HMGB2 Gene: High Mobility Group Box 2 - Function, Disease Associations, and Expression
A comprehensive biomedical overview of HMGB2, including gene card, expression, mutations, and clinical relevance.
Gene Information Card
| Symbol | HMGB2 |
|---|---|
| Full Name | High Mobility Group Box 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 4q31.1 (GRCh38) |
| NCBI Gene ID | 3148 ncbi.nlm.nih.gov/gene/3148 |
| Ensembl ID | ENSG00000164104 |
| UniProt ID | P26583 |
| OMIM ID | 163906 |
| HGNC ID | 5000 |
| Aliases | HMG2, HMG-2, high mobility group protein B2 |
Description
HMGB2 encodes a member of the high mobility group box family of chromatin-associated proteins. This protein binds DNA non-specifically, bending it to facilitate chromatin remodeling, transcription, and V(D)J recombination. HMGB2 is involved in cell proliferation, differentiation, and DNA damage response. It is overexpressed in various cancers and has been linked to inflammatory and autoimmune conditions.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cancer (e.g., hepatocellular carcinoma, gastric cancer) | Overexpression promotes cell proliferation, invasion, and metastasis via regulation of oncogenic pathways (e.g., Wnt/β-catenin, NF-κB). | Multiple studies in cell lines and animal models; COSMIC lists HMGB2 as frequently altered in various cancers. |
| Rheumatoid arthritis | HMGB2 is expressed in synovial tissue and contributes to inflammation and joint destruction. | Expression analysis in patient samples; functional studies in animal models. |
| Osteoarthritis | HMGB2 loss in chondrocytes leads to reduced cartilage maintenance and increased apoptosis. | Expression studies in human cartilage; knockout mouse models. |
| Systemic lupus erythematosus (SLE) | HMGB2 may act as a danger-associated molecular pattern (DAMP) promoting autoimmunity. | Elevated HMGB2 levels in serum of SLE patients; mechanistic studies in immune cells. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 25.3 | High |
| Spleen | 22.1 | High |
| Bone marrow | 18.7 | High |
| Testis | 15.2 | Medium |
| Lung | 12.8 | Medium |
| Liver | 8.5 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HeLa (cervical carcinoma) | 30.2 | High expression; used in functional studies |
| A549 (lung carcinoma) | 22.5 | High expression; associated with proliferation |
| MCF7 (breast carcinoma) | 18.9 | Moderate expression; role in estrogen signaling |
| K562 (leukemia) | 15.3 | Moderate expression; involved in differentiation |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.371G>A (p.Arg124His) | Missense | 0.01% (gnomAD) | Potential impact on DNA binding; not well characterized |
| c.412C>T (p.Arg138Trp) | Missense | 0.005% (gnomAD) | May affect protein stability; clinical significance unknown |
| c.523_524insA (frameshift) | Insertion | Rare | Predicted loss of function; not reported in ClinVar |
| c.1A>G (p.Met1Val) | Start loss | Rare | Likely loss of function; not reported in ClinVar |
Mutation functional classification
Loss of Function (LOF)
Loss-of-function mutations in HMGB2 are rare and not well documented. Knockout mouse models show reduced fertility and impaired V(D)J recombination, but no specific human disease is clearly linked to biallelic loss.
Gain of Function (GOF)
Gain-of-function is primarily due to overexpression, not mutations. Amplification of the HMGB2 locus or transcriptional upregulation leads to increased protein levels, promoting oncogenic phenotypes.
Dominant Negative (DN)
No dominant-negative mutations have been reported for HMGB2. The protein functions as a non-histone chromatin factor, and dominant-negative effects would likely require disruption of its DNA-binding domain, but such variants are not yet characterized.
View complete mutation data：
Gene Ontology (GO)
| • DNA binding | • chromatin binding |
| • transcription regulatory region DNA binding | • damaged DNA binding |
| • protein heterodimerization activity | • nucleosome binding |
| • chromatin remodeling | • regulation of transcription by RNA polymerase II |
| • DNA recombination | • cellular response to DNA damage stimulus |
Pathways
• Apoptosis
• Cellular senescence
• Innate Immune System
• RAGE signaling
• TLR signaling
• Wnt signaling pathway
• NF-kappaB signaling
• V(D)J recombination
Protein Summary
HMGB2 is a 209-amino acid protein with two HMG-box domains that bind DNA with high affinity, inducing bends and promoting chromatin architecture. It lacks intrinsic transcriptional activity but recruits other factors to enhance transcription. HMGB2 is post-translationally modified by acetylation, phosphorylation, and methylation, affecting its nuclear localization and extracellular release. It is widely expressed in embryonic and adult tissues, with highest levels in lymphoid organs. Extracellular HMGB2 acts as a DAMP, triggering inflammatory responses via receptors like TLR4 and RAGE.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HMGB2 Knockout HEK293 Cell Line | EDJ-KQ13762 | Human | 3148 | Details Get a Quote |
| HMGB2 Knockout A-549 Cell Line | EDJ-KQ42282 | Human | 3148 | Details Get a Quote |
| HMGB2 Knockout HCT 116 Cell Line | EDJ-KQ43546 | Human | 3148 | Details Get a Quote |
| HMGB2 Knockout HeLa Cell Line | EDJ-KQ43547 | Human | 3148 | Details Get a Quote |
| HMGB2 Knockout Huh-7 Cell Line | EDJ-KZ286 | Human | 3148 | Details Get a Quote |
