LRP1B

Summary

LRP1B (LDL receptor related protein 1B, HGNC:6693) is a protein-coding gene on chromosome 2q22.1-q22.2, encoding Low-density lipoprotein receptor-related protein 1B (Q9NZR2). Potential cell surface proteins that bind and internalize ligands in the process of receptor-mediated endocytosis. In precision oncology, LRP1B Loss-of-function confers sensitivity to Immune Checkpoint Inhibitor in Solid Tumor (CIViC Level B); 2 further curated variant–drug associations are listed below.

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.

Source: NCBI Gene 53353 — RefSeq curated summary.

At a glance

• GWAS associations: 54
• Clinical variants (ClinVar): 714 total — 6 likely-pathogenic
• Precision-oncology evidence (CIViC): 3 curated variant–drug associations
• Cancer driver (intOGen): activating (oncogene-like) across 40 cancer types
• MANE Select transcript: NM_018557

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:6693
Approved symbol	LRP1B
Name	LDL receptor related protein 1B
Location	2q22.1-q22.2
Locus type	gene with protein product
Status	Approved
Aliases	LRP-DIT, LRPDIT
Ensembl gene	ENSG00000168702
Ensembl biotype	protein_coding
OMIM	608766
Entrez	53353

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 4 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000389484, ENST00000434794, ENST00000437977, ENST00000442974, ENST00000486364

RefSeq mRNA: 1 — MANE Select: NM_018557 NM_018557

CCDS: CCDS2182

Canonical transcript exons

ENST00000389484 — 91 exons

Exon	Start	End
ENSE00001124874	141229183	141229440
ENSE00001124879	141247226	141247354
ENSE00001131786	141005335	141005457
ENSE00001131795	141015696	141015915
ENSE00001131802	140839991	140840085
ENSE00001131810	140840918	140841092
ENSE00001131825	140867590	140867834
ENSE00001131832	140868099	140868263
ENSE00001131837	140883817	140884021
ENSE00001131845	140886138	140886335
ENSE00001131848	140902920	140903165
ENSE00001131853	140907877	140908077
ENSE00001131860	140922965	140923147
ENSE00001131885	140701721	140701845
ENSE00001131890	140536581	140536709
ENSE00001131896	140540973	140541098
ENSE00001131904	140487617	140487739
ENSE00001131912	140492608	140492693
ENSE00001131919	140495565	140495748
ENSE00001131923	140501687	140501874
ENSE00001131930	140502963	140503103
ENSE00001131937	140506796	140506918
ENSE00001131947	140509928	140510056
ENSE00001131958	140444330	140444449
ENSE00001131968	140444563	140444679
ENSE00001131978	140450568	140450661
ENSE00001131982	140456455	140456603
ENSE00001131988	140457463	140457651
ENSE00001131995	140323893	140324066
ENSE00001131999	140325762	140325878
ENSE00001132004	140334453	140334559
ENSE00001132013	140335615	140335838
ENSE00001132019	140350797	140351038
ENSE00001132026	140352953	140353072
ENSE00001132029	140356342	140356476
ENSE00001132034	140357979	140358116
ENSE00001132045	140239442	140239532
ENSE00001132051	140247086	140247162
ENSE00001132056	140270242	140270346
ENSE00001132065	140274424	140274598
ENSE00001151431	141254522	141254641
ENSE00001153759	141019922	141020102
ENSE00001153769	140813657	140813806
ENSE00001153804	140534021	140534140
ENSE00001153813	140541779	140541971
ENSE00001153824	140485343	140485524
ENSE00001153830	140514653	140514772
ENSE00001153839	140442504	140442623
ENSE00001153849	140475138	140475337
ENSE00001153862	140321963	140322088
ENSE00001153896	140297808	140297969
ENSE00001182289	140234786	140234884
ENSE00001182326	140314935	140315099
ENSE00001182394	140358821	140358946
ENSE00001182403	140364661	140364783
ENSE00001182417	140371179	140371285
ENSE00001182423	140373008	140373137
ENSE00001182430	140378180	140378286
ENSE00001182437	140385893	140386009
ENSE00001182504	140516889	140517011
ENSE00001182509	140525844	140525993
ENSE00001182513	140526237	140526350
ENSE00001182529	140598631	140598835
ENSE00001182536	140601450	140601639
ENSE00001182554	140702141	140702292
ENSE00001182559	140702427	140702553
ENSE00001182564	140715973	140716102
ENSE00001182569	140716682	140716816
ENSE00001182573	140769213	140769344
ENSE00001182578	140770881	140771006
ENSE00001182584	140776098	140776238
ENSE00001182608	140851652	140851783
ENSE00001182645	141048986	141049222
ENSE00001182650	141058883	141059054
ENSE00001182652	141062051	141062273
ENSE00001290608	140950235	140950402
ENSE00001293480	141480396	141480533
ENSE00001299374	140238152	140238296
ENSE00001300429	140989532	140989657
ENSE00001302656	141188421	141188583
ENSE00001312881	140850102	140850329
ENSE00001316880	140700250	140700621
ENSE00001320558	141055116	141055259
ENSE00001323698	140993995	140994135
ENSE00001325750	140982160	140982276
ENSE00001327802	141013556	141013745
ENSE00001328871	140370710	140370842
ENSE00001505998	140951860	140951940
ENSE00001513461	140231423	140233326
ENSE00001794248	142130648	142131016
ENSE00003625400	141810279	141810401

Expression profiles

Bgee: expression breadth ubiquitous, 194 present calls, max score 91.67.

