HEXIM1: A Key Regulator of Transcriptional Elongation and Cellular Stress Responses
Comprehensive genomic and functional analysis of HEXIM1, a negative regulator of P-TEFb with roles in cardiac development, cancer, and HIV latency.
Gene Information Card
| Symbol | HEXIM1 |
|---|---|
| Full Name | Hexamethylene bis-acetamide inducible 1 |
| Gene Type | Protein coding |
| Chromosomal Location | 17q21.31 |
| NCBI Gene ID | 10614 ncbi.nlm.nih.gov/gene/10614 |
| Ensembl ID | ENSG00000186891 |
| UniProt ID | O94992 |
| OMIM ID | 607544 |
| HGNC ID | 24953 |
| Aliases | CLP-1, EDG1, HIS1, MAQ1, HEXIM1 |
Description
HEXIM1 (hexamethylene bis-acetamide inducible 1) encodes a protein that inhibits positive transcription elongation factor b (P-TEFb) by sequestering it into the 7SK small nuclear ribonucleoprotein (snRNP) complex. This regulation controls RNA polymerase II elongation and is critical for cell cycle progression, cardiac development, and stress responses. HEXIM1 also modulates NF-κB signaling and has tumor suppressor properties in breast cancer. Mutations and altered expression are linked to cardiac hypertrophy, various cancers, and HIV latency.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Cardiac hypertrophy | HEXIM1 loss reduces P-TEFb inhibition, leading to increased transcription of hypertrophic genes (e.g., ANP, BNP). | PMID: 20089853; Mouse models show HEXIM1 deletion causes dilated cardiomyopathy. |
| Breast cancer | HEXIM1 acts as a tumor suppressor; reduced expression correlates with poor prognosis and increased metastasis via NF-κB and ERα pathways. | PMID: 21911473; Clinical samples show HEXIM1 downregulation in invasive ductal carcinoma. |
| HIV-1 latency | HEXIM1 overexpression promotes HIV-1 latency by inhibiting P-TEFb, reducing Tat-dependent transcription. | PMID: 17609209; In vitro studies show HEXIM1 knockdown reactivates latent HIV. |
| Acute myeloid leukemia (AML) | HEXIM1 mutations (e.g., frameshift) are found in AML, potentially disrupting P-TEFb regulation. | COSMIC; COSMIC ID: COSM14268; frequency <1% in AML samples. |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Heart | 12.5 | Medium |
| Breast | 8.3 | Low |
| Lung | 6.7 | Low |
| Brain | 4.2 | Low |
| Liver | 3.1 | Not detected |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 10.2 | HEXIM1 expression reduced vs. normal breast epithelium |
| HEK293 (embryonic kidney) | 15.8 | High baseline expression |
| K562 (leukemia) | 7.5 | Moderate expression; mutation reported in COSMIC |
| HeLa (cervical cancer) | 9.1 | Expression responsive to HMBA treatment |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.742_743insA (p.T248Nfs*5) | Frameshift | <1% (AML) | Loss of function; truncated protein unable to bind P-TEFb |
| c.107C>T (p.P36L) | Missense | <0.1% (breast cancer) | Unknown; located in N-terminal domain, may affect 7SK binding |
| c.421G>A (p.E141K) | Missense | <0.1% (colorectal cancer) | Unknown; predicted damaging by SIFT |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., p.T248Nfs*5) abolish the C-terminal P-TEFb binding domain, preventing inhibition of CDK9/cyclin T1 and leading to unchecked transcriptional elongation.
Gain of Function (GOF)
No gain-of-function mutations reported in HEXIM1.
Dominant Negative (DN)
No dominant-negative mutations reported; HEXIM1 functions as a dimer, but no dominant-negative variants are documented.
View complete mutation data：
Gene Ontology (GO)
Pathways
• 7SK snRNP complex (Reactome: R-HSA-167162)
• P-TEFb elongation complex (Reactome: R-HSA-112382)
• HIV life cycle (Reactome: R-HSA-162906)
• NF-κB signaling (KEGG: hsa04064)
Protein Summary
HEXIM1 is a 359-amino acid protein (UniProt O94992) that forms a dimer and binds to the 7SK snRNA scaffold to sequester P-TEFb (CDK9/cyclin T1) into an inactive complex. The N-terminal region mediates dimerization and 7SK binding, while the C-terminal domain directly interacts with CDK9. HEXIM1 is induced by hexamethylene bis-acetamide (HMBA) and other stress stimuli. It shuttles between nucleus and cytoplasm, and its phosphorylation by CDK2 regulates its activity. The protein also interacts with NF-κB p65 and estrogen receptor alpha, linking it to inflammatory and hormonal signaling.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HEXIM1 Knockout HEK293 Cell Line | EDJ-KQ7110 | Human | 10614 | Details Get a Quote |
| HEXIM1 Knockout A-549 Cell Line | EDJ-KQ31974 | Human | 10614 | Details Get a Quote |
| HEXIM1 Knockout HCT 116 Cell Line | EDJ-KQ31975 | Human | 10614 | Details Get a Quote |
| HEXIM1 Knockout HeLa Cell Line | EDJ-KQ31976 | Human | 10614 | Details Get a Quote |
