HOXB3

Chr 17

homeobox B3

Also known as: HOX2, HOX2G, Hox-2.7

NCBI Gene: 3213UniProt: P14651

This gene is a member of the Antp homeobox family and encodes a nuclear protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded protein functions as a sequence-specific transcription factor that is involved in development. Increased expression of this gene is associated with a distinct biologic subset of acute myeloid leukemia (AML). [provided by RefSeq, Jul 2008]

0
Active trials
132
ClinVar variants
10
Pathogenic / LP
0.1
Missense Z
0.41
LOEUF
7
Pubs (2 yr)
Clinical Summary— HOXB3
⚡
Population Constraint (gnomAD)
Moderately constrained gene (pLI 0.89) — some intolerance to loss-of-function variants.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 121 VUS of 132 total submissions
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Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Moderate LoF intolerance
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.
0.41LOEUF
pLI 0.892
Z-score 2.88
OE 0.09 (0.03–0.41)
Moderately constrained

More LoF-intolerant than ~75% 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.
0.12Z-score
OE missense 0.98 (0.89–1.08)
270 obs / 275.4 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.0.09 (0.03–0.41)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.98 (0.89–1.08)
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.1.02
0≤1.21.6
LoF obs/exp: 1 / 11.6Missense obs/exp: 270 / 275.4Syn Z: -0.16

ClinVar Variant Classifications

132 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS121
Likely Benign1
9
Pathogenic
1
Likely Pathogenic
121
VUS
1
Likely Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
9
0
9
Likely Pathogenic
0
0
1
0
1
VUS
1
118
2
0
121
Likely Benign
0
0
0
1
1
Benign
0
0
0
0
0
Total1118121132

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXB3 · 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
HOMEOBOX B3; HOXB3
MIM #142966 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Identification of spatially-resolved markers of malignant transformation in Intraductal Papillary Mucinous Neoplasms.
Agostini A et al.·Nat Commun
2024
The role of HOXB2 and HOXB3 in acute myeloid leukemia.
Lindblad O et al.·Biochem Biophys Res Commun
2015
High expression of HOXB3 predicts poor prognosis and correlates with tumor immunity in lung adenocarcinoma.
Yan M et al.·Mol Biol Rep
2022
HoxB3 promotes prostate cancer cell progression by transactivating CDCA3.
Chen J et al.·Cancer Lett
2013
Novel genetic associations with childhood adipocytokines in Indian adolescents.
Nair JM et al.·Cytokine
2025
miR-375 inhibits cancer stem cell phenotype and tamoxifen resistance by degrading HOXB3 in human ER-positive breast cancer.
Fu H et al.·Oncol Rep
2017
Identification and validation of HOXB3 hypomethylation as a novel prognostically epigenetic biomarker in acute myeloid leukemia.
Zhang TJ et al.·Front Immunol
2026
Sequential gene expression analysis of myelodysplastic syndrome transformation identifies HOXB3 and HOXB7 as the novel targets for mesenchymal cells in disease.
Yin C et al.·BMC Cancer
2024
Cerebrospinal fluid level of neurofilament light chain is associated with increased disease activity in neuro-Behçet's disease.
Karaaslan Z et al.·Turk J Med Sci
2022
The absence of mutations in homeobox candidate genes HOXA3, HOXB3, HOXD3 and PITX2 in familial and sporadic thyroid hemiagenesis.
Kizys MM et al.·J Pediatr Endocrinol Metab
2014
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

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients