VPREB3

Summary

VPREB3 (V-set pre-B cell surrogate light chain 3, HGNC:12710) is a protein-coding gene on chromosome 22q11.23, encoding Pre-B lymphocyte protein 3 (Q9UKI3). Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells.

The protein encoded by this gene is the human ortholog of the mouse VpreB3 (8HS20) protein, is thought to be involved in B-cell maturation, and may play a role in assembly of the pre-B cell receptor (pre-BCR). While the role of this protein in B-cell development has not yet been elucidated, studies with the chicken ortholog of this protein have found that when overexpressed, this protein localizes to the endoplasmic reticulum. The mouse ortholog of this protein has been shown to associate with membrane mu heavy chains early in the course of pre-B cell receptor biosynthesis. Expression of this gene has been observed in some lymphomas.

Source: NCBI Gene 29802 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 33 total — 1 pathogenic
• MANE Select transcript: NM_013378

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12710
Approved symbol	VPREB3
Name	V-set pre-B cell surrogate light chain 3
Location	22q11.23
Locus type	gene with protein product
Status	Approved
Aliases	8HS20
Ensembl gene	ENSG00000128218
Ensembl biotype	protein_coding
OMIM	605017
Entrez	29802

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000248948, ENST00000398465

RefSeq mRNA: 1 — MANE Select: NM_013378 NM_013378

CCDS: CCDS13813

Canonical transcript exons

ENST00000248948 — 2 exons

Exon	Start	End
ENSE00001153626	23754315	23754425
ENSE00001952800	23752743	23753198

Expression profiles

Bgee: expression breadth ubiquitous, 167 present calls, max score 92.65.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 4.3756 / max 755.3778, expressed in 115 samples.

FANTOM5 promoters (2 alternative TSS)

Promoter ID	TPM avg	Samples expressed
193329	4.2307	106
193330	0.1449	30

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
lymph node	UBERON:0000029	92.65	gold quality
spleen	UBERON:0002106	92.11	gold quality
vermiform appendix	UBERON:0001154	89.73	gold quality
granulocyte	CL:0000094	88.09	gold quality
ileal mucosa	UBERON:0000331	87.20	gold quality
caecum	UBERON:0001153	82.73	gold quality
bone marrow	UBERON:0002371	82.69	gold quality
mucosa of transverse colon	UBERON:0004991	80.48	gold quality
small intestine Peyer’s patch	UBERON:0003454	80.26	gold quality
bone marrow cell	CL:0002092	79.66	gold quality
blood	UBERON:0000178	77.52	gold quality
right adrenal gland	UBERON:0001233	76.38	gold quality
right adrenal gland cortex	UBERON:0035827	76.24	gold quality
tonsil	UBERON:0002372	76.04	gold quality
left adrenal gland	UBERON:0001234	75.82	gold quality
adrenal gland	UBERON:0002369	75.18	gold quality
small intestine	UBERON:0002108	74.91	gold quality
left adrenal gland cortex	UBERON:0035825	73.19	gold quality
adrenal cortex	UBERON:0001235	72.51	gold quality
rectum	UBERON:0001052	70.58	gold quality
adrenal tissue	UBERON:0018303	69.62	gold quality
superficial temporal artery	UBERON:0001614	68.76	gold quality
epithelium of nasopharynx	UBERON:0001951	68.58	gold quality
nasopharynx	UBERON:0001728	68.57	silver quality
colonic epithelium	UBERON:0000397	68.07	gold quality
gall bladder	UBERON:0002110	67.50	gold quality
right lobe of liver	UBERON:0001114	64.44	gold quality
trabecular bone tissue	UBERON:0002483	64.37	gold quality
gastrocnemius	UBERON:0001388	64.27	gold quality
corpus epididymis	UBERON:0004359	63.52	gold quality

Single-cell (SCXA)

Detected in 21 experiment(s), a significant marker in 20.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	3284.57
E-MTAB-10042	yes	2898.36
E-CURD-112	yes	2836.78
E-MTAB-9906	yes	2619.38
E-HCAD-4	yes	2078.04
E-MTAB-9067	yes	2047.87
E-MTAB-7407	yes	1973.55
E-MTAB-8221	yes	1555.87
E-HCAD-10	yes	1449.44
E-CURD-122	yes	1418.48
E-MTAB-9801	yes	942.50
E-ANND-5	yes	685.89
E-CURD-88	yes	676.36
E-HCAD-32	yes	672.83
E-GEOD-130473	yes	412.63

