PBX3 encodes a transcriptional activator that binds specific DNA sequences to regulate gene expression during embryonic development, particularly affecting nervous system, eye, and organ development. Mutations cause autosomal recessive congenital fibrosis of the extraocular muscles with developmental delay, ptosis, and intellectual disability. The gene shows moderate constraint against loss-of-function variants (LOEUF 0.476), and the associated disorder typically presents from birth with characteristic ocular abnormalities.

OMIMResearchSummary from RefSeq, UniProt
DNmechanismLOEUF 0.48
Clinical SummaryPBX3
Population Constraint (gnomAD)
Constrained for loss-of-function variants (OE-LoF 0.23) despite low pLI — interpret in context.

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Moderate LoF intolerance
LoF Constraint
0.48LOEUF
pLI 0.363
Z-score 3.37
OE 0.23 (0.120.48)
Moderately constrained

More LoF-intolerant than ~75% of genes

Missense Constraint
2.16Z-score
OE missense 0.61 (0.530.70)
147 obs / 241.7 exp
Mild constraint

Moderately missense-constrained (top ~2.5%)

Observed / Expected Ratios
LoF OE0.23 (0.120.48)
00.351.4
Missense OE0.61 (0.530.70)
00.61.4
Synonymous OE0.92
01.21.6
LoF obs/exp: 5 / 22.1Missense obs/exp: 147 / 241.7Syn Z: 0.58
DN
0.74top 25%
GOF
0.4085th %ile
LOF
0.58top 25%

The highest-scoring mechanism for this gene is dominant-negative.

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.

ClinVar Variant Classifications

0 submitted variants in ClinVar

Protein Context — Lollipop Plot

PBX3 · 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.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →