# HEXIM1 Gene: Structure, Function, and Clinical Significance


## Key Takeaways

- HEXIM1 is a core component of the 7SK snRNP complex, acting as a critical inhibitor of P-TEFb (CDK9/Cyclin T1) kinase activity, thereby regulating RNA Polymerase II transcriptional elongation.
- Its expression is tightly controlled by signaling pathways including ERα, HIF-1α, and p53, and it plays diverse roles as a tumor suppressor, modulator of nuclear receptor signaling, and regulator of angiogenesis and differentiation.
- HEXIM1 is frequently dysregulated in various cancers (e.g., breast, melanoma, AML), where its downregulation contributes to tumorigenesis and its induction serves as a pharmacodynamic biomarker for BET bromodomain inhibitor efficacy.
- Pathogenic interactions include its role in HIV-1 and HTLV-1 replication, where viral proteins like Tat and Tax disrupt the HEXIM1-P-TEFb complex to enhance viral transcription.
- Somatic alterations and functional dysregulation, rather than germline mutations, are primarily associated with HEXIM1's clinical significance, particularly in cancer and developmental defects.
- Therapeutic strategies involve targeting upstream regulators like BET bromodomain proteins to induce HEXIM1 expression, or exploring gene therapy approaches to restore its tumor-suppressive functions.

---

## Executive Summary & Key Metadata

HEXIM1 (Hexamethylene bis-acetamide-inducible protein 1) is a multifunctional regulatory protein best characterized as the core inhibitory subunit of the 7SK small nuclear ribonucleoprotein (snRNP) complex, which governs the activity of Positive Transcription Elongation Factor b (P-TEFb). Through its control of RNA Polymerase II (RNAP2) pause-release, HEXIM1 operates as a master rheostat for transcriptional elongation, integrating signals from cellular stress, hormonal stimuli, developmental cues, and pathogenic infections. Beyond its canonical role in transcription, HEXIM1 functions as a tumor suppressor, a modulator of nuclear receptor signaling, a regulator of developmental angiogenesis, and a critical determinant of hematopoietic and neuronal differentiation. Its expression is frequently dysregulated in cancer, and its induction serves as a pharmacodynamic biomarker for BET bromodomain inhibitor efficacy.

| Attribute | Detail |
| :--- | :--- |
| **HGNC Symbol** | HEXIM1 |
| **UniProt Accession** | O94992 |
| **Representative PDB ID** | True (e.g., 4Z8F, 5LTO; see Section 2) |
| **Chromosomal Locus** | 17q21.31 (GRCh38: chr17:45,147,950-45,150,355; minus strand) |
| **Primary Molecular Function** | RNA-binding; inhibition of P-TEFb (CDK9/Cyclin T1) kinase activity; regulation of RNAP2 transcriptional elongation |
| **Disease & Pathology Associations** | Breast cancer, melanoma, acute myeloid leukemia (AML), prostate cancer, cardiac hypertrophy, heart/vascular development defects, Alzheimer's disease, HIV-1 latency, Chagas disease susceptibility |

## 1. Genomic Locus, Chromosomal Organization & Isoforms

### 1.1 Chromosomal Localization and Gene Structure

The human *HEXIM1* gene is located on the long arm of chromosome 17 at cytogenetic band 17q21.31. This region is notable for its gene density and its association with several neurodevelopmental and cancer-related loci. The gene is transcribed from the minus (Crick) strand, with the primary transcript spanning approximately 2.4 kilobases of genomic DNA. The mature messenger RNA is composed of 7 exons, which are variably spliced to generate multiple transcript variants.

The core promoter of *HEXIM1* lacks a canonical TATA box but is rich in GC content, a feature common to housekeeping and developmentally regulated genes. Promoter-proximal elements include binding sites for Sp1 (Specificity Protein 1), which is constitutively expressed and contributes to basal transcription. Importantly, the promoter region contains functional response elements for several signal-dependent transcription factors, including:
- **Estrogen Receptor α (ERα):** Estrogen-bound ERα represses *HEXIM1* transcription, providing a direct mechanistic link between hormonal signaling and transcriptional elongation control [21].
- **Hypoxia-Inducible Factor 1α (HIF-1α):** Hypoxic conditions downregulate *HEXIM1* expression, partly through HIF-1α-dependent mechanisms, which in turn relieves the repression of pro-angiogenic genes [76][77].
- **p53:** HEXIM1 is a positive regulator of p53 stability, and p53 can in turn influence *HEXIM1* expression, forming a positive feedback loop that is critical for tumor suppression [79].

### 1.2 Enhancer Elements and Chromatin Architecture

Chromatin immunoprecipitation followed by sequencing (ChIP-seq) studies in erythroid cells and keratinocytes have revealed that the *HEXIM1* locus is marked by active enhancer-associated histone modifications, including H3K4me1 and H3K27ac, particularly in progenitor cell populations. The locus also contains a putative super-enhancer element that is occupied by the BET family bromodomain protein BRD4. This interaction is of high clinical relevance: treatment with BET inhibitors (e.g., OTX015, JQ1) leads to a rapid and robust displacement of BRD4 from this enhancer, resulting in the transcriptional de-repression and upregulation of *HEXIM1* [16][28][33]. This mechanism underpins the utility of HEXIM1 as a pharmacodynamic biomarker for BET inhibitor target engagement.

### 1.3 Alternative Splicing and Isoforms

Alternative splicing of the *HEXIM1* primary transcript gives rise to several mRNA isoforms. The predominant, canonical isoform (ENST00000254852) encodes a 359-amino acid protein with a molecular weight of approximately 41 kDa. However, a second major isoform, which utilizes an alternative acceptor site in exon 4, results in a protein product with a 13-amino acid insertion in the central region of the protein. This insertion lies within the dimerization domain and has been shown to modulate the affinity of HEXIM1 for the 7SK snRNA, thereby altering the stability of the 7SK snRNP complex.

Additional minor splice variants have been reported in expressed sequence tag (EST) databases, some of which predict C-terminally truncated proteins. These truncated isoforms, if translated, would lack the critical P-TEFb inhibitory domain and could potentially act as dominant-negative regulators. However, the endogenous expression and physiological relevance of these minor isoforms remain to be fully validated.

## 2. 3D Protein Domain Architecture & Structural Biology

### 2.1 Primary Structure and Domain Organization

The HEXIM1 protein is a 359-amino acid polypeptide that can be structurally and functionally divided into four distinct regions, proceeding from the N-terminus to the C-terminus:

1.  **N-Terminal Proline-Rich Region (aa 1–130):** This region is intrinsically disordered and contains a polyproline tract. It is not required for 7SK snRNA binding or P-TEFb inhibition but is implicated in protein-protein interactions with factors such as the histone demethylase KDM5B [50] and the glucocorticoid receptor (GR) [36][38].

2.  **Dimerization Domain (aa 130–180):** This region contains a coiled-coil motif that mediates the homo-dimerization of HEXIM1. Dimerization is a prerequisite for high-affinity 7SK snRNA binding and for the subsequent recruitment and inhibition of P-TEFb [91]. The dimerization interface is critical for the stability of the entire 7SK snRNP complex.

3.  **Basic RNA-Binding Region (aa 150–200):** This is a highly basic, arginine- and lysine-rich region that directly interacts with the 5' hairpin of 7SK snRNA. Structural studies have shown that this region adopts an extended conformation upon RNA binding. The basic region also confers HEXIM1 with the ability to bind to other double-stranded RNAs (dsRNAs) with low affinity and promiscuity, suggesting a broader role in RNA metabolism beyond 7SK snRNP regulation [34].

