VPREB1

Summary

VPREB1 (V-set pre-B cell surrogate light chain 1, HGNC:12709) is a protein-coding gene on chromosome 22q11.22, encoding Immunoglobulin iota chain (P12018). 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 belongs to the immunoglobulin superfamily and is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. This gene encodes the iota polypeptide chain that is associated with the Ig-mu chain to form a molecular complex which is expressed on the surface of pre-B cells. The complex is thought to regulate Ig gene rearrangements in the early steps of B-cell differentiation. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 7441 — RefSeq curated summary.

At a glance

• GWAS associations: 3
• Clinical variants (ClinVar): 1 total — 1 pathogenic
• MANE Select transcript: NM_007128

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:12709
Approved symbol	VPREB1
Name	V-set pre-B cell surrogate light chain 1
Location	22q11.22
Locus type	gene with protein product
Status	Approved
Aliases	VpreB, CD179A
Ensembl gene	ENSG00000169575
Ensembl biotype	protein_coding
OMIM	605141
Entrez	7441

Gene structure

Transcript identifiers

Ensembl transcripts: 2 — 2 protein_coding

ENST00000302273, ENST00000403807

RefSeq mRNA: 2 — MANE Select: NM_007128 NM_001303509, NM_007128

CCDS: CCDS13798

Canonical transcript exons

ENST00000403807 — 2 exons

Exon	Start	End
ENSE00001135667	22244946	22245515
ENSE00001819717	22244786	22244859

Expression profiles

Bgee: expression breadth broad, 25 present calls, max score 99.33.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 1.0909 / max 746.9056, expressed in 23 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
191220	1.0076	19
191219	0.0462	9
191216	0.0252	6
191218	0.0062	2
191217	0.0058	4

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	99.33	gold quality
bone marrow	UBERON:0002371	78.68	gold quality
bone marrow cell	CL:0002092	70.45	gold quality
trabecular bone tissue	UBERON:0002483	65.07	silver quality
decidua	UBERON:0002450	56.55	gold quality
granulocyte	CL:0000094	55.16	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
cranial nerve II	UBERON:0000941	49.99	silver quality
lymph node	UBERON:0000029	49.71	gold quality
Brodmann (1909) area 46	UBERON:0006483	49.30	gold quality
blood vessel layer	UBERON:0004797	49.29	gold quality
cervix squamous epithelium	UBERON:0006922	49.20	gold quality
olfactory bulb	UBERON:0002264	48.92	gold quality
choroid plexus epithelium	UBERON:0003911	48.89	gold quality
myocardium	UBERON:0002349	48.87	gold quality
type B pancreatic cell	CL:0000169	48.83	gold quality
quadriceps femoris	UBERON:0001377	48.63	gold quality
cardiac muscle of right atrium	UBERON:0003379	48.55	gold quality
CA1 field of hippocampus	UBERON:0003881	48.50	gold quality
vastus lateralis	UBERON:0001379	48.25	gold quality
left ventricle myocardium	UBERON:0006566	48.24	gold quality
orbitofrontal cortex	UBERON:0004167	48.20	gold quality
upper arm skin	UBERON:0004263	48.06	gold quality
cervix epithelium	UBERON:0004801	48.04	gold quality
oviduct epithelium	UBERON:0004804	48.00	gold quality
tongue squamous epithelium	UBERON:0006919	47.92	gold quality
epithelial cell of pancreas	CL:0000083	47.83	gold quality
mucosa of urinary bladder	UBERON:0001259	47.80	gold quality
nasal cavity epithelium	UBERON:0005384	47.70	gold quality
thymus	UBERON:0002370	47.42	gold quality

Single-cell (SCXA)

Detected in 14 experiment(s), a significant marker in 13.

