Trichothiodystrophy 7, nonphotosensitive

Summary

Trichothiodystrophy 7, nonphotosensitive (MONDO:0032806) is a disease with 1 cohort gene.

At a glance

• Cohort genes: 1
• ClinVar variants: 8

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trichothiodystrophy 7, nonphotosensitive
Mondo ID	MONDO:0032806
OMIM	618546
DOID	DOID:0111870
NCIT	C173102
UMLS	C5231403
MedGen	1684762
GARD	0016362
Is cancer (heuristic)	no

Also known as: TTD7

Data availability: 8 ClinVar variants · 2 GenCC gene-disease records · 2 cell lines.

Disease family

Classification path: disease › human disease › disease by body system or component › syndromic disease › ectodermal dysplasia syndrome › trichothiodystrophy › trichothiodystrophy 7, nonphotosensitive

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

8 retrieved; paginated sample, class counts are floors:

3 benign, 3 pathogenic, 1 likely pathogenic, 1 benign/likely benign

ClinVar	Variant (HGVS)	Gene	Classification	Review
689397	NM_152295.5(TARS1):c.1912C>T (p.Arg638Ter)	TARS1	Pathogenic	no assertion criteria provided
689398	NM_152295.5(TARS1):c.826A>G (p.Lys276Glu)	TARS1	Pathogenic	no assertion criteria provided
689399	NM_152295.5(TARS1):c.680T>C (p.Leu227Pro)	TARS1	Pathogenic	no assertion criteria provided
3899295	NM_152295.5(TARS1):c.1829dup (p.Lys611fs)	TARS1	Likely pathogenic	criteria provided, single submitter
1334924	NM_152295.5(TARS1):c.984+27T>A	TARS1	Benign	criteria provided, multiple submitters, no conflicts
1334925	NM_152295.5(TARS1):c.985-35G>A	TARS1	Benign	criteria provided, multiple submitters, no conflicts
1334926	NM_152295.5(TARS1):c.1653G>A (p.Ala551=)	TARS1	Benign	criteria provided, multiple submitters, no conflicts
782449	NM_152295.5(TARS1):c.62G>A (p.Gly21Asp)	TARS1	Benign/Likely benign	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 3 · 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
TARS1	Moderate	Autosomal recessive	trichothiodystrophy 7, nonphotosensitive	3

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
TARS1	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
TARS1	HGNC:11572	ENSG00000113407	P26639	Threonine–tRNA ligase 1, cytoplasmic	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
TARS1	Threonine–tRNA ligase 1, cytoplasmic	Catalyzes the attachment of threonine to tRNA(Thr) in a two-step reaction: threonine is first activated by ATP to form Thr-AMP and then transferred to the acceptor end of tRNA(Thr).

Protein-family classification

Druggable: 1 · Difficult: 0 · Unknown: 0 · Druggable fraction: 1.0

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
Enzyme (other)	1	12.0×	0.083

Per-gene assignment

Symbol	Family	Druggable?	EC	InterPro (top 3)
TARS1	Enzyme (other)	yes	6.1.1.3	aa-tRNA-synt_IIb, Thr-tRNA-ligase_IIa, TGS

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
sural nerve	1
tongue squamous epithelium	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
TARS1	296	ubiquitous	marker	sural nerve, adrenal tissue, tongue squamous epithelium

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
TARS1	2,811

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
TARS1	P26639	5

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 4. 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
Cytosolic tRNA aminoacylation	1	439.2×	0.007	TARS1
tRNA Aminoacylation	1	285.5×	0.007	TARS1
Translation	1	62.1×	0.021	TARS1
Metabolism of proteins	1	12.4×	0.081	TARS1

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
threonyl-tRNA aminoacylation	1	5617.3×	2e-04	TARS1

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
TARS1	0	0

Bioactivity and enzyme data

Enzyme cohort genes (≥1 EC): 1.

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

Symbol	Assays	Type breakdown
TARS1	53	Binding:53

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
TARS1	6.1.1.3	threonine-tRNA ligase

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	1	TARS1
D	Druggable family + AlphaFold only, no drug	0
E	Difficult family or no structure, no drug	0

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)
TARS1	53	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.