muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
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Also known as MDDGA9muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9
Summary
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 (MONDO:0014683) is a disease caused by DAG1 (GenCC Definitive), with 2 cohort genes.
At a glance
- Causal gene: DAG1 (GenCC Definitive)
- Cohort genes: 2
- ClinVar variants: 587
Clinical features
No curated clinical features (Orphanet) for this disease.
Identifiers
Disease identifiers
| Field | Value |
|---|---|
| Canonical name | muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9 |
| Mondo ID | MONDO:0014683 |
| OMIM | 616538 |
| DOID | DOID:0111232 |
| UMLS | C4225291 |
| MedGen | 902513 |
| GARD | 0016134 |
| Is cancer (heuristic) | no |
Also known as: MDDGA9 · muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 9
Data availability: 587 ClinVar variants · 2 GenCC gene-disease records.
Disease family
Classification path: disease › human disease › disease by body system or component › nervous system disorder › congenital nervous system disorder › congenital muscular dystrophy › muscular dystrophy-dystroglycanopathy › muscular dystrophy-dystroglycanopathy, type A › muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
Related subtypes (13): muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 4, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A2, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A5, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A6, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A, 7, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 8, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 10, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 11, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type a, 12, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A13, muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A14
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
587 retrieved; paginated sample, class counts are floors:
326 uncertain significance, 179 likely benign, 56 conflicting classifications of pathogenicity, 10 pathogenic, 9 benign, 6 benign/likely benign, 1 likely pathogenic
| ClinVar | Variant (HGVS) | Gene | Classification | Review |
|---|---|---|---|---|
| 3246864 | NC_000003.11:g.(?48895920)(49570632_?)del | AMT | Pathogenic | criteria provided, single submitter |
| 1073860 | NM_004393.6(DAG1):c.41C>A (p.Ser14Ter) | DAG1 | Pathogenic | criteria provided, single submitter |
| 208543 | NM_004393.6(DAG1):c.743del (p.Ala248fs) | DAG1 | Pathogenic | no assertion criteria provided |
| 3246914 | NC_000003.11:g.(?49568210)(49570632_?)del | DAG1 | Pathogenic | criteria provided, single submitter |
| 4785636 | NM_004393.6(DAG1):c.1056_1057del (p.Glu352fs) | DAG1 | Pathogenic | criteria provided, single submitter |
| 4786300 | NM_004393.6(DAG1):c.616del (p.Gln206fs) | DAG1 | Pathogenic | criteria provided, single submitter |
| 539125 | NM_004393.6(DAG1):c.440del (p.Gln147fs) | DAG1 | Pathogenic | criteria provided, single submitter |
| 654870 | NM_004393.6(DAG1):c.235C>T (p.Arg79Ter) | DAG1 | Pathogenic | criteria provided, single submitter |
| 842859 | NM_004393.6(DAG1):c.285+1G>A | DAG1 | Pathogenic | criteria provided, single submitter |
| 958922 | NM_004393.6(DAG1):c.330G>A (p.Trp110Ter) | DAG1 | Pathogenic | criteria provided, single submitter |
| 471776 | NM_004393.6(DAG1):c.454_467del (p.Phe152fs) | DAG1 | Likely pathogenic | criteria provided, single submitter |
| 1054355 | NM_004393.6(DAG1):c.2215_2216del (p.Arg739fs) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1079508 | NM_004393.6(DAG1):c.1251T>C (p.Ala417=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 1176024 | NM_004393.6(DAG1):c.15G>A (p.Val5=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 195220 | NM_004393.6(DAG1):c.258G>C (p.Leu86Phe) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 195221 | NM_004393.6(DAG1):c.183T>C (p.Val61=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 196385 | NM_004393.6(DAG1):c.498G>A (p.Ser166=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 196386 | NM_004393.6(DAG1):c.2196G>A (p.Pro732=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 196387 | NM_004393.6(DAG1):c.735G>A (p.Pro245=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 208542 | NM_004393.6(DAG1):c.2006G>T (p.Cys669Phe) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 257585 | NM_004393.6(DAG1):c.1308G>A (p.Thr436=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 281825 | NM_004393.6(DAG1):c.278T>C (p.Ile93Thr) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 282414 | NM_004393.6(DAG1):c.1905C>T (p.Phe635=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 282535 | NM_004393.6(DAG1):c.717G>A (p.Ser239=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 282862 | NM_004393.6(DAG1):c.2561G>A (p.Arg854Gln) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 283113 | NM_004393.6(DAG1):c.2192C>T (p.Ala731Val) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 283248 | NM_004393.6(DAG1):c.1690C>A (p.Leu564Ile) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 283316 | NM_004393.6(DAG1):c.1022C>T (p.Thr341Ile) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 283992 | NM_004393.6(DAG1):c.2451C>T (p.Leu817=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
| 284115 | NM_004393.6(DAG1):c.510C>T (p.Ala170=) | DAG1 | Conflicting classifications of pathogenicity | criteria provided, conflicting classifications |
Genes & proteins
Mendelian disease overlap and somatic drivers
GenCC: 8 · Orphanet: 7 · 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 |
|---|---|---|---|---|
| DAG1 | Definitive | Autosomal recessive | autosomal recessive limb-girdle muscular dystrophy type 2P | 8 |
Orphanet rare-disease linkage (cohort genes)
| Gene | Orphanet ID | Rare disease |
|---|---|---|
| DAG1 | Orphanet:206599 | Isolated asymptomatic elevation of creatine phosphokinase |
| DAG1 | Orphanet:280333 | Alpha-dystroglycan-related limb-girdle muscular dystrophy R16 |
| DAG1 | Orphanet:370997 | Muscle-eye-brain disease with bilateral multicystic leucodystrophy |
| DAG1 | Orphanet:899 | Walker-Warburg syndrome |
| AMT | Orphanet:289857 | Neonatal glycine encephalopathy |
| AMT | Orphanet:289860 | Infantile glycine encephalopathy |
| AMT | Orphanet:289863 | Atypical glycine encephalopathy |
Cohort genes → proteins
2 cohort genes, 2 distinct canonical proteins.