Experiment	Marker?	Max mean expression
E-HCAD-6	yes	3145.59
E-MTAB-6505	yes	3081.10
E-CURD-112	yes	2486.31
E-MTAB-9906	yes	2354.03
E-CURD-122	yes	2224.49
E-MTAB-9067	yes	2131.36
E-HCAD-4	yes	1962.75
E-MTAB-10042	yes	1735.58
E-MTAB-7407	yes	1435.69
E-MTAB-10432	yes	865.10
E-CURD-6	yes	807.33
E-ANND-5	yes	655.08
E-HCAD-10	yes	15.81
E-ANND-3	no	1.47

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): EBF1, GLI3, IKZF1, NEUROD1, PAX5, PREB, RUNX1, TCF3

miRNA regulators (miRDB)

11 targeting VPREB1, 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-548P	99.98	72.25	3784
HSA-MIR-515-5P	99.92	69.82	2343
HSA-MIR-519E-5P	99.92	69.62	2358
HSA-MIR-6857-5P	99.87	65.32	985
HSA-MIR-548AZ-5P	99.83	69.94	3230
HSA-MIR-548T-5P	99.83	69.91	3220
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-3938	98.72	66.07	834
HSA-MIR-4450	98.26	68.35	725
HSA-MIR-665	97.60	65.64	1781
HSA-MIR-1469	65.89	55.19	6

Literature-anchored findings (GeneRIF, showing 8)

• The 5’ region of the VpreB gene contains a promoter which displays higher relative activity in preB cells compared with cells at other stages or from other lineages. (PMID:11994467)
• Pre-B cell integrins and their stromal cell ligands together with the pre-B cell receptor and galectin-1 form a homogeneous lattice at the contact area between bone marrow pre-B and stromal cells. (PMID:16818733)
• The proportion of the individuals with <2 copies of the VPREB1 gene was significantly higher in the patient group than that in the controls, while that of the individuals with >2 copies was lower in the patient group than that in the controls. (PMID:21144590)
• VPREB1 focal deletions are common in B-ALL and occur independent of V(D)J light chain recombination. Focal deletions of VPREB1 correlate with decreased expression levels and high-risk patients with focal deletions tend to have poorer overall survival (PMID:23881307)
• Irrespective of subtype, Acute Lymphoblastic Leukemia with high levels of IGHM, IGLL1 and VPREB1 are arrested at the pre-B stage and correlate with good prognosis in high-risk pediatric B-cell precursor acute lymphoblastic leukemia. (PMID:27611867)
• Association of VPREB1 Gene Copy Number Variation and Rheumatoid Arthritis Susceptibility. (PMID:33101545)
• CRISPR/Cas9 mediated knock-out of VPREB1 gene induces a cytotoxic effect in myeloma cells. (PMID:33418558)
• Mutational Analysis of the VPREB1 Gene of Pre-BCR Complex in a Cohort of Sporadic Pediatric Patients With B-Cell Acute Lymphoblastic Leukemia. (PMID:35398858)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Vpreb1b	ENSMUSG00000059280
mus_musculus	Vpreb1a	ENSMUSG00000059305
rattus_norvegicus	Vpreb1b	ENSRNOG00000001839
rattus_norvegicus	Vpreb1a	ENSRNOG00000052348

Paralogs (93): VPREB3 (ENSG00000128218), 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

Immunoglobulin iota chain — P12018 (reviewed: P12018)

Alternative names: CD179 antigen-like family member A, Protein VPreB1, V(pre)B protein

All UniProt accessions (2): P12018, F8W8C9

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. This complex presumably regulates Ig gene rearrangements in the early steps of B-cell differentiation.

Subunit / interactions. Interacts with IGLL1. Interacts with SYNV1/HRD1 (via N-terminus); this interaction leads to increased VPREB1 ubiquitination and degradation in pre-B cells, possibly through a lysosomal, not proteasomal, pathway.

Subcellular location. Endoplasmic reticulum.

Tissue specificity. Only expressed by pre-B-cells.

Similarity. Belongs to the immunoglobulin superfamily.

RefSeq proteins (2): NP_001290438, NP_009059* (*=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 (28 total): strand 10, region of interest 6, sequence variant 3, helix 3, signal peptide 1, chain 1, disulfide bond 1, sequence conflict 1, domain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

3 structures.