FANTOM5 (CAGE): breadth broad, TPM avg 7.6504 / max 488.4674, expressed in 579 samples.

FANTOM5 promoters (10 alternative TSS)

Promoter ID	TPM avg	Samples expressed
30855	3.2090	407
30856	1.8389	330
30857	1.1428	266
30854	0.6606	139
30860	0.5767	167
30853	0.0738	45
30858	0.0717	48
30859	0.0547	26
30861	0.0130	2
30862	0.0092	2

Top tissues by expression

272 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endothelial cell	CL:0000115	91.67	gold quality
Brodmann (1909) area 23	UBERON:0013554	83.46	gold quality
cortical plate	UBERON:0005343	83.32	gold quality
CA1 field of hippocampus	UBERON:0003881	81.53	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	81.50	gold quality
gluteal muscle	UBERON:0002000	81.46	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.73	gold quality
prefrontal cortex	UBERON:0000451	80.61	gold quality
primary visual cortex	UBERON:0002436	80.41	gold quality
anterior cingulate cortex	UBERON:0009835	80.26	gold quality
cingulate cortex	UBERON:0003027	80.13	gold quality
amygdala	UBERON:0001876	79.92	gold quality
Brodmann (1909) area 9	UBERON:0013540	79.92	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	79.74	gold quality
neocortex	UBERON:0001950	78.76	gold quality
frontal cortex	UBERON:0001870	78.40	gold quality
cerebral cortex	UBERON:0000956	78.26	gold quality
temporal lobe	UBERON:0001871	78.07	gold quality
caudate nucleus	UBERON:0001873	77.89	gold quality
nucleus accumbens	UBERON:0001882	77.59	gold quality
telencephalon	UBERON:0001893	77.58	gold quality
substantia nigra	UBERON:0002038	77.48	gold quality
biceps brachii	UBERON:0001507	77.19	gold quality
right frontal lobe	UBERON:0002810	77.19	gold quality
corpus callosum	UBERON:0002336	77.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	77.02	gold quality
Ammon’s horn	UBERON:0001954	76.60	gold quality
entorhinal cortex	UBERON:0002728	76.37	gold quality
hindlimb stylopod muscle	UBERON:0004252	76.04	gold quality
occipital lobe	UBERON:0002021	76.02	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-GEOD-180759	yes	9470.92
E-HCAD-35	yes	8381.24
E-HCAD-25	yes	24.13
E-ANND-3	yes	16.02

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SREBF2

miRNA regulators (miRDB)

192 targeting LRP1B, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4775	99.98	75.00	6394
HSA-LET-7F-2-3P	99.98	70.98	2588
HSA-MIR-1185-1-3P	99.98	71.04	2593
HSA-MIR-1185-2-3P	99.98	71.04	2593
HSA-MIR-548P	99.98	72.25	3784
HSA-MIR-3617-3P	99.98	67.86	918
HSA-MIR-5696	99.98	72.36	4487

Literature-anchored findings (GeneRIF, showing 40)