4.  **C-Terminal P-TEFb Inhibitory Domain (aa 200–359):** This domain is responsible for the direct binding and inhibition of the CDK9/Cyclin T1 heterodimer. Within this domain, a highly conserved peptide sequence (residues 202–210, with the core motif YGNILQNLI) has been identified as the minimal inhibitory element. This peptide binds directly to the catalytic cleft of CDK9, acting as a steric and allosteric blocker of substrate access [71]. The extreme C-terminus also contains a nuclear localization signal (NLS) and a binding site for Cyclin T1 [90].

### 2.2 Quaternary Structure and the 7SK snRNP Complex

The functional unit of HEXIM1 is a dimer. In the context of the 7SK snRNP, a single 7SK snRNA molecule coordinates a dimer of HEXIM1 and two molecules of P-TEFb (each composed of CDK9 and Cyclin T1 or T2), forming a large, inactive complex of approximately 450 kDa [30]. The stoichiometry is precisely controlled: one 7SK RNA, one HEXIM1 dimer, and two P-TEFb heterodimers [30]. The binding of 7SK snRNA induces a conformational change in HEXIM1 that exposes the C-terminal inhibitory domain, allowing it to engage CDK9 and block its kinase activity [89].

### 2.3 Post-Translational Modifications and Structural Dynamics

The activity of HEXIM1 is exquisitely regulated by post-translational modifications (PTMs), which induce conformational changes that control its association with the 7SK snRNP:

- **Phosphorylation:** Phosphorylation of specific tyrosine residues (Tyr271 and Tyr274) within the C-terminal domain by kinases such as c-Abl promotes the release of P-TEFb from the 7SK snRNP, thereby activating transcription [9]. Conversely, phosphorylation of CDK9 at Threonine 186 (T186) within the activation loop is required for the stable incorporation of P-TEFb into the inactive complex [30].
- **Acetylation:** The deacetylase HDAC3 can deacetylate HEXIM1, promoting its association with the 7SK snRNP and enhancing transcriptional repression under hypoxic conditions [11].
- **Redox Regulation:** The intracellular redox state influences the assembly of the 7SK snRNP. Oxidative stress can lead to the dissociation of HEXIM1 and P-TEFb from the complex, a process modulated by the protein Tip110 (SART3) [12].

> **[Interactive 3D Protein Visualizer: Load HEXIM1 (PDB: true)](/tools/protein-structure-viewer?source=alphafold&accession=O94992)**
>
> This interactive viewer allows for the exploration of the HEXIM1 three-dimensional structure. Users can rotate the molecule, highlight specific domains (e.g., the dimerization domain, the basic RNA-binding region, and the C-terminal inhibitory domain), and visualize the spatial arrangement of key post-translational modification sites, including Tyr271 and Tyr274. The viewer is pre-loaded with the representative PDB structure, enabling a detailed analysis of the protein's surface electrostatic potential, which is critical for its interaction with the negatively charged 7SK snRNA backbone.

## 3. Cellular Signaling Pathways & Molecular Function

### 3.1 The Canonical Pathway: P-TEFb Regulation and Transcriptional Elongation

The central function of HEXIM1 is the negative regulation of P-TEFb, a kinase complex composed of Cyclin-Dependent Kinase 9 (CDK9) and a cyclin partner (Cyclin T1, T2, or K). P-TEFb is the master regulator of the elongation phase of transcription by RNA Polymerase II (RNAP2). It phosphorylates the C-terminal domain (CTD) of RNAP2 at Serine 2 and Serine 5, as well as the negative elongation factors NELF (Negative Elongation Factor) and DSIF (DRB Sensitivity Inducing Factor). This phosphorylation event releases RNAP2 from promoter-proximal pausing and allows for productive processive elongation [43].

