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10 sources retrieved · Most recent: April 2026 · Index updated 14 days ago
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HBZ
hemoglobin subunit zeta
Chromosome 16 · 16p13.3
NCBI Gene: 3050Ensembl: ENSG00000130656.6HGNC: HGNC:4835UniProt: P02008
52PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transporter
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
extracellular exosomeoxygen transportprotein bindingnucleoplasmtropical spastic paraparesisBlackfan-Diamond anemiaanemia (phenotype)Hereditary persistence of fetal hemoglobin - beta-thalassemia
✦AI Summary

HBZ (HTLV-1 basic leucine-zipper factor) is a viral protein encoded by human T-cell leukemia virus-1 (HTLV-1), not a human hemoglobin gene as the gene name suggests. HBZ functions as a critical oncogenic factor in HTLV-1 pathogenesis 1. Unlike the viral transactivator Tax-1, HBZ is constitutively expressed in all adult T-cell leukemia (ATL) cases and is essential for maintaining the neoplastic state 1. Mechanistically, HBZ promotes T-cell proliferation and lymphoma development in transgenic mice 2, while modulating host cell signaling pathways including NF-κB and microRNA networks 3. HBZ demonstrates distinct subcellular localization patterns during HTLV-1 infection: exclusive cytoplasmic localization in asymptomatic carriers and HAM/TSP patients, transitioning to nuclear localization in leukemic cells 4. HBZ expression levels correlate with proviral load and disease severity in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients 5. Clinically, HBZ serves as a potential prognostic biomarker and therapeutic target 6, with elevated HBZ expression distinguishing ATL patients from asymptomatic carriers 6. These findings establish HBZ as a central viral factor in both ATL oncogenesis and inflammatory HTLV-1 disease pathogenesis 7.

Sources cited
1
HBZ is constitutively expressed in all ATL cases and plays an essential role in oncogenesis by regulating viral transcription and modulating host factors and cellular signaling pathways
PMID: 26848677
2
HBZ promotes T-cell proliferation and causes lymphoma in transgenic mice, making it a critical contributing factor in ATL development
PMID: 26979059
3
HBZ, together with Tax-1, deregulates NF-κB pathway and microRNA expression in HTLV-1 pathogenesis
PMID: 31835460
4
HBZ shows exclusive cytoplasmic localization in asymptomatic carriers and HAM/TSP patients with progressive cytoplasmic-to-nuclear transition in leukemic cells
PMID: 35812456
5
HBZ mRNA expression is higher in HAM/TSP patients than asymptomatic carriers and correlates with proviral load and disease severity
PMID: 29312243
6
HBZ gene expression is significantly higher in ATLL subjects compared to asymptomatic carriers and can be used as a prognostic marker
PMID: 37565279
7
HBZ is a regulatory protein that mediates viral persistence by altering host cell signaling, immune responses, and genomic stability in HTLV-1 infection
PMID: 40431676
Disease Associationsⓘ20
tropical spastic paraparesisOpen Targets
0.11Weak
Blackfan-Diamond anemiaOpen Targets
0.10Weak
anemia (phenotype)Open Targets
0.09Suggestive
Hereditary persistence of fetal hemoglobin - beta-thalassemiaOpen Targets
0.09Suggestive
hereditary persistence of fetal hemoglobin-sickle cell disease syndromeOpen Targets
0.09Suggestive
inosine triphosphatase deficiencyOpen Targets
0.09Suggestive
alpha thalassemia-intellectual disability syndrome type 1Open Targets
0.08Suggestive
Alpha-thalassemia - intellectual disability syndrome linked to chromosome 16Open Targets
0.08Suggestive
Iron deficiency anemiaOpen Targets
0.08Suggestive
Alpha-thalassemia - myelodysplastic syndromeOpen Targets
0.08Suggestive
alpha-thalassemia-myelodysplastic syndromeOpen Targets
0.08Suggestive
Hemoglobin E - beta-thalassemiaOpen Targets
0.08Suggestive
hemoglobin E-beta-thalassemia syndromeOpen Targets
0.08Suggestive
delta-beta-thalassemiaOpen Targets
0.08Suggestive
Autosomal dominant methemoglobinemiaOpen Targets
0.07Suggestive
hemoglobin D diseaseOpen Targets
0.07Suggestive
autosomal dominant sideroblastic anemiaOpen Targets
0.07Suggestive
Constitutional sideroblastic anemiaOpen Targets
0.07Suggestive
Hemoglobin C - beta-thalassemiaOpen Targets
0.07Suggestive
hemoglobin C-beta-thalassemia syndromeOpen Targets
0.07Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
JUNProtein interaction100%CREB1Protein interaction97%AHSPProtein interaction94%EP300Protein interaction93%JUNDProtein interaction92%SMAD2Protein interaction91%
Tissue Expression6 tissues
Bone Marrow
100%
Brain
17%
Lung
7%
Ovary
3%
Liver
0%
Heart
0%
Gene Interaction Network
Click a node to explore
HBZJUNCREB1AHSPEP300JUNDSMAD2
PROTEIN STRUCTURE
Preparing viewer…
PDB3W4U · 1.95 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
1.82LoF Tolerant
pLIⓘ
0.11Tolerant
Observed/Expected LoF0.80 [0.31–1.82]
RankingsWhere HBZ stands among ~20K protein-coding genes
  • #8,559of 20,598
    Most Researched52
  • #16,650of 17,882
    Most Constrained (LOEUF)1.82
Genes detectedHBZ
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
The Road to HTLV-1-Induced Leukemia by Following the Subcellular Localization of HTLV-1-Encoded HBZ Protein.
PMID: 35812456
Front Immunol · 2022
1.00
2
HTLV-1 Infection and Pathogenesis: New Insights from Cellular and Animal Models.
PMID: 34360767
Int J Mol Sci · 2021
0.90
3
PMID: 28095504
0.80
4
Human T-Lymphotropic Virus (HTLV): Epidemiology, Genetic, Pathogenesis, and Future Challenges.
PMID: 40431676
Viruses · 2025
0.70
5
The Role of HBZ in HTLV-1-Induced Oncogenesis.
PMID: 26848677
Viruses · 2016
0.60