1 in vitro.;

Recessive Scores

pRec: 0.152

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.273

Gene Damage Prediction

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