In actively dividing cells, a significant portion of the cellular P-TEFb pool is sequestered in the inactive 7SK snRNP complex, where HEXIM1 acts as the primary inhibitor. The equilibrium between the active (free) and inactive (7SK-bound) pools of P-TEFb is a dynamic and highly regulated process that determines the transcriptional output of the cell. HEXIM1, therefore, functions as a global gatekeeper of gene expression, controlling the magnitude and kinetics of the transcriptional response to various stimuli.

```mermaid
graph TD
    subgraph "Inactive 7SK snRNP Complex"
        A["7SK snRNA"] --> B["HEXIM1 Dimer"]
        B --> C["P-TEFb (CDK9/Cyclin T1)"]
        C --> D["RNAP2 CTD"]
        D -->|"Phosphorylation Blocked"| E["Paused RNAP2"]
    end

    subgraph "Stimuli & Activators"
        F["HMBA, Stress, BET inhibitors"]
        G["Tat (HIV-1), Tax (HTLV-1)"]
        H["Signaling Kinases (e.g., c-Abl)"]
    end

    F --> I["HEXIM1 Upregulation / 7SK snRNP Disassembly"]
    G --> I
    H --> I

    I --> J["Release of Active P-TEFb"]
    J --> K["Phosphorylation of RNAP2 CTD, NELF, DSIF"]
    K --> L["Transcriptional Elongation of Target Genes"]

    E --> L
```

### 3.2 Context-Dependent Functions: Beyond Global Repression

While HEXIM1 is a global repressor of transcription, its effects are highly gene-specific. This specificity is achieved through its interaction with various transcription factors and chromatin modifiers, which tether HEXIM1 to specific genomic loci.

- **Nuclear Receptor Signaling:** HEXIM1 directly interacts with the ligand-binding domains of Estrogen Receptor α (ERα) and Androgen Receptor (AR). By competing with these receptors for binding to Cyclin T1, HEXIM1 disrupts the recruitment of P-TEFb to estrogen- and androgen-responsive gene promoters, thereby inhibiting their transcriptional activity [46][26]. This mechanism is central to its tumor-suppressive role in hormone-dependent cancers. HEXIM1 also forms a transcriptionally abortive complex with the Glucocorticoid Receptor (GR), repressing GR target genes in a 7SK RNA- and P-TEFb-independent manner [36][38].

- **Hypoxia Signaling:** HEXIM1 downregulates the protein stability of Hypoxia-Inducible Factor 1α (HIF-1α), a master regulator of the cellular response to low oxygen. This leads to reduced expression of pro-angiogenic factors such as Vascular Endothelial Growth Factor (VEGF) [76][77]. This function is critical for normal heart and vascular development [4][22] and for the prevention of pathological angiogenesis in cancer.

- **p53 Pathway:** HEXIM1 directly binds to the tumor suppressor p53 and enhances its protein stability by inhibiting its ubiquitination and proteasomal degradation. This interaction potentiates p53-dependent transcriptional responses to DNA damage and cellular stress, reinforcing HEXIM1's role as a tumor suppressor [79].

- **Cell Cycle and Differentiation:** HEXIM1 expression is dynamically regulated during cell cycle progression and differentiation. In human pluripotent stem cells (hPSCs), HEXIM1 overexpression is sufficient to induce differentiation [32]. In the epidermis, a switch in CDK9 association from the Super Elongation Complex (SEC) component AFF1 to HEXIM1 controls the initiation of differentiation from progenitor cells [70]. Similarly, HEXIM1 is essential for proper erythroid maturation, where it regulates the expression of genes critical for hemoglobin production and enucleation [5][7][8][69]. In neurons, HEXIM1 controls the rapid and robust induction of immediate early genes (IEGs) following depolarization, a process essential for synaptic plasticity and memory formation [2][10].

### 3.3 Protein-Protein Interaction Networks

HEXIM1 is a hub in a complex network of protein-protein interactions. Key interacting partners, curated from BioGRID and STRING databases, include:

- **Core Complex Members:** CDK9, Cyclin T1, Cyclin T2, 7SK snRNA, LARP7, MEPCE, BCDIN3D.
- **Transcription Factors:** ERα, AR, GR, p53, HIF-1α, NF-κB (p65) [19], CIITA [95].
- **Chromatin Regulators:** BRD4, KDM5B, HDAC3.
- **Viral Proteins:** HIV-1 Tat [88], HTLV-1 Tax [31], Alpha-herpesvirus proteins [6].
- **Other Regulators:** Tip110/SART3 [12], hnRNP A1 [29].

## 4. Pathogenic Hotspot Mutations & Clinical Differentials

While germline mutations in *HEXIM1* are not a common cause of Mendelian disease, somatic alterations and functional dysregulation are strongly implicated in a wide range of pathologies. The clinical significance of HEXIM1 is primarily driven by its altered expression levels and post-translational modifications rather than by frequent, recurring point mutations.

### 4.1 Somatic Mutations and Expression Changes in Cancer

- **Breast Cancer:** *HEXIM1* expression is significantly decreased in a large proportion of human breast tumors, particularly in aggressive, hormone-resistant, and metastatic subtypes [17][20]. This downregulation is mediated by estrogen signaling [21] and by the histone demethylase KDM5B, which represses *HEXIM1* transcription [50]. Loss of HEXIM1 leads to unchecked ERα and AR activity, increased VEGF expression, and enhanced tumor angiogenesis [87]. Critically, low HEXIM1 expression is a predictor of poor response to tamoxifen therapy [85].
- **Melanoma:** *HEXIM1* functions as a melanoma tumor suppressor. Its expression is low in melanoma cell lines and patient samples. Mechanistically, HEXIM1 responds to nucleotide stress; its overexpression suppresses melanoma growth, while its loss accelerates tumorigenesis [14][74][80].
- **Acute Myeloid Leukemia (AML):** In AML, particularly in subtypes expressing mutant Nucleophosmin 1 (NPMc+) or MLL-fusion proteins, autophagy is activated, leading to the degradation of HEXIM1. This degradation relieves the brake on P-TEFb, contributing to the aberrant transcriptional program that drives leukemogenesis [23]. Consequently, the induction of HEXIM1 is a key mechanistic event in the anti-leukemic activity of BET inhibitors [28][33].
- **Prostate Cancer:** Similar to breast cancer, HEXIM1 acts as a co-repressor of the Androgen Receptor (AR). Its expression is lost in advanced prostate cancer, and its restoration enhances the efficacy of anti-androgens [26].

### 4.2 Mutations in Model Systems and Developmental Defects

Studies in genetically modified mice have provided profound insights into the physiological roles of HEXIM1. A knock-in mouse model expressing a mutant HEXIM1 protein with a disrupted C-terminus (which cannot bind P-TEFb) exhibits severe defects in heart and vascular development, characterized by aberrant VEGF expression and embryonic lethality [4][40]. These studies established HEXIM1 as a critical regulator of cardiovascular morphogenesis. Furthermore, heterozygous loss of *Hexim1* in mice leads to a rapidly progressive and more severe course of *Trypanosoma cruzi* infection, the causative agent of Chagas disease, highlighting a role for HEXIM1 in the host immune response [1].

### 4.3 Neurodegenerative Disease

Recent evidence links HEXIM1 to Alzheimer's disease (AD) pathology. HEXIM1 expression is correlated with AD pathology in human brain samples, and its regulation of immediate early gene (IEG) dynamics in neurons is critical for cognitive function [10]. Dysregulation of HEXIM1 may contribute to the transcriptional dysfunction observed in AD.

### 4.4 ClinVar and Pathogenic Variants

As of the latest data update, ClinVar contains a limited number of variants in *HEXIM1*. Most are of uncertain significance (VUS) or benign. However, a few missense variants have been reported in the C-terminal domain that are predicted to be damaging by in silico tools (e.g., SIFT, PolyPhen-2). These variants are hypothesized to disrupt P-TEFb binding, but their clinical phenotypes have not been fully established. Large-scale sequencing efforts in cancer (e.g., TCGA) have identified recurrent, but low-frequency, somatic mutations in *HEXIM1*, primarily in the dimerization and RNA-binding domains, which may act as loss-of-function alleles.

## 5. Host-Pathogen & Viral Interactions

HEXIM1 sits at the nexus of the host transcriptional machinery and several viral pathogens that depend on it for their replication.

### 5.1 Human Immunodeficiency Virus Type 1 (HIV-1)

The most well-characterized viral interaction is with the HIV-1 transactivator protein Tat. HIV-1 transcription is highly dependent on P-TEFb. The viral Tat protein binds to the TAR (Trans-Activation Response) element on the nascent viral RNA and recruits P-TEFb to the viral promoter to stimulate processive transcription. To do this, Tat must liberate P-TEFb from the inactive 7SK snRNP complex. Tat achieves this by directly competing with HEXIM1 for binding to Cyclin T1 [88][90]. The binding of Tat to the 7SK snRNP induces a conformational change in the 7SK RNA, leading to the release of both P-TEFb and HEXIM1 [84]. This competition is so critical that a single point mutation in Cyclin T1 that eliminates HEXIM1 binding but retains Tat binding can enforce repression of HIV transcription [27]. Furthermore, a chimeric protein fusing HEXIM1 to Tat has been engineered to act as a dominant-negative inhibitor of HIV-1 replication, demonstrating the therapeutic potential of targeting this interaction [18]. The phosphorylation of HEXIM1 at Tyr271/Tyr274, which promotes P-TEFb release, also enhances proviral HIV gene expression [9].

### 5.2 Human T-Lymphotropic Virus Type 1 (HTLV-1)

The HTLV-1 Tax protein also targets the P-TEFb regulatory axis. Tax complexes with P-TEFb and competes with both BRD4 and the 7SK snRNP/HEXIM1 complex for binding [31][60]. This competition serves to increase the active pool of P-TEFb, driving viral transcription and dysregulating cellular gene expression, contributing to HTLV-1-induced oncogenesis.

### 5.3 Alpha-Herpesviruses

Recent research has demonstrated that an alpha-herpesvirus (e.g., Marek's disease virus) employs host HEXIM1 to promote viral transcription. The virus appears to manipulate the 7SK snRNP complex, potentially by recruiting HEXIM1 to viral promoters or by altering its phosphorylation status, to ensure robust expression of viral genes [6].

### 5.4 Parasitic Infections

As mentioned in Section 4.2, HEXIM1 plays a role in the host response to *Trypanosoma cruzi* infection. Mice heterozygous for *Hexim1* show a rapidly progressive and fatal course of infection, suggesting that HEXIM1 is required for an effective immune response, possibly through its regulation of inflammatory gene expression [1].

## 6. Pharmacogenomics, Drug Targets & Small-Molecule Inhibitors

HEXIM1 is not a classical drug target (i.e., an enzyme or receptor that can be directly inhibited by a small molecule). Instead, its therapeutic relevance lies in its role as a downstream effector and a pharmacodynamic biomarker for other classes of drugs.

### 6.1 BET Bromodomain Inhibitors

The most significant pharmacological connection is with BET (Bromodomain and Extra-Terminal) inhibitors. These drugs (e.g., JQ1, OTX015/MK-8628, INCB054329, BI 894999, ABBV-075) target the bromodomains of BRD2, BRD3, and BRD4, displacing them from chromatin [44][55][59]. Since BRD4 is a key activator of P-TEFb and occupies the *HEXIM1* super-enhancer, BET inhibition leads to a rapid and robust upregulation of *HEXIM1* expression [16][28][33][73]. This induction is a direct consequence of target engagement and is required for the full anti-proliferative and pro-differentiative effects of BET inhibitors in AML and other cancers [28][33]. Consequently, HEXIM1 is now widely used as a robust pharmacodynamic marker to monitor BET inhibitor activity in tumors and surrogate tissues like peripheral blood mononuclear cells (PBMCs) [16][72]. The upregulation of HEXIM1 by BET inhibitors also contributes to their on-target but dose-limiting toxicity, such as thrombocytopenia [39].

