VPREB1

Chr 22

V-set pre-B cell surrogate light chain 1

Also known as: CD179a, IGI, IGVPB, VPREB

NCBI Gene: 7441ENSG00000169575UniProt: P12018

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. [provided by RefSeq, Jan 2015]

122
ClinVar variants
84
Pathogenic / LP
0.10
pLI score
0
Active trials
Clinical Summary— VPREB1
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.10) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
84 Pathogenic / Likely Pathogenic· 36 VUS of 122 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
1.88LOEUF
pLI 0.096
Z-score 0.09
OE 0.90 (0.25–1.88)
Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
0.13Z-score
OE missense 0.96 (0.80–1.16)
81 obs / 84.3 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.90 (0.25–1.88)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.96 (0.80–1.16)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.05
0≤1.21.6
LoF obs/exp: 1 / 1.1Missense obs/exp: 81 / 84.3Syn Z: -0.25

ClinVar Variant Classifications

122 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic80
Likely Pathogenic4
VUS36
Likely Benign1
Benign1
80
Pathogenic
4
Likely Pathogenic
36
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
80
0
80
Likely Pathogenic
0
0
4
0
4
VUS
0
24
12
0
36
Likely Benign
0
1
0
0
1
Benign
0
0
1
0
1
Total025970122

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

VPREB1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Molecular characterization and predictors of relapse in patients with Ph + ALL after frontline ponatinib and blinatumomab.
Short NJ et al.·J Hematol Oncol
2025Clinical trial
Association of VPREB1 Gene Copy Number Variation and Rheumatoid Arthritis Susceptibility.
Aslam MM et al.·Dis Markers
2020
Genetic Approaches for Definitive Diagnosis of Agammaglobulinemia in Consanguineous Families.
Ben-Ali M et al.·J Clin Immunol
2020
Application of Gene Expression Microarray for the Classification of Ph-Like B-Cell Acute Lymphoblastic Leukemia.
Thangrua N et al.·Int J Lab Hematol
2025
Optical Genome Mapping Reveals and Characterizes Recurrent Aberrations and New Fusion Genes in Adult ALL.
Vieler LM et al.·Genes (Basel)
2023
VpreB surrogate light chain expression in B-lineage ALL: a report from the Children's Oncology Group.
Winter SS et al.·Blood Adv
2022
Comparative analysis of dynamic transcriptomes reveals specific COVID-19 features and pathogenesis of immunocompromised populations.
Yang X et al.·mSystems
2024
The Expression Pattern of the Pre-B Cell Receptor Components Correlates with Cellular Stage and Clinical Outcome in Acute Lymphoblastic Leukemia.
Chen D et al.·PLoS One
2016
Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF.
Kato K et al.·Hum Cell
2025
Construction of a five-gene-based prognostic model for relapsed/refractory acute lymphoblastic leukemia.
Zhou B et al.·Hematology
2024Functional
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools