Trichothiodystrophy 9, nonphotosensitive

disease

On this page

Also known as TTD9

Summary

Trichothiodystrophy 9, nonphotosensitive (MONDO:0030518) is a disease with 1 cohort gene.

At a glance

Cohort genes: 1
ClinVar variants: 6

Clinical features

No curated clinical features (Orphanet) for this disease.

Identifiers

Disease identifiers

Field	Value
Canonical name	trichothiodystrophy 9, nonphotosensitive
Mondo ID	MONDO:0030518
OMIM	619692
DOID	DOID:0061024
UMLS	C5562058
MedGen	1794268
GARD	0025590
Is cancer (heuristic)	no

Also known as: TTD9

Data availability: 6 ClinVar variants · 2 GenCC gene-disease records.

Disease family

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

6 retrieved; paginated sample, class counts are floors:

5 uncertain significance, 1 likely pathogenic

ClinVar	Variant (HGVS)	Gene	Classification	Review
4845906	NM_004990.4(MARS1):c.1133_1134del (p.Phe378fs)	MARS1	Likely pathogenic	criteria provided, single submitter
1331685	NM_004990.4(MARS1):c.1201G>A (p.Val401Met)	MARS1	Uncertain significance	criteria provided, single submitter
2190237	NM_004990.4(MARS1):c.1102G>T (p.Asp368Tyr)	MARS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
2637952	NM_004990.4(MARS1):c.1316_1327dup (p.Pro442_Val443insGlySerCysPro)	MARS1	Uncertain significance	criteria provided, single submitter
2637953	NM_004990.4(MARS1):c.1450T>C (p.Ser484Pro)	MARS1	Uncertain significance	criteria provided, multiple submitters, no conflicts
523880	NM_004990.4(MARS1):c.2569C>T (p.Arg857Ter)	MARS1	Uncertain significance	criteria provided, multiple submitters, no conflicts

Genes & proteins

Mendelian disease overlap and somatic drivers

GenCC: 12 · Orphanet: 3 · 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
MARS1	Strong	Autosomal recessive	trichothiodystrophy	12

Orphanet rare-disease linkage (cohort genes)

Gene	Orphanet ID	Rare disease
MARS1	Orphanet:397735	Autosomal dominant Charcot-Marie-Tooth disease type 2U
MARS1	Orphanet:401835	Autosomal recessive spastic paraplegia type 70
MARS1	Orphanet:440427	Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency

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
MARS1	HGNC:6898	ENSG00000166986	P56192	Methionine–tRNA ligase, cytoplasmic	gencc,clinvar

Cohort function summary

Lead sentence per gene, UniProt-curated.

Symbol	Protein name	Function (lead sentence)
MARS1	Methionine–tRNA ligase, cytoplasmic	Catalyzes the specific attachment of an amino acid to its cognate tRNA in a 2 step reaction: the amino acid (AA) is first activated by ATP to form AA-AMP and then transferred to the acceptor end of the tRNA.

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)
MARS1	Enzyme (other)	yes	6.1.1.10	WHEP-TRS_dom, aa-tRNA-synth_I_CS, GST_C

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
cerebellar cortex	1
cerebellar hemisphere	1
right hemisphere of cerebellum	1

Per-gene tissue summary (top 30)

Symbol	Bgee breadth	FANTOM5 breadth	SCXA	Top tissues
MARS1	301	ubiquitous	marker	right hemisphere of cerebellum, cerebellar hemisphere, cerebellar cortex

Protein interactions among cohort

Intra-cohort edges: 0.

Hub genes (top 10 by interactor count)

Symbol	Interactor count
MARS1	5,727

Structural data

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

Cohort genes with PDB structures (top 30)

Symbol	UniProt	PDB entries
MARS1	P56192	7

Function

Pathway analysis

Distinct Reactome pathways touched by cohort: 10. 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×	0.014	MARS1
tRNA Aminoacylation	1	285.5×	0.014	MARS1
Selenoamino acid metabolism	1	196.9×	0.014	MARS1
Transcriptional and post-translational regulation of MITF-M expression and activity	1	178.4×	0.014	MARS1
MITF-M-regulated melanocyte development	1	114.2×	0.018	MARS1
Metabolism of amino acids and derivatives	1	67.6×	0.023	MARS1
Translation	1	62.1×	0.023	MARS1
Developmental Biology	1	14.5×	0.086	MARS1
Metabolism of proteins	1	12.4×	0.086	MARS1
Metabolism	1	11.6×	0.086	MARS1

GO biological processes by enrichment

GO term	Cohort genes	Fold	FDR	Sample cohort genes
methionyl-tRNA aminoacylation	1	8426.0×	7e-04	MARS1
positive regulation of transcription of nucleolar large rRNA by RNA polymerase I	1	1532.0×	0.002	MARS1
rRNA transcription	1	991.3×	0.002	MARS1
tRNA aminoacylation for protein translation	1	842.6×	0.002	MARS1
cellular response to platelet-derived growth factor stimulus	1	648.1×	0.002	MARS1
cellular response to epidermal growth factor stimulus	1	318.0×	0.003	MARS1

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
MARS1	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
MARS1	26	Binding:26

Cohort enzymes (BRENDA EC)

Symbol	EC numbers	Names
MARS1	6.1.1.10	methionine-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	MARS1
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)
MARS1	26	—

Clinical trials & evidence

Clinical trials

Clinical trials: 0.

Cohort genes: MARS1