• The LRP1B gene is a candidate tumor suppressor gene in urothelial cancer. (PMID:12004004)
• LRP1B can function as a negative regulator of uPAR regeneration and cell migration. (PMID:12194987)
• These findings reveal that low density lipoprotein receptor-related protein 1B is a novel binding partner of beta-amyloid precursor protein (APP) that functions to decrease APP processing to amyloid beta peptides. (PMID:15126508)
• LRP1B modulates the catabolism of uPAR and PDGFR, affecting the migration of smooth muscle cells. (PMID:15166012)
• Loss of LRP1B function in esophageal carcinogenesis most often occurs either by homozygous deletion or by transcriptional silencing through hypermethylation of its CpG island. (PMID:15172977)
• Although mouse LRP1B expresses in the forms of both full-length receptor tail and an alternatively spliced form lacking a 33-amino acid insert, human LRP1B is expressed exclusively in the form of full-length receptor tail (PMID:15963947)
• LRP1B functions as a receptor for Pseudomonas exotoxin. (PMID:16095885)
• Frequent inactivation of LRP1B mainly occurs by means of epigenetic mechanisms in oral squamous cell carcinoma, which might play an important role in oral tumorigenesis. (PMID:16918994)
• LRP1B has tumor suppression function that is mediated by proteolytic processing of the receptor resulting in intracellular domain release. (PMID:17227771)
• results suggest that haplotypes in the gene LRP1B are significant/protective for successful aging without cognitive decline (PMID:19367585)
• LRP1B was hypermethylated in four gastric cancer cell lines, and low LRP1B mRNA expression was associated with high methylation levels in gastric cancer cell lines. (PMID:20095042)
• Epigenomics and microRNAs inactivate LRP1B, a modulator of the extracellular environment of thyroid cancer cells, and it is deleted in neoplasms. (PMID:21057533)
• LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE–carrying lipoproteins (PMID:21420681)
• genetic association studies in Danish population: Quantitative metabolic phenotypes in obesity are associated with SNP in various genes: LRP1B (rs2890652) is associated with body mass index and insulin resistance. (PMID:21953277)
• Silencing of LRP1B altered the expression of focal adhesion complex-associated proteins, and Cdc42/RhoA activities. (PMID:23521319)
• LRP1B presents with frequent molecular alterations for glioblastoma patients; its deletion may impact patient outcome. (PMID:26428308)
• LRP1B, BRD2 and CACNA1D are new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. (PMID:26586120)
• Data show that overexpression of full-length mouse Lrp1b leads to impaired cellular proliferation, while humsn LRP1B knockdown has the opposite effect. (PMID:27626682)
• LRP1B gene is a target for human papillomavirus integrations and chromosome rearrangements in oropharyngeal squamous cell carcinoma. (PMID:27636103)
• that LRP1B interacted with DVL2, inhibited the interaction between DVL2 and Axin, and negatively regulated beta-catenin/TCF signaling (PMID:28408316)
• LRP1B mutations are highly prevalent among the lung adenocarcinoma patients with COPD. (PMID:28522810)
• Nuclear LRP1B was significantly associated with poor patient prognosis. Nuclear LRP1B increased Matrigel invasion activity of breast cancer cells. (PMID:30607440)
• The genetic and epigenetic association of LDL Receptor Related Protein 1B (LRP1B) gene with childhood obesity. (PMID:30755693)
• LRP1B was identified as a target of miR-500 and was significantly decreased in prostate cancer tissues. (PMID:30877185)
• this study shows that somatic mutation of LRP1B is associated with tumor mutational burden in patients with lung cancer (PMID:31054778)
• Low LRP1B expression is associated with proliferation, migration and invasion of prostate cancer. (PMID:31442444)
• Translational study of the whole transcriptome in rats and genetic polymorphisms in humans identifies LRP1B and VPS13A as key genes involved in tolerance to cocaine-induced motor disturbances. (PMID:33159041)
• LRP1B mutations are associated with favorable outcomes to immune checkpoint inhibitors across multiple cancer types. (PMID:33653800)
• LRP1B mutation is associated with tumor HPV status and promotes poor disease outcomes with a higher mutation count in HPV-related cervical carcinoma and head & neck squamous cell carcinoma. (PMID:33994859)
• Screening and clinical significance of lymph node metastasis-related genes within esophagogastric junction adenocarcinoma. (PMID:34152098)
• Development and validation of LRP1B mutation-associated prognostic model for hepatocellular carcinoma. (PMID:34386813)
• LRP1B Expression Is Correlated With Age and Perineural Invasion in Metastatic Cutaneous Squamous Cell Carcinoma: A Pilot Study. (PMID:34889813)
• Co-Mutation of FAT3 and LRP1B in Lung Adenocarcinoma Defines a Unique Subset Correlated With the Efficacy of Immunotherapy. (PMID:35069585)
• Downregulation of Low-density lipoprotein receptor-related protein 1B (LRP1B) inhibits the progression of hepatocellular carcinoma cells by activating the endoplasmic reticulum stress signaling pathway. (PMID:35389768)
• LRP1B mutation associates with increased tumor mutation burden and inferior prognosis in liver hepatocellular carcinoma. (PMID:35777027)
• Analysis of copy number alterations in bladder cancer stem cells revealed a prognostic role of LRP1B. (PMID:35841413)
• Association between the LRP1B and APOE loci and the development of Parkinson’s disease dementia. (PMID:36348503)
• Integrative analysis of the proteome and transcriptome in gastric cancer identified LRP1B as a potential biomarker. (PMID:36606427)
• MicroRNA-196a-5p targeting LRP1B modulates phenotype of thyroid carcinoma cells. (PMID:36916542)
• LRP1B-a prognostic marker in tubo-ovarian high-grade serous carcinoma. (PMID:37742945)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrp1ba	ENSDARG00000004789
danio_rerio	lrp1bb	ENSDARG00000061517
mus_musculus	Lrp1b	ENSMUSG00000049252
rattus_norvegicus	Lrp1b	ENSRNOG00000030243
drosophila_melanogaster	arr	FBGN0000119

Paralogs (14): LRP6 (ENSG00000070018), LRP2 (ENSG00000081479), NID2 (ENSG00000087303), NID1 (ENSG00000116962), LRP1 (ENSG00000123384), LDLR (ENSG00000130164), LRP3 (ENSG00000130881), LRP4 (ENSG00000134569), EGF (ENSG00000138798), LRP12 (ENSG00000147650), VLDLR (ENSG00000147852), LRP8 (ENSG00000157193), LRP5 (ENSG00000162337), LRP10 (ENSG00000197324)

Protein

Protein identifiers

Low-density lipoprotein receptor-related protein 1B — Q9NZR2 (reviewed: Q9NZR2)

Alternative names: Low-density lipoprotein receptor-related protein-deleted in tumor

All UniProt accessions (4): E7ERG8, Q9NZR2, H0Y7T7, H7C0A8

UniProt curated annotations — full annotation on UniProt →

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

Subunit / interactions. Binds LRPAP1, PLAU, PLAT and SERPINE1; binding is followed by internalization and degradation of the ligands.

Subcellular location. Membrane.

Tissue specificity. Expressed in thyroid gland and in salivary gland, as well as in adult and fetal brain.

Miscellaneous. The gene is preferentially inactivated in one histological type of lung cancer (non-small cell lung cancer (NSCLC)). May thus play an important role in tumorigenesis of NSCLCs.

Similarity. Belongs to the LDLR family.

RefSeq proteins (1): NP_061027* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000033	LDLR_classB_rpt	Repeat
IPR000152	EGF-type_Asp/Asn_hydroxyl_site	PTM
IPR000742	EGF	Domain
IPR001881	EGF-like_Ca-bd_dom	Domain
IPR002172	LDrepeatLR_classA_rpt	Repeat
IPR009030	Growth_fac_rcpt_cys_sf	Homologous_superfamily
IPR011042	6-blade_b-propeller_TolB-like	Homologous_superfamily
IPR018097	EGF_Ca-bd_CS	Conserved_site
IPR023415	LDLR_class-A_CS	Conserved_site
IPR026823	cEGF	Domain
IPR032485	LRP1-like_beta_prop	Domain
IPR036055	LDL_receptor-like_sf	Homologous_superfamily
IPR049883	NOTCH1_EGF-like	Domain
IPR051221	LDLR-related	Family

Pfam: PF00008, PF00057, PF00058, PF07645, PF12662, PF14670, PF16472

UniProt features (288 total): disulfide bond 137, domain 54, glycosylation site 46, repeat 34, sequence variant 6, sequence conflict 4, topological domain 2, short sequence motif 2, signal peptide 1, chain 1, transmembrane region 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

No AlphaFold model available for Q9NZR2 — AlphaFold DB does not currently provide models for proteins above ~3000 aa.

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (137): 32–45, 39–58, 52–69, 77–90, 84–103, 97–113, 120–129, 125–138, 140–153, 159–169, 165–178, 180–193, 798–809, 805–818, 820–833, 845–857, 852–870, 864–881, 886–898, 893–911 …

Glycosylation sites (46): 443, 725, 758, 829, 883, 919, 1041, 1089, 1145, 1209, 1298, 1502, 1549, 1636, 1754, 1816, 1921, 1983, 2105, 2458 …

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 175 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, AP1_01, ACTACCT_MIR196A_MIR196B, TGCTGCT_MIR15A_MIR16_MIR15B_MIR195_MIR424_MIR497, NKX25_02, TATTATA_MIR374, GOBP_VESICLE_MEDIATED_TRANSPORT, DING_LUNG_CANCER_BY_MUTATION_RATE, chr2q22, DELYS_THYROID_CANCER_DN, TGANTCA_AP1_C, TGACATY_UNKNOWN, NRF2_Q4, DOUGLAS_BMI1_TARGETS_DN, AACTTT_UNKNOWN

GO Biological Process (4): receptor-mediated endocytosis (GO:0006898), protein transport (GO:0015031), endocytosis (GO:0006897), vesicle-mediated transport (GO:0016192)

GO Molecular Function (3): low-density lipoprotein particle receptor activity (GO:0005041), calcium ion binding (GO:0005509), protein binding (GO:0005515)

GO Cellular Component (3): plasma membrane (GO:0005886), signaling receptor complex (GO:0043235), membrane (GO:0016020)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
transport	2
endocytosis	1
intracellular protein localization	1
establishment of protein localization	1
vesicle budding from membrane	1
membrane invagination	1
vesicle-mediated transport	1
import into cell	1
cellular process	1
low-density lipoprotein particle binding	1
lipoprotein particle receptor activity	1
metal ion binding	1
binding	1
membrane	1
cell periphery	1
protein-containing complex	1
cellular anatomical structure	1

Protein interactions and networks

STRING

1878 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRP1B	MUC16	Q8WXI7	774
LRP1B	CSMD3	Q7Z407	767
LRP1B	PTPRD	P23468	727
LRP1B	PCLO	Q9Y6V0	654
LRP1B	SYNE1	Q8NF91	621
LRP1B	TTN	Q8WZ42	606
LRP1B	ZFHX4	Q86UP3	600
LRP1B	KMT2D	O14686	599
LRP1B	TP53	P04637	593
LRP1B	APP	P05067	587
LRP1B	ARID1A	O14497	584
LRP1B	USH2A	O75445	583
LRP1B	KMT2C	Q8NEZ4	582
LRP1B	PIK3CA	P42336	581
LRP1B	SPTA1	P02549	580

IntAct

81 interactions, top by confidence:

A	B	Type	Score
ZNF8	TRIM28	psi-mi:“MI:0914”(association)	0.730
CHRNA4	LRP1B	psi-mi:“MI:0915”(physical association)	0.560
PPP2R2A	LRP1B	psi-mi:“MI:0915”(physical association)	0.560
APP	LRP1B	psi-mi:“MI:0915”(physical association)	0.560
SCGB1D1	FAM234B	psi-mi:“MI:0914”(association)	0.530
ZNF169	ZNF316	psi-mi:“MI:0914”(association)	0.530
ZNF331	USP9Y	psi-mi:“MI:0914”(association)	0.530
CHRDL1	ZZEF1	psi-mi:“MI:0914”(association)	0.530
LRPAP1	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF563	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF224	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF517	GGPS1	psi-mi:“MI:0914”(association)	0.530
FBXO2	TMEM131L	psi-mi:“MI:0914”(association)	0.530
ZFP41	LRP4	psi-mi:“MI:0914”(association)	0.530
ZNF408	LRP4	psi-mi:“MI:0914”(association)	0.530
LRP1B	HNRNPCL2	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (96): LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS), LRP1B (Affinity Capture-MS)

ESM2 similar proteins: A2ARV4, C0HL13, F1RWC3, G3V928, O57409, O60494, O70244, P01130, P01131, P01132, P07522, P20063, P35950, P35951, P35952, P35953, P41413, P46023, P56677, P78504, P98155, P98156, P98157, P98158, P98163, P98164, P98165, P98166, Q04592, Q04833, Q07954, Q0IIH7, Q20176, Q28832, Q63722, Q6X0I2, Q90Y57, Q91ZX7, Q92673, Q92824

Diamond homologs: A1Z877, O08523, O75443, O75581, O88572, P01131, P20063, P35950, P35951, P35952, Q14114, Q28832, Q5ZQU0, Q6X0I2, Q70E20, Q8TER0, Q91VN0, Q98931, Q99087, Q9JI18, Q9NZR2, Q9YH85, A2AR95, A2ARV4, A4IHY6, C0HL13, E9Q6D8, G3V928, O75074, O75197, O88204, O88307, P0DSP1, P13671, P35953, P56677, P61134, P61135, P86091, P98153

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
LRP1B	down-regulates	Proliferation
LRP1B	“down-regulates activity”	DVL2	binding

Disease & clinical

Cancer significance

From CIViC — curated cancer-variant interpretation:

LRP1B is a putative tumor suppressor and a member of the low-density lipoprotein (LDL) receptor family. The LDL receptor family have roles related to clearance of extracellular ligand and are proposed to be involved in extracellular signal transduction. silencing and down-expression of LRP1B as been observed in renal cell carcinoma and thyroid cancer. Further Deletion of LRP1B has been associated with chemotherapy resistance in high-grade serous cancers.

From intOGen — cancer-driver classification: activating (oncogene-like) across 40 cancer types — AML, BCC, BRCA, CCRCC, CHOL, CLLSLL, COAD, COADREAD, CSCC, ESCA, GB, GBM…(+28 more).

Clinical variants and AI predictions

ClinVar

714 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	6
Uncertain significance	477
Likely benign	82
Benign	72

Top pathogenic / likely-pathogenic (6)

Variant ID	HGVS	Classification
2584748	NM_018557.3(LRP1B):c.4357C>A (p.Leu1453Ile)	Likely pathogenic
2584749	NM_018557.3(LRP1B):c.3978T>C (p.Ile1326=)	Likely pathogenic
2584750	NM_018557.3(LRP1B):c.5062A>G (p.Ile1688Val)	Likely pathogenic
2584751	NM_018557.3(LRP1B):c.12253A>G (p.Ile4085Val)	Likely pathogenic
2584752	NM_018557.3(LRP1B):c.3699C>A (p.His1233Gln)	Likely pathogenic
2584753	NM_018557.3(LRP1B):c.3581G>T (p.Gly1194Val)	Likely pathogenic

SpliceAI

9381 predictions. Top by Δscore:

