GTF2H5

Chr 6AR

general transcription factor IIH subunit 5

Also known as: C6orf175, TFB5, TFIIH, TGF2H5, TTD, TTD-A, TTD3, TTDA

NCBI Gene: 404672ENSG00000272047UniProt: Q6ZYL4

This gene encodes a subunit of transcription/repair factor TFIIH, which functions in gene transcription and DNA repair. This protein stimulates ERCC3/XPB ATPase activity to trigger DNA opening during DNA repair, and is implicated in regulating cellular levels of TFIIH. Mutations in this gene result in trichothiodystrophy, complementation group A. [provided by RefSeq, Mar 2009]

Primary Disease Associations & Inheritance

Trichothiodystrophy 3, photosensitiveMIM #616395
AR
106
ClinVar variants
39
Pathogenic / LP
0.05
pLI score
0
Active trials
Clinical Summary— GTF2H5
⚡
Population Constraint (gnomAD)
Low constraint (pLI 0.05) — loss-of-function variants are relatively tolerated in the population.
📋
ClinVar Variants
39 Pathogenic / Likely Pathogenic· 37 VUS of 106 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.
1.71LOEUF
pLI 0.045
Z-score 0.58
OE 0.65 (0.26–1.71)
Tolerant

Highly tolerant — LoF variants common in population

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.
-0.12Z-score
OE missense 1.06 (0.82–1.38)
40 obs / 37.9 exp
Tolerant

Tolerant to missense variation

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.0.65 (0.26–1.71)
0≤0.351.4
Missense OE?Ratio of observed to expected missense variants. OE ≤ 0.6 = fewer missense variants than expected by chance.1.06 (0.82–1.38)
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.1.10
0≤1.21.6
LoF obs/exp: 2 / 3.1Missense obs/exp: 40 / 37.9Syn Z: -0.32

ClinVar Variant Classifications

106 submitted variants in ClinVar

ClinVar

Classification Summary

Pathogenic33
Likely Pathogenic6
VUS37
Likely Benign25
Benign5
33
Pathogenic
6
Likely Pathogenic
37
VUS
25
Likely Benign
5
Benign

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
2
3
28
0
33
Likely Pathogenic
1
1
4
0
6
VUS
0
29
8
0
37
Likely Benign
0
0
9
16
25
Benign
0
0
5
0
5
Total3335416106

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

View in ClinVar →

Protein Context — Lollipop Plot

GTF2H5 · protein map & ClinVar variants

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

Gene2Phenotype Curations

GTF2H5-related trichothiodystrophy photosensitive

definitive
ARLoss Of FunctionAbsent Gene Product
Dev. Disorders
G2P ↗

Gene2Phenotype curations · DECIPHER consortium patient cohort (public variants) · deciphergenomics.org

OMIM — Genotype-Phenotype Relationships

1 OMIM entry

OMIM

Trichothiodystrophy 3, photosensitive

MIM #616395

Molecular basis of disorder known

Autosomal recessive
Clinical Literature
Landmark / reviewRecent case evidence
Key Publications
Landmark & review papers · by relevance
PubMed
Severe trichothiodystrophy and cardiac malformation in a newborn carrying a novel GTF2H5 homozygous truncating variant.
Sorrentino U et al.·Clin Genet
2023Case report
Trichothiodystrophy type 3 with a mutation in the GTF2H5 gene: A case report in Argentina.
Dri J et al.·Arch Argent Pediatr
2025Case report
A case of severe trichothiodystrophy 3 in a neonate due to mutation in the GTF2H5 gene: Clinical report.
Michalska E et al.·Eur J Med Genet
2019Case report
TTDA: big impact of a small protein.
Theil AF et al.·Exp Cell Res
2014Review
PIBIDS syndrome in two Brazilian siblings.
Abagge KT et al.·BMJ Case Rep
2018Case report
TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.
Singh A et al.·Am J Hum Genet
2015
Updated strategies for the management, pathogenesis and molecular genetics of different forms of ichthyosis syndromes with prominent hair abnormalities.
Rasheed M et al.·Arch Dermatol Res
2017Review
Developing a novel immune infiltration-associated mitophagy prediction model for amyotrophic lateral sclerosis using bioinformatics strategies.
Du R et al.·Front Immunol
2024Functional
[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
Phenotype-specific adverse effects of XPD mutations on human prenatal development implicate impairment of TFIIH-mediated functions in placenta.
Moslehi R et al.·Eur J Hum Genet
2012
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