HEXIM2

Chr 17

HEXIM P-TEFb complex subunit 2

Also known as: L3

The protein functions as a transcriptional regulator that inhibits RNA polymerase II by sequestering the P-TEFb kinase complex within the 7SK ribonucleoprotein complex, thereby preventing transcriptional elongation. Based on the low pLI score (0.028) and high LOEUF score (0.931), HEXIM2 appears to tolerate loss-of-function variants well, and no specific human diseases have been clearly associated with mutations in this gene to date.

Summary from RefSeq, UniProt
0
Active trials
2
Pubs (1 yr)
10
P/LP submissions
0%
P/LP missense
0.93
LOEUF
DN
Mechanism· predicted
Clinical SummaryHEXIM2
Population Constraint (gnomAD)
Low constraint (pLI 0.03) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
10 unique Pathogenic / Likely Pathogenic· 46 VUS of 62 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.93LOEUF
pLI 0.028
Z-score 1.72
OE 0.41 (0.200.93)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
0.09Z-score
OE missense 0.98 (0.861.11)
168 obs / 171.2 exp
Tolerant

Mild missense constraint

Observed / Expected Ratios
LoF OE0.41 (0.200.93)
00.351.4
Missense OE0.98 (0.861.11)
00.61.4
Synonymous OE1.11
01.21.6
LoF obs/exp: 4 / 9.8Missense obs/exp: 168 / 171.2Syn Z: -0.75
DN
0.6552th %ile
GOF
0.5170th %ile
LOF
0.4233th %ile

The highest-scoring mechanism for this gene is dominant-negative.

DNprediction above median

Note: In-silico variant effect predictors (SIFT, PolyPhen, REVEL, CADD) may underestimate pathogenicity of missense variants in genes with GOF or DN mechanisms. Consider functional evidence and clinical context.

Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.

ClinVar Variant Classifications

62 submitted variants in ClinVar

Classification Summary

Pathogenic10
VUS46
10
Pathogenic
46
VUS

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
44
2
0
46
Likely Benign
0
0
0
0
0
Benign
0
0
0
0
0
Total04412056

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

View in ClinVar →

Protein Context — Lollipop Plot

HEXIM2 · protein map & ClinVar variants

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

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →
Clinical Literature
Open Research Assistant →
Key Publications
Landmark & review papers · by relevance
PubMed
Top 1 results · since 2015Search PubMed ↗