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

9 targeting VPREB3, 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-126-5P	100.00	72.71	3180
HSA-MIR-3919	99.87	69.45	2489
HSA-MIR-561-3P	99.64	70.90	3647
HSA-MIR-24-3P	99.59	69.97	1934
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-4708-3P	99.51	67.99	870
HSA-MIR-653-5P	99.46	67.35	1300
HSA-MIR-650	99.45	65.77	1309
HSA-MIR-660-5P	98.16	68.27	680

Literature-anchored findings (GeneRIF, showing 7)

• VpreB3 may play a role in the regulation of the maturation and secretion of free IgLC in chicken B cells (PMID:14670953)
• the present study confirms the co-existence of surrogate lambda and kappa receptors that are proposed to work in concert to promote B lymphocyte maturation. (PMID:15757909)
• Data show that the absence of VpreB3 is virtually always associated with wild-type c-MYC alleles. (PMID:20823132)
• the combined immunohistochemical detection of VPREB3 and ID3 is applicable to the routine diagnostic in case of mature aggressive B-cell lymphomas. (PMID:24493312)
• A possible role for VPREB3 in aldosterone biosynthesis. (PMID:25861052)
• levels of VPREB3 mRNA in aldosterone-producing adenomas directly correlate to plasma aldosterone concentrations in peripheral blood of respective patients (PMID:25861052)
• mouse VpreB3 associates with mu heavy chains early in pre-B cell receptor biosynthesis (PMID:8491176)

Cross-species orthologs

2 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vpreb3	ENSMUSG00000000903
rattus_norvegicus		ENSRNOG00000075030

Paralogs (93): VPREB1 (ENSG00000169575), IGKV4-1 (ENSG00000211598), IGKV5-2 (ENSG00000211599), IGKV6-21 (ENSG00000211611), IGKV2D-26 (ENSG00000211623), IGKV3D-20 (ENSG00000211625), IGKV6D-41 (ENSG00000211626), IGKV3D-11 (ENSG00000211632), IGKV1D-42 (ENSG00000211633), IGLV4-69 (ENSG00000211637), IGLV8-61 (ENSG00000211638), IGLV4-60 (ENSG00000211639), IGLV6-57 (ENSG00000211640), IGLV11-55 (ENSG00000211641), IGLV10-54 (ENSG00000211642), IGLV5-52 (ENSG00000211643), IGLV1-51 (ENSG00000211644), IGLV1-50 (ENSG00000211645), IGLV5-48 (ENSG00000211647), IGLV1-47 (ENSG00000211648), IGLV7-46 (ENSG00000211649), IGLV5-45 (ENSG00000211650), IGLV1-44 (ENSG00000211651), IGLV7-43 (ENSG00000211652), IGLV1-40 (ENSG00000211653), IGLV5-37 (ENSG00000211654), IGLV1-36 (ENSG00000211655), IGLV2-33 (ENSG00000211656), IGLV3-32 (ENSG00000211657), IGLV3-27 (ENSG00000211658), IGLV3-25 (ENSG00000211659), IGLV2-23 (ENSG00000211660), IGLV3-22 (ENSG00000211661), IGLV3-21 (ENSG00000211662), IGLV3-19 (ENSG00000211663), IGLV2-18 (ENSG00000211664), IGLV3-16 (ENSG00000211665), IGLV2-14 (ENSG00000211666), IGLV3-12 (ENSG00000211667), IGLV2-11 (ENSG00000211668)

Protein

Protein identifiers

Pre-B lymphocyte protein 3 — Q9UKI3 (reviewed: Q9UKI3)

Alternative names: N27C7-2, Protein VPreB3

All UniProt accessions (2): Q9UKI3, A8MX21

UniProt curated annotations — full annotation on UniProt →

Function. Associates with the Ig-mu chain to form a molecular complex that is expressed on the surface of pre-B-cells.

Tissue specificity. Expressed in B-cell precursors. Expressed in fetal liver, bone marrow, spleen and lymph node.

Similarity. Belongs to the immunoglobulin superfamily.