Variant	Effect	Δscore
2:140247084:A:AC	donor_gain	1.0000
2:140247085:C:CC	donor_gain	1.0000
2:140270235:TACT:T	donor_loss	1.0000
2:140270236:AC:A	donor_loss	1.0000
2:140270237:C:CG	donor_loss	1.0000
2:140270238:TCACA:T	donor_loss	1.0000
2:140270239:CAC:C	donor_loss	1.0000
2:140270240:A:AC	donor_gain	1.0000
2:140270240:A:T	donor_loss	1.0000
2:140270241:C:CC	donor_gain	1.0000
2:140270241:CAGA:C	donor_gain	1.0000
2:140270342:TGCAG:T	acceptor_gain	1.0000
2:140270347:C:CC	acceptor_gain	1.0000
2:140274422:A:AC	donor_gain	1.0000
2:140274423:C:CC	donor_gain	1.0000
2:140274423:CTTG:C	donor_gain	1.0000
2:140274482:CACA:C	donor_gain	1.0000
2:140274488:TGTCA:T	donor_gain	1.0000
2:140274594:CACGT:C	acceptor_gain	1.0000
2:140274595:ACGT:A	acceptor_gain	1.0000
2:140274595:ACGTC:A	acceptor_loss	1.0000
2:140274596:CGT:C	acceptor_gain	1.0000
2:140274596:CGTC:C	acceptor_gain	1.0000
2:140274597:GTCT:G	acceptor_loss	1.0000
2:140274598:TC:T	acceptor_loss	1.0000
2:140274599:C:CC	acceptor_gain	1.0000
2:140274599:CTAG:C	acceptor_loss	1.0000
2:140274600:T:A	acceptor_loss	1.0000
2:140297806:A:AC	donor_gain	1.0000
2:140297807:C:CC	donor_gain	1.0000

AlphaMissense

30830 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
2:140442533:C:G	C3462S	1.000
2:140442534:A:T	C3462S	1.000
2:140442590:C:G	C3443S	1.000
2:140442591:A:T	C3443S	1.000
2:140444377:C:G	C3416S	1.000
2:140444378:A:T	C3416S	1.000
2:140444591:A:C	C3382W	1.000
2:140444592:C:G	C3382S	1.000
2:140444592:C:T	C3382Y	1.000
2:140444593:A:G	C3382R	1.000
2:140444593:A:T	C3382S	1.000
2:140444609:A:C	C3376W	1.000
2:140444610:C:G	C3376S	1.000
2:140444610:C:T	C3376Y	1.000
2:140444611:A:G	C3376R	1.000
2:140444611:A:T	C3376S	1.000
2:140444631:C:G	C3369S	1.000
2:140444632:A:G	C3369R	1.000
2:140444632:A:T	C3369S	1.000
2:140444646:C:G	C3364S	1.000
2:140444647:A:T	C3364S	1.000
2:140444652:A:C	F3362C	1.000
2:140444667:C:G	C3357S	1.000
2:140444668:A:G	C3357R	1.000
2:140444668:A:T	C3357S	1.000
2:140450599:A:C	C3342W	1.000
2:140450600:C:G	C3342S	1.000
2:140450600:C:T	C3342Y	1.000
2:140450601:A:G	C3342R	1.000
2:140450601:A:T	C3342S	1.000

dbSNP variants (sampled 300 via entrez): RS1000000436 (2:140957190 T>C), RS1000004448 (2:141933162 C>T), RS1000005728 (2:140670323 G>C,T), RS1000006279 (2:141275327 C>A), RS1000007364 (2:140421309 T>G), RS1000010881 (2:140626491 T>C), RS1000012335 (2:141952923 A>G), RS1000013789 (2:142035788 C>T), RS1000014962 (2:141830246 A>G), RS1000017788 (2:141624284 T>C), RS1000018844 (2:141463367 C>G), RS1000020317 (2:140444912 CAT>C), RS1000022085 (2:141571383 A>T), RS1000022791 (2:140994850 G>T), RS1000024606 (2:141746372 T>C)

Disease associations

OMIM: gene MIM:608766 | disease phenotypes: MIM:189800

GenCC curated gene-disease

Mondo (3): preeclampsia (MONDO:0005081), prostate cancer (MONDO:0008315), cancer (MONDO:0004992)

Orphanet (2): Preeclampsia (Orphanet:275555), Familial prostate cancer (Orphanet:1331)

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

54 associations (top):

Study	Trait	p-value
GCST000378_1	Aging	6.000000e-09
GCST000657_4	Optic nerve measurement (disc area)	3.000000e-07
GCST000824_17	Erectile dysfunction and prostate cancer treatment	2.000000e-06
GCST000830_26	Body mass index	1.000000e-10
GCST000880_28	Menarche (age at onset)	2.000000e-07
GCST002126_11	Periodontitis (CDC/AAP)	5.000000e-06
GCST002541_40	Menarche (age at onset)	7.000000e-10
GCST002587_2	Blood pressure (smoking interaction)	3.000000e-07
GCST002759_26	Motion sickness	3.000000e-09
GCST002759_32	Motion sickness	8.000000e-09
GCST002783_266	Body mass index	2.000000e-08
GCST002783_621	Body mass index	2.000000e-08
GCST002783_67	Body mass index	4.000000e-07
GCST002875_160	Diisocyanate-induced asthma	5.000000e-06
GCST003123_7	Severe influenza A (H1N1) infection	6.000000e-21
GCST003125_14	Influenza A (H1N1) infection	4.000000e-08
GCST003139_14	Glomerular filtration rate in chronic kidney disease	7.000000e-06
GCST003262_594	Post bronchodilator FEV1	2.000000e-06
GCST003542_161	Night sleep phenotypes	3.000000e-06
GCST003832_8	Asthma (childhood onset)	5.000000e-06
GCST003944_33	Hepcidin/ferritin ratio	7.000000e-06
GCST004718_9	Congenital heart disease (inherited effect)	7.000000e-07
GCST004744_29	Lung adenocarcinoma	3.000000e-07
GCST004904_17	Body mass index	6.000000e-09
GCST005174_3	Coronary artery calcified atherosclerotic plaque score in type 2 diabetes	1.000000e-06
GCST005175_2	Coronary artery calcified atherosclerotic plaque (90 or 130 HU threshold) in type 2 diabetes	3.000000e-07
GCST005926_6	Peak cortisol response to low dose short synacthen test in corticosteroid treated asthma	5.000000e-08
GCST006484_20	Type 2 diabetes	8.000000e-07
GCST007324_109	Adventurousness	1.000000e-08
GCST007324_135	Adventurousness	1.000000e-09

