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GeneE
26 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HEXIM1
HEXIM P-TEFb complex subunit 1
Chromosome 17 · 17q21.31
NCBI Gene: 10614Ensembl: ENSG00000186834.4HGNC: HGNC:24953UniProt: O94992
165PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Highly ConstrainedTranscription Factor
RESEARCH IMPACT
Trending
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
protein kinase inhibitor activitycyclin-dependent protein serine/threonine kinase inhibitor activityprotein bindingsnRNA bindingintelligenceneurodegenerative diseaseinsomniaallergic disease
✦AI Summary

HEXIM1 is a transcriptional regulator that functions as a general inhibitor of RNA polymerase II transcription elongation 1. As a core component of the 7SK ribonucleoprotein (RNP) complex, HEXIM1 sequesters the positive transcription elongation factor b (P-TEFb) into an inactive state, preventing P-TEFb-mediated phosphorylation of RNA polymerase II and blocking transcriptional elongation 2. This inhibitory mechanism is dynamically regulated—EGF signaling triggers METTL3-mediated methylation of 7SK RNA, causing HEXIM1/P-TEFb complex release and transcriptional activation 3. Beyond transcriptional control, HEXIM1 assembles into the HDP-RNP complex with NEAT1 long non-coding RNA and paraspeckle proteins, serving as a platform for innate immune response activation by facilitating IRF3 phosphorylation through the cGAS-STING pathway 4. HEXIM1 expression is significantly correlated with Alzheimer's disease pathology and regulates immediate early gene dynamics critical for memory formation, with its P-TEFb-inhibitory function controlling the rapid neuronal gene transcription required for synaptic plasticity 5. Dysregulation of HEXIM1-mediated P-TEFb control contributes to inflammatory and neoplastic conditions, establishing HEXIM1 as a multifunctional tumor suppressor involved in transcriptional and immune regulation 6.

Sources cited
1
P-TEFb regulation by HEXIM1 in 7SK snRNP and its role in transcription elongation control
PMID: 36599353
2
HEXIM1 as opposing regulator of P-TEFb and its roles in cancer and cell cycle progression
PMID: 24592384
3
HEXIM1 assembly into HDP-RNP complex and regulation of DNA-mediated innate immune response via cGAS-STING-IRF3 pathway
PMID: 28712728
4
7SK methylation by METTL3 promotes HEXIM1/P-TEFb complex release and transcriptional activation
PMID: 37163588
5
HEXIM1 correlation with Alzheimer's disease pathology and regulation of neuronal immediate early genes and synaptic plasticity
PMID: 39386727
6
HEXIM1 as P-TEFb inhibitor involved in cancer, inflammation, AIDS, and cardiac hypertrophy
PMID: 17671421
Disease Associationsⓘ20
intelligenceOpen Targets
0.40Moderate
neurodegenerative diseaseOpen Targets
0.37Weak
insomniaOpen Targets
0.37Weak
Abnormal thrombosisOpen Targets
0.34Weak
allergic diseaseOpen Targets
0.34Weak
respiratory system diseaseOpen Targets
0.34Weak
deep vein thrombosisOpen Targets
0.32Weak
femur fractureOpen Targets
0.29Weak
bowel dysfunctionOpen Targets
0.15Weak
hypertensionOpen Targets
0.13Weak
osteoarthritisOpen Targets
0.12Weak
neoplasmOpen Targets
0.09Suggestive
breast cancerOpen Targets
0.08Suggestive
triple-negative breast cancerOpen Targets
0.08Suggestive
left ventricular noncompactionOpen Targets
0.07Suggestive
hypertrophic cardiomyopathyOpen Targets
0.07Suggestive
Rare familial disorder with hypertrophic cardiomyopathyOpen Targets
0.07Suggestive
dilated cardiomyopathyOpen Targets
0.06Suggestive
dilated cardiomyopathy 2AOpen Targets
0.05Suggestive
dilated cardiomyopathy 1MOpen Targets
0.05Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
CCNT1Protein interaction100%CCNT2Protein interaction100%CDK9Protein interaction100%AFF1Protein interaction100%PPM1GProtein interaction100%SART3Protein interaction100%
Tissue Expression6 tissues
Bone Marrow
100%
Liver
65%
Lung
55%
Heart
50%
Ovary
39%
Brain
38%
Gene Interaction Network
Click a node to explore
HEXIM1CCNT1CCNT2CDK9AFF1PPM1GSART3
PROTEIN STRUCTURE
Preparing viewer…
PDB3S9G · 2.10 Å · X-ray
View on RCSB ↗
Constraintⓘ
LOEUFⓘ
0.15Highly Constrained
pLIⓘ
1.00Intolerant
Observed/Expected LoF0.03 [0.01–0.15]
RankingsWhere HEXIM1 stands among ~20K protein-coding genes
  • #2,710of 20,598
    Most Researched165 · top quartile
  • #201of 17,882
    Most Constrained (LOEUF)0.15 · top 5%
Genes detectedHEXIM1
Sources retrieved26 papers
Response time—
📄 Sources
26▼
1
P-TEFb: The master regulator of transcription elongation.
PMID: 36599353
Mol Cell · 2023
1.00
2
Brd4 and HEXIM1: multiple roles in P-TEFb regulation and cancer.
PMID: 24592384
Biomed Res Int · 2014
0.90
3
HEXIM1 and NEAT1 Long Non-coding RNA Form a Multi-subunit Complex that Regulates DNA-Mediated Innate Immune Response.
PMID: 28712728
Mol Cell · 2017
0.80
4
cGAS/STING-Independent Induction of Type I Interferon by Inhibitors of the Histone Methylase KDM5B.
PMID: 40353728
FASEB J · 2025
0.76
5
Hexim1, an RNA-controlled protein hub.
PMID: 29345523
Transcription · 2018
0.70