HMGB3: High Mobility Group Box 3 – Chromatin Regulator and Cancer-Associated Gene
Comprehensive genomic and proteomic overview of HMGB3, a member of the HMG-box family involved in transcription, DNA repair, and oncogenesis.
Gene Information Card
| Symbol | HMGB3 |
|---|---|
| Full Name | High Mobility Group Box 3 |
| Gene Type | Protein coding |
| Chromosomal Location | Xq28 |
| NCBI Gene ID | 3149 ncbi.nlm.nih.gov/gene/3149 |
| Ensembl ID | ENSG00000129988 |
| UniProt ID | O15347 |
| OMIM ID | 300193 |
| HGNC ID | 5004 |
| Aliases | HMG2A, HMG-2a, HMG2, HMG-2 |
Description
HMGB3 (High Mobility Group Box 3) encodes a member of the high mobility group (HMG) box family of non-histone chromatin proteins. The protein contains two HMG box domains that bind DNA with low sequence specificity but high structural affinity, particularly to distorted or bent DNA structures. HMGB3 functions as an architectural chromatin factor that facilitates nucleosome remodeling, transcription factor assembly, and DNA repair. It is highly expressed during embryonic development and in certain adult tissues, and its dysregulation is implicated in several cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast Cancer | HMGB3 overexpression promotes proliferation and metastasis via NF-κB and Wnt/β-catenin signaling | PMID: 25944712 |
| Lung Cancer | Upregulation of HMGB3 enhances cell migration and invasion through EMT induction | PMID: 29393451 |
| Gastric Cancer | HMGB3 acts as an oncogene by activating PI3K/Akt pathway and inhibiting apoptosis | PMID: 27683189 |
| Colorectal Cancer | HMGB3 overexpression correlates with poor prognosis and promotes tumor growth | PMID: 30323318 |
| Hepatocellular Carcinoma | HMGB3 silencing reduces cell viability and induces G1 arrest | PMID: 31065072 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Bone Marrow | 12.5 | Medium |
| Lymph Node | 8.3 | Low |
| Spleen | 7.1 | Low |
| Testis | 6.8 | Low |
| Brain | 2.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa | 15.2 | Cervical cancer cell line |
| A549 | 11.4 | Lung cancer cell line |
| MCF7 | 9.8 | Breast cancer cell line |
| HepG2 | 8.5 | Liver cancer cell line |
| K562 | 7.3 | Leukemia cell line |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1A>G (p.Met1?) | Missense | <0.1% | Likely loss of start codon; predicted loss of function |
| c.214C>T (p.Arg72Trp) | Missense | <0.1% | Unknown significance; rare population variant |
| c.403G>A (p.Glu135Lys) | Missense | <0.1% | Reported in COSMIC; potential gain-of-function in cancer |
Mutation functional classification
Loss of Function (LOF)
No well-characterized loss-of-function mutations reported in HMGB3; homozygous knockout in mice is lethal.
Gain of Function (GOF)
Overexpression and copy number gains are observed in multiple cancers, suggesting oncogenic gain-of-function.
Dominant Negative (DN)
No dominant-negative mutations have been described for HMGB3.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Wnt signaling pathway (Reactome: R-HSA-195721)
• NF-κB signaling (Reactome: R-HSA-975138)
• PI3K/Akt signaling (Reactome: R-HSA-1257604)
• Epithelial-to-mesenchymal transition (Reactome: R-HSA-6798695)
Protein Summary
HMGB3 is a 200-amino-acid protein (23 kDa) belonging to the HMG-box family. It contains two tandem HMG boxes (box A and box B) and a C-terminal acidic tail. The protein binds to the minor groove of DNA, inducing bends and facilitating the assembly of higher-order nucleoprotein complexes. HMGB3 shuttles between the nucleus and cytoplasm, and its post-translational modifications (e.g., acetylation, phosphorylation) regulate its DNA-binding affinity and cellular localization. It is essential for embryonic development and stem cell maintenance, and its overexpression in cancer correlates with poor prognosis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HMGB3 Knockout HEK293 Cell Line | EDJ-KQ50351 | Human | 3149 | Details Get a Quote |
| HMGB3 Knockout HeLa Cell Line | EDJ-KQ53530 | Human | 3149 | Details Get a Quote |
| HMGB3 Knockout A-549 Cell Line | EDJ-KQ62003 | Human | 3149 | Details Get a Quote |
| HMGB3 Knockout HCT 116 Cell Line | EDJ-KQ70480 | Human | 3149 | Details Get a Quote |