Evidence partition
| Subset | Genes |
|---|---|
| multi_evidence | 2 |
Cohort genes (full)
| Symbol | HGNC | Ensembl | UniProt | Name | Evidence |
|---|---|---|---|---|---|
| DAG1 | HGNC:2666 | ENSG00000173402 | Q14118 | Dystroglycan 1 | gencc,clinvar |
| AMT | HGNC:473 | ENSG00000145020 | P48728 | Aminomethyltransferase, mitochondrial | clinvar |
Cohort function summary
Lead sentence per gene, UniProt-curated.
| Symbol | Protein name | Function (lead sentence) |
|---|---|---|
| DAG1 | Dystroglycan 1 | The dystroglycan complex is involved in a number of signaling events and processes including laminin deposition and extracellular matrix assembly, acetylcholine receptor clustering, sarcolemmal stability, cell survival, peripheral nerve my… |
| AMT | Aminomethyltransferase, mitochondrial | The glycine cleavage system catalyzes the degradation of glycine. |
Protein-family classification
Druggable: 2 · 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 |
|---|---|---|---|
| Antibody/Immunoglobulin | 1 | 14.6× | 0.135 |
| Enzyme (other) | 1 | 6.0× | 0.160 |
Per-gene assignment
| Symbol | Family | Druggable? | EC | InterPro (top 3) |
|---|---|---|---|---|
| DAG1 | Antibody/Immunoglobulin | yes | Cadg, DAG1_C, Ig-like_fold | |
| AMT | Enzyme (other) | yes | 1.4.1.27 | GCVT_N, GcvT, GcvT_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) | 2 |
| unknown | 0 |
Top tissues across cohort
| Tissue | Cohort genes |
|---|---|
| dorsal root ganglion | 1 |
| olfactory bulb | 1 |
| trigeminal ganglion | 1 |
| liver | 1 |
| right lobe of liver | 1 |
| right uterine tube | 1 |
Per-gene tissue summary (top 30)
| Symbol | Bgee breadth | FANTOM5 breadth | SCXA | Top tissues |
|---|---|---|---|---|
| DAG1 | 299 | ubiquitous | marker | olfactory bulb, trigeminal ganglion, dorsal root ganglion |
| AMT | 140 | broad | yes | right lobe of liver, liver, right uterine tube |
Protein interactions among cohort
Intra-cohort edges: 0.
Hub genes (top 10 by interactor count)
| Symbol | Interactor count |
|---|---|
| DAG1 | 2,301 |
| AMT | 1,716 |
Structural data
PDB: 2 · AlphaFold-only: 0 · No structure: 0
Cohort genes with PDB structures (top 30)
| Symbol | UniProt | PDB entries |
|---|---|---|
| DAG1 | Q14118 | 8 |
| AMT | P48728 | 2 |
Function
Pathway analysis
Distinct Reactome pathways touched by cohort: 13. Enrichment computed across 2 evidence-associated genes (2 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 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| Pathway | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| Defective POMGNT1 causes MDDGA3, MDDGB3 and MDDGC3 | 1 | 2855.0× | 0.002 | DAG1 |
| Defective POMT2 causes MDDGA2, MDDGB2 and MDDGC2 | 1 | 1903.3× | 0.002 | DAG1 |
| Defective POMT1 causes MDDGA1, MDDGB1 and MDDGC1 | 1 | 1903.3× | 0.002 | DAG1 |
| DAG1 core M1 glycosylations | 1 | 1427.5× | 0.002 | DAG1 |
| DAG1 core M2 glycosylations | 1 | 1142.0× | 0.002 | DAG1 |
| DAG1 core M3 glycosylations | 1 | 951.7× | 0.002 | DAG1 |
| Glycine degradation | 1 | 815.7× | 0.002 | AMT |
| Matriglycan biosynthesis on DAG1 | 1 | 407.9× | 0.004 | DAG1 |
| EGR2 and SOX10-mediated initiation of Schwann cell myelination | 1 | 184.2× | 0.008 | DAG1 |
| Formation of the dystrophin-glycoprotein complex (DGC) | 1 | 154.3× | 0.008 | DAG1 |
| Non-integrin membrane-ECM interactions | 1 | 77.2× | 0.014 | DAG1 |
| ECM proteoglycans | 1 | 75.1× | 0.014 | DAG1 |
| Regulation of expression of SLITs and ROBOs | 1 | 34.6× | 0.029 | DAG1 |
GO biological processes by enrichment
Over-representation of cohort genes vs the genome-wide background (hypergeometric test, Benjamini-Hochberg FDR; fold = observed/expected over 2 annotated cohort genes). Counts and members are kept as ground-truth; sorted by enrichment.