RefSeq proteins (1): NP_037510* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003599	Ig_sub	Domain
IPR007110	Ig-like_dom	Domain
IPR013106	Ig_V-set	Domain
IPR013783	Ig-like_fold	Homologous_superfamily
IPR036179	Ig-like_dom_sf	Homologous_superfamily
IPR050150	IgV_Light_Chain	Family

Pfam: PF07686

UniProt features (5 total): signal peptide 1, chain 1, domain 1, disulfide bond 1, sequence variant 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKI3-F1	86.08	0.71

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 (1): 40–115

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-202733	Cell surface interactions at the vascular wall

MSigDB gene sets: 153 (showing top): GSE37336_LY6C_POS_VS_NEG_NAIVE_CD4_TCELL_DN, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, HOWLIN_PUBERTAL_MAMMARY_GLAND, SENGUPTA_NASOPHARYNGEAL_CARCINOMA_DN, HEN1_01, OCT1_06, SABATES_COLORECTAL_ADENOMA_DN, OCT1_B, MORI_MATURE_B_LYMPHOCYTE_DN, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, VANTVEER_BREAST_CANCER_BRCA1_UP, GOCC_IMMUNOGLOBULIN_COMPLEX, SMID_BREAST_CANCER_LUMINAL_B_DN, PASQUALUCCI_LYMPHOMA_BY_GC_STAGE_DN, YATGNWAAT_OCT_C

GO Biological Process (1): immune response (GO:0006955)

GO Molecular Function (0):

GO Cellular Component (3): extracellular region (GO:0005576), endoplasmic reticulum (GO:0005783), immunoglobulin complex (GO:0019814)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Hemostasis	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
immune system process	1
response to stimulus	1
cellular anatomical structure	1
cytoplasm	1
endomembrane system	1
intracellular membrane-bounded organelle	1
protein-containing complex	1

Protein interactions and networks

STRING

1131 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPREB3	IGLL1	P15814	890
VPREB3	FCRLA	Q7L513	653
VPREB3	CD79A	P11912	651
VPREB3	CD79B	P40259	646
VPREB3	MS4A1	P08984	500
VPREB3	CD72	P21854	487
VPREB3	FCMR	O60667	434
VPREB3	MS4A2	Q01362	418
VPREB3	GNG3	P29798	407
VPREB3	POU2AF1	Q16633	400
VPREB3	CAMSAP1	Q5T5Y3	400
VPREB3	LRRC75B	Q2VPJ9	395
VPREB3	CD200	P41217	386
VPREB3	JCHAIN	P01591	383
VPREB3	PHF6	Q8IWS0	380

IntAct

0 interactions, top by confidence:

BioGRID (2): VPREB3 (Co-fractionation), VPREB3 (Co-fractionation)

ESM2 similar proteins: A0A075B6H8, A0A075B6I4, A0A075B6J2, A0A075B6J6, A0A075B6K0, A0A075B6K2, A0A075B6K4, A0A075B6K5, A0A075B6K6, A0A075B6P5, A0A087WW87, A0A0A0MRZ7, A0A0A0MS00, A0A0A0MT36, A0A0B4J1U3, A0A0C4DH24, A0A0C4DH26, P01614, P01615, P01627, P01633, P01634, P01635, P01637, P01638, P01639, P01641, P01642, P01661, P01664, P01666, P01668, P01669, P01714, P01715, P01717, P01718, P01721, P01723, P01724

Diamond homologs: A0A075B6H7, A0A075B6H9, A0A075B6I0, A0A075B6I1, A0A075B6I3, A0A075B6I4, A0A075B6I6, A0A075B6I7, A0A075B6I9, A0A075B6J1, A0A075B6J6, A0A075B6J9, A0A075B6K0, A0A075B6K2, A0A075B6K4, A0A075B6K5, A0A075B6K6, A0A075B6S4, A0A075B6S5, A0A075B6S9, A0A087WSX0, A0A087WSY6, A0A087WSZ0, A0A0A0MRZ8, A0A0A0MRZ9, A0A0A0MS00, A0A0A0MT36, A0A0B4J1U3, A0A0B4J1Y8, A0A0B4J1Z2, A0A0B4J2D9, A0A0C4DH24, A0A0C4DH25, A0A0C4DH26, A0A0C4DH55, A0A0C4DH67, A0A0C4DH69, A0A0C4DH72, A0A0C4DH73, A0A0G2JS06

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	26
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
684901	GRCh37/hg19 22q11.22-11.23(chr22:22962196-25145601)x3	Pathogenic

SpliceAI

259 predictions. Top by Δscore:

