Trichothiodystrophy 3, photosensitive

Summary

Trichothiodystrophy 3, photosensitive (MONDO:0014619) is a disease caused by GTF2H5 (GenCC Definitive), with 1 cohort gene.

At a glance

• Causal gene: GTF2H5 (GenCC Definitive)
• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trichothiodystrophy 3, photosensitive
Mondo ID	MONDO:0014619
OMIM	616395
DOID	DOID:0111871
NCIT	C173099
UMLS	C4017171
MedGen	865608
GARD	0016102
Is cancer (heuristic)	no

Also known as: trichothiodystrophy 3, photosensitive · TTD3

Data availability: 8 ClinVar variants · 4 GenCC gene-disease records · 9 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › trichothiodystrophy › photosensitive trichothiodystrophy › trichothiodystrophy 3, photosensitive

Related subtypes (2): trichothiodystrophy 1, photosensitive, trichothiodystrophy 2, photosensitive

Genetics & variants

GWAS landscape

No GWAS associations recorded — common-variant (GWAS) studies don’t cover this disease (typical for Mendelian / rare diseases). See the curated gene cohort and Mendelian overlap below.

Variant details and genetic-evidence tiers

ClinVar germline variants

8 retrieved; paginated sample, class counts are floors:

4 pathogenic, 2 uncertain significance, 1 pathogenic/likely pathogenic, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
2103	NM_207118.3(GTF2H5):c.166C>T (p.Arg56Ter)	GTF2H5	Pathogenic/Likely pathogenic	criteria provided, multiple submitters, no conflicts
2104	NM_207118.3(GTF2H5):c.62T>C (p.Leu21Pro)	GTF2H5	Pathogenic	no assertion criteria provided
975158	NM_207118.3(GTF2H5):c.163G>T (p.Glu55Ter)	GTF2H5	Pathogenic	no assertion criteria provided
975159	NM_207118.3(GTF2H5):c.49A>T (p.Lys17Ter)	GTF2H5	Pathogenic	criteria provided, single submitter
975160	NM_207118.3(GTF2H5):c.29T>A (p.Ile10Lys)	GTF2H5	Pathogenic	no assertion criteria provided
587425	NM_207118.3(GTF2H5):c.36-2A>G	GTF2H5	Likely pathogenic	criteria provided, single submitter
1050091	NM_207118.3(GTF2H5):c.167G>A (p.Arg56Gln)	GTF2H5	Uncertain significance	criteria provided, multiple submitters, no conflicts
1065503	NM_207118.3(GTF2H5):c.116A>T (p.Asp39Val)	GTF2H5	Uncertain significance	criteria provided, single submitter

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 5 · Orphanet: 1 · OMIM-shared: 0 · Dual-evidence (GWAS+Mendelian): 0

GenCC gene–disease validity (cohort genes)

the Disease column is the GenCC-asserted condition — a cohort gene’s strongest validity may be for a related predisposition syndrome.

Gene	Classification	Inheritance	Disease	Records
GTF2H5	Definitive	Autosomal recessive	trichothiodystrophy 3, photosensitive	5

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GTF2H5	Orphanet:33364	Trichothiodystrophy

Cohort genes → proteins

1 cohort genes, 1 distinct canonical proteins.

Evidence partition

Subset	Genes
multi_evidence	1

Cohort genes (full)

Symbol	HGNC	Ensembl	UniProt	Name	Evidence
GTF2H5	HGNC:21157	ENSG00000272047	Q6ZYL4	General transcription factor IIH subunit 5	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GTF2H5	General transcription factor IIH subunit 5	Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA transcription…

Protein-family classification

Druggable: 0 · Difficult: 0 · Unknown: 1 · Druggable fraction: 0.0

Family distribution

Cohort families vs a genome-wide background (hypergeometric, BH-FDR; fold = observed/expected). Counts kept; sorted by enrichment, so the catch-all Other/Unknown bucket no longer leads.

Family	Genes	Fold	FDR
Other/Unknown	1	1.8×	0.558

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
GTF2H5	Other/Unknown	no		TFIIH_TTDA/Tfb5, TFB5-like_sf

Expression context

Cohort genes with no expression data: 0.

1 cohort gene are a single-cell marker in ≥1 SCXA experiment.

Breadth distribution (Bgee present_calls)

Bucket	Genes
narrow (1-5 tissues)	0
moderate (6-20)	0
broad (>20)	1
unknown	0

Top tissues across cohort

Tissue	Cohort genes
renal medulla	1
saphenous vein	1
superior surface of tongue	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GTF2H5	293	ubiquitous	marker	renal medulla, superior surface of tongue, saphenous vein

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GTF2H5	1,855

Structural data

PDB: 1 · AlphaFold-only: 0 · No structure: 0

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GTF2H5	Q6ZYL4	53

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 48. Enrichment computed across 1 evidence-associated genes (1 with Reactome annotation).