| GO term | Cohort genes | Fold | FDR | Sample cohort genes |
|---|---|---|---|---|
| muscle attachment | 1 | 8426.0× | 0.002 | DAG1 |
| nerve maturation | 1 | 8426.0× | 0.002 | DAG1 |
| glycine catabolic process | 1 | 4213.0× | 0.002 | AMT |
| calcium-dependent cell-matrix adhesion | 1 | 4213.0× | 0.002 | DAG1 |
| glycine decarboxylation via glycine cleavage system | 1 | 2808.7× | 0.002 | AMT |
| retrograde trans-synaptic signaling by trans-synaptic protein complex | 1 | 2808.7× | 0.002 | DAG1 |
| response to denervation involved in regulation of muscle adaptation | 1 | 1203.7× | 0.005 | DAG1 |
| morphogenesis of an epithelial sheet | 1 | 842.6× | 0.005 | DAG1 |
| angiogenesis involved in wound healing | 1 | 842.6× | 0.005 | DAG1 |
| branching involved in salivary gland morphogenesis | 1 | 702.2× | 0.005 | DAG1 |
| microtubule anchoring | 1 | 648.1× | 0.005 | DAG1 |
| axon regeneration | 1 | 561.7× | 0.005 | DAG1 |
| commissural neuron axon guidance | 1 | 495.6× | 0.005 | DAG1 |
| nerve development | 1 | 468.1× | 0.005 | DAG1 |
| myelination in peripheral nervous system | 1 | 443.5× | 0.005 | DAG1 |
| skeletal muscle tissue regeneration | 1 | 443.5× | 0.005 | DAG1 |
| regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | 1 | 443.5× | 0.005 | DAG1 |
| epithelial tube branching involved in lung morphogenesis | 1 | 421.3× | 0.005 | DAG1 |
| cellular response to cholesterol | 1 | 421.3× | 0.005 | DAG1 |
| positive regulation of myelination | 1 | 383.0× | 0.005 | DAG1 |
| positive regulation of cell-matrix adhesion | 1 | 337.0× | 0.005 | DAG1 |
| positive regulation of oligodendrocyte differentiation | 1 | 337.0× | 0.005 | DAG1 |
| membrane protein ectodomain proteolysis | 1 | 324.1× | 0.005 | DAG1 |
| positive regulation of Rac protein signal transduction | 1 | 324.1× | 0.005 | DAG1 |
| regulation of synapse organization | 1 | 324.1× | 0.005 | DAG1 |
| inhibitory synapse assembly | 1 | 312.1× | 0.005 | DAG1 |
| response to muscle activity | 1 | 290.6× | 0.005 | DAG1 |
| basement membrane organization | 1 | 255.3× | 0.005 | DAG1 |
| response to peptide hormone | 1 | 195.9× | 0.007 | DAG1 |
| heart morphogenesis | 1 | 187.2× | 0.007 | DAG1 |
Therapeutics
Drug target analysis
Approved (phase 4): 0 · Phase ≥3: 0 · Phased (≥1): 0 · Undrugged: 2
Druggability breadth: 1 of 2 evidence-associated genes (50%) have a ChEMBL target (buckets above are over the deeply-mined display cohort).
Top cohort targets by molecule count
| Symbol | Molecules | Max phase |
|---|---|---|
| DAG1 | 0 | 0 |
| AMT | 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 |
|---|---|---|
| DAG1 | 4 | Binding:4 |
Cohort enzymes (BRENDA EC)
| Symbol | EC numbers | Names |
|---|---|---|
| AMT | 1.4.1.27, 2.1.2.10 | glycine cleavage system, aminomethyltransferase |
Pharmacogenomics
Cohort genes with a PharmGKB record: 2; 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 | 2 | DAG1, AMT |
| D | Druggable family + AlphaFold only, no drug | 0 | |
| E | Difficult family or no structure, no drug | 0 |
Undrugged target profiles
2 cohort genes are undrugged. Ranked by ‘starting-point quality’ (assay depth + drugged-partner adjacency).
| Symbol | ChEMBL assays | Drugged partners (top 3) |
|---|---|---|
| DAG1 | 4 | — |
| AMT | 0 | — |
Clinical trials & evidence
Clinical trials
Clinical trials: 0.