Variant	Effect	Δscore
22:23753199:C:CC	acceptor_gain	0.9900
22:23754310:TTCA:T	donor_loss	0.9900
22:23754311:TCA:T	donor_loss	0.9900
22:23754312:CACCT:C	donor_loss	0.9900
22:23753195:GAAA:G	acceptor_gain	0.9700
22:23753197:AA:A	acceptor_gain	0.9700
22:23753197:AACT:A	acceptor_gain	0.9700
22:23753197:AACTG:A	acceptor_loss	0.9700
22:23753198:ACT:A	acceptor_loss	0.9700
22:23753198:ACTG:A	acceptor_gain	0.9700
22:23753199:C:CG	acceptor_loss	0.9700
22:23753199:CTGC:C	acceptor_gain	0.9700
22:23753200:T:A	acceptor_gain	0.9600
22:23754316:TG:T	donor_gain	0.9600
22:23753196:AAA:A	acceptor_gain	0.9500
22:23753196:AAACT:A	acceptor_gain	0.9400
22:23753194:GGAAA:G	acceptor_gain	0.9300
22:23754345:TGAGG:T	donor_gain	0.9200
22:23753121:T:A	acceptor_gain	0.9000
22:23754314:CCTGA:C	donor_gain	0.9000
22:23753195:GAAAC:G	acceptor_gain	0.8800
22:23753649:AG:A	donor_gain	0.8800
22:23753081:C:CT	acceptor_gain	0.8300
22:23753119:GCT:G	acceptor_gain	0.8300
22:23753202:C:CT	acceptor_gain	0.8300
22:23754101:TGA:T	donor_gain	0.8300
22:23753126:G:C	acceptor_gain	0.8200
22:23754313:A:AC	donor_gain	0.8000
22:23754314:C:CC	donor_gain	0.8000
22:23753120:C:G	acceptor_gain	0.7900

AlphaMissense

789 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:23752987:G:C	F87L	0.985
22:23752987:G:T	F87L	0.985
22:23752989:A:G	F87L	0.985
22:23752943:A:G	I102T	0.980
22:23752988:A:C	F87C	0.976
22:23752988:A:G	F87S	0.976
22:23752943:A:T	I102N	0.964
22:23752943:A:C	I102S	0.961
22:23753080:C:A	W56C	0.959
22:23753080:C:G	W56C	0.959
22:23753082:A:G	W56R	0.957
22:23753082:A:T	W56R	0.957
22:23752949:A:T	L100H	0.955
22:23752923:C:G	D109H	0.948
22:23752949:A:G	L100P	0.934
22:23752922:T:A	D109V	0.932
22:23752921:G:C	D109E	0.927
22:23752921:G:T	D109E	0.927
22:23752911:A:G	Y113H	0.923
22:23752922:T:G	D109A	0.923
22:23753075:T:G	Q58P	0.923
22:23752917:C:G	A111P	0.918
22:23753085:A:G	S55P	0.915
22:23752959:C:G	A97P	0.911
22:23752961:T:A	N96I	0.905
22:23752982:G:T	A89E	0.901
22:23752904:C:G	C115S	0.899
22:23752905:A:T	C115S	0.899
22:23753045:A:T	L68H	0.899
22:23753129:C:G	C40S	0.896

dbSNP variants (sampled 300 via entrez): RS1000406583 (22:23752297 C>T), RS1000631368 (22:23756214 T>A,C,G), RS1000874050 (22:23756201 G>A,T), RS1001342369 (22:23755517 C>G), RS1002293904 (22:23754230 C>A,T), RS1003257784 (22:23752784 G>A,C), RS1003298858 (22:23752973 T>C), RS1003943554 (22:23756356 A>G), RS1007093476 (22:23756024 T>C), RS1007112733 (22:23754841 T>C,G), RS1007168612 (22:23756165 C>T), RS1008094433 (22:23754535 C>G,T), RS1008167883 (22:23754749 C>T), RS1008211102 (22:23754130 C>T), RS1009092584 (22:23753262 G>T)

Disease associations

OMIM: gene MIM:605017 | 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
GCST009860_10	IgG N-glycosylation phenotypes (multivariate analysis)	1.000000e-41

EFO canonical traits (1, from GWAS)

EFO ID	Trait name
EFO:0005193	serum IgG glycosylation measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

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

CTD chemical–gene interactions

15 total (human), top 15 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	decreases expression	2
propionaldehyde	increases expression	1
pentanal	increases expression	1
CGP 52608	affects binding, increases reaction	1
2-palmitoylglycerol	increases expression	1
licochalcone B	increases expression	1
Sunitinib	increases expression	1
Atrazine	increases expression	1
Camptothecin	increases expression	1
Fluorouracil	affects expression	1
Malathion	increases expression	1
Dronabinol	increases expression	1
Tobacco Smoke Pollution	increases expression	1
Aflatoxin B1	increases methylation	1
Cadmium Chloride	decreases expression	1

Clinical trials (associated diseases)

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