LRP2BP

Summary

LRP2BP (LRP2 binding protein, HGNC:25434) is a protein-coding gene on chromosome 4q35.1, encoding LRP2-binding protein (Q9P2M1). May act as an adapter that regulates LRP2 function.

Predicted to be located in cytoplasm.

Source: NCBI Gene 55805 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 51 total
• MANE Select transcript: NM_001377440

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:25434
Approved symbol	LRP2BP
Name	LRP2 binding protein
Location	4q35.1
Locus type	gene with protein product
Status	Approved
Aliases	DKFZp761O0113
Ensembl gene	ENSG00000109771
Ensembl biotype	protein_coding
OMIM	619020
Entrez	55805

Gene structure

Transcript identifiers

Ensembl transcripts: 8 — 8 protein_coding

ENST00000328559, ENST00000505916, ENST00000510776, ENST00000511404, ENST00000904434, ENST00000927575, ENST00000943162, ENST00000943163

RefSeq mRNA: 11 — MANE Select: NM_001377440 NM_001377440, NM_001377441, NM_001377442, NM_001377443, NM_001385601, NM_001385602, NM_001385603, NM_001385604, NM_001385605, NM_001385606, NM_018409

CCDS: CCDS3840

Canonical transcript exons

ENST00000505916 — 9 exons

Exon	Start	End
ENSE00000886819	185370640	185370814
ENSE00000886820	185372856	185373079
ENSE00000886821	185374135	185374240
ENSE00000886822	185374319	185374461
ENSE00000886823	185375613	185375726
ENSE00001001436	185376909	185377018
ENSE00002029440	185394779	185395924
ENSE00002037471	185378081	185378207
ENSE00002072574	185363872	185367245

Expression profiles

Bgee: expression breadth ubiquitous, 182 present calls, max score 88.61.

FANTOM5 (CAGE): breadth broad, TPM avg 1.2743 / max 117.4482, expressed in 401 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
55249	0.8794	309
55252	0.3949	146

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	88.61	gold quality
male germ cell	CL:0000015	85.31	gold quality
right uterine tube	UBERON:0001302	85.19	gold quality
adenohypophysis	UBERON:0002196	84.45	gold quality
pituitary gland	UBERON:0000007	83.33	gold quality
right hemisphere of cerebellum	UBERON:0014890	83.28	gold quality
cerebellar hemisphere	UBERON:0002245	82.88	gold quality
cerebellar cortex	UBERON:0002129	82.76	gold quality
cerebellum	UBERON:0002037	80.32	gold quality
bronchial epithelial cell	CL:0002328	79.95	gold quality
right frontal lobe	UBERON:0002810	78.80	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	78.12	gold quality
left testis	UBERON:0004533	77.95	gold quality
right testis	UBERON:0004534	77.76	gold quality
anterior cingulate cortex	UBERON:0009835	77.50	gold quality
cingulate cortex	UBERON:0003027	77.41	gold quality
left ovary	UBERON:0002119	77.28	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	77.02	gold quality
caudate nucleus	UBERON:0001873	76.82	gold quality
amygdala	UBERON:0001876	76.79	gold quality
nucleus accumbens	UBERON:0001882	76.71	gold quality
testis	UBERON:0000473	76.46	gold quality
calcaneal tendon	UBERON:0003701	76.25	gold quality
ascending aorta	UBERON:0001496	76.23	gold quality
Brodmann (1909) area 9	UBERON:0013540	76.13	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	76.04	gold quality
thoracic aorta	UBERON:0001515	76.01	gold quality
descending thoracic aorta	UBERON:0002345	75.69	gold quality
aorta	UBERON:0000947	75.37	gold quality
popliteal artery	UBERON:0002250	75.19	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.24

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

137 targeting LRP2BP, 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-6867-5P	100.00	82.21	3464
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-8485	100.00	77.57	4731
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4425	100.00	67.59	1049
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-513B-5P	99.99	69.96	2150
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-181A-5P	99.99	72.96	2995
HSA-MIR-181B-5P	99.99	72.97	2996
HSA-MIR-181C-5P	99.99	72.95	2996
HSA-MIR-181D-5P	99.99	73.04	2997
HSA-MIR-19A-3P	99.98	75.33	2762
HSA-MIR-19B-3P	99.98	75.44	2754
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3658	99.96	73.87	4379
HSA-MIR-1468-3P	99.96	72.74	3797

Literature-anchored findings (GeneRIF, showing 5)

• both in the cytoplasm and nucleus, 4 ankyrin repeats (PMID:15809689)
• Aberrant shedding of megalin and cubilin may contribute to albuminuria in diabetes and to deficiency states of important vitamins and hormones. (PMID:19366958)
• A 56-year-old female patient with FOAR syndrome and a novel mutation is reported. (PMID:19577669)
• RP11-714G18.1 may play an athero-protective role by inhibiting vascular cell migration via RP11-714G18.1/LRP2BP/MMP1 signaling pathway. (PMID:29363163)
• Exome-Wide Association Analysis Suggests LRP2BP as a Susceptibility Gene for Endothelial Injury in Systemic Sclerosis in the Han Chinese Population. (PMID:33069728)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	lrp2bp	ENSDARG00000040478
mus_musculus	Lrp2bp	ENSMUSG00000031637
rattus_norvegicus	Lrp2bp	ENSRNOG00000011178
caenorhabditis_elegans		WBGENE00004759