PDB	Method	Resolution (Å)
3BJ9	X-RAY DIFFRACTION	2
2H3N	X-RAY DIFFRACTION	2.3
2H32	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P12018-F1	88.01	0.64

Antibody-complex structures (SAbDab): 3 — 2H32, 2H3N, 3BJ9

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): 41–115

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

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

MSigDB gene sets: 82 (showing top): GSE45365_NK_CELL_VS_CD11B_DC_UP, VERHAAK_AML_WITH_NPM1_MUTATED_DN, GCANCTGNY_MYOD_Q6, SHIN_B_CELL_LYMPHOMA_CLUSTER_5, REACTOME_CELL_SURFACE_INTERACTIONS_AT_THE_VASCULAR_WALL, BOYLAN_MULTIPLE_MYELOMA_C_D_UP, GOCC_IMMUNOGLOBULIN_COMPLEX, DIAZ_CHRONIC_MYELOGENOUS_LEUKEMIA_DN, RAY_TUMORIGENESIS_BY_ERBB2_CDC25A_DN, RHEIN_ALL_GLUCOCORTICOID_THERAPY_DN, VILIMAS_NOTCH1_TARGETS_DN, HATADA_METHYLATED_IN_LUNG_CANCER_UP, CHYLA_CBFA2T3_TARGETS_UP, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A12, BONOME_OVARIAN_CANCER_SURVIVAL_SUBOPTIMAL_DEBULKING

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

988 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
VPREB1	IGLL1	P15814	999
VPREB1	CD79A	P11912	994
VPREB1	CD79B	P40259	993
VPREB1	IGHV4-38-2	P0DP08	967
VPREB1	IGLL5	B9A064	776
VPREB1	RAG1	P15918	740
VPREB1	RAG2	P55895	732
VPREB1	GGT2P	P36268	678
VPREB1	DNTT	P04053	676
VPREB1	KIR3DL2	P43630	668
VPREB1	EBF1	Q9UH73	666
VPREB1	PAX5	Q02548	660
VPREB1	IL7R	P16871	619
VPREB1	TCF3	P15883	604
VPREB1	BLNK	Q8WV28	593

IntAct

2 interactions, top by confidence:

A	B	Type	Score
VPREB1	ABL1	psi-mi:“MI:0915”(physical association)	0.400

BioGRID (2): VPREB1 (Affinity Capture-MS), VPREB1 (Affinity Capture-RNA)

ESM2 similar proteins: A0A075B6L2, A0A075B6N2, A0A075B6R0, A0A075B6T8, A0A075B6U4, A0A075B6X5, A0A087WSZ9, A0A087WT02, A0A0A0MS00, A0A0A0MS01, A0A0A0MS02, A0A0A6YYJ7, A0A0A6YYK1, A0A0A6YYK6, A0A0B4J1U4, A0A0B4J237, A0A0B4J238, A0A0B4J244, A0A0B4J245, A0A0B4J248, A0A0B4J262, A0A0B4J272, A0A0B4J277, A0A0B4J280, A0A0C4DH27, A0A0C4DH28, A0A0K0K1B3, A0A5B7, A0JD36, A0JD37, P01637, P01641, P01734, P01735, P01737, P01738, P01740, P03978, P03979, P04212

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

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

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

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
929328	GRCh37/hg19 22q11.21-11.22(chr22:21979096-22941426)x3	Pathogenic

SpliceAI

127 predictions. Top by Δscore:

