PBX2

Chr 6

PBX homeobox 2

Also known as: G17, HOX12, PBX2MHC

NCBI Gene: 5089ENSG00000204304UniProt: P40425

This gene encodes a ubiquitously expressed member of the TALE/PBX homeobox family. It was identified by its similarity to a homeobox gene which is involved in t(1;19) translocation in acute pre-B-cell leukemias. This protein is a transcriptional activator which binds to the TLX1 promoter. The gene is located within the major histocompatibility complex (MHC) on chromosome 6. [provided by RefSeq, Jul 2008]

53
ClinVar variants
5
Pathogenic / LP
1.00
pLI score· haploinsufficient
0
Active trials
Clinical Summary— PBX2
⚡
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.
📋
ClinVar Variants
5 Pathogenic / Likely Pathogenic· 47 VUS of 53 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
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.
0.23LOEUF
pLI 0.995
Z-score 3.97
OE 0.05 (0.02–0.23)
Highly constrained

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

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.
1.84Z-score
OE missense 0.67 (0.59–0.77)
170 obs / 252.1 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.0.05 (0.02–0.23)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.67 (0.59–0.77)
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.0.68
0≤1.21.6
LoF obs/exp: 1 / 20.3Missense obs/exp: 170 / 252.1Syn Z: 2.51

ClinVar Variant Classifications

53 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic4
Likely Pathogenic1
VUS47
Likely Benign1
4
Pathogenic
1
Likely Pathogenic
47
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
4
0
4
Likely Pathogenic
0
0
1
0
1
VUS
0
41
6
0
47
Likely Benign
0
1
0
0
1
Benign
0
0
0
0
0
Total04211053

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

View in ClinVar →

Protein Context — Lollipop Plot

PBX2 · 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
PRMT1-Mediated SWI/SNF Complex Recruitment via SMARCC1 Drives IGF2BP2 Transcription to Enhance Carboplatin Resistance in Head and Neck Squamous Cell Carcinoma.
Liu S et al.·Adv Sci (Weinh)
2025
The E2F1-HOXB9/PBX2-CDK6 axis drives gastric tumorigenesis and serves as a therapeutic target in gastric cancer.
Zhang J et al.·J Pathol
2023
Prognostic significance of pre B cell leukemia transcription factor 2 (PBX2) expression in non-small cell lung carcinoma.
Qiu Y et al.·Cancer Sci
2009
[Correlation of PBX2/ELF2 expression with prognosis of non-small cell lung cancer].
Jin SQ et al.·Zhejiang Da Xue Xue Bao Yi Xue Ban
2014
Variant of PBX2 gene in the 6p21.3 asthma susceptibility locus is associated with allergic rhinitis in Chinese subjects.
Zhao Y et al.·Int Forum Allergy Rhinol
2016
Genetic Commonalities Between Metabolic Syndrome and Rheumatic Diseases Through Disease Interactome Modules.
Shi Y et al.·J Cell Mol Med
2025
Celiac disease-associated loci show considerable genetic overlap with neuropsychiatric diseases but with limited transethnic applicability.
Sharma N et al.·J Genet
2023
Meis1 is an essential and rate-limiting regulator of MLL leukemia stem cell potential.
Wong P et al.·Genes Dev
2007
miRNA let-7c promotes granulocytic differentiation in acute myeloid leukemia.
Pelosi A et al.·Oncogene
2013
Oncogenic HoxB7 requires TALE cofactors and is inactivated by a dominant-negative Pbx1 mutant in a cell-specific manner.
Fernandez LC et al.·Cancer Lett
2008
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