ID3 Gene (Inhibitor of DNA Binding 3)
A key regulator of cell differentiation, cell cycle, and transcriptional activity in development and cancer.
Gene Information Card
| Symbol | ID3 |
|---|---|
| Full Name | Inhibitor of DNA Binding 3, HLH Protein |
| Gene Type | Protein coding |
| Chromosomal Location | 1p36.12 |
| NCBI Gene ID | 3399 ncbi.nlm.nih.gov/gene/3399 |
| Ensembl ID | ENSG00000117318 |
| UniProt ID | Q02535 |
| OMIM ID | 600277 |
| HGNC ID | 5362 |
| Aliases | bHLHb25, HEIR-1, ID3_HUMAN |
Description
ID3 (Inhibitor of DNA Binding 3) encodes a helix-loop-helix (HLH) protein that lacks a basic DNA-binding domain. It functions as a dominant-negative regulator of basic HLH transcription factors by forming heterodimers, thereby inhibiting DNA binding and transcriptional activation. ID3 plays critical roles in cell differentiation, cell cycle regulation, and apoptosis, and is implicated in various cancers and developmental disorders.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Breast cancer | Overexpression of ID3 promotes cell proliferation and metastasis by inhibiting E-protein transcription factors. | NCBI Gene, COSMIC |
| Colorectal cancer | ID3 upregulation correlates with poor prognosis and enhanced tumor growth. | COSMIC, ClinVar |
| Gastric cancer | ID3 overexpression linked to increased invasion and metastasis. | NCBI Gene, COSMIC |
| T-cell acute lymphoblastic leukemia (T-ALL) | ID3 mutations (e.g., loss-of-function) disrupt T-cell differentiation and promote leukemogenesis. | ClinVar, OMIM |
| Autoimmune diseases | ID3 dysregulation affects T-cell and B-cell development, contributing to autoimmunity. | OMIM, NCBI Gene |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Lymph node | 12.5 | Medium |
| Spleen | 10.8 | Medium |
| Bone marrow | 9.2 | Medium |
| Thymus | 8.7 | Medium |
| Lung | 6.4 | Low |
| Breast | 5.1 | Low |
| Colon | 4.3 | Low |
| Stomach | 3.9 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| K562 (leukemia) | 15.2 | High expression |
| MCF7 (breast cancer) | 8.9 | Medium expression |
| HCT116 (colorectal) | 7.5 | Medium expression |
| A549 (lung) | 5.3 | Low expression |
| HEK293 (embryonic kidney) | 4.1 | Low expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.172C>T (p.Arg58*) | Nonsense | <0.1% in T-ALL | Loss-of-function; truncated protein |
| c.94_95del (p.Leu32fs) | Frameshift | <0.1% in T-ALL | Loss-of-function; premature stop |
| c.200G>A (p.Arg67Gln) | Missense | <0.1% in cancer | Unknown significance |
| c.1A>G (p.Met1?) | Start loss | <0.1% in T-ALL | Loss-of-function; no translation |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in ID3 (e.g., p.Arg58*, p.Leu32fs) result in truncated or absent protein, impairing its ability to inhibit E-protein transcription factors, leading to uncontrolled cell proliferation in T-ALL.
Gain of Function (GOF)
No well-characterized gain-of-function mutations reported for ID3.
Dominant Negative (DN)
ID3 itself acts as a natural dominant-negative regulator of bHLH transcription factors; mutations that alter its dimerization domain may enhance or disrupt this activity, but specific dominant-negative mutations are not well documented.
View complete mutation data：
Gene Ontology (GO)
| • DNA-binding transcription factor activity | • RNA polymerase II-specific |
| • Protein heterodimerization activity | • Negative regulation of transcription by RNA polymerase II |
| • Cell differentiation | • Cell cycle arrest |
| • Apoptotic process | • Regulation of cell population proliferation |
Pathways
• Notch signaling pathway
• TGF-beta signaling pathway
• p53 signaling pathway
• Transcriptional misregulation in cancer
Protein Summary
The ID3 protein (UniProt Q02535) is a 119-amino-acid helix-loop-helix (HLH) protein that lacks a basic DNA-binding domain. It functions by forming heterodimers with E-proteins (e.g., TCF3, TCF4, TCF12), sequestering them and preventing their binding to E-box DNA sequences. This inhibition regulates transcription of genes involved in cell differentiation, cell cycle progression, and apoptosis. ID3 is highly expressed in lymphoid tissues and is critical for normal T-cell and B-cell development. Dysregulation of ID3 contributes to oncogenesis, particularly in T-ALL and solid tumors.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| ID3 Knockout HEK293 Cell Line | EDJ-KQ123 | Human | 3399 | Details Get a Quote |
| ID3 Knockout A-549 Cell Line | EDJ-KQ18595 | Human | 3399 | Details Get a Quote |
| ID3 Knockout HCT 116 Cell Line | EDJ-KQ18596 | Human | 3399 | Details Get a Quote |
| ID3 Knockout HeLa Cell Line | EDJ-KQ18597 | Human | 3399 | Details Get a Quote |
