Trichothiodystrophy 6, nonphotosensitive

Summary

Trichothiodystrophy 6, nonphotosensitive (MONDO:0014841) is a disease caused by GTF2E2 (GenCC Strong), with 1 cohort gene.

At a glance

• Causal gene: GTF2E2 (GenCC Strong)
• Cohort genes: 1
• ClinVar variants: 4

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trichothiodystrophy 6, nonphotosensitive
Mondo ID	MONDO:0014841
OMIM	616943
DOID	DOID:0111872
UMLS	C4310785
MedGen	934752
GARD	0016172
Is cancer (heuristic)	no

Also known as: GTF2E2 nonphotosensitive trichothiodystrophy · nonphotosensitive trichothiodystrophy caused by mutation in GTF2E2 · trichothiodystrophy 6, nonphotosensitive · trichothiodystrophy 6, nonphotosensitive; TTD6 · TTD6

Data availability: 4 ClinVar variants · 5 GenCC gene-disease records.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › trichothiodystrophy › trichothiodystrophy 6, nonphotosensitive

Related subtypes (6): photosensitive trichothiodystrophy, trichothiodystrophy 5, nonphotosensitive, trichothiodystrophy 4, nonphotosensitive, trichothiodystrophy 8, nonphotosensitive, trichothiodystrophy 9, nonphotosensitive, trichothiodystrophy 7, nonphotosensitive

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

4 retrieved; paginated sample, class counts are floors:

2 pathogenic, 1 benign, 1 uncertain significance

ClinVar	Variant (HGVS)	Gene	Classification	Review
225840	NM_002095.6(GTF2E2):c.448G>C (p.Ala150Pro)	GTF2E2	Pathogenic	no assertion criteria provided
225841	NM_002095.6(GTF2E2):c.559G>T (p.Asp187Tyr)	GTF2E2	Pathogenic	criteria provided, single submitter
3779713	NM_002095.6(GTF2E2):c.549+4A>G	GTF2E2	Uncertain significance	criteria provided, single submitter
1170214	NM_002095.6(GTF2E2):c.549+11T>G	GTF2E2	Benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 6 · 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
GTF2E2	Strong	Autosomal recessive	trichothiodystrophy 6, nonphotosensitive	6

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
GTF2E2	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
GTF2E2	HGNC:4651	ENSG00000197265	P29084	Transcription initiation factor IIE subunit beta	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
GTF2E2	Transcription initiation factor IIE subunit beta	Recruits TFIIH to the initiation complex and stimulates the RNA polymerase II C-terminal domain kinase and DNA-dependent ATPase activities of TFIIH.

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)
GTF2E2	Other/Unknown	no		TFIIE_bsu_DNA-bd, TFIIE-bsu, WH-like_DNA-bd_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
adrenal tissue	1
body of pancreas	1
pancreas	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
GTF2E2	274	ubiquitous	marker	adrenal tissue, body of pancreas, pancreas

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
GTF2E2	2,377

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
GTF2E2	P29084	42

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 17. 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
HIV Transcription Initiation	1	233.1×	0.011	GTF2E2
RNA Polymerase II HIV Promoter Escape	1	233.1×	0.011	GTF2E2
RNA Polymerase II Promoter Escape	1	233.1×	0.011	GTF2E2
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening	1	233.1×	0.011	GTF2E2
RNA Polymerase II Transcription Initiation	1	233.1×	0.011	GTF2E2
RNA Polymerase II Transcription Initiation And Promoter Clearance	1	233.1×	0.011	GTF2E2
Transcription of the HIV genome	1	173.0×	0.011	GTF2E2
Late Phase of HIV Life Cycle	1	167.9×	0.011	GTF2E2
HIV Life Cycle	1	160.8×	0.011	GTF2E2
RNA polymerase II transcribes snRNA genes	1	154.3×	0.011	GTF2E2
RNA Polymerase II Pre-transcription Events	1	137.6×	0.011	GTF2E2
HIV Infection	1	119.0×	0.012	GTF2E2
Viral Infection Pathways	1	30.8×	0.042	GTF2E2
Infectious disease	1	24.8×	0.049	GTF2E2
RNA Polymerase II Transcription	1	22.5×	0.050	GTF2E2
Gene expression (Transcription)	1	17.8×	0.060	GTF2E2
Disease	1	13.1×	0.076	GTF2E2

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
transcription initiation at RNA polymerase II promoter	1	374.5×	0.005	GTF2E2
transcription by RNA polymerase II	1	70.5×	0.014	GTF2E2

Therapeutics

Drug target analysis

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

Druggability breadth: 1 of 1 evidence-associated genes (100%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).

Top cohort targets by molecule count

Symbol	Molecules	Max phase
GTF2E2	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 0.

Cohort genes with ChEMBL bioactivity (full, sorted by assay count)

Symbol	Assays	Type breakdown
GTF2E2	1	Binding:1

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	GTF2E2

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)
GTF2E2	1	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.