GTF2H4

Chr 6AR

general transcription factor IIH subunit 4

Also known as: P52, TFB2, TFIIH, XPJ

NCBI Gene: 2968ENSG00000213780UniProt: Q92759

Enables RNA polymerase II general transcription initiation factor activity. Involved in transcription by RNA polymerase II. Located in nuclear speck. Part of core TFIIH complex portion of holo TFIIH complex and transcription factor TFIID complex. [provided by Alliance of Genome Resources, Jul 2025]

Primary Disease Associations & Inheritance

?Xeroderma pigmentosum, complementation group JMIM #621435
AR
59
ClinVar variants
7
Pathogenic / LP
0.00
pLI score
0
Active trials
Clinical Summary— GTF2H4
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
7 Pathogenic / Likely Pathogenic· 47 VUS of 59 total submissions

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD
Tolerant — LoF & missense variants common in population
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.
0.81LOEUF
pLI 0.000
Z-score 2.34
OE 0.53 (0.35–0.81)
Tolerant

Typical tolerance to LoF variation

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.
1.10Z-score
OE missense 0.81 (0.73–0.91)
221 obs / 272.0 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.0.53 (0.35–0.81)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.0.81 (0.73–0.91)
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.0.73
0≤1.21.6
LoF obs/exp: 15 / 28.5Missense obs/exp: 221 / 272.0Syn Z: 2.19

ClinVar Variant Classifications

59 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic6
Likely Pathogenic1
VUS47
Likely Benign3
Benign2
6
Pathogenic
1
Likely Pathogenic
47
VUS
3
Likely Benign
2
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
0
0
6
0
6
Likely Pathogenic
0
0
1
0
1
VUS
0
42
5
0
47
Likely Benign
0
1
1
1
3
Benign
0
0
1
1
2
Total04314259

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF2H4 · 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

?Xeroderma pigmentosum, complementation group J

MIM #621435

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
[Bioinformatics-based analysis of the effect of general Transcription Factor IIH on prognosis of Prostate cancer].
Li JC et al.·Zhonghua Yi Xue Za Zhi
2024
Lack of association between GTF2H4 genetic variants and AERD development and FEV1 decline by aspirin provocation.
Kim JY et al.·Int J Immunogenet
2012
Genetic variant in DNA repair gene GTF2H4 is associated with lung cancer risk: a large-scale analysis of six published GWAS datasets in the TRICL consortium.
Wang M et al.·Carcinogenesis
2016
Age-stratified proteomic characteristics and identification of promising precise clinical treatment targets of colorectal cancer.
Wang Q et al.·J Proteomics
2023
Somatic Variants in DNA Damage Response Genes in Ovarian Cancer Patients Using Whole-exome Sequencing.
Lopacinska-Joergensen J et al.·Anticancer Res
2023Cohort
Identification of genes associated with tumorigenesis of meibomian cell carcinoma by microarray analysis.
Kumar A et al.·Genomics
2007
Single nucleotide polymorphisms of nucleotide excision repair pathway are significantly associated with outcomes of platinum-based chemotherapy in lung cancer.
Song X et al.·Sci Rep
2017Clinical trial
Construction of a prediction model for hepatocellular carcinoma based on machine learning and its prognostic characteristics.
Wang J et al.·Medicine (Baltimore)
2025Functional
Variation within DNA repair pathway genes and risk of multiple sclerosis.
Briggs FB et al.·Am J Epidemiol
2010
Top 10 resultsSearch PubMed ↗
Recent Gene-Specific Literature
Gene in title · MEDLINE · newest first
Europe PMC
Top 5 resultsSearch Europe PMC ↗

Clinical Trials

Active and recruiting trials from ClinicalTrials.gov

ClinicalTrials.gov

No active trials found for this gene.

Search ClinicalTrials.gov →

External Resources

Links to major genomics databases and tools