Maternally-inherited diabetes and deafness
diseaseOn this page
Also known as Ballinger Wallace syndromediabetes and deafness, maternally inheriteddiabetes mellitus type II with deafnessmaternally inherited diabetes and deafnessMIDDmitochondrial diabetes
Summary
Maternally-inherited diabetes and deafness (MONDO:0010785) is a disease caused by MT-TL1 (GenCC Strong), with 4 cohort genes and 6 clinical trials. Top therapeutic interventions include sonlicromanol.
At a glance
- Causal gene: MT-TL1 (GenCC Strong)
- Cohort genes: 4
- ClinVar variants: 5
- Clinical trials: 6
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | maternally-inherited diabetes and deafness |
| Mondo ID | MONDO:0010785 |
| MeSH | C536246 |
| OMIM | 520000 |
| Orphanet | 225 |
| ICD-11 | 2133824111 |
| NCIT | C131859 |
| SNOMED CT | 237619009 |
| UMLS | C0342289 |
| MedGen | 90979 |
| GARD | 0027358 |
| Is cancer (heuristic) | no |
Also known as: Ballinger Wallace syndrome · diabetes and deafness, maternally inherited · diabetes mellitus type II with deafness · maternally inherited diabetes and deafness · MIDD · mitochondrial diabetes
Data availability: 5 ClinVar variants · 1 GenCC gene-disease record · 17 cell lines.
Disease family
Classification path: disease › human disease › disease by body system or component › digestive system disorder › pancreas disorder › endocrine pancreas disorder › diabetes mellitus › maternally-inherited diabetes and deafness
Related subtypes (7): type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes, diabetic ketoacidosis, monogenic diabetes, type 5 diabetes mellitus, cystic fibrosis-related diabetes
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
5 retrieved; paginated sample, class counts are floors:
2 uncertain significance, 1 conflicting classifications of pathogenicity, 1 pathogenic, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 9589 | NC_012920.1(MT-TL1):m.3243A>G | MT-TL1 | Pathogenic | reviewed by expert panel |
| 9617 | NC_012920.1(MT-TE):m.14709T>C | MT-TE | Likely pathogenic | reviewed by expert panel |
| 690182 | NC_012920.1(MT-TL2):m.12278T>C | MT-TL2 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 267298 | NC_012920.1(MT-TE):m.14692A>G | MT-TE | Uncertain significance | reviewed by expert panel |
| 9584 | NC_012920.1(MT-TK):m.8296A>G | MT-TK | Uncertain significance | reviewed by expert panel |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 3 · Orphanet: 13 · 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 |
|---|---|---|---|---|
| MT-TL1 | Strong | Mitochondrial | maternally-inherited diabetes and deafness | 3 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| MT-TL1 | Orphanet:255210 | Mitochondrial DNA-associated Leigh syndrome |
| MT-TL1 | Orphanet:324525 | Hypertrophic cardiomyopathy with kidney anomalies due to mitochondrial DNA mutation |
| MT-TL1 | Orphanet:480 | Kearns-Sayre syndrome |
| MT-TL1 | Orphanet:550 | MELAS |
| MT-TL1 | Orphanet:551 | MERRF |
| MT-TL1 | Orphanet:663 | Mitochondrial DNA-related progressive external ophthalmoplegia |
| MT-TE | Orphanet:254864 | Mitochondrial myopathy with reversible cytochrome C oxidase deficiency |
| MT-TE | Orphanet:2596 | Myopathy and diabetes mellitus |
| MT-TK | Orphanet:1349 | Mitochondrial DNA-related cardiomyopathy and hearing loss |
| MT-TK | Orphanet:255210 | Mitochondrial DNA-associated Leigh syndrome |
| MT-TK | Orphanet:551 | MERRF |
| MT-TL2 | Orphanet:2131 | Alternating hemiplegia of childhood |
| MT-TL2 | Orphanet:663 | Mitochondrial DNA-related progressive external ophthalmoplegia |
Cohort genes → proteins
4 cohort genes, 0 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 4 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| MT-TL1 | HGNC:7490 | ENSG00000209082 | mitochondrially encoded tRNA-Leu (UUA/G) 1 | gencc,clinvar | |
| MT-TE | HGNC:7479 | ENSG00000210194 | mitochondrially encoded tRNA-Glu (GAA/G) | clinvar | |
| MT-TK | HGNC:7489 | ENSG00000210156 | mitochondrially encoded tRNA-Lys (AAA/G) | clinvar | |
| MT-TL2 | HGNC:7491 | ENSG00000210191 | mitochondrially encoded tRNA-Leu (CUN) 2 | clinvar |
Protein-family classification
Druggable: 0 · Difficult: 0 · Unknown: 4 · 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 | 4 | 1.8× | 0.097 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| MT-TL1 | Other/Unknown | no | ||
| MT-TE | Other/Unknown | no | ||
| MT-TK | Other/Unknown | no | ||
| MT-TL2 | Other/Unknown | no |
Expression context
Cohort genes with no expression data: 0.