### 6.2 KDM5B Inhibitors

Inhibitors of the histone demethylase KDM5B have been shown to upregulate HEXIM1 expression. Since KDM5B represses *HEXIM1* transcription, its inhibition relieves this repression, leading to increased HEXIM1 levels. This mechanism contributes to the anti-tumor effects of KDM5B inhibitors in triple-negative breast cancer [50][97]. Furthermore, KDM5B inhibition can induce a cGAS/STING-independent type I interferon response, which is partly mediated by HEXIM1 [97].

### 6.3 Other Inducers and Modulators

- **HMBA (Hexamethylene bis-acetamide):** The compound from which HEXIM1 derives its name. HMBA is a potent inducer of *HEXIM1* expression and cellular differentiation [35][92]. It is also a putative HSP70 activator, and this activity may contribute to its ability to stimulate HEXIM1 expression [21].
- **DNMT1 Inhibitors:** Non-epigenetic induction of HEXIM1 by DNMT1 inhibitors has been reported, adding another layer of complexity to their mechanism of action [15].
- **CDK9 Inhibitors:** While not directly targeting HEXIM1, CDK9 inhibitors (e.g., those in development for cancer) functionally mimic the effect of HEXIM1 by blocking P-TEFb kinase activity. Combining CDK9 inhibitors with BET inhibitors has shown synergistic activity in preclinical models [65].

### 6.4 Gene Therapy and Biologicals

Given its tumor-suppressive functions, restoring HEXIM1 expression is a therapeutic goal. While no gene therapy vectors are currently in clinical trials, adenoviral or lentiviral vectors expressing *HEXIM1* have been used in preclinical models to demonstrate its anti-tumor and anti-hypertrophic effects [37][75]. The HEXIM1-Tat chimera represents a novel biological approach to inhibit HIV-1 replication [18].

## 7. Bioinformatic Resources & Database Accessions

| Database | Accession ID / Link |
| :--- | :--- |
| **HGNC** | [HEXIM1 (HGNC:4874)](https://www.genenames.org/data/gene-symbol-report/#!/hgnc_id/HGNC:4874) |
| **NCBI Gene** | [Gene ID: 10614](https://www.ncbi.nlm.nih.gov/gene/10614) |
| **Ensembl** | [ENSG00000138399](https://www.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000138399) |
| **UniProt** | [O94992](https://www.uniprot.org/uniprotkb/O94992/entry) |
| **RCSB PDB** | [Search for HEXIM1](https://www.rcsb.org/search?q=HEXIM1) |
| **OMIM** | [607654](https://www.omim.org/entry/607654) |
| **ClinVar** | [HEXIM1](https://www.ncbi.nlm.nih.gov/clinvar/?term=HEXIM1%5Bgene%5D) |
| **STRING** | [HEXIM1 Network](https://string-db.org/network/9606.ENSP00000263867) |
| **BioGRID** | [HEXIM1](https://thebiogrid.org/109361) |
| **Gene Ontology (GO)** | [GO:0006355 (regulation of transcription)](https://www.ebi.ac.uk/QuickGO/term/GO:0006355), [GO:0003723 (RNA binding)](https://www.ebi.ac.uk/QuickGO/term/GO:0003723), [GO:0004693 (cyclin-dependent protein serine/threonine kinase inhibitor activity)](https://www.ebi.ac.uk/QuickGO/term/GO:0004693) |
| **CCLE (Cancer Cell Line Encyclopedia)** | [HEXIM1 Expression](https://portals.broadinstitute.org/ccle) |
| **TCGA (The Cancer Genome Atlas)** | [HEXIM1 in Pan-Cancer](https://portal.gdc.cancer.gov/) |

## Related Clinical & Scientific Guides

* [TARM1 Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/tarm1-gene-structure-function-pathway)
* [TRAC Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/trac-gene-structure-function-pathway)
* [CFD Gene: Structure, Function, and Clinical Significance](/knowledge/bioinformatics/genes/immunology-checkpoints/cfd-gene-structure-function-pathway)


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