HEXIM1

Chr 17

HEXIM P-TEFb complex subunit 1

Also known as: EDG1, HIS1, MAQ1

NCBI Gene: 10614ENSG00000186834UniProt: O94992

Expression of this gene is induced by hexamethylene-bis-acetamide in vascular smooth muscle cells. This gene has no introns. [provided by RefSeq, Jul 2008]

1
Active trials
10
Pathogenic / LP
51
ClinVar variants
4
Pubs (1 yr)
1.4
Missense Z
0.24
LOEUF· LoF intolerant
Clinical Summary— HEXIM1
⚡
Population Constraint (gnomAD)
Highly constrained gene — heterozygous loss-of-function variants are very rare in the population (pLI 0.98). One damaged copy is likely sufficient to cause disease.
📋
ClinVar Variants
10 Pathogenic / Likely Pathogenic· 39 VUS of 51 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
LoF intolerant — likely haploinsufficient
LoF Constraint?LOEUF (Loss-of-function Observed/Expected Upper bound Fraction) is the upper bound of the 90% CI for LoF OE — the preferred gnomAD v4 metric. Lower = more intolerant to LoF. LOEUF < 0.35 = highly constrained.
0.24LOEUF
pLI 0.984
Z-score 3.28
OE 0.00 (0.00–0.24)
Highly constrained

Highly LoF-intolerant (top ~10% of genes)

Missense Constraint?Missense Z-score: standard deviations fewer missense variants observed vs. expected. Z > 3.09 (p < 0.001) = gene does not tolerate missense variation. OE missense < 0.6 is also considered constrained.
1.41Z-score
OE missense 0.72 (0.63–0.82)
141 obs / 196.6 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios?Shaded band = 90% confidence interval. Vertical tick = point estimate. Grey threshold line = gnomAD constraint cutoff for that variant class.
LoF OE?Ratio of observed to expected LoF variants. Upper CI bound (LOEUF) ≤ 0.35 = strong LoF constraint signal.0.00 (0.00–0.24)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.72 (0.63–0.82)
0≤0.61.4
Synonymous OE?Control metric — synonymous variants are largely neutral and expected near OE = 1.0. Significant deviation may indicate annotation issues.1.25
0≤1.21.6
LoF obs/exp: 0 / 12.6Missense obs/exp: 141 / 196.6Syn Z: -1.88

ClinVar Variant Classifications

51 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic10
VUS39
Likely Benign1
Benign1
10
Pathogenic
39
VUS
1
Likely Benign
1
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
10
0
10
Likely Pathogenic
0
0
0
0
0
VUS
0
37
2
0
39
Likely Benign
0
1
0
0
1
Benign
0
0
0
1
1
Total03812151

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

HEXIM1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
USP44 regulates HEXIM1 stability to inhibit tumorigenesis and metastasis of oral squamous cell carcinoma.
Chen S et al.·Biol Direct
2024
cGAS/STING-Independent Induction of Type I Interferon by Inhibitors of the Histone Methylase KDM5B.
Montano MM et al.·FASEB J
2025
Non-epigenetic induction of HEXIM1 by DNMT1 inhibitors and functional relevance.
Sharma V et al.·Sci Rep
2020Functional
BET Inhibition Induces HEXIM1- and RAD51-Dependent Conflicts between Transcription and Replication.
Bowry A et al.·Cell Rep
2018
Clinical efficacy and chemoresistance analysis of precision neoadjuvant chemotherapy for borderline resectable pancreatic cancer: a prospective, single-arm pilot study.
He Y et al.·Int J Surg
2025
HEXIM1 is a critical determinant of the response to tamoxifen.
Ketchart W et al.·Oncogene
2011
Inhibition of the histone demethylase, KDM5B, directly induces re-expression of tumor suppressor protein HEXIM1 in cancer cells.
Montano MM et al.·Breast Cancer Res
2019
Therapeutic impact of BET inhibitor BI 894999 treatment: backtranslation from the clinic.
Tontsch-Grunt U et al.·Br J Cancer
2022
Phase I Results of Bromodomain and Extra-Terminal Inhibitor PLX51107 in Combination with Azacitidine in Patients with Relapsed/Refractory Myeloid Malignancies.
Senapati J et al.·Clin Cancer Res
2023Cohort
Identification of CCR2 and CD180 as Robust Pharmacodynamic Tumor and Blood Biomarkers for Clinical Use with BRD4/BET Inhibitors.
Yeh TC et al.·Clin Cancer Res
2017
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗
Full-Text Mentions
NLP-detected gene mentions in article bodies · via PubTator3
PubTator3
Downregulation of Dihydrotestosterone and Estradiol Levels by HEXIM1.
Mozar F et al.·Endocrinology
2022
HEXIM1 is correlated with Alzheimer's disease pathology and regulates immediate early gene dynamics in neurons.
Htet M et al.·bioRxiv
2024
HEXIM1 homodimer binds two sites on 7SK RNA to release autoinhibition for P-TEFb inactivation.
Yang Y et al.·bioRxiv
2024
CDK9 activity switch associated with AFF1 and HEXIM1 controls differentiation initiation from epidermal progenitors
Lloyd SM et al.·Nat Commun
2022
Tip110 Expression Facilitates the Release of HEXIM1 and pTEFb from the 7SK Ribonucleoprotein Complex Involving Regulation of the Intracellular Redox Level
Liu Y et al.·Aging Dis
2021
Erratum to "Tip110 expression facilitates the release of HEXIM1 and pTEFb from the 7SK ribonucleoprotein complex involving regulation of the intracellular redox level"
Liu Y et al.·Aging Dis
2023
Top 6 full-text resultsSearch PubTator3 ↗

External Resources

Links to major genomics databases and tools

Franklin by Genoox
AI-powered variant curation and clinical analysis
DECIPHER
Genomic variants and phenotypes in rare disease patients