EFO canonical traits (27, from GWAS)

EFO ID	Trait name
EFO:0022597	aging
EFO:0004340	body mass index
EFO:0004703	age at menarche
EFO:0006335	systolic blood pressure
EFO:0006526	pack-years measurement
EFO:0006928	motion sickness
EFO:0006995	response to diisocyanate
EFO:1001488	influenza A (H1N1)
EFO:0004314	forced expiratory volume
EFO:0007901	hepcidin:ferritin ratio
EFO:0004723	coronary artery calcification
EFO:0005843	cortisol measurement
EFO:0009175	response to synacthen
EFO:0008579	risk-taking behaviour
EFO:0009369	diffusing capacity of the lung for carbon monoxide
EFO:0009892	facial attractiveness measurement
EFO:0008475	mood instability measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004363	information processing speed
EFO:0009658	adverse effect
EFO:0008320	white matter volume measurement
EFO:0009695	household income
EFO:0010816	dietary fat liking measurement
EFO:0009819	comparative body size at age 10, self-reported
EFO:0004952	disease recurrence
EFO:0008343	sex interaction measurement

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D011225	Pre-Eclampsia	C12.050.703.395.249
D011471	Prostatic Neoplasms	C04.588.945.440.770; C12.100.500.260.750; C12.100.500.565.625; C12.200.294.260.750; C12.200.294.565.625; C12.200.758.409.750; C12.900.619.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

Clinical evidence (CIViC)

Drug × variant × indication: 3 predictive associations from 3 curated evidence items; also 1 prognostic.

Variant	Therapy	Indication	Effect	Level	CIViC
LRP1B Loss-of-function	Immune Checkpoint Inhibitor	Solid Tumor	Sensitivity/Response	CIViC B	EID12252
LRP1B Loss-of-function	Immune Checkpoint Inhibitor	Lung Adenocarcinoma	Sensitivity/Response	CIViC B	EID12652
LRP1B Exon 12-22 Deletion	Doxorubicin	Ovarian Cancer	Resistance	CIViC D	EID679

PharmGKB: 1 entry (VIP=true, CPIC=false)

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs874295	LRP1B		0.00	0

CTD chemical–gene interactions

19 total (human), top 19 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression, decreases methylation, increases methylation, affects methylation	4
Aflatoxin B1	affects methylation, decreases expression, decreases methylation	4
aristolochic acid I	decreases expression	1
2,4,6-tribromophenol	increases expression	1
methyleugenol	decreases expression	1
bisphenol A	increases expression	1
decabromobiphenyl ether	decreases expression	1
S-(1,2-dichlorovinyl)cysteine	affects response to substance, increases expression	1
2,2’,4,4’-tetrabromodiphenyl ether	decreases expression	1
pentabrominated diphenyl ether 100	decreases expression	1
hexabrominated diphenyl ether 153	decreases expression	1
theaflavin-3,3’-digallate	affects expression	1
Carbamazepine	affects expression	1
Cytarabine	decreases expression	1
Lipopolysaccharides	increases expression, affects response to substance	1
Phthalic Acids	increases methylation	1
Valproic Acid	affects expression	1
1-Methyl-4-phenylpyridinium	decreases expression	1
Okadaic Acid	decreases expression	1

