PAX5

Chr 9

paired box 5

Also known as: ALL3, BSAP, PAX-5

This transcription factor is essential for B-lymphocyte lineage commitment, repressing inappropriate genes while activating B-cell-specific genes, and regulating immunoglobulin gene recombination. Mutations cause susceptibility to acute lymphoblastic leukemia, with inheritance pattern not specified in available data. The gene is highly constrained against loss-of-function variants (pLI 1.0, LOEUF 0.17), indicating that heterozygous loss-of-function mutations are likely pathogenic.

OMIMResearchSummary from RefSeq, OMIM, UniProt
MultiplemechanismLOEUF 0.171 OMIM phenotype
Clinical SummaryPAX5
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Gene-Disease Validity (ClinGen)
PAX5-related B lymphopenia and autism spectrum disorder · ARModerate

Moderate evidence — consider for supplementary testing

2 total gene-disease associations curated

Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 1.00). One damaged copy is likely sufficient to cause disease.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

LoF intolerant — likely haploinsufficient
LoF Constraint
0.17LOEUF
pLI 0.998
Z-score 3.95
OE 0.00 (0.000.17)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint
2.45Z-score
OE missense 0.56 (0.490.65)
139 obs / 247.6 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.00 (0.000.17)
00.351.4
Missense OE0.56 (0.490.65)
00.61.4
Synonymous OE1.06
01.21.6
LoF obs/exp: 0 / 18.1Missense obs/exp: 139 / 247.6Syn Z: -0.47
DN
0.6162th %ile
GOF
0.3491th %ile
LOF
0.78top 5%

This gene has evidence for multiple mechanisms of pathogenicity (loss-of-function and dominant-negative). Both the Badonyi & Marsh prediction and the broader genomic evidence point to loss-of-function as the predominant mechanism. Different variants in this gene may act through different mechanisms — interpret in context of the specific variant.

LOFprediction above median · LOEUF 0.17
DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312. Mechanism ranking also informed by gnomAD constraint, ClinVar, and ClinGen data.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PAX5 · protein map & ClinVar variants

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

3D Protein StructureAlphaFold

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

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Clinical Literature
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