Paralogs (4): SEL1L (ENSG00000071537), DELE1 (ENSG00000081791), SEL1L3 (ENSG00000091490), SEL1L2 (ENSG00000101251)

Protein

Protein identifiers

LRP2-binding protein — Q9P2M1 (reviewed: Q9P2M1)

Alternative names: Megalin-binding protein

All UniProt accessions (3): Q9P2M1, D6RGF6, G5E9Z9

UniProt curated annotations — full annotation on UniProt →

Function. May act as an adapter that regulates LRP2 function.

Subunit / interactions. Interacts with LRP2.

Subcellular location. Cytoplasm.

Isoforms (2)

UniProt ID	Names	Canonical?
Q9P2M1-1	1	yes
Q9P2M1-2	2

RefSeq proteins (11): NP_001364369, NP_001364370, NP_001364371, NP_001364372, NP_001372530, NP_001372531, NP_001372532, NP_001372533, NP_001372534, NP_001372535, NP_060879 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR006597	Sel1-like	Repeat
IPR011990	TPR-like_helical_dom_sf	Homologous_superfamily
IPR019734	TPR_rpt	Repeat
IPR052323	LRP2-binding	Family

Pfam: PF08238

UniProt features (9 total): repeat 7, chain 1, splice variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9P2M1-F1	92.51	0.84

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 96 (showing top): chr4q35, HIF1_Q3, GFI1_01, IK3_01, TGGAAA_NFAT_Q4_01, MARSON_BOUND_BY_FOXP3_STIMULATED, MARSON_BOUND_BY_FOXP3_UNSTIMULATED, DODD_NASOPHARYNGEAL_CARCINOMA_DN, PEDRIOLI_MIR31_TARGETS_UP, TAVAZOIE_METASTASIS, IL15_UP.V1_DN, IL2_UP.V1_DN, IL21_UP.V1_DN, FOXD2_TARGET_GENES, SETD7_TARGET_GENES

GO Biological Process (0):

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (1): cytoplasm (GO:0005737)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
binding	1
intracellular anatomical structure	1
cellular anatomical structure	1

Protein interactions and networks

STRING

440 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
LRP2BP	PRPSAP1	Q14558	614
LRP2BP	LRP2	P98164	596
LRP2BP	ANKRA2	Q9H9E1	532
LRP2BP	MYO9A	B2RTY4	451
LRP2BP	SEL1L2	Q5TEA6	446
LRP2BP	MAPK8IP1	Q9UQF2	424
LRP2BP	BBS7	Q8IWZ6	422
LRP2BP	EHBP1	Q8NDI1	414
LRP2BP	LRIT3	Q3SXY7	403
LRP2BP	WSCD2	Q2TBF2	388
LRP2BP	MARCHF3	Q86UD3	357
LRP2BP	MAPK8IP2	Q13387	322
LRP2BP	LRP1B	Q9NZR2	319
LRP2BP	ZNF407	Q9C0G0	311
LRP2BP	SLCO5A1	Q9H2Y9	303

IntAct

58 interactions, top by confidence:

A	B	Type	Score
LRP2BP	GSTT1	psi-mi:“MI:0915”(physical association)	0.590
SMARCC1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
P4HA3	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
HOXC8	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
FAAP20	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
GEM	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
CCDC24	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
GSTP1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
CDKL3	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
CDKN1A	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
DTX2	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
GPKOW	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
LENG1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
SCNM1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
FAM90A1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
GAS2L2	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
C1orf50	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
RAB33A	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
ZNF587	LRP2BP	psi-mi:“MI:0915”(physical association)	0.560
LRP2BP	H2BC21	psi-mi:“MI:0915”(physical association)	0.400
GEM	LRP2BP	psi-mi:“MI:0915”(physical association)	0.000
CCDC24	LRP2BP	psi-mi:“MI:0915”(physical association)	0.000
GSTP1	LRP2BP	psi-mi:“MI:0915”(physical association)	0.000
CDKL3	LRP2BP	psi-mi:“MI:0915”(physical association)	0.000
CDKN1A	LRP2BP	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (25): LRP2BP (Two-hybrid), GSTT1 (Affinity Capture-MS), LRP2BP (Two-hybrid), LRP2BP (Two-hybrid), LRP2BP (Two-hybrid), LRP2BP (Two-hybrid), LRP2BP (Two-hybrid), LRP2BP (Two-hybrid), CDKN1A (Two-hybrid), RAB33A (Two-hybrid), P4HA3 (Two-hybrid), CCDC24 (Two-hybrid), C1orf86 (Two-hybrid), SCNM1 (Two-hybrid), C1orf50 (Two-hybrid)

ESM2 similar proteins: A0AVF1, A1L1K3, A4III8, A5PLI4, A6H6E9, A8JA42, E9Q6P5, P09913, Q06AN9, Q14DN9, Q2KHY7, Q2TBM9, Q32NR4, Q3U213, Q3V172, Q4R3N2, Q4R6M4, Q4R7Z9, Q4V7F0, Q569C2, Q57ZL2, Q5PR66, Q5RE52, Q5TEA6, Q5U2N8, Q5W5X9, Q5XI05, Q5ZKK3, Q60462, Q64112, Q64282, Q66GN3, Q6AYP3, Q6IND7, Q80VM3, Q80YE7, Q86TV6, Q86TZ1, Q8BGB2, Q8BS45

Diamond homologs: A5PLI4, Q4R3N2, Q569C2, Q6IND7, Q9D4C6, Q9P2M1, Q9JZ25

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	41
Likely benign	3
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1560 predictions. Top by Δscore:

Variant	Effect	Δscore
4:185370638:A:AC	donor_gain	1.0000
4:185370639:C:CC	donor_gain	1.0000
4:185370825:G:C	acceptor_gain	1.0000
4:185370831:T:C	acceptor_gain	1.0000
4:185370831:T:TC	acceptor_gain	1.0000
4:185370833:G:C	acceptor_gain	1.0000
4:185370833:G:GC	acceptor_gain	1.0000
4:185372908:C:CA	donor_gain	1.0000
4:185372918:C:A	donor_gain	1.0000
4:185374129:CGTTA:C	donor_loss	1.0000
4:185374130:GTTA:G	donor_loss	1.0000
4:185374131:TTAC:T	donor_loss	1.0000
4:185374132:TACCT:T	donor_loss	1.0000
4:185374133:A:AC	donor_gain	1.0000
4:185374133:ACCTT:A	donor_loss	1.0000
4:185374134:C:CC	donor_gain	1.0000
4:185374236:ACAGT:A	acceptor_gain	1.0000
4:185374237:CAGT:C	acceptor_gain	1.0000
4:185374237:CAGTC:C	acceptor_gain	1.0000
4:185374238:AGT:A	acceptor_gain	1.0000
4:185374239:GT:G	acceptor_gain	1.0000
4:185374240:TC:T	acceptor_loss	1.0000
4:185374241:C:CC	acceptor_gain	1.0000
4:185374328:T:TA	donor_gain	1.0000
4:185375607:A:C	donor_gain	1.0000
4:185375611:A:AC	donor_gain	1.0000
4:185375612:C:CC	donor_gain	1.0000
4:185375612:CAG:C	donor_gain	1.0000
4:185375657:G:C	donor_gain	1.0000
4:185375724:TCC:T	acceptor_gain	1.0000

AlphaMissense

2273 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
4:185374224:C:G	A164P	0.994
4:185374236:A:G	W160R	0.993
4:185374236:A:T	W160R	0.993
4:185374176:C:A	G180W	0.992
4:185372913:A:G	L249P	0.991
4:185374373:C:T	G140E	0.991
4:185372947:C:G	A238P	0.990
4:185373034:A:G	S209P	0.990
4:185374198:A:C	S172R	0.990
4:185374198:A:T	S172R	0.990
4:185374200:T:G	S172R	0.990
4:185372950:C:G	A237P	0.989
4:185373058:C:G	A201P	0.989
4:185373070:A:G	W197R	0.989
4:185373070:A:T	W197R	0.989
4:185374175:C:T	G180E	0.989
4:185374326:C:G	A156P	0.989
4:185375653:C:T	G97E	0.989
4:185375654:C:G	G97R	0.989
4:185375654:C:T	G97R	0.989
4:185376928:C:T	G66D	0.989
4:185375711:C:G	A78P	0.988
4:185372933:G:C	N242K	0.987
4:185372933:G:T	N242K	0.987
4:185373019:C:A	G214W	0.987
4:185373064:A:G	S199P	0.987
4:185374176:C:G	G180R	0.987
4:185374176:C:T	G180R	0.987
4:185374226:G:T	A163E	0.987
4:185374374:C:G	G140R	0.987

dbSNP variants (sampled 300 via entrez): RS1000035665 (4:185381569 C>A), RS1000157102 (4:185396159 C>T), RS1000296286 (4:185378317 C>T), RS1000377933 (4:185396345 G>A,C), RS1000404904 (4:185390085 C>T), RS1000595470 (4:185395893 G>A), RS1000684036 (4:185391159 A>G), RS1000754587 (4:185389726 G>A), RS10007747 (4:185377439 C>A,G,T), RS1000832011 (4:185368191 C>T), RS1000858836 (4:185384964 T>TC), RS1000933647 (4:185396707 C>G,T), RS1000949814 (4:185395646 A>G), RS1000999807 (4:185379966 G>A), RS1001140593 (4:185391485 C>T)

Disease associations

OMIM: gene MIM:619020 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST011709_4	Systemic sclerosis	4.000000e-08

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
methylmercuric chloride	increases expression	1
sodium arsenite	increases expression	1
S-(1,2-dichlorovinyl)cysteine	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Lead	affects expression	1
Lipopolysaccharides	affects cotreatment, increases expression	1
Tobacco Smoke Pollution	decreases expression	1
Acrylamide	increases expression	1

Clinical trials (associated diseases)

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