Variant	Effect	Δscore
22:22244855:CACAG:C	donor_loss	0.9800
22:22244856:ACAG:A	donor_loss	0.9800
22:22244860:GT:G	donor_loss	0.9800
22:22244861:T:A	donor_loss	0.9800
22:22244945:GGTT:G	acceptor_gain	0.8000
22:22244860:G:GG	donor_gain	0.7800
22:22244941:ACCAG:A	acceptor_loss	0.7400
22:22244942:CCA:C	acceptor_loss	0.7400
22:22244943:CA:C	acceptor_loss	0.7400
22:22244944:A:AG	acceptor_gain	0.7400
22:22244945:G:GG	acceptor_gain	0.7400
22:22244961:C:A	acceptor_gain	0.7400
22:22244935:T:A	acceptor_loss	0.6800
22:22244862:G:GG	donor_loss	0.6700
22:22245230:GC:G	donor_gain	0.6200
22:22244942:CCAGG:C	acceptor_gain	0.5900
22:22244943:CAGG:C	acceptor_gain	0.5700
22:22244958:AGCC:A	acceptor_gain	0.5500
22:22244959:GCCG:G	acceptor_gain	0.5500
22:22244942:C:G	acceptor_gain	0.5300
22:22244951:G:GT	acceptor_gain	0.5200
22:22244940:CACCA:C	acceptor_gain	0.5100
22:22245231:C:G	donor_gain	0.5100
22:22244857:CAG:C	donor_gain	0.5000
22:22244933:T:G	acceptor_loss	0.5000
22:22244931:CATCT:C	acceptor_loss	0.4900
22:22244934:CTGT:C	acceptor_loss	0.4800
22:22245224:G:GT	donor_gain	0.4800
22:22245286:G:GT	donor_gain	0.4700
22:22244938:GTC:G	acceptor_loss	0.4600

AlphaMissense

941 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
22:22245158:T:C	F87L	0.979
22:22245160:C:A	F87L	0.979
22:22245160:C:G	F87L	0.979
22:22245198:T:C	L100S	0.977
22:22245067:G:C	W56C	0.975
22:22245067:G:T	W56C	0.975
22:22245236:T:C	Y113H	0.972
22:22245098:T:C	F67L	0.970
22:22245100:C:A	F67L	0.970
22:22245100:C:G	F67L	0.970
22:22245204:T:C	I102T	0.970
22:22245159:T:C	F87S	0.968
22:22245237:A:G	Y113C	0.965
22:22245068:T:G	Y57D	0.961
22:22245236:T:G	Y113D	0.958
22:22245237:A:C	Y113S	0.957
22:22245065:T:A	W56R	0.953
22:22245065:T:C	W56R	0.953
22:22245172:A:C	K91N	0.952
22:22245172:A:T	K91N	0.952
22:22245072:A:C	Q58P	0.950
22:22245159:T:G	F87C	0.943
22:22245242:T:A	C115S	0.943
22:22245243:G:C	C115S	0.943
22:22245020:T:A	C41S	0.941
22:22245021:G:C	C41S	0.941
22:22245165:G:A	G89E	0.938
22:22245204:T:A	I102N	0.938
22:22245186:A:T	N96I	0.937
22:22245224:G:C	D109H	0.936

dbSNP variants (sampled 300 via entrez): RS1000474553 (22:22243662 A>C,T), RS1002247176 (22:22245781 A>G), RS1003785685 (22:22243831 C>T), RS1004929482 (22:22244760 T>A,C,G), RS1005032993 (22:22244563 A>T), RS1005807407 (22:22244114 C>A,T), RS1005933190 (22:22245681 C>G,T), RS1006190749 (22:22244384 C>A,T), RS1006780037 (22:22243207 C>T), RS1006937683 (22:22243019 G>A), RS1008292887 (22:22245575 C>A,G,T), RS1009335633 (22:22244236 A>G), RS1010288661 (22:22245094 C>T), RS1010689539 (22:22245595 G>A), RS1011276553 (22:22244659 C>A,T)

Disease associations

OMIM: gene MIM:605141 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST002136_8	Periodontitis (PAL4Q3)	8.000000e-06
GCST003801_1	Response to selective serotonin reuptake inhibitors in depression	5.000000e-07
GCST005169_3	Diastolic blood pressure	2.000000e-06

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0005658	response to selective serotonin reuptake inhibitor
EFO:0006336	diastolic blood pressure

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
bis(tri-n-butyltin)oxide	increases expression	1
tributyltin	increases expression	1
cypermethrin	decreases expression	1
perfluorooctanoic acid	decreases expression	1
CGP 52608	affects binding, increases reaction	1
enniatins	increases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Aldicarb	decreases expression	1
Benzo(a)pyrene	affects methylation	1
Diazinon	increases methylation	1
Chlorpyrifos	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Tetrachlorodibenzodioxin	increases expression	1
Valproic Acid	increases methylation	1
Zearalenone	decreases expression	1

Clinical trials (associated diseases)

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