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10 sources retrieved · Most recent: April 2026 · Index updated 15 days ago
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HEXIM2
HEXIM P-TEFb complex subunit 2
Chromosome 17 · 17q21.31
NCBI Gene: 124790Ensembl: ENSG00000168517.12HGNC: HGNC:28591UniProt: Q96MH2
52PubMed Papers
20Diseases
0Drugs
0Pathogenic Variants
FUNCTIONAL ROLE
Transcription Factor
DATA QUALITY
✓ Experimental GO Evidence✓ Swiss-Prot Reviewed
cyclin-dependent protein serine/threonine kinase inhibitor activityprotein bindingsnRNA bindingidentical protein bindingneurodegenerative diseaseaortic stenosisintelligenceessential hypertension
✦AI Summary

HEXIM2 is a transcriptional regulator functioning as a general RNA polymerase II transcription inhibitor 12. It serves as a core component of the 7SK ribonucleoprotein (RNP) complex, where it cooperates with 7SK snRNA to sequester P-TEFb (positive transcription elongation factor b) in an inactive state, preventing RNA polymerase II C-terminal domain phosphorylation and blocking transcriptional elongation 12. HEXIM2 binds the 7SK hairpin loop region (nucleotides 23-88) with high affinity and forms stable homo- and hetero-oligomers, likely dimers, with HEXIM1 34. The inactive P-TEFb complex contains one 7SK molecule, a HEXIM dimer, and two P-TEFb molecules 4. HEXIM1 and HEXIM2 exhibit functionally redundant but tissue-specific expression patterns; HEXIM2 can compensate for HEXIM1 loss to maintain balanced active/inactive P-TEFb ratios controlling global transcription and cell growth 12. Beyond transcriptional control, HEXIM2 has shown associations with disease susceptibility, including a positive causal relationship with Type 2 diabetes mellitus 5 and potential involvement in esophageal cancer prognosis 6 and glioma progression 7. These findings establish HEXIM2 as a critical regulator of transcriptional elongation with broader roles in metabolic and oncologic disease pathogenesis.

Sources cited
1
HEXIM2 inactivates P-TEFb through 7SK-mediated interaction and functionally compensates for HEXIM1 loss
PMID: 15713661
2
HEXIM2 forms complexes with 7SK and P-TEFb, inhibiting P-TEFb kinase activity
PMID: 15713662
3
HEXIM2 binds 7SK hairpin loop (nucleotides 23-88) with tight affinity and forms tripartite complexes with Cyclin T and importin alpha
PMID: 19883659
4
HEXIM2 functions as a dimer in the inactive P-TEFb complex containing one 7SK molecule and two P-TEFb molecules
PMID: 15965233
5
HEXIM2 shows positive causal association with Type 2 diabetes mellitus risk
PMID: 40026415
6
HEXIM2 identified as prognosis-associated gene in esophageal cancer radiotherapy response
PMID: 40381695
7
HEXIM2 included in RNA-binding protein signature associated with glioma prognosis prediction
PMID: 34482648
Disease Associationsⓘ20
neurodegenerative diseaseOpen Targets
0.24Weak
aortic stenosisOpen Targets
0.22Weak
intelligenceOpen Targets
0.21Weak
essential hypertensionOpen Targets
0.14Weak
hypertensionOpen Targets
0.11Weak
femur fractureOpen Targets
0.11Weak
osteoarthritisOpen Targets
0.07Suggestive
respiratory system diseaseOpen Targets
0.06Suggestive
insomniaOpen Targets
0.06Suggestive
deep vein thrombosisOpen Targets
0.05Suggestive
Abnormal thrombosisOpen Targets
0.05Suggestive
allergic diseaseOpen Targets
0.05Suggestive
ovarian neoplasmOpen Targets
0.04Suggestive
bowel dysfunctionOpen Targets
0.02Suggestive
COVID-19Open Targets
0.01Suggestive
infectionOpen Targets
0.01Suggestive
esophageal cancerOpen Targets
0.01Suggestive
myelodysplastic syndromeOpen Targets
0.01Suggestive
Alzheimer diseaseOpen Targets
0.00Suggestive
hepatocellular carcinomaOpen Targets
0.00Suggestive
Pathogenic Variants
No pathogenic variants reported on ClinVar for this gene.
View on ClinVar ↗
Related Genes
PDIK1LShared pathway100%STK35Shared pathway100%BRD4Protein interaction100%CCNT2Protein interaction99%CCNT1Protein interaction94%CDK9Protein interaction94%
Tissue Expression6 tissues
Liver
100%
Brain
97%
Ovary
75%
Heart
63%
Lung
50%
Bone Marrow
30%
Gene Interaction Network
Click a node to explore
HEXIM2PDIK1LSTK35BRD4CCNT2CCNT1CDK9
PROTEIN STRUCTURE
Preparing viewer…
AlphaFoldAI-predicted · UniProt Q96MH2
View on AlphaFold ↗
Constraintⓘ
LOEUFⓘ
1.69LoF Tolerant
pLIⓘ
0.42Tolerant
Observed/Expected LoF0.00 [0.00–1.69]
RankingsWhere HEXIM2 stands among ~20K protein-coding genes
  • #8,561of 20,598
    Most Researched52
  • #16,079of 17,882
    Most Constrained (LOEUF)1.69
Genes detectedHEXIM2
Sources retrieved10 papers
Response time—
📄 Sources
10▼
1
Specificity of Hexim1 and Hexim2 complex formation with cyclin T1/T2, importin alpha and 7SK snRNA.
PMID: 19883659
J Mol Biol · 2010
1.00
2
Compensatory contributions of HEXIM1 and HEXIM2 in maintaining the balance of active and inactive positive transcription elongation factor b complexes for control of transcription.
PMID: 15713661
J Biol Chem · 2005
0.90
3
HEXIM2, a HEXIM1-related protein, regulates positive transcription elongation factor b through association with 7SK.
PMID: 15713662
J Biol Chem · 2005
0.80
4
Exploring Potential Drug Targets in Multiple Cardiovascular Diseases: A Study Based on Proteome-Wide Mendelian Randomization and Colocalization Analysis.
PMID: 40026415
Cardiovasc Ther · 2025
0.70
5
Machine learning-based multimodal radiomics and transcriptomics models for predicting radiotherapy sensitivity and prognosis in esophageal cancer.
PMID: 40381695
J Biol Chem · 2025
0.60