2 cohort genes 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) | 4 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| caudate nucleus | 3 |
| apex of heart | 2 |
| skeletal muscle tissue | 2 |
| sural nerve | 2 |
| frontal cortex | 1 |
| right frontal lobe | 1 |
| putamen | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| MT-TL1 | 118 | ubiquitous | marker | frontal cortex, right frontal lobe, caudate nucleus |
| MT-TE | 118 | broad | marker | skeletal muscle tissue, sural nerve, apex of heart |
| MT-TK | 118 | yes | sural nerve, skeletal muscle tissue, caudate nucleus | |
| MT-TL2 | 118 | broad | yes | apex of heart, putamen, caudate nucleus |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| MT-TL1 | 0 |
| MT-TE | 0 |
| MT-TK | 0 |
| MT-TL2 | 0 |
Structural data
PDB: 0 · AlphaFold-only: 0 · No structure: 4
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 0. Enrichment computed across 4 evidence-associated genes (0 with Reactome annotation).
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 4
Druggability breadth: 0 of 4 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 |
|---|---|---|
| MT-TL1 | 0 | 0 |
| MT-TE | 0 | 0 |
| MT-TK | 0 | 0 |
| MT-TL2 | 0 | 0 |
Bioactivity and enzyme data
Enzyme cohort genes (≥1 EC): 0.
Pharmacogenomics
Cohort genes with a PharmGKB record: 4; 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 | 4 | MT-TL1, MT-TE, MT-TK, MT-TL2 |
Undrugged target profiles
4 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| MT-TL1 | 0 | — |
| MT-TE | 0 | — |
| MT-TK | 0 | — |
| MT-TL2 | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 6.
Phase distribution (across all retrieved trials)
| Phase | Trials |
|---|---|
| PHASE2 | 3 |
| Not specified | 2 |
| PHASE3 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06451757 | PHASE3 | RECRUITING | KHENERFIN Study: A Trial to Evaluate the Efficacy and Safety of Sonlicromanol in Primary Mitochondrial Diseases |
| NCT02909400 | PHASE2 | COMPLETED | The KHENERGY Study |
| NCT04165239 | PHASE2 | COMPLETED | The KHENERGYZE Study |
| NCT04604548 | PHASE2 | COMPLETED | The KHENEREXT Study |
| NCT03988764 | Not specified | RECRUITING | Monogenic Diabetes Misdiagnosed as Type 1 |
| NCT05554835 | Not specified | RECRUITING | Global Registry and Natural History Study for Mitochondrial Disorders |
Drugs tested across these trials (top 30)
| Molecule | Max phase | Trials referencing |
|---|---|---|
| SONLICROMANOL | 3 | 3 |
Related Atlas pages
- Cohort genes: MT-TL1, MT-TE, MT-TK, MT-TL2
- Drugs: Sonlicromanol