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00117546	PHASE4	UNKNOWN	Cardiovascular and Autonomic Reactivity in Women With a History of Pre-eclampsia
NCT00567957	PHASE4	UNKNOWN	Remifentanil for General Anesthesia in Preeclamptics
NCT01030627	PHASE4	COMPLETED	Treatment Approaches to Preeclampsia
NCT01352234	PHASE4	COMPLETED	Comparison of Doses of Acetylsalicylic Acid in Women With Previous History of Preeclampsia
NCT01361425	PHASE4	UNKNOWN	Anti-Hypertensive Treatment In Stable Pregnant Women With Severe Pre-Eclampsia (Metildopape)
NCT01729468	PHASE4	COMPLETED	Prevention of Pre-eclampsia and SGA by Low-Dose Aspirin in Nulliparous Women With Abnormal First-trimester Uterine Artery Dopplers
NCT01761916	PHASE4	COMPLETED	Clonidine Versus Captopril for Treatment of Postpartum Very High Blood Pressure
NCT01912677	PHASE4	COMPLETED	Oral Antihypertensive Regimens for Management of Hypertension in Pregnancy
NCT02025426	PHASE4	TERMINATED	Phenylephrine Versus Ephedrine in Pre-eclampsia
NCT02091401	PHASE4	COMPLETED	A Trial Comparing Treatment With the Springfusor Infusion Pump to the IV Magnesium Sulfate Regimen
NCT02163655	PHASE4	COMPLETED	Diuretics for Postpartum High Blood Pressure in Preeclampsia
NCT02338687	PHASE4	COMPLETED	Low Dose Calcium to Prevent Preeclampsia
NCT02396030	PHASE4	TERMINATED	Different Schemes of Magnesium Sulfate for Preeclampsia
NCT02531490	PHASE4	UNKNOWN	Early Vascular Adjustments During Hypertensive Pregnancy
NCT02699827	PHASE4	COMPLETED	Adding MgSO4 to Epidural Levobupivacaine in CS for Patients With Preeclampsia
NCT02835339	PHASE4	COMPLETED	Magnesium Sulfate in Obese Preeclamptics
NCT02891174	PHASE4	COMPLETED	The Effect of Ibuprofen on Post-partum Blood Pressure in Women With Hypertensive Disorders of Pregnancy
NCT02911701	PHASE4	COMPLETED	Effect of Acetaminophen on Postpartum Blood Pressure Control in Preeclampsia With Severe Features
NCT03171480	PHASE4	COMPLETED	Use of Nitrous Oxide Donor for Labor Induction in Women With PreEclampsia
NCT03233880	PHASE4	UNKNOWN	Impact of Antichlamydial Treatment on the Rate of Preeclampsia
NCT03237000	PHASE4	UNKNOWN	Effect of Administering Intravenous Magnesium Sulfate on Fetal Cardiotocography and Neonatal Outcome in Preeclamptic Patients
NCT03506724	PHASE4	COMPLETED	Response to Anti-hypertensives in Pregnant and Postpartum Patients
NCT03674606	PHASE4	COMPLETED	Trial of Early Screening Test for Pre-eclampsia and Growth Restriction
NCT03735433	PHASE4	TERMINATED	The Effect of Two Aspirin Dosing Strategies for Obese Women at High Risk for Preeclampsia
NCT03824119	PHASE4	UNKNOWN	Postpartum NSAIDS and Maternal Hypertension
NCT04051567	PHASE4	UNKNOWN	Low-dose Aspirin for Prevention of Adverse Pregnancy Outcomes in Twin Pregnancies
NCT04077853	PHASE4	COMPLETED	Progesterone in Expectantly Managed Early-onset Preeclampsia
NCT04158830	PHASE4	WITHDRAWN	Aspirin (ASA) Therapy and Preeclampsia Prevention
NCT04424693	PHASE4	UNKNOWN	Comparing the Incidence of Preeclampsia Between Pregnant Women Receiving Tdap Vaccinations at Week 28 or at Week 36
NCT04631627	PHASE4	UNKNOWN	Early Prediction and Randomised Prevention of Preeclampsia With Low Dose Aspirin in Chinese Cohort
NCT04656665	PHASE4	UNKNOWN	The Effectiveness of Aspirin on Preventing Pre-eclampsia
NCT04797949	PHASE4	WITHDRAWN	Adherence to Universal Aspirin Compared to Screening Indicated Aspirin for Prevention of Preeclampsia
NCT04908982	PHASE4	UNKNOWN	Aspirin for the Prevention of Preeclampsia in Women With Stage 1 Hypertension
NCT05221164	PHASE4	UNKNOWN	162 mg of Aspirin for Prevention of Preeclampsia
NCT05294952	PHASE4	UNKNOWN	co Ihibtory Receptor in Preeclampsia
NCT05514847	PHASE4	ACTIVE_NOT_RECRUITING	Low Dose Aspirin for Preterm Preeclampsia Preventionmg/day Dose in High-risk Patients
NCT05586373	PHASE4	COMPLETED	Ibuprofen vs Dipyrone After C-section in Preeclampsia
NCT06069102	PHASE4	COMPLETED	Optimal Blood Pressure Treatment Thresholds Postpartum
NCT06107335	PHASE4	NOT_YET_RECRUITING	Effect of Albumin Versus Routine Care on Hemodynamic Response and Stability in Patients With Preeclampsia Guided by a Non-invasive Hemodynamic Monitoring System During Cesarean Delivery With Spinal Anesthesia
NCT06281665	PHASE4	RECRUITING	Treatment With Aspirin After Preeclampsia: TAP Trial