Pathways by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

Pathway	Cohort genes	Fold	FDR	Sample cohort genes
Global Genome Nucleotide Excision Repair (GG-NER)	1	456.8×	0.009	GTF2H5
RNA Pol II CTD phosphorylation and interaction with CE during HIV infection	1	407.9×	0.009	GTF2H5
RNA Pol II CTD phosphorylation and interaction with CE	1	407.9×	0.009	GTF2H5
mRNA Capping	1	380.7×	0.009	GTF2H5
Formation of the Early Elongation Complex	1	335.9×	0.009	GTF2H5
Formation of the HIV-1 Early Elongation Complex	1	335.9×	0.009	GTF2H5
HIV Transcription Elongation	1	335.9×	0.009	GTF2H5
RNA Polymerase I Transcription Termination	1	326.3×	0.009	GTF2H5
RNA Polymerase I Promoter Clearance	1	292.8×	0.009	GTF2H5
Nucleotide Excision Repair	1	285.5×	0.009	GTF2H5
RNA Polymerase I Transcription	1	285.5×	0.009	GTF2H5
Transcription-Coupled Nucleotide Excision Repair (TC-NER)	1	265.6×	0.009	GTF2H5
Formation of HIV-1 elongation complex containing HIV-1 Tat	1	259.6×	0.009	GTF2H5
Tat-mediated elongation of the HIV-1 transcript	1	259.6×	0.009	GTF2H5
Negative epigenetic regulation of rRNA expression	1	259.6×	0.009	GTF2H5
Dual Incision in GG-NER	1	259.6×	0.009	GTF2H5
Formation of Incision Complex in GG-NER	1	253.8×	0.009	GTF2H5
Formation of HIV elongation complex in the absence of HIV Tat	1	248.3×	0.009	GTF2H5
HIV Transcription Initiation	1	233.1×	0.009	GTF2H5
RNA Polymerase II HIV Promoter Escape	1	233.1×	0.009	GTF2H5
RNA Polymerase II Promoter Escape	1	233.1×	0.009	GTF2H5
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	233.1×	0.009	GTF2H5
RNA Polymerase II Transcription Initiation	1	233.1×	0.009	GTF2H5
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	233.1×	0.009	GTF2H5
RNA Polymerase I Transcription Initiation	1	223.9×	0.009	GTF2H5
Formation of TC-NER Pre-Incision Complex	1	211.5×	0.009	GTF2H5
Formation of RNA Pol II elongation complex	1	193.6×	0.009	GTF2H5
RNA Polymerase II Transcription Elongation	1	193.6×	0.009	GTF2H5
TP53 Regulates Transcription of DNA Repair Genes	1	181.3×	0.009	GTF2H5
Gap-filling DNA repair synthesis and ligation in TC-NER	1	178.4×	0.009	GTF2H5

GO biological processes by enrichment

Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 1 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.

GO term	Cohort genes	Fold	FDR	Sample cohort genes
nucleotide-excision repair, preincision complex assembly	1	16852.0×	4e-04	GTF2H5
transcription elongation by RNA polymerase I	1	2106.5×	0.002	GTF2H5
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	1	674.1×	0.003	GTF2H5
cellular response to gamma radiation	1	601.9×	0.003	GTF2H5
nucleotide-excision repair	1	383.0×	0.003	GTF2H5
transcription initiation at RNA polymerase II promoter	1	374.5×	0.003	GTF2H5
transcription by RNA polymerase II	1	70.5×	0.014	GTF2H5

Therapeutics

Drug target analysis

Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 1

Druggability breadth: 0 of 1 evidence-associated genes (0%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GTF2H5	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Pharmacogenomics

Cohort genes with a PharmGKB record: 1; with CPIC/DPWG dosing guidelines: 0.

No cohort gene has a CPIC/DPWG genotype-guided dosing guideline (PharmGKB).

Chemical tractability of cohort targets

0 approved/phased compounds have measured bioactivity against a cohort gene (and aren’t yet in disease-level trials). This is a research / tractability signal, NOT a therapeutic recommendation — a bioactivity row often reflects off-target or screening binding (e.g. promiscuous kinase inhibitors against a cohort kinase), implying no disease mechanism.

Druggability pyramid

Cohort genes binned by druggability tier (high → low):

Tier	Definition	Genes	Symbols
A	Approved (phase 4 drug)	0
B	Phased (≥1) drug, not yet approved	0
C	Druggable family + PDB, no drug	0
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	1	GTF2H5

Undrugged target profiles

1 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).

Symbol	ChEMBL assays	Drugged partners (top 3)
GTF2H5	0	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.