HOXB4

Chr 17

homeobox B4

Also known as: HOX-2.6, HOX2, HOX2F

NCBI Gene: 3214UniProt: P17483

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. Intracellular or ectopic expression of this protein expands hematopoietic stem and progenitor cells in vivo and in vitro, making it a potential candidate for therapeutic stem cell expansion. [provided by RefSeq, Jul 2008]

55
ClinVar variants
10
Pathogenic / LP
0.06
pLI score
1
Active trials
Clinical Summary— HOXB4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.06) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 45 VUS of 55 total submissions
💊
Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
Some data sources returned errors (1)

ensembl: Error: Ensembl fetch failed: 500 for https://rest.ensembl.org/lookup/symbol/homo_sapiens/HOXB4?content-type=application/json&expand=1

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.
1.02LOEUF
pLI 0.060
Z-score 1.55
OE 0.39 (0.18–1.02)
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.
0.55Z-score
OE missense 0.86 (0.73–1.01)
106 obs / 123.2 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.0.39 (0.18–1.02)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.86 (0.73–1.01)
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.0.97
0≤1.21.6
LoF obs/exp: 3 / 7.6Missense obs/exp: 106 / 123.2Syn Z: 0.16

ClinVar Variant Classifications

55 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic9
Likely Pathogenic1
VUS45
9
Pathogenic
1
Likely Pathogenic
45
VUS

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
0
43
2
0
45
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04312055

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

View in ClinVar →

Protein Context — Lollipop Plot

HOXB4 · 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 B4; HOXB4
MIM #142965 · *
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Hematopoietic cells.
Moore MA et al.·Methods Enzymol
2006
[Ex vivo expansion of human hematopoietic stem/progenitor cells by TAT-HOXB4 homeoprotein and the prospect of its clinical use].
Xu C et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2013Review
ASXL1 truncating variants in BOS and myeloid leukemia drive shared disruption of Wnt-signaling pathways but have differential isoform usage of RUNX3.
Lin I et al.·BMC Med Genomics
2024
Mechanism of action of HOXB4 on the hematopoietic differentiation of embryonic stem cells.
Forrester LM et al.·Stem Cells
2012Review
Activated HoxB4-induced hematopoietic stem cells from murine pluripotent stem cells via long-term programming.
Izawa K et al.·Exp Hematol
2020
[Expression of HOXB4, PRDM16 and HOXA9 in Patients with Acute Myeloid Leukemia and Its Clinical Significance].
Li L et al.·Zhongguo Shi Yan Xue Ye Xue Za Zhi
2016Cohort
High-level ectopic HOXB4 expression confers a profound in vivo competitive growth advantage on human cord blood CD34+ cells, but impairs lymphomyeloid differentiation.
Schiedlmeier B et al.·Blood
2003
Enforced Expression of HOXB4 in Human Embryonic Stem Cells Enhances the Production of Hematopoietic Progenitors but Has No Effect on the Maturation of Red Blood Cells.
Jackson M et al.·Stem Cells Transl Med
2016
HOXB4 Promotes Bladder Cancer Progression in Part Through Transcriptional Activation of Smoothened.
Jin Z et al.·FASEB J
2026
Effects of HOXB4 overexpression on ex vivo expansion and immortalization of hematopoietic cells from different species.
Zhang XB et al.·Stem Cells
2007
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
Breast Cancer

Carboplatin and Nab-Paclitaxel With or Without Vorinostat in Treating Women With Newly Diagnosed Operable Breast Cancer

ACTIVE NOT RECRUITING
NCT00616967Phase PHASE2Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsStarted 2008-05
carboplatinpaclitaxel albumin-stabilized nanoparticle formulationvorinostat

External Resources

Links